View source for Medicine:Bipolar disorder

{{Short description|Mental disorder that causes periods of depression and abnormally elevated mood}}
{{Pp-semi|small=yes}}
{{Infobox medical condition (new)
| name            = Bipolar disorder
| image           = P culture.svg
| alt             =
| caption         = Bipolar disorder is characterized by episodes of depression and hypomania or mania.
| field           = [[Biology:Psychiatry|Psychiatry]]
| synonyms        = Bipolar affective disorder (BPAD),<ref>{{cite journal | vauthors = Gautam S, Jain A, Gautam M, Gautam A, Jagawat T | title = Clinical Practice Guidelines for Bipolar Affective Disorder (BPAD) in Children and Adolescents | journal = Indian Journal of Psychiatry | volume = 61 | issue = Suppl 2 | pages = 294–305 | date = January 2019 | pmid = 30745704 | pmc = 6345130 | doi = 10.4103/psychiatry.IndianJPsychiatry_570_18 | doi-access = free }}</ref> bipolar illness, manic depression, manic depressive disorder, manic–depressive illness (historical),<ref name=Shorter2005/> manic–depressive psychosis, circular insanity (historical),<ref name=Shorter2005/> bipolar disease<ref>{{cite book| vauthors = Coyle N, Paice JA |title=Oxford Textbook of Palliative Nursing|date=2015|publisher=Oxford University Press, Incorporated|isbn=9780199332342|page=623}}</ref>
| symptoms        = Periods of [[Medicine:Depression (mood)|depression]] and elevated mood<ref name=BMJ2012 /><ref name=DSM5 />
| complications   = [[Medicine:Suicide|Suicide]], [[Medicine:Self-harm|self-harm]]<ref name=BMJ2012/>
| onset           = 25 years old<ref name=BMJ2012 />
| duration        =
| types           = [[Medicine:Bipolar I disorder|Bipolar I disorder]], [[Medicine:Bipolar II disorder|bipolar II disorder]], others<ref name=DSM5 />
| causes          = Environmental and [[Biology:Genetics|genetic]]<ref name=BMJ2012 />
| risks           = Family history, childhood abuse, long-term stress<ref name=BMJ2012 />
| diagnosis       =
| differential    = [[Medicine:Attention deficit hyperactivity disorder|Attention deficit hyperactivity disorder]], [[Medicine:Personality disorder|personality disorder]]s, [[Medicine:Schizophrenia|schizophrenia]], [[Medicine:Substance use disorder|substance use disorder]]<ref name=BMJ2012 />
| prevention      =
| treatment       = [[Medicine:Psychotherapy|Psychotherapy]], [[Chemistry:Medication|medication]]s<ref name=BMJ2012 />
| medication      = [[Chemistry:Lithium (medication)|Lithium]], [[Chemistry:Antipsychotic|antipsychotic]]s, [[Chemistry:Anticonvulsant|anticonvulsant]]s<ref name=BMJ2012 />
| prognosis       =
| frequency       = 1–3%<ref name=BMJ2012/><ref name=Schmitt2014/>
| deaths          =
}}

'''Bipolar disorder''', previously known as '''manic depression''', is a [[Medicine:Mental disorder|mental disorder]] characterized by periods of [[Medicine:Depression (mood)|depression]] and periods of abnormally elevated mood that each last from days to weeks.<ref name="BMJ2012" /><ref name="DSM5" /> If the elevated mood is severe or associated with [[Medicine:Psychosis|psychosis]], it is called [[Medicine:Mania|mania]]; if it is less severe, it is called [[Medicine:Hypomania|hypomania]].<ref name=BMJ2012 /> During mania, an individual behaves or feels abnormally energetic, happy or irritable,<ref name=BMJ2012 /> and they often make impulsive decisions with little regard for the consequences.<ref name=DSM5 /> There is usually also a reduced need for sleep during manic phases.<ref name=DSM5 /> During periods of depression, the individual may experience crying and have a negative outlook on life and poor eye contact with others.<ref name=BMJ2012 /> The risk of [[Medicine:Suicide|suicide]] is high; over a period of 20 years, 6% of those with bipolar disorder died by suicide, while 30–40% engaged in [[Medicine:Self-harm|self-harm]].<ref name=BMJ2012>{{cite journal | vauthors = Anderson IM, Haddad PM, Scott J |title=Bipolar disorder|journal=BMJ (Clinical Research Ed.)|date=December 27, 2012 |volume=345 |page=e8508 |pmid=23271744 |doi=10.1136/bmj.e8508|s2cid=22156246}}</ref> Other mental health issues, such as [[Medicine:Anxiety disorder|anxiety disorder]]s and [[Medicine:Substance use disorder|substance use disorder]]s, are commonly associated with bipolar disorder.<ref name=BMJ2012 />

While the causes of this [[Medicine:Mood disorder|mood disorder]] are not clearly understood, both [[Biology:Genetics|genetic]] and environmental factors are thought to play a role.<ref name=BMJ2012 /> Many genes, each with small effects, may contribute to the development of the disorder.<ref name=BMJ2012 /><ref>{{cite journal| vauthors = Goodwin GM |title=Bipolar disorder |journal=Medicine |volume=40 |issue=11 |pages=596–598 |doi=10.1016/j.mpmed.2012.08.011|year=2012}}</ref> [[Philosophy:Heritability|Genetic factors]] account for about 70–90% of the risk of developing bipolar disorder.<ref>{{cite book| vauthors = Charney A, Sklar P | veditors = Charney D, Nestler E, Sklar P, Buxbaum J |title=Charney & Nestler's Neurobiology of Mental Illness|date=2018|publisher=Oxford University Press|location=New York|page=162|edition=5th|chapter=Genetics of Schizophrenia and Bipolar Disorder|isbn=9780190681425|chapter-url=https://books.google.com/books?id=y8M9DwAAQBAJ&q=Charney%20%26%20Nestler's%20Neurobiology%20of%20Mental%20Illness&pg=PA162}}</ref><ref name="Bobo2017"/> Environmental risk factors include a history of childhood abuse and long-term stress.<ref name=BMJ2012 /> The condition is classified as [[Medicine:Bipolar I disorder|bipolar I disorder]] if there has been at least one manic episode, with or without depressive episodes, and as [[Medicine:Bipolar II disorder|bipolar II disorder]] if there has been at least one hypomanic episode (but no full manic episodes) and one major depressive episode.<ref name=DSM5 /> It is classified as [[Medicine:Cyclothymia|cyclothymia]] if there are hypomanic episodes with periods of depression that do not meet the criteria for major depressive episodes.<ref name="Van Meter 2012" />
If these symptoms are due to drugs or medical problems, they are not diagnosed as bipolar disorder.<ref name=DSM5>{{cite book|author=American Psychiatry Association|title=Diagnostic and Statistical Manual of Mental Disorders|date=2013|publisher=American Psychiatric Publishing |location=Arlington |isbn=978-0-89042-555-8 |pages=123–154 |edition=5th}}</ref> Other conditions that have overlapping symptoms with bipolar disorder include [[Medicine:Attention deficit hyperactivity disorder|attention deficit hyperactivity disorder]], [[Medicine:Personality disorder|personality disorder]]s, [[Medicine:Schizophrenia|schizophrenia]], and [[Medicine:Substance use disorder|substance use disorder]] as well as many other medical conditions.<ref name=BMJ2012 /> [[Medicine:Medical test|Medical test]]ing is not required for a [[Medicine:Diagnosis|diagnosis]], though blood tests or [[Medicine:Medical imaging|medical imaging]] can rule out other problems.<ref name=NIH2016Test>{{cite web|title=Bipolar Disorder|url=https://www.nimh.nih.gov/health/topics/bipolar-disorder/index.shtml#part_145405|author=NIMH|publisher=National Institutes of Health|date=April 2016|access-date=August 13, 2016|url-status=live|archive-url=https://web.archive.org/web/20160727230418/http://www.nimh.nih.gov/health/topics/bipolar-disorder/index.shtml#part_145405|archive-date=July 27, 2016}}</ref>

Mood stabilizers—[[Chemistry:Lithium (medication)|lithium]] and certain [[Chemistry:Anticonvulsant|anticonvulsant]]s such as [[Biology:Valproate|valproate]] and [[Chemistry:Carbamazepine|carbamazepine]] as well as atypical antipsychotics such as [[Chemistry:Aripiprazole|aripiprazole]]—are the mainstay of long-term pharmacologic relapse prevention.<ref name=Lancet2016/> [[Chemistry:Antipsychotic|Antipsychotic]]s are additionally given during acute manic episodes as well as in cases where mood stabilizers are poorly tolerated or ineffective. In patients where compliance is of concern, long-acting injectable formulations are available.<ref name=Lancet2016/><!-- Quote: 'Mood stabilisers and antipsychotics are the mainstay of acute management of bipolar mania and depression.' --> There is some evidence that [[Medicine:Psychotherapy|psychotherapy]] improves the course of this disorder.<ref>{{cite journal | vauthors = Goodwin GM, Haddad PM, Ferrier IN, Aronson JK, Barnes T, Cipriani A, Coghill DR, Fazel S, Geddes JR, Grunze H, Holmes EA, Howes O, Hudson S, Hunt N, Jones I, Macmillan IC, McAllister-Williams H, Miklowitz DR, Morriss R, Munafò M, Paton C, Saharkian BJ, Saunders K, Sinclair J, Taylor D, Vieta E, Young AH | title = Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology | journal = Journal of Psychopharmacology | volume = 30 | issue = 6 | pages = 495–553 | date = June 2016 | pmid = 26979387 | pmc = 4922419 | doi = 10.1177/0269881116636545 | quote = Currently, medication remains the key to successful practice for most patients in the long term. ... At present the preferred strategy is for continuous rather than intermittent treatment with oral medicines to prevent new mood episodes. }}</ref> The use of antidepressants in depressive episodes is controversial: they can be effective but have been implicated in triggering manic episodes.<ref>{{cite journal | vauthors = Cheniaux E, Nardi AE | title = Evaluating the efficacy and safety of antidepressants in patients with bipolar disorder | journal = Expert Opinion on Drug Safety | volume = 18 | issue = 10 | pages = 893–913 | date = October 2019 | pmid = 31364895 | doi = 10.1080/14740338.2019.1651291 | s2cid = 198997808 }}</ref> The treatment of depressive episodes, therefore, is often difficult.<ref name=Lancet2016>{{cite journal | vauthors = Grande I, Berk M, Birmaher B, Vieta E | title = Bipolar disorder | journal = Lancet | volume = 387 | issue = 10027 | pages = 1561–1572 | date = April 2016 | pmid = 26388529 | doi = 10.1016/S0140-6736(15)00241-X | s2cid = 205976059 }}</ref> [[Biology:Electroconvulsive therapy|Electroconvulsive therapy]] (ECT) is effective in acute manic and depressive episodes, especially with psychosis or [[Medicine:Catatonia|catatonia]].{{efn|1=Catatonia is a syndrome characterized by profound unresponsiveness or stupor with abnormal movements in a person who is otherwise awake.<ref name="DSM-5-introduction">{{cite book| last=American Psychiatric Association| year=2013| title=Diagnostic and Statistical Manual of Mental Disorders| edition=Fifth| publisher=American Psychiatric Publishing| location=Arlington, VA| pages=[https://archive.org/details/diagnosticstatis0005unse/page/119 119–121]| isbn=978-0-89042-555-8| url=https://archive.org/details/diagnosticstatis0005unse/page/119}}</ref>}}<ref name=Lancet2016/> Admission to a psychiatric hospital may be required if a person is a risk to themselves or others; [[Social:Involuntary treatment|involuntary treatment]] is sometimes necessary if the affected person refuses treatment.<ref name=BMJ2012 />

Bipolar disorder occurs in approximately 2% of the global population.<ref name="Nierenberg 2023">{{cite journal |last1=Nierenberg |first1=Andrew A. |last2=Agustini |first2=Bruno |last3=Köhler-Forsberg |first3=Ole |last4=Cusin |first4=Cristina |last5=Katz |first5=Douglas |last6=Sylvia |first6=Louisa G. |last7=Peters |first7=Amy |last8=Berk |first8=Michael |title=Diagnosis and Treatment of Bipolar Disorder: A Review |journal=JAMA |date=10 October 2023 |volume=330 |issue=14 |pages=1370–1380 |doi=10.1001/jama.2023.18588|pmid=37815563 |s2cid=263801832 }}</ref> In the United States, about 3% are estimated to be affected at some point in their life; rates appear to be similar in females and males.<ref name=Schmitt2014>{{cite journal | vauthors = Schmitt A, Malchow B, Hasan A, Falkai P | title = The impact of environmental factors in severe psychiatric disorders | journal = Frontiers in Neuroscience | volume = 8 | issue = 19 | pages = 19 | date = February 2014 | pmid = 24574956 | pmc = 3920481 | doi = 10.3389/fnins.2014.00019 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Diflorio A, Jones I | title = Is sex important? Gender differences in bipolar disorder | journal = International Review of Psychiatry | volume = 22 | issue = 5 | pages = 437–452 | year = 2010 | pmid = 21047158 | doi = 10.3109/09540261.2010.514601 | s2cid = 45781872 }}</ref> Symptoms most commonly begin between the ages of 20 and 25 years old; an earlier onset in life is associated with a worse prognosis.<ref name="Carvalho" /> Interest in functioning in the assessment of patients with bipolar disorder is growing, with an emphasis on specific domains such as work, education, social life, family, and cognition.<ref>{{cite journal | vauthors = Chen M, Fitzgerald HM, Madera JJ, Tohen M | title = Functional outcome assessment in bipolar disorder: A systematic literature review | journal = Bipolar Disorders | volume = 21 | issue = 3 | pages = 194–214 | date = May 2019 | pmid = 30887632 | pmc = 6593429 | doi = 10.1111/bdi.12775 }}</ref> Around one-quarter to one-third of people with bipolar disorder have financial, social or work-related problems due to the illness.<ref name=BMJ2012 /> Bipolar disorder is among the top 20 causes of disability worldwide and leads to substantial costs for society.<ref name="Ferrari2016">{{cite journal | vauthors = Ferrari AJ, Stockings E, Khoo JP, Erskine HE, Degenhardt L, Vos T, Whiteford HA | title = The prevalence and burden of bipolar disorder: findings from the Global Burden of Disease Study 2013 | journal = Bipolar Disorders | volume = 18 | issue = 5 | pages = 440–450 | date = August 2016 | pmid = 27566286 | doi = 10.1111/bdi.12423 | type = Review | s2cid = 46097223 | hdl = 11343/291577 | hdl-access = free }}</ref> Due to lifestyle choices and the side effects of medications, the risk of death from natural causes such as coronary heart disease in people with bipolar disorder is twice that of the general population.<ref name=BMJ2012 />

== Signs and symptoms ==

Late adolescence and early adulthood are peak years for the onset of bipolar disorder.<ref name="Christie88">{{cite journal |vauthors=Christie KA, Burke JD, Regier DA, Rae DS, Boyd JH, Locke BZ | title = Epidemiologic evidence for early onset of mental disorders and higher risk of drug abuse in young adults | journal = The American Journal of Psychiatry | volume = 145 | issue = 8 | pages = 971–975 | year = 1988 | pmid = 3394882 | doi=10.1176/ajp.145.8.971}}</ref>{{sfn|Goodwin|Jamison|2007|p=1945}} The condition is characterized by intermittent episodes of [[Medicine:Mania|mania]], commonly (but not in every patient) alternating with bouts of [[Medicine:Depression (mood)|depression]], with an absence of symptoms in between.<ref name="Chen2011"/><ref name=":3">{{cite book |last=Reus |first=Victor |title=Harrison's Principles of Internal Medicine |date=2022 |publisher=McGraw Hill |year=2022 |isbn=978-1-264-26850-4 |edition=21st |location=New York |chapter=Chapter 452: Psychiatric Disorders}}</ref> During these episodes, people with bipolar disorder exhibit disruptions in normal mood, psychomotor activity (the level of physical activity that is influenced by mood)—e.g. constant fidgeting during mania or slowed movements during depression—[[Biology:Circadian rhythm|circadian rhythm]] and cognition. Mania can present with varying levels of mood disturbance, ranging from [[Chemistry:Euphoria|euphoria]], which is associated with "classic mania", to [[Medicine:Dysphoria|dysphoria]] and irritability.<ref name=akiskalsadock>{{cite book| vauthors = Akiskal H | veditors = Sadock B, Sadock V, Ruiz P |title=Kaplan and Sadock's Comprehensive Textbook of Psychiatry|date=2017|publisher=Wolters Kluwer|location=New York|edition=10th|chapter=13.4 Mood Disorders: Clinical Features}}{{ISBN?}}</ref> Psychotic symptoms such as delusions or hallucinations may occur in both manic and depressive episodes; their content and nature are consistent with the person's prevailing mood.<ref name=BMJ2012/> In some people with bipolar disorder, depressive symptoms predominate, and the episodes of mania are always the more subdued [[Medicine:Hypomania|hypomania]] type.<ref name=":3" />

According to the DSM-5 criteria, mania is distinguished from hypomania by the duration: hypomania is present if elevated mood symptoms persist for at least four consecutive days, while mania is present if such symptoms persist for more than a week. Unlike mania, hypomania is not always associated with impaired functioning.<ref name=Lancet2016/><!-- cites 2 previous sentences --> The biological mechanisms responsible for switching from a manic or hypomanic episode to a depressive episode, or vice versa, remain poorly understood.<ref name="Salvadore2010">{{cite journal | vauthors = Salvadore G, Quiroz JA, Machado-Vieira R, Henter ID, Manji HK, Zarate CA | title = The neurobiology of the switch process in bipolar disorder: a review | journal = The Journal of Clinical Psychiatry | volume = 71 | issue = 11 | pages = 1488–1501 | date = November 2010 | pmid = 20492846 | pmc = 3000635 | doi = 10.4088/JCP.09r05259gre }}</ref>

=== Manic episodes ===
[[File:A woman diagnosed as suffering from hilarious mania. Colour Wellcome L0026687.jpg|thumb|left|An 1892 color lithograph depicting a woman diagnosed with ''hilarious mania'']]

Also known as a manic episode, mania is a distinct period of at least one week of elevated or irritable mood, which can range from euphoria to [[Medicine:Delirium|delirium]]. The core symptom of mania involves an [[Medicine:Psychomotor agitation|increase in energy of psychomotor activity]]. Mania can also present with increased self-esteem or [[Philosophy:Grandiosity|grandiosity]], [[Social:Racing thoughts|racing thoughts]], [[Medicine:Pressure of speech|pressured speech]] that is difficult to interrupt, decreased need for sleep, disinhibited social behavior,<ref name=akiskalsadock/> increased goal-oriented activities and impaired judgement, which can lead to exhibition of behaviors characterized as impulsive or high-risk, such as [[Medicine:Hypersexuality|hypersexuality]] or excessive spending.<ref name="Barnett2009" /><ref name="Tarr2011">{{cite journal|vauthors=Tarr GP, Glue P, Herbison P|date=November 2011|title=Comparative efficacy and acceptability of mood stabilizer and second generation antipsychotic monotherapy for acute mania—a systematic review and meta-analysis|journal=J Affect Disord|volume=134|issue=1–3|pages=14–19|doi=10.1016/j.jad.2010.11.009|pmid=21145595}}</ref><ref name="Beentjes2012">{{cite journal|vauthors=Beentjes TA, Goossens PJ, Poslawsky IE|date=October 2012|title=Caregiver burden in bipolar hypomania and mania: a systematic review|journal=Perspect Psychiatr Care|volume=48|issue=4|pages=187–197|doi=10.1111/j.1744-6163.2012.00328.x|pmid=23005586|doi-access=free}}</ref> To fit the definition of a manic episode, these behaviors must impair the individual's ability to socialize or work.<ref name="Barnett2009" /><ref name="Beentjes2012" /> If untreated, a manic episode usually lasts three to six months.<ref>{{cite journal | author = Titmarsh S | title = Characteristics and duration of mania: implications for continuation treatment | journal = Progress in Neurology and Psychiatry | date = May–June 2013 | volume = 17 | issue = 3 | pages = 26–27 | doi = 10.1002/pnp.283 | s2cid = 144883133 | doi-access = free }}</ref>

In severe manic episodes, a person can experience [[Medicine:Psychosis|psychotic]] symptoms, where thought content is affected along with mood.<ref name="Beentjes2012" /> They may feel unstoppable, [[Philosophy:Persecutory delusion|persecuted]], or as if they have a special relationship with God, a great mission to accomplish, or other grandiose or delusional ideas.<ref name="Knowles2011">{{cite journal |vauthors=Knowles R, McCarthy-Jones S, Rowse G | title = Grandiose delusions: a review and theoretical integration of cognitive and affective perspectives | journal = Clin Psychol Rev | volume = 31 | issue = 4 | pages = 684–696 | date = June 2011 | pmid = 21482326 | doi = 10.1016/j.cpr.2011.02.009 }}</ref><ref>{{cite journal |last1=Baethge |first1=Christopher |last2=Baldessarini |first2=Ross J |last3=Freudenthal |first3=Klaus |last4=Streeruwitz |first4=Anna |last5=Bauer |first5=Michael |last6=Bschor |first6=Tom |date=April 2005 |title=Hallucinations in bipolar disorder: characteristics and comparison to unipolar depression and schizophrenia |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1399-5618.2004.00175.x |journal=Bipolar Disorders |language=en |volume=7 |issue=2 |pages=136–145 |doi=10.1111/j.1399-5618.2004.00175.x |pmid=15762854 |issn=1398-5647}}</ref> This may lead to violent behavior and, sometimes, hospitalization in an inpatient psychiatric hospital.<ref name="Tarr2011" /><ref name="Beentjes2012" /> The severity of manic symptoms can be measured by rating scales such as the [[Social:Young Mania Rating Scale|Young Mania Rating Scale]], though questions remain about the reliability of these scales.<ref>{{cite journal | author = Furukawa TA | title = Assessment of mood: Guides for clinicians | journal = Journal of Psychosomatic Research | volume = 68 | issue = 6 | pages = 581–589 | year = 2010 | pmid = 20488276 | doi = 10.1016/j.jpsychores.2009.05.003 }}</ref>

The onset of a manic or depressive episode is often foreshadowed by [[Medicine:Sleep disorder|sleep disturbance]].<ref name="McKenna2012">{{cite journal |vauthors=McKenna BS, Eyler LT | title = Overlapping prefrontal systems involved in cognitive and emotional processing in euthymic bipolar disorder and following sleep deprivation: a review of functional neuroimaging studies | journal = Clin Psychol Rev | volume = 32 | issue = 7 | pages = 650–663 | date = November 2012 | pmid = 22926687 | pmc = 3922056 | doi = 10.1016/j.cpr.2012.07.003 }}</ref> Manic individuals often have a history of [[Medicine:Substance use disorder|substance use disorder]] developed over years as a form of "self-medication".<ref name="Post2013">{{cite journal|vauthors=Post RM, Kalivas P|date=March 2013|title=Bipolar disorder and substance misuse: pathological and therapeutic implications of their comorbidity and cross-sensitisation|journal=Br J Psychiatry|volume=202|issue=3|pages=172–176|doi=10.1192/bjp.bp.112.116855|pmc=4340700|pmid=23457180|df=mdy-all}}</ref>

=== Hypomanic episodes ===
[[File:'Melancholy passing into mania' Wellcome L0022595 (cropped).jpg|thumb|An 1858 lithograph captioned 'Melancholy passing into mania']]

[[Medicine:Hypomania|Hypomania]] is the milder form of mania, defined as at least four days of the same criteria as mania,<ref name="Beentjes2012" /> but which does not cause a significant decrease in the individual's ability to socialize or work, lacks psychotic features such as delusions or hallucinations, and does not require psychiatric hospitalization.<ref name="Barnett2009" /> Overall functioning may actually increase during episodes of hypomania and is thought to serve as a defense mechanism against depression by some.<ref name="Bowins2013" /> Hypomanic episodes rarely progress to full-blown manic episodes.<ref name="Bowins2013" /> Some people who experience hypomania show increased creativity,<ref name="Beentjes2012" /><ref name="pmid20936438">{{cite journal|vauthors=Srivastava S, Ketter TA|date=December 2010|title=The link between bipolar disorders and creativity: evidence from personality and temperament studies.|journal=Current Psychiatry Reports|volume=12|issue=6|pages=522–530|doi=10.1007/s11920-010-0159-x|pmid=20936438|s2cid=1880847}}</ref> while others are irritable or demonstrate poor judgment.<ref name="Bobo2017">{{cite journal | vauthors = Bobo WV | title = The Diagnosis and Management of Bipolar I and II Disorders: Clinical Practice Update | journal = Mayo Clinic Proceedings | volume = 92 | issue = 10 | pages = 1532–1551 | date = October 2017 | pmid = 28888714 | doi = 10.1016/j.mayocp.2017.06.022 | type = Review | doi-access = free }}</ref>

Hypomania may feel good to some individuals who experience it, though most people who experience hypomania state that the stress of the experience is very painful.<ref name="Beentjes2012" /> People with bipolar disorder who experience hypomania tend to forget the effects of their actions on those around them. Even when family and friends recognize [[Philosophy:Mood swing|mood swing]]s, the individual will often deny that anything is wrong.<ref>{{cite web|url=http://www.pueblo.gsa.gov/cic_text/health/bipolar/bipolar.htm |title=Bipolar Disorder: NIH Publication No. 95-3679|publisher=U.S. National Institutes of Health|date=September 1995 |archive-url = https://web.archive.org/web/20080429204140/http://www.pueblo.gsa.gov/cic_text/health/bipolar/bipolar.htm |archive-date = April 29, 2008}}</ref> If not accompanied by depressive episodes, hypomanic episodes are often not deemed problematic unless the mood changes are uncontrollable or volatile.<ref name="Bowins2013">{{cite journal | author = Bowins B | title = Cognitive regulatory control therapies | journal = Am J Psychother | volume = 67 | issue = 3 | pages = 215–236 | year = 2007 | pmid = 24236353 | doi = 10.1176/appi.psychotherapy.2013.67.3.215 | doi-access = free }}</ref> Most commonly, symptoms continue for time periods from a few weeks to a few months.<ref>{{cite web|url=http://www.webmd.com/bipolar-disorder/guide/bipolar-2-disorder|title=Bipolar II Disorder Symptoms and Signs|publisher=Web M.D.|access-date=December 6, 2010|url-status=live|archive-url=https://web.archive.org/web/20101209213147/http://www.webmd.com/bipolar-disorder/guide/bipolar-2-disorder|archive-date=December 9, 2010}}</ref>

=== Depressive episodes ===
{{Main|Medicine:Depression (mood)}}
[[File:'Melancholy' by W. Bagg Wellcome L0022594.jpg|thumb|left|''Melancholy'' by William Bagg, after a photograph by Hugh Welch Diamond]]

Symptoms of the depressive phase of bipolar disorder include persistent feelings of sadness, irritability or anger, [[Medicine:Anhedonia|loss of interest in previously enjoyed activities]], excessive or inappropriate [[Philosophy:Guilt (emotion)|guilt]], [[Medicine:Depression (mood)|hopelessness]], [[Medicine:Hypersomnia|sleeping too much]] or [[Medicine:Insomnia|not enough]], changes in appetite and/or weight, [[Medicine:Fatigue|fatigue]], problems concentrating, self-loathing or feelings of worthlessness, and thoughts of death or [[Medicine:Suicide|suicide]].<ref name="Muneer2013" /> Although the DSM-5 criteria for diagnosing unipolar and bipolar episodes are the same, some clinical features are more common in the latter, including increased sleep, sudden onset and resolution of symptoms, significant weight gain or loss, and severe episodes after childbirth.<ref name=Lancet2016/>

The earlier the age of onset, the more likely the first few episodes are to be depressive.<ref name="Bowden">{{cite journal | author = Bowden CL | title = Strategies to reduce misdiagnosis of bipolar depression | journal = Psychiatr Serv | volume = 52 | issue = 1 | pages = 51–55 |date=January 2001  | pmid = 11141528 | doi = 10.1176/appi.ps.52.1.51 }}</ref> For most people with bipolar types 1 and 2, the depressive episodes are much longer than the manic or hypomanic episodes.<ref name="Carvalho" /> Since a diagnosis of bipolar disorder requires a manic or hypomanic episode, many affected individuals are initially misdiagnosed as having major depression and incorrectly treated with prescribed antidepressants.<ref name=Muzina2007>{{cite journal |vauthors=Muzina DJ, Kemp DE, McIntyre RS | title = Differentiating bipolar disorders from major depressive disorders: treatment implications | journal = Ann Clin Psychiatry | volume = 19 | issue = 4 | pages = 305–312 | date = October–December 2007 | pmid = 18058287 | doi = 10.1080/10401230701653591 }}</ref>

=== Mixed affective episodes ===
{{Main|Medicine:Mixed affective state}}

In bipolar disorder, a [[Medicine:Mixed affective state|mixed state]] is an episode during which symptoms of both mania and depression occur simultaneously.<ref name="Swann2013">{{cite journal |vauthors=Swann AC, Lafer B, Perugi G, Frye MA, Bauer M, Bahk WM, Scott J, Ha K, Suppes T | title = Bipolar mixed states: an international society for bipolar disorders task force report of symptom structure, course of illness, and diagnosis | journal = Am J Psychiatry | volume = 170 | issue = 1 | pages = 31–42 | date = January 2013 | pmid = 23223893 | doi = 10.1176/appi.ajp.2012.12030301 }}</ref> Individuals experiencing a mixed state may have manic symptoms such as grandiose thoughts while simultaneously experiencing depressive symptoms such as excessive guilt or feeling suicidal.<ref name="Swann2013" /> They are considered to have a higher risk for suicidal behavior as depressive emotions such as hopelessness are often paired with [[Medicine:Emotional lability|mood swings]] or [[Social:Impulsivity|difficulties with impulse control]].<ref name="Swann2013" /> [[Medicine:Anxiety disorder|Anxiety disorder]]s occur more frequently as a comorbidity in mixed bipolar episodes than in non-mixed bipolar depression or mania.<ref name="Swann2013" /> Substance (including alcohol) use also follows this trend, thereby appearing to depict bipolar symptoms as no more than a consequence of substance use.<ref name="Swann2013" />

=== Comorbid conditions ===
People with bipolar disorder often have other co-existing psychiatric conditions such as [[Medicine:Anxiety|anxiety]] (present in about 71% of people with bipolar disorder), substance abuse (56%), personality disorders (36%) and [[Medicine:Attention deficit hyperactivity disorder|attention deficit hyperactivity disorder]] (10–20%) which can add to the burden of illness and worsen the prognosis.<ref name="Carvalho">{{cite journal |vauthors=Carvalho AF, Firth J, Vieta E |title=Bipolar Disorder |journal=N. Engl. J. Med. |volume=383 |issue=1 |pages=58–66 |date=July 2020 |pmid=32609982 |doi=10.1056/NEJMra1906193 |s2cid=220309576 }}</ref> Certain medical conditions are also more common in people with bipolar disorder as compared to the general population. This includes increased rates of [[Medicine:Metabolic syndrome|metabolic syndrome]] (present in 37% of people with bipolar disorder), migraine headaches (35%), obesity (21%) and [[Medicine:Type 2 diabetes|type 2 diabetes]] (14%).<ref name="Carvalho" /> This contributes to a risk of death that is two times higher in those with bipolar disorder as compared to the general population.<ref name="Carvalho" />

[[Medicine:Substance use disorder|Substance use disorder]] is a common comorbidity in bipolar disorder; the subject has been widely reviewed.<ref>{{cite journal | vauthors = Cassidy F, Ahearn EP, Carroll BJ | title = Substance abuse in bipolar disorder | journal = Bipolar Disorders | volume = 3 | issue = 4 | pages = 181–188 | date = August 2001 | pmid = 11552957 | doi = 10.1034/j.1399-5618.2001.30403.x }}</ref>{{update inline|date=August 2022}}<ref>{{cite journal | vauthors = Messer T, Lammers G, Müller-Siecheneder F, Schmidt RF, Latifi S | title = Substance abuse in patients with bipolar disorder: A systematic review and meta-analysis | journal = Psychiatry Research | volume = 253 | pages = 338–350 | date = July 2017 | pmid = 28419959 | doi = 10.1016/j.psychres.2017.02.067 | s2cid = 24177245 }}</ref>

== Causes ==
The causes of bipolar disorder likely vary between individuals and the exact mechanism underlying the disorder remains unclear.<ref name="Nierenberg2013">{{cite journal |vauthors=Nierenberg AA, Kansky C, Brennan BP, Shelton RC, Perlis R, Iosifescu DV | title = Mitochondrial modulators for bipolar disorder: a pathophysiologically informed paradigm for new drug development | journal = Aust N Z J Psychiatry | volume = 47 | issue = 1 | pages = 26–42 | date = January 2013 | pmid = 22711881 | doi = 10.1177/0004867412449303 | s2cid = 22983555 }}</ref> Genetic influences are believed to account for 73–93% of the risk of developing the disorder indicating a strong hereditary component.<ref name="Bobo2017"/> The overall [[Philosophy:Heritability|heritability]] of the bipolar spectrum has been estimated at 0.71.<ref name="Edvardsen2008">{{cite journal |vauthors=Edvardsen J, Torgersen S, Røysamb E, Lygren S, Skre I, Onstad S, Oien PA | title = Heritability of bipolar spectrum disorders. Unity or heterogeneity? | journal = Journal of Affective Disorders | volume = 106 | issue = 3 | pages = 229–240 | year = 2008 | pmid = 17692389 | doi = 10.1016/j.jad.2007.07.001 }}</ref> Twin studies have been limited by relatively small sample sizes but have indicated a substantial genetic contribution, as well as environmental influence. For bipolar I disorder, the rate at which identical twins (same genes) will both have bipolar I disorder (concordance) is around 40%, compared to about 5% in fraternal twins.<ref name="Barnett2009" /><ref name="Kieseppa_2004">{{cite journal |vauthors=Kieseppä T, Partonen T, Haukka J, Kaprio J, Lönnqvist J | title = High Concordance of Bipolar I Disorder in a Nationwide Sample of Twins | journal = American Journal of Psychiatry | volume = 161 | issue = 10 | pages = 1814–1821 | year = 2004 | pmid = 15465978 | doi = 10.1176/appi.ajp.161.10.1814 }}</ref> A combination of bipolar I, II, and [[Medicine:Cyclothymia|cyclothymia]] similarly produced rates of 42% and 11% (identical and fraternal twins, respectively).<ref name="Edvardsen2008" /> The rates of bipolar II combinations without bipolar I are lower{{Em dash}}bipolar II at 23 and 17%, and bipolar II combining with cyclothymia at 33 and 14%{{Em dash}}which may reflect relatively higher genetic [[Chemistry:Homogeneity and heterogeneity|heterogeneity]].<ref name="Edvardsen2008" />

The cause of bipolar disorders overlaps with major depressive disorder. When defining concordance as the co-twins having either bipolar disorder or major depression, then the concordance rate rises to 67% in identical twins and 19% in fraternal twins.<ref name=McGuffin2003>{{cite journal |vauthors=McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A | title = The Heritability of Bipolar Affective Disorder and the Genetic Relationship to Unipolar Depression | journal = Archives of General Psychiatry | volume = 60 | issue = 5 | pages = 497–502 | year = 2003 | pmid = 12742871 | doi = 10.1001/archpsyc.60.5.497 | doi-access = free }}</ref> The relatively low concordance between fraternal twins brought up together suggests that shared family environmental effects are limited, although the ability to detect them has been limited by small sample sizes.<ref name="Edvardsen2008" />

=== Genetic ===
Behavioral genetic studies have suggested that many chromosomal regions and [[Biology:Candidate gene|candidate gene]]s are related to bipolar disorder susceptibility with each gene exerting a mild to moderate effect.<ref name="Kerner2014">{{cite journal|author=Kerner B|date=February 2014|title=Genetics of bipolar disorder|journal=Appl Clin Genet|volume=7|pages=33–42|doi=10.2147/tacg.s39297|pmc=3966627|pmid=24683306 |doi-access=free }}</ref> The risk of bipolar disorder is nearly ten-fold higher in [[Social:First-degree relatives|first-degree relatives]] of those with bipolar disorder than in the general population; similarly, the risk of major depressive disorder is three times higher in relatives of those with bipolar disorder than in the general population.<ref name="Barnett2009" />

Although the first [[Biology:Genetic linkage|genetic linkage]] finding for mania was in 1969,<ref>{{cite journal| vauthors = Reich T, Clayton PJ, Winokur G | s2cid = 33268 | title = Family history studies: V. The genetics of mania | journal = The American Journal of Psychiatry | volume = 125 | issue = 10 | pages = 1358–1369 | date = April 1969 | pmid = 5304735 | doi = 10.1176/ajp.125.10.1358 }}</ref> linkage studies have been inconsistent.<ref name="Barnett2009">{{cite journal | vauthors = Barnett JH, Smoller JW | title = The genetics of bipolar disorder | journal = Neuroscience | volume = 164 | issue = 1 | pages = 331–343 | date = November 2009 | pmid = 19358880 | pmc = 3637882 | doi = 10.1016/j.neuroscience.2009.03.080 }}</ref> Findings point strongly to heterogeneity, with different genes implicated in different families.<ref>{{cite journal |vauthors=Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger JI, Craddock N, DePaulo JR, Baron M, Gershon ES, Ekholm J, Cichon S, Turecki G, Claes S, Kelsoe JR, Schofield PR, Badenhop RF, Morissette J, Coon H, Blackwood D, McInnes LA, Foroud T, Edenberg HJ, Reich T, Rice JP, Goate A, McInnis MG, McMahon FJ, Badner JA, Goldin LR, Bennett P, Willour VL, Zandi PP, Liu J, Gilliam C, Juo SH, Berrettini WH, Yoshikawa T, Peltonen L, Lönnqvist J, Nöthen MM, Schumacher J, Windemuth C, Rietschel M, Propping P, Maier W, Alda M, Grof P, Rouleau GA, Del-Favero J, Van Broeckhoven C, Mendlewicz J, Adolfsson R, Spence MA, Luebbert H, Adams LJ, Donald JA, Mitchell PB, Barden N, Shink E, Byerley W, Muir W, Visscher PM, Macgregor S, Gurling H, Kalsi G, McQuillin A, Escamilla MA, Reus VI, Leon P, Freimer NB, Ewald H, Kruse TA, Mors O, Radhakrishna U, Blouin JL, Antonarakis SE, Akarsu N | display-authors = 6 | title = Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part III: Bipolar Disorder | journal = The American Journal of Human Genetics | volume = 73 | issue = 1 | pages = 49–62 | year = 2003 | pmid = 12802785 | pmc = 1180589 | doi = 10.1086/376547 }}</ref> Robust and replicable genome-wide significant associations showed several common [[Biology:Single-nucleotide polymorphism|single-nucleotide polymorphism]]s (SNPs) are associated with bipolar disorder, including variants within the genes ''CACNA1C'', ''ODZ4'', and ''NCAN''.<ref name="Kerner2014" /><ref name="Craddock2013">{{cite journal |vauthors=Craddock N, Sklar P | title = Genetics of bipolar disorder | journal = Lancet | volume = 381 | issue = 9878 | pages = 1654–1662 | date = May 2013 | pmid = 23663951 | doi = 10.1016/S0140-6736(13)60855-7 | s2cid = 9502929 }}</ref> The largest and most recent [[Philosophy:Genome-wide association study|genome-wide association study]] failed to find any locus that exerts a large effect, reinforcing the idea that no single gene is responsible for bipolar disorder in most cases.<ref name="Craddock2013" /> Polymorphisms in ''BDNF'', ''DRD4'', ''DAO'', and ''[[Biology:TPH1|TPH1]]'' have been frequently associated with bipolar disorder and were initially associated in a [[Meta-analysis|meta-analysis]], but this association disappeared after correction for multiple testing.<ref>{{cite journal | vauthors = Seifuddin F, Mahon PB, Judy J, Pirooznia M, Jancic D, Taylor J, Goes FS, Potash JB, Zandi PP | title = Meta-analysis of genetic association studies on bipolar disorder | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 159B | issue = 5 | pages = 508–518 | date = July 2012 | pmid = 22573399 | pmc = 3582382 | doi = 10.1002/ajmg.b.32057 }}</ref> On the other hand, two polymorphisms in ''[[Biology:TPH2|TPH2]]'' were identified as being associated with bipolar disorder.<ref>{{cite journal | vauthors = Gao J, Jia M, Qiao D, Qiu H, Sokolove J, Zhang J, Pan Z | title = TPH2 gene polymorphisms and bipolar disorder: A meta-analysis | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 171B | issue = 2 | pages = 145–152 | date = March 2016 | pmid = 26365518 | doi = 10.1002/ajmg.b.32381 | s2cid = 9467242 | doi-access = free }}</ref>

Due to the inconsistent findings in a [[Philosophy:Genome-wide association study|genome-wide association study]], multiple studies have undertaken the approach of analyzing SNPs in biological pathways. Signaling pathways traditionally associated with bipolar disorder that have been supported by these studies include [[Biology:Corticotropin-releasing hormone|corticotropin-releasing hormone]] signaling, cardiac β-adrenergic signaling, [[Biology:Phospholipase C|phospholipase C]] signaling, glutamate receptor signaling,<ref>{{cite journal | vauthors = Torkamani A, Topol EJ, Schork NJ | title = Pathway analysis of seven common diseases assessed by genome-wide association | journal = Genomics | volume = 92 | issue = 5 | pages = 265–272 | date = November 2008 | pmid = 18722519 | pmc = 2602835 | doi = 10.1016/j.ygeno.2008.07.011 }}</ref> cardiac hypertrophy signaling, [[Biology:Wnt signaling pathway|Wnt signaling]], Notch signaling,<ref>{{cite journal | vauthors = Pedroso I, Lourdusamy A, Rietschel M, Nöthen MM, Cichon S, McGuffin P, Al-Chalabi A, Barnes MR, Breen G | title = Common genetic variants and gene-expression changes associated with bipolar disorder are over-represented in brain signaling pathway genes | journal = Biological Psychiatry | volume = 72 | issue = 4 | pages = 311–317 | date = August 2012 | pmid = 22502986 | doi = 10.1016/j.biopsych.2011.12.031 | s2cid = 30065607 | url = https://zenodo.org/record/9822 }}</ref> and [[Chemistry:Endothelin 1|endothelin 1]] signaling. Of the 16 genes identified in these pathways, three were found to be dysregulated in the [[Biology:Dorsolateral prefrontal cortex|dorsolateral prefrontal cortex]] portion of the brain in post-mortem studies: ''CACNA1C'', ''[[Biology:GNG2|GNG2]]'', and ''[[Biology:ITPR2|ITPR2]]''.<ref>{{cite journal | vauthors = Nurnberger JI, Koller DL, Jung J, Edenberg HJ, Foroud T, Guella I, Vawter MP, Kelsoe JR | title = Identification of pathways for bipolar disorder: a meta-analysis | journal = JAMA Psychiatry | volume = 71 | issue = 6 | pages = 657–664 | date = June 2014 | pmid = 24718920 | pmc = 4523227 | doi = 10.1001/jamapsychiatry.2014.176 }}</ref>

Bipolar disorder is associated with reduced expression of specific [[Biology:DNA repair|DNA repair]] enzymes and increased levels of oxidative [[Biology:DNA damage (naturally occurring)|DNA damages]].<ref name="pmid27126805">{{cite journal |vauthors=Raza MU, Tufan T, Wang Y, Hill C, Zhu MY |title=DNA Damage in Major Psychiatric Diseases |journal=Neurotox Res |volume=30 |issue=2 |pages=251–267 |date=August 2016 |pmid=27126805 |pmc=4947450 |doi=10.1007/s12640-016-9621-9 }}</ref>

=== Environmental ===
[[Social:Psychosocial|Psychosocial]] factors play a significant role in the development and course of bipolar disorder, and individual psychosocial variables may interact with genetic dispositions.<ref name="Serretti">{{cite journal |vauthors=Serretti A, Mandelli L | title = The genetics of bipolar disorder: Genome 'hot regions,' genes, new potential candidates and future directions | journal = Molecular Psychiatry | volume = 13 | issue = 8 | pages = 742–71 | year = 2008 | pmid = 18332878 | doi = 10.1038/mp.2008.29 | doi-access = free }}</ref> Recent life events and interpersonal relationships likely contribute to the onset  and recurrence of bipolar mood episodes, just as they do for unipolar depression.<ref name="Geddestreatment" /> In surveys, 30–50% of adults diagnosed with bipolar disorder report traumatic/abusive experiences in childhood, which is associated with earlier onset, a higher rate of suicide attempts, and more co-occurring disorders such as post-traumatic stress disorder.<ref name="Brietzke2012">{{cite journal | vauthors = Brietzke E, Kauer Sant'anna M, Jackowski A, Grassi-Oliveira R, Bucker J, Zugman A, Mansur RB, Bressan RA | title = Impact of childhood stress on psychopathology | journal = Rev Bras Psiquiatr | volume = 34 | issue = 4 | pages = 480–488 | date = December 2012 | pmid = 23429820 | doi = 10.1016/j.rbp.2012.04.009 | doi-access = free }}</ref> The number of reported stressful events in childhood is higher in those with an adult diagnosis of bipolar spectrum disorder than in those without, particularly events stemming from a harsh environment rather than from the child's own behavior.<ref>{{cite journal |vauthors=Miklowitz DJ, Chang KD | title = Prevention of bipolar disorder in at-risk children: Theoretical assumptions and empirical foundations | journal = Development and Psychopathology | volume = 20 | issue = 3 | pages = 881–497 | year = 2008 | pmid = 18606036 | pmc = 2504732 | doi = 10.1017/S0954579408000424 }}</ref> Acutely, mania can be induced by [[Medicine:Sleep deprivation|sleep deprivation]] in around 30% of people with bipolar disorder.<ref>{{cite journal | vauthors = Young JW, Dulcis D | title = Investigating the mechanism(s) underlying switching between states in bipolar disorder | journal = European Journal of Pharmacology | volume = 759 | pages = 151–162 | date = July 2015 | pmid = 25814263 | pmc = 4437855 | doi = 10.1016/j.ejphar.2015.03.019 }}</ref>

=== Neurological ===
Less commonly, bipolar disorder or a bipolar-like disorder may occur as a result of or in association with a neurological condition or injury including [[Medicine:Stroke|stroke]], [[Medicine:Traumatic brain injury|traumatic brain injury]], HIV infection, multiple sclerosis, [[Medicine:Porphyria|porphyria]], and rarely [[Medicine:Temporal lobe epilepsy|temporal lobe epilepsy]].<ref>Murray ED, Buttner N, Price BH. (2012) "Depression and Psychosis in Neurological Practice". In: ''Neurology in Clinical Practice'', 6th Edition. Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds.) Butterworth Heinemann. {{ISBN|978-1-4377-0434-1}}</ref>

==Proposed mechanisms==
{{see|Biology of bipolar disorder}}

[[File:Fpsyt-05-00098-g002.jpg|alt=3-D image of human brain emphasizing emotional regulation circuits|thumb|upright=1.6|Brain imaging studies have revealed differences in the volume of various brain regions between patients with bipolar disorder and healthy control subjects.]]

The precise mechanisms that cause bipolar disorder are not well understood. Bipolar disorder is thought to be associated with abnormalities in the structure and function of certain brain areas responsible for cognitive tasks and the processing of emotions.<ref name="Chen2011"/> A neurologic model for bipolar disorder proposes that the emotional circuitry of the brain can be divided into two main parts.<ref name="Chen2011"/> The ventral system (regulates emotional perception) includes brain structures such as the [[Medicine:Amygdala|amygdala]], [[Biology:Insular cortex|insula]], ventral [[Biology:Striatum|striatum]], ventral [[Biology:Anterior cingulate cortex|anterior cingulate cortex]], and the [[Biology:Prefrontal cortex|prefrontal cortex]].<ref name="Chen2011"/> The dorsal system (responsible for emotional regulation) includes the [[Biology:Hippocampus|hippocampus]], dorsal anterior cingulate cortex, and other parts of the prefrontal cortex.<ref name="Chen2011"/> The model hypothesizes that bipolar disorder may occur when the ventral system is overactivated and the dorsal system is underactivated.<ref name="Chen2011"/> Other models suggest the ability to regulate emotions is disrupted in people with bipolar disorder and that dysfunction of the ventricular prefrontal cortex is crucial to this disruption.<ref name="Chen2011"/>

[[Meta-analysis|Meta-analyses]] of structural [[Physics:Magnetic resonance imaging|MRI]] studies have shown that certain brain regions (e.g., the left rostral [[Biology:Anterior cingulate cortex|anterior cingulate cortex]], [[Biology:Insular cortex|fronto-insular cortex]], ventral prefrontal cortex, and [[Biology:Claustrum|claustrum]]) are smaller in people with bipolar disorder, whereas other regions are larger (lateral ventricles, [[Biology:Globus pallidus|globus pallidus]], [[Biology:Brodmann area 25|subgenual anterior cingulate]], and the amygdala). Additionally, these meta-analyses found that people with bipolar disorder have higher rates of deep [[Biology:White matter|white matter]] hyperintensities.<ref>{{cite journal | vauthors = Bora E, Fornito A, Yücel M, Pantelis C | title = Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder | journal = Biological Psychiatry | volume = 67 | issue = 11 | pages = 1097–1105 | date = June 2010 | pmid = 20303066 | doi = 10.1016/j.biopsych.2010.01.020 | s2cid = 24812539 }}</ref><ref>{{cite journal | vauthors = Kempton MJ, Geddes JR, Ettinger U, Williams SC, Grasby PM | title = Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder | journal = Archives of General Psychiatry | volume = 65 | issue = 9 | pages = 1017–1032 | date = September 2008 | pmid = 18762588 | doi = 10.1001/archpsyc.65.9.1017 | doi-access = free }}</ref><ref name="pmid19721106">{{cite journal | vauthors = Arnone D, Cavanagh J, Gerber D, Lawrie SM, Ebmeier KP, McIntosh AM | title = Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis | journal = The British Journal of Psychiatry | volume = 195 | issue = 3 | pages = 194–201 | date = September 2009 | pmid = 19721106 | doi = 10.1192/bjp.bp.108.059717 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Selvaraj S, Arnone D, Job D, Stanfield A, Farrow TF, Nugent AC, Scherk H, Gruber O, Chen X, Sachdev PS, Dickstein DP, Malhi GS, Ha TH, Ha K, Phillips ML, McIntosh AM | title = Grey matter differences in bipolar disorder: a meta-analysis of voxel-based morphometry studies | journal = Bipolar Disorders | volume = 14 | issue = 2 | pages = 135–145 | date = March 2012 | pmid = 22420589 | doi = 10.1111/j.1399-5618.2012.01000.x | s2cid = 2548825 | doi-access = free }}</ref>

[[Physics:Functional magnetic resonance imaging|Functional MRI]] findings suggest that the ventricular prefrontal cortex regulates the [[Philosophy:Limbic system|limbic system]], especially the amygdala.<ref name="Strakowski2012"/> In people with bipolar disorder, decreased ventricular prefrontal cortex activity allows for the dysregulated activity of the amygdala, which likely contributes to labile mood and poor emotional regulation.<ref name="Strakowski2012">{{cite journal | vauthors = Strakowski SM, Adler CM, Almeida J, Altshuler LL, Blumberg HP, Chang KD, DelBello MP, Frangou S, McIntosh A, Phillips ML, Sussman JE, Townsend JD | title = The functional neuroanatomy of bipolar disorder: a consensus model | journal = Bipolar Disorders | volume = 14 | issue = 4 | pages = 313–325 | date = June 2012 | pmid = 22631617 | pmc = 3874804 | doi = 10.1111/j.1399-5618.2012.01022.x }}</ref> Consistent with this, pharmacological treatment of mania returns ventricular prefrontal cortex activity to the levels in non-manic people, suggesting that ventricular prefrontal cortex activity is an indicator of mood state. However, while pharmacological treatment of mania reduces amygdala hyperactivity, it remains more active than the amygdala of those without bipolar disorder, suggesting amygdala activity may be a marker of the disorder rather than the current mood state.<ref>{{cite journal | vauthors = Pavuluri M | title = Brain biomarkers of treatment for multi-domain dysfunction: pharmacological FMRI studies in pediatric mania | journal = Neuropsychopharmacology | volume = 40 | issue = 1 | pages = 249–251 | date = January 2015 | pmid = 25482178 | pmc = 4262909 | doi = 10.1038/npp.2014.229 }}</ref> Manic and depressive episodes tend to be characterized by dysfunction in different regions of the ventricular prefrontal cortex. Manic episodes appear to be associated with decreased activation of the right ventricular prefrontal cortex whereas depressive episodes are associated with decreased activation of the left ventricular prefrontal cortex.<ref name="Strakowski2012"/> These disruptions often occur during development linked with [[Biology:Synaptic pruning|synaptic pruning]] dysfunction.<ref>{{cite journal | vauthors = Eltokhi A, Janmaat IE, Genedi M, Haarman BC, Sommer IE | title = Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders | journal = Journal of Neuroscience Research | volume = 98 | issue = 7 | pages = 1335–1369 | date = July 2020 | pmid = 32239720 | doi = 10.1002/jnr.24616 | s2cid = 214772559 | doi-access = free }}</ref>

People with bipolar disorder who are in a [[Medicine:Euthymia|euthymic mood state]] show decreased activity in the [[Biology:Lingual gyrus|lingual gyrus]] compared to people without bipolar disorder.<ref name="Chen2011"/> In contrast, they demonstrate decreased activity in the inferior frontal cortex during manic episodes compared to people without the disorder.<ref name="Chen2011"/> Similar studies examining the differences in brain activity between people with bipolar disorder and those without did not find a consistent area in the brain that was more or less active when comparing these two groups.<ref name="Chen2011">{{cite journal | vauthors = Chen CH, Suckling J, Lennox BR, Ooi C, Bullmore ET | title = A quantitative meta-analysis of fMRI studies in bipolar disorder | journal = Bipolar Disorders | volume = 13 | issue = 1 | pages = 1–15 | date = February 2011 | pmid = 21320248 | doi = 10.1111/j.1399-5618.2011.00893.x }}</ref> People with bipolar have increased activation of left hemisphere ventral limbic areas{{Em dash}}which mediate emotional experiences and generation of emotional responses{{Em dash}}and decreased activation of right hemisphere cortical structures related to cognition{{Em dash}}structures associated with the regulation of emotions.<ref>{{cite journal | vauthors = Houenou J, Frommberger J, Carde S, Glasbrenner M, Diener C, Leboyer M, Wessa M | title = Neuroimaging-based markers of bipolar disorder: evidence from two meta-analyses | journal = Journal of Affective Disorders | volume = 132 | issue = 3 | pages = 344–355 | date = August 2011 | pmid = 21470688 | doi = 10.1016/j.jad.2011.03.016 }}</ref>

Neuroscientists have proposed additional models to try to explain the cause of bipolar disorder. One proposed model for bipolar disorder suggests that hypersensitivity of reward circuits consisting of [[Biology:Frontostriatal circuit|frontostriatal circuit]]s causes mania, and decreased sensitivity of these circuits causes depression.<ref>{{cite journal | vauthors = Nusslock R, Young CB, Damme KS | title = Elevated reward-related neural activation as a unique biological marker of bipolar disorder: assessment and treatment implications | journal = Behaviour Research and Therapy | volume = 62 | pages = 74–87 | date = November 2014 | pmid = 25241675 | pmc = 6727647 | doi = 10.1016/j.brat.2014.08.011 }}</ref> According to the "kindling" hypothesis, when people who are genetically predisposed toward bipolar disorder experience stressful events, the stress threshold at which mood changes occur becomes progressively lower, until the episodes eventually start (and recur) spontaneously. There is evidence supporting an association between early-life stress and dysfunction of the hypothalamic-pituitary-adrenal axis leading to its overactivation, which may play a role in the pathogenesis of bipolar disorder.<ref name="Bender2011">{{cite journal |vauthors=Bender RE, Alloy LB | title = Life stress and kindling in bipolar disorder: review of the evidence and integration with emerging biopsychosocial theories | journal = Clin Psychol Rev | volume = 31 | issue = 3 | pages = 383–398 | date = April 2011 | pmid = 21334286 | pmc = 3072804 | doi = 10.1016/j.cpr.2011.01.004 }}</ref><ref name="Lee2013">{{cite journal |vauthors=Lee HJ, Son GH, Geum D | title = Circadian Rhythm Hypotheses of Mixed Features, Antidepressant Treatment Resistance, and Manic Switching in Bipolar Disorder | journal = Psychiatry Investig | volume = 10 | issue = 3 | pages = 225–232 | date = September 2013 | pmid = 24302944 | pmc = 3843013 | doi=10.4306/pi.2013.10.3.225}}</ref> Other brain components that have been proposed to play a role in bipolar disorder are the [[Biology:Mitochondria|mitochondria]]<ref name="Nierenberg2013" /> and a sodium [[Biology:ATPase|ATPase]] pump.{{sfn|Brown|Basso|2004|p=16}} [[Biology:Circadian rhythm|Circadian rhythm]]s and regulation of the hormone [[Chemistry:Melatonin|melatonin]] also seem to be altered.<ref>{{cite journal |vauthors=Dallaspezia S, Benedetti F | title = Melatonin, circadian rhythms, and the clock genes in bipolar disorder | journal = Curr Psychiatry Rep | volume = 11 | issue = 6 | pages = 488–493 | date = December 2009 | pmid = 19909672 | doi=10.1007/s11920-009-0074-1| s2cid = 24799032 }}</ref>

[[Biology:Dopamine|Dopamine]], a [[Biology:Neurotransmitter|neurotransmitter]] responsible for mood cycling, has increased transmission during the manic phase.<ref name="Salvadore2010" /><ref>{{cite journal |vauthors=Lahera G, Freund N, Sáiz-Ruiz J |title=Salience and dysregulation of the dopaminergic system |journal=Rev Psquiatr Salud Ment |volume=6 |issue=1 |pages=45–51 |date=January–March 2013 |pmid=23084802 |doi=10.1016/j.rpsm.2012.05.003 }}</ref> The dopamine hypothesis states that the increase in dopamine results in secondary [[Homeostasis|homeostatic]] [[Biology:Downregulation and upregulation|downregulation]] of key system elements and receptors such as lower sensitivity of dopaminergic receptors. This results in decreased dopamine transmission characteristic of the depressive phase.<ref name="Salvadore2010" /> The depressive phase ends with homeostatic upregulation potentially restarting the cycle over again.<ref>{{cite journal |vauthors=Berk M, Dodd S, Kauer-Sant'anna M, Malhi GS, Bourin M, Kapczinski F, Norman T |title=Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder |journal=Acta Psychiatr Scand Suppl |volume=116 |issue=Supplement s434 |pages=41–49 |year=2007 |pmid=17688462 |doi=10.1111/j.1600-0447.2007.01058.x|s2cid=41155120 }}</ref> Glutamate is significantly increased within the left dorsolateral prefrontal cortex during the manic phase of bipolar disorder, and returns to normal levels once the phase is over.<ref>{{cite journal |vauthors=Michael N, Erfurth A, Ohrmann P, Gössling M, Arolt V, Heindel W, Pfleiderer B |title=Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex |journal=Psychopharmacology |volume=168 |issue=3 |pages=344–346 |year=2003 |pmid=12684737 |doi=10.1007/s00213-003-1440-z|s2cid=19662149 }}</ref>

Medications used to treat bipolar may exert their effect by modulating intracellular signaling, such as through depleting myo-[[Chemistry:Inositol|inositol]] levels, inhibition of cAMP signaling, and through altering subunits of the dopamine-associated G-protein.<ref name="Malhi2013">{{cite journal | vauthors = Malhi GS, Tanious M, Das P, Coulston CM, Berk M | title = Potential mechanisms of action of lithium in bipolar disorder. Current understanding | journal = CNS Drugs | volume = 27 | issue = 2 | pages = 135–153 | date = February 2013 | pmid = 23371914 | doi = 10.1007/s40263-013-0039-0 | hdl-access = free | type = Review | s2cid = 26907074 | hdl = 11343/218106 }}</ref> Consistent with this, elevated levels of [[Biology:Gi alpha subunit|G<sub>αi</sub>]], [[Biology:Gs alpha subunit|G<sub>αs</sub>]], and [[Biology:Gq alpha subunit|G<sub>αq/11</sub>]] have been reported in brain and blood samples, along with increased [[Biology:Protein kinase A|protein kinase A]] (PKA) expression and sensitivity;<ref>{{cite book | veditors = Manji HK, Zarate CA | title = Behavioral neurobiology of bipolar disorder and its treatment | url = https://archive.org/details/behavioralneurob00manj | url-access = limited | date = 2011 | publisher = Springer | location = Berlin | isbn = 9783642157561 | pages = [https://archive.org/details/behavioralneurob00manj/page/n159 143], 147}}</ref> typically, PKA activates as part of the intracellular signalling cascade downstream from the detachment of G<sub>αs</sub> subunit from the G protein complex.

Decreased levels of 5-hydroxyindoleacetic acid, a byproduct of [[Chemistry:Serotonin|serotonin]], are present in the [[Biology:Cerebrospinal fluid|cerebrospinal fluid]] of persons with bipolar disorder during both the depressed and manic phases. Increased dopaminergic activity has been hypothesized in manic states due to the ability of [[Biology:Dopamine|dopamine]] agonists to stimulate mania in people with bipolar disorder. Decreased sensitivity of regulatory α<sub>2</sub> [[Biology:Adrenergic receptor|adrenergic receptor]]s as well as increased cell counts in the locus coeruleus indicated increased noradrenergic activity in manic people. Low plasma GABA levels on both sides of the mood spectrum have been found.<ref>{{cite journal | vauthors = Kapczinski F, Frey BN, Zannatto V | title = [Physiopathology of bipolar disorders: what have changed in the last 10 years?] | journal = Revista Brasileira de Psiquiatria | volume = 26 | issue = Suppl 3 | pages = 17–21 | date = October 2004 | pmid = 15597134 | doi = 10.1590/S1516-44462004000700005 | doi-access = free | hdl = 10183/20098 | hdl-access = free }}</ref> One review found no difference in monoamine levels, but found abnormal norepinephrine turnover in people with bipolar disorder.<ref>{{cite journal | vauthors = Berns GS, Nemeroff CB | title = The neurobiology of bipolar disorder | journal = American Journal of Medical Genetics. Part C, Seminars in Medical Genetics | volume = 123C | issue = 1 | pages = 76–84 | date = November 2003 | pmid = 14601039 | doi = 10.1002/ajmg.c.20016 | citeseerx = 10.1.1.1033.7393 | s2cid = 6550069 }}</ref> [[Chemistry:Tyrosine|Tyrosine]] depletion was found to reduce the effects of [[Chemistry:Methamphetamine|methamphetamine]] in people with bipolar disorder as well as symptoms of mania, implicating dopamine in mania. VMAT2 binding was found to be increased in one study of people with bipolar mania.<ref>{{cite journal | vauthors = Manji HK, Quiroz JA, Payne JL, Singh J, Lopes BP, Viegas JS, Zarate CA | title = The underlying neurobiology of bipolar disorder | journal = World Psychiatry | volume = 2 | issue = 3 | pages = 136–146 | date = October 2003 | pmid = 16946919 | pmc = 1525098 }}</ref>

== Diagnosis ==
Bipolar disorder is commonly diagnosed during adolescence or early adulthood, but onset can occur throughout life.<ref name=DSM5 /><ref name="Price2012">{{cite journal | vauthors = Price AL, Marzani-Nissen GR | title = Bipolar disorders: a review | journal = American Family Physician | volume = 85 | issue = 5 | pages = 483–493 | date = March 2012 | pmid = 22534227 | url = http://www.aafp.org/afp/2012/0301/p483.html | archive-url = https://web.archive.org/web/20140324014832/http://www.aafp.org/afp/2012/0301/p483.html | df = mdy-all | url-status=live | archive-date = March 24, 2014 }}</ref> Its diagnosis is based on the self-reported experiences of the individual, abnormal behavior reported by family members, friends or co-workers, observable signs of illness as assessed by a clinician, and ideally a medical work-up to rule out other causes. Caregiver-scored rating scales, specifically from the mother, have shown to be more accurate than teacher and youth-scored reports in identifying youths with bipolar disorder.<ref name="Youngstrom2015">{{cite journal| vauthors = Youngstrom EA, Genzlinger JE, Egerton GA, Van Meter AR |title=Multivariate Meta-Analysis of the Discriminative Validity of Caregiver, Youth, and Teacher Rating Scales for Pediatric Bipolar Disorder: Mother Knows Best About Mania|journal=Archives of Scientific Psychology|volume=3|issue=1|pages=112–137|doi=10.1037/arc0000024|year=2015|doi-access=free}}</ref> Assessment is usually done on an outpatient basis; admission to an inpatient facility is considered if there is a risk to oneself or others.

The most widely used criteria for diagnosing bipolar disorder are from the American Psychiatric Association's (APA) ''Diagnostic and Statistical Manual of Mental Disorders'', Fifth Edition (DSM-5) and the [[Organization:World Health Organization|World Health Organization]]'s (WHO) [[Medicine:ICD-10|''International Statistical Classification of Diseases and Related Health Problems'', 10th Edition]] (ICD-10). The ICD-10 criteria are used more often in clinical settings outside of the U.S. while the DSM criteria are used within the U.S. and are the prevailing criteria used internationally in research studies. The DSM-5, published in 2013, includes further and more accurate specifiers compared to its predecessor, the DSM-IV-TR.<ref>{{cite book | vauthors = Perugi G, Ghaemi SN, Akiskal H | title = Bipolar Psychopharmacotherapy: Caring for the Patient | pages = 193–234 | year = 2006 | doi = 10.1002/0470017953.ch11 | chapter = Diagnostic and Clinical Management Approaches to Bipolar Depression, Bipolar II and Their Comorbidities | isbn = 978-0-470-01795-1 }}</ref> This work has influenced the eleventh revision of the ICD, which includes the various diagnoses within the bipolar spectrum of the DSM-V.<ref name=":0">{{cite web|url=https://icd.who.int/browse11/l-m/en|title=ICD-11 for Mortality and Morbidity Statistics|date=April 2019|website=World Health Organization|page=6A60, 6A61, 6A62|access-date=March 7, 2020}}</ref>

Several [[Social:Rating scale|rating scale]]s for the screening and evaluation of bipolar disorder exist,<ref name="Carvalho2015" /> including the Bipolar spectrum diagnostic scale, [[Social:Mood Disorder Questionnaire|Mood Disorder Questionnaire]], the [[Social:General Behavior Inventory|General Behavior Inventory]] and the Hypomania Checklist.<ref name="pmid19122534">{{cite journal | vauthors = Picardi A | title = Rating scales in bipolar disorder | journal = Current Opinion in Psychiatry | volume = 22 | issue = 1 | pages = 42–49 | date = January 2009 | pmid = 19122534 | doi = 10.1097/YCO.0b013e328315a4d2 | s2cid = 20010797 }}</ref> The use of evaluation scales cannot substitute a full clinical interview but they serve to systematize the recollection of symptoms.<ref name="pmid19122534" /> On the other hand, instruments for screening bipolar disorder tend to have lower [[Sensitivity and specificity|sensitivity]].<ref name="Carvalho2015">{{cite journal | vauthors = Carvalho AF, Takwoingi Y, Sales PM, Soczynska JK, Köhler CA, Freitas TH, Quevedo J, Hyphantis TN, McIntyre RS, Vieta E | title = Screening for bipolar spectrum disorders: A comprehensive meta-analysis of accuracy studies | journal = Journal of Affective Disorders | volume = 172 | pages = 337–346 | date = February 2015 | pmid = 25451435 | doi = 10.1016/j.jad.2014.10.024 | s2cid = 44868545 | display-authors = etal | url = http://www.repositorio.ufc.br/handle/riufc/23654 }}</ref>

=== Differential diagnosis ===
Bipolar disorder is classified by the [[International Classification of Diseases]] as a [[Medicine:Mental disorder|mental]] and behavioural [[Disease#Disorder|disorder]].<ref>Drs; {{cite web|url=https://www.who.int/classifications/icd/en/bluebook.pdf|title=The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines | vauthors =  Sartorius N, Henderson A, Strotzka H, Lipowski Z, Yu-cun S, You-xin X, Strömgren E, Glatzel J, Kühne G, Misès R, Soldatos C, Pull C, Giel R, Jegede R, Malt U, Nadzharov R, Smulevitch A, Hagberg B, Perris C, Scharfetter C, Clare A, Cooper J, Corbett J, Griffith Edwards J, Gelder M, Goldberg D, Gossop M, Graham P, Kendell R, Marks I, Russell G, Rutter M, Shepherd M, West D, Wing J, Wing L, Neki J, Benson F, Cantwell D, Guze S, Helzer J, Holzman P, Kleinman A, Kupfer D, Mezzich J, Spitzer R, Lokar J | display-authors = 6 |website=www.who.int [[Organization:World Health Organization|World Health Organization]]|publisher=[[Software:Microsoft Word|Microsoft Word]]|agency=bluebook.doc|pages=92, 97–99|access-date=23 June 2021|url-status=live|via=[[Software:Microsoft Bing|Microsoft Bing]]|archive-url= https://web.archive.org/web/20041017011412/http://www.who.int/classifications/icd/en/bluebook.pdf|archive-date=October 17, 2004}}</ref> Mental disorders that can have symptoms similar to those seen in bipolar disorder include [[Medicine:Schizophrenia|schizophrenia]], major depressive disorder,<ref name="Baldessarini2013" /> attention deficit hyperactivity disorder (ADHD), and certain personality disorders, such as [[Medicine:Borderline personality disorder|borderline personality disorder]].<ref name="Sood2005">{{cite journal |vauthors=Sood AB, Razdan A, Weller EB, Weller RA | title = How to differentiate bipolar disorder from attention deficit hyperactivity disorder and other common psychiatric disorders: A guide for clinicians | journal = Current Psychiatry Reports | volume = 7 | issue = 2 | pages = 98–103 | year = 2005 | pmid = 15802085 | doi=10.1007/s11920-005-0005-8| s2cid = 32254230 }}</ref><ref name="Magill2004">{{cite journal | author = Magill CA | title = The boundary between borderline personality disorder and bipolar disorder: Current concepts and challenges | journal = Canadian Journal of Psychiatry| volume = 49 | issue = 8 | pages = 551–556 | year = 2004 | pmid = 15453104 | doi = 10.1177/070674370404900806 | doi-access = free }}</ref><ref name="Bassett2012">{{cite journal | author = Bassett D | title = Borderline personality disorder and bipolar affective disorder. Spectra or spectre? A review | journal = Australian and New Zealand Journal of Psychiatry | volume = 46 | issue = 4 | pages = 327–339 | year = 2012 | pmid = 22508593 | doi = 10.1177/0004867411435289 | s2cid = 33811755 }}</ref> A key difference between bipolar disorder and borderline personality disorder is the nature of the mood swings; in contrast to the sustained changes to mood over days to weeks or longer, those of the latter condition (more accurately called [[Philosophy:Emotional dysregulation|emotional dysregulation]]) are sudden and often short-lived, and secondary to social stressors.<ref>{{cite book |vauthors=Paris J |title=Bipolar II Disorder: Modelling, Measuring and Managing |date=2012 |publisher=Cambridge University Press |location=Cambridge, UK |isbn=978-1-107-60089-8 |pages=81–84 |url=https://books.google.com/books?id=eNcqJpOQ6aIC&pg=PA81 | editor=Parker G}}</ref>

Although there are no biological tests that are diagnostic of bipolar disorder,<ref name="Craddock2013" /> blood tests and/or imaging are carried out to investigate whether medical illnesses with clinical presentations similar to that of bipolar disorder are present before making a definitive diagnosis. Neurologic diseases such as multiple sclerosis, complex partial seizures, [[Medicine:Stroke|stroke]]s, brain tumors, [[Medicine:Wilson's disease|Wilson's disease]], [[Medicine:Traumatic brain injury|traumatic brain injury]], [[Medicine:Huntington's disease|Huntington's disease]], and complex migraines can mimic features of bipolar disorder.<ref name="Price2012"/> An [[Biology:Electroencephalography|EEG]] may be used to exclude [[Medicine:Neurological disorder|neurological disorder]]s such as [[Medicine:Epilepsy|epilepsy]], and a [[CT scan]] or MRI of the head may be used to exclude brain lesions.<ref name="Price2012" /> Additionally, disorders of the endocrine system such as [[Medicine:Hypothyroidism|hypothyroidism]], [[Medicine:Hyperthyroidism|hyperthyroidism]], and Cushing's disease are in the differential as is the connective tissue disease [[Medicine:Systemic lupus erythematosus|systemic lupus erythematosus]]. Infectious causes of mania that may appear similar to bipolar mania include herpes encephalitis, [[Biology:HIV|HIV]], [[Medicine:Influenza|influenza]], or [[Medicine:Neurosyphilis|neurosyphilis]].<ref name="Price2012" /> Certain vitamin deficiencies such as [[Medicine:Pellagra|pellagra]] ([[Chemistry:Niacin (nutrient)|niacin]] deficiency), [[Medicine:Vitamin B12 deficiency|vitamin B<sub>12</sub> deficiency]], [[Medicine:Folate deficiency|folate deficiency]], and [[Medicine:Wernicke–Korsakoff syndrome|Wernicke–Korsakoff syndrome]] ([[Medicine:Thiamine deficiency|thiamine deficiency]]) can also lead to mania.<ref name="Price2012"/> Common medications that can cause manic symptoms include antidepressants, [[Chemistry:Prednisone|prednisone]], [[Medicine:Parkinson's disease|Parkinson's disease]] medications, [[Biology:Levothyroxine|thyroid hormone]], stimulants (including [[Biology:Cocaine|cocaine]] and methamphetamine), and certain [[Chemistry:Antibiotic|antibiotic]]s.<ref>{{cite journal | vauthors = Peet M, Peters S | title = Drug-induced mania | journal = Drug Safety | volume = 12 | issue = 2 | pages = 146–153 | date = February 1995 | pmid = 7766338 | doi = 10.2165/00002018-199512020-00007 | s2cid = 1226279 }}</ref>

=== Bipolar spectrum ===
[[File:E. Kraepelin.jpg|alt=Kraepelin looking to the side|thumb|right|Since Emil Kraepelin's distinction between bipolar disorder and schizophrenia in the 19th century, researchers have defined a spectrum of different types of bipolar disorder.]]
Bipolar spectrum disorders include: bipolar I disorder, bipolar II disorder, cyclothymic disorder and cases where subthreshold symptoms are found to cause clinically significant impairment or distress.<ref name=DSM5 /><ref name="Price2012" /><ref name=":0" /> These disorders involve major depressive episodes that alternate with manic or hypomanic episodes, or with mixed episodes that feature symptoms of both mood states.<ref name=DSM5 /> The concept of the bipolar spectrum is similar to that of [[Biography:Emil Kraepelin|Emil Kraepelin]]'s original concept of manic depressive illness.<ref>{{cite web | author = Korn ML | title = Across the Bipolar Spectrum: From Practice to Research | url = http://www.medscape.com/viewarticle/441617 | publisher = Medscape | url-status=live | archive-url = https://web.archive.org/web/20031214022212/http://www.medscape.com/viewarticle/441617 | archive-date = December 14, 2003 | df = mdy-all }}</ref> Bipolar II disorder was established as a diagnosis in 1994 within DSM IV; though debate continues over whether it is a distinct entity, part of a spectrum, or exists at all.<ref name=gitlin20>{{cite journal |vauthors=Gitlin M, Malhi G |title=The existential crisis of bipolar II disorder |journal=International Journal of Bipolar Disorders |year=2020 |volume=8 |issue=5 |page=5 |doi=10.1186/s40345-019-0175-7 |pmid=31993793 |pmc=6987267 |doi-access=free }}</ref>

=== Criteria and subtypes ===
[[File:Bipolar_disorder_subtypes_comparison_between_Bipolar_I,_II_disorder_and_Cyclothymia.svg|thumb|Simplified graphical comparison of bipolar I, bipolar II and cyclothymia<ref>{{cite web|url=https://www.health.harvard.edu/newsletter_article/Bipolar_disorder|title=Bipolar disorder |work = Harvard Health Publishing |date=November 2007 |access-date=April 11, 2019}}</ref><ref>{{cite book | title = Essentials of abnormal psychology. | vauthors = Durand VM | date = 2015 | publisher = Cengage Learning | isbn = 978-1305633681 | location = [Place of publication not identified] | oclc = 884617637 | page = 267}}</ref>{{Rp|267}}]]
The DSM and the ICD characterize bipolar disorder as a spectrum of disorders occurring on a continuum. The DSM-5 and ICD-11 lists three specific subtypes:<ref name=DSM5 /><ref name=":0" />
* [[Medicine:Bipolar I disorder|Bipolar I disorder]]: At least one manic episode is necessary to make the diagnosis;<ref name="Renk2014">{{cite journal|vauthors=Renk K, White R, Lauer BA, McSwiggan M, Puff J, Lowell A |title=Bipolar Disorder in Children|journal=Psychiatry J|volume=2014 |issue=928685|pages=928685|date=February 2014|pmid=24800202|pmc=3994906|doi=10.1155/2014/928685|doi-access=free}}</ref> depressive episodes are common in the vast majority of cases with bipolar disorder I, but are unnecessary for the diagnosis.<ref name="Barnett2009" /> Specifiers such as "mild, moderate, moderate-severe, severe" and "with psychotic features" should be added as applicable to indicate the presentation and course of the disorder.<ref name=DSM5 />
* [[Medicine:Bipolar II disorder|Bipolar II disorder]]: No manic episodes and one or more hypomanic episodes and one or more major depressive episodes.<ref name="Renk2014" /> Hypomanic episodes do not go to the full extremes of mania (''i.e.'', do not usually cause severe social or occupational impairment, and are without psychosis), and this can make bipolar II more difficult to diagnose, since the hypomanic episodes may simply appear as periods of successful high productivity and are reported less frequently than a distressing, crippling depression.
* [[Medicine:Cyclothymia|Cyclothymia]]: A history of hypomanic episodes with periods of depression that do not meet criteria for major depressive episodes.<ref name="Van Meter 2012">{{cite journal|vauthors=Van Meter AR, Youngstrom EA, Findling RL |title=Cyclothymic disorder: a critical review|journal=Clinical Psychology Review|volume=32|issue=4|pages=229–243|date=June 2012|pmid=22459786|doi=10.1016/j.cpr.2012.02.001}}</ref>

When relevant, specifiers for ''peripartum onset'' and ''with rapid cycling'' should be used with any subtype. Individuals who have subthreshold symptoms that cause clinically significant distress or impairment, but do not meet full criteria for one of the three subtypes may be diagnosed with other specified or unspecified bipolar disorder. Other specified bipolar disorder is used when a clinician chooses to explain why the full criteria were not met (e.g., hypomania without a prior major depressive episode).<ref name=DSM5 /> If the condition is thought to have a non-psychiatric medical cause, the diagnosis of ''bipolar and related disorder due to another medical condition'' is made, while ''substance/medication-induced bipolar and related disorder'' is used if a medication is thought to have triggered the condition.<ref>{{cite journal | vauthors = Angst J | title = Bipolar disorders in DSM-5: strengths, problems and perspectives | journal = International Journal of Bipolar Disorders | volume = 1 | issue = 12 | pages = 12 |year = 2013 | pmid = 25505679 | doi = 10.1186/2194-7511-1-12 | pmc = 4230689 | doi-access = free }}</ref>

==== Rapid cycling ====
Most people who meet criteria for bipolar disorder experience a number of episodes, on average 0.4 to 0.7 per year, lasting three to six months.<ref>{{cite journal | vauthors = Angst J, Sellaro R | title = Historical perspectives and natural history of bipolar disorder | journal = Biological Psychiatry | volume = 48 | issue = 6 | pages = 445–457 | date = September 2000 | pmid = 11018218 | doi = 10.1016/s0006-3223(00)00909-4 | type = Review | s2cid = 6629039 }}</ref> ''Rapid cycling'', however, is a course specifier that may be applied to any bipolar subtype. It is defined as having four or more mood disturbance episodes within a one-year span. Rapid cycling is usually temporary but is common amongst people with bipolar disorder and affects 25.8–45.3% of them at some point in their life.<ref name="Muneer2013">{{cite journal | vauthors = Muneer A | title = Treatment of the depressive phase of bipolar affective disorder: a review | journal = JPMA. The Journal of the Pakistan Medical Association | volume = 63 | issue = 6 | pages = 763–769 | date = June 2013 | pmid = 23901682 | type = Review }}</ref><ref name="Buoli2017">{{cite journal | vauthors = Buoli M, Serati M, Altamura AC | title = Biological aspects and candidate biomarkers for rapid-cycling in bipolar disorder: A systematic review | journal = Psychiatry Research | volume = 258 | pages = 565–575 | date = December 2017 | pmid = 28864122 | doi = 10.1016/j.psychres.2017.08.059 | s2cid = 13653149 | type = Review }}</ref> These episodes are separated from each other by a remission (partial or full) for at least two months or a switch in mood polarity (i.e., from a depressive episode to a manic episode or vice versa).<ref name="Barnett2009" /> The definition of rapid cycling most frequently cited in the literature (including the DSM-V and ICD-11) is that of Dunner and Fieve: at least four major depressive, manic, hypomanic or mixed episodes during a 12-month period.<ref name=Bauer2008>{{cite journal | vauthors = Bauer M, Beaulieu S, Dunner DL, Lafer B, Kupka R | title = Rapid cycling bipolar disorder—diagnostic concepts | journal = Bipolar Disorders | volume = 10 | issue = 1 Pt 2 | pages = 153–162 | date = February 2008 | pmid = 18199234 | doi = 10.1111/j.1399-5618.2007.00560.x }}</ref> The literature examining the pharmacological treatment of rapid cycling is sparse and there is no clear consensus with respect to its optimal pharmacological management.<ref name=Fountoulakis2013>{{cite journal | vauthors = Fountoulakis KN, Kontis D, Gonda X, Yatham LN | title = A systematic review of the evidence on the treatment of rapid cycling bipolar disorder | journal = Bipolar Disorders | volume = 15 | issue = 2 | pages = 115–137 | date = March 2013 | pmid = 23437958 | doi = 10.1111/bdi.12045 | type = Systematic Review | s2cid = 20001176 | url = http://repo.lib.semmelweis.hu//handle/123456789/514 }}</ref> People with the rapid cycling or ultradian subtypes of bipolar disorder tend to be more difficult to treat and less responsive to medications than other people with bipolar disorder.<ref name="Post2016">{{cite journal | vauthors = Post RM | title = Treatment of Bipolar Depression: Evolving Recommendations | journal = The Psychiatric Clinics of North America | volume = 39 | issue = 1 | pages = 11–33 | date = March 2016 | pmid = 26876316 | doi = 10.1016/j.psc.2015.09.001 | type = Review }}</ref>

=== Coexisting psychiatric conditions ===
The diagnosis of bipolar disorder can be complicated by coexisting ([[Medicine:Comorbidity|comorbid]]) psychiatric conditions including [[Medicine:Obsessive–compulsive disorder|obsessive–compulsive disorder]], [[Medicine:Substance use disorder|substance-use disorder]], [[Medicine:Eating disorder|eating disorder]]s, [[Medicine:Attention deficit hyperactivity disorder|attention deficit hyperactivity disorder]], [[Medicine:Social anxiety disorder|social phobia]], [[Medicine:Premenstrual syndrome|premenstrual syndrome]] (including premenstrual dysphoric disorder), or [[Medicine:Panic disorder|panic disorder]].<ref name="Post2013" /><ref name="Muneer2013" /><ref name="Kerner2014" /><ref name="Cirillo2012">{{cite journal | vauthors = Cirillo PC, Passos RB, Bevilaqua MC, López JR, Nardi AE | title = Bipolar disorder and Premenstrual Syndrome or Premenstrual Dysphoric Disorder comorbidity: a systematic review | journal = Revista Brasileira de Psiquiatria | volume = 34 | issue = 4 | pages = 467–479 | date = December 2012 | pmid = 23429819 | doi = 10.1016/j.rbp.2012.04.010 | doi-access = free }}</ref> A thorough longitudinal analysis of symptoms and episodes, assisted if possible by discussions with friends and family members, is crucial to establishing a treatment plan where these comorbidities exist.<ref>{{cite journal|vauthors=Sagman D, Tohen M|year=2009|title=Comorbidity in Bipolar Disorder: The Complexity of Diagnosis and Treatment|url=http://www.psychiatrictimes.com/display/article/10168/1391541|url-status=live|journal=Psychiatric Times|archive-url=https://web.archive.org/web/20090428052207/http://www.psychiatrictimes.com/display/article/10168/1391541|archive-date=April 28, 2009}}</ref> Children of parents with bipolar disorder more frequently have other mental health problems.{{update after|2020|8|13}}<ref>{{update after|2020|8|13}}{{cite journal | vauthors = DelBello MP, Geller B | title = Review of studies of child and adolescent offspring of bipolar parents | journal = Bipolar Disorders | volume = 3 | issue = 6 | pages = 325–334 | date = December 2001 | pmid = 11843782 | doi = 10.1034/j.1399-5618.2001.30607.x | doi-access = free }}</ref>

=== Children ===
{{Main|Medicine:Bipolar disorder in children}}
[[File:Lithium carbonate.jpg|thumb|Lithium is the only medication approved by the FDA for treating mania in children.]]
In the 1920s, Kraepelin noted that manic episodes are rare before puberty.<ref name="pmid17195735" /> In general, bipolar disorder in children was not recognized in the first half of the twentieth century. This issue diminished with an increased following of the DSM criteria in the last part of the twentieth century.<ref name="pmid17195735" /><ref>{{cite journal | vauthors = Anthony J, Scott P | title = Manic–depressive Psychosis in Childhood | journal = Journal of Child Psychology and Psychiatry | volume = 1 | pages = 53–72 | year = 1960 | doi = 10.1111/j.1469-7610.1960.tb01979.x }}</ref> The diagnosis of childhood bipolar disorder, while formerly controversial,<ref name=Lei2008 /> has gained greater acceptance among childhood and adolescent psychiatrists.<ref name="Diler2019">{{cite book | vauthors = Diler RS, Birmaher B |title=JM Rey's IACAPAP e-Textbook of Child and Adolescent Mental Health. |date=2019 |publisher=International Association for Child and Adolescent Psychiatry and Allied Professions |location=Geneva |chapter=Chapter E2 Bipolar Disorders in Children and Adolescents|pages=1–37 |url=https://iacapap.org/content/uploads/E.2-Bipolar-2019.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://iacapap.org/content/uploads/E.2-Bipolar-2019.pdf |archive-date=2022-10-09 |url-status=live |access-date=March 18, 2020}}</ref> American children and adolescents diagnosed with bipolar disorder in community hospitals increased 4-fold reaching rates of up to 40% in 10 years around the beginning of the 21st century, while in outpatient clinics it doubled reaching 6%.<ref name=Lei2008 /> Studies using DSM criteria show that up to 1% of youth may have bipolar disorder.<ref name="pmid17195735" /> The DSM-5 has established a diagnosis—[[Medicine:Disruptive mood dysregulation disorder|disruptive mood dysregulation disorder]]—that covers children with long-term, persistent irritability that had at times been misdiagnosed as having bipolar disorder,<ref>{{cite journal | vauthors = Roy AK, Lopes V, Klein RG | title = Disruptive mood dysregulation disorder: a new diagnostic approach to chronic irritability in youth | journal = The American Journal of Psychiatry | volume = 171 | issue = 9 | pages = 918–924 | date = September 2014 | pmid = 25178749 | pmc = 4390118 | doi = 10.1176/appi.ajp.2014.13101301 }}</ref> distinct from irritability in bipolar disorder that is restricted to discrete mood episodes.<ref name="Diler2019"/>

=== Elderly ===
Bipolar disorder is uncommon in older patients, with a measured lifetime prevalence of 1% in over 60s and a 12-month prevalence of 0.1{{ndash}}0.5% in people over 65. Despite this, it is overrepresented in psychiatric admissions, making up 4{{ndash}}8% of inpatient admission to aged care psychiatry units, and the incidence of mood disorders is increasing overall with the aging population. Depressive episodes more commonly present with sleep disturbance, fatigue, hopelessness about the future, slowed thinking, and poor concentration and memory; the last three symptoms are seen in what is known as [[Medicine:Pseudodementia|pseudodementia]]. Clinical features also differ between those with late-onset bipolar disorder and those who developed it early in life; the former group present with milder manic episodes, more prominent cognitive changes and have a background of worse psychosocial functioning, while the latter present more commonly with mixed affective episodes,<ref name=Forlenza16/><!-- cites all previous in para --> and have a stronger family history of illness.<ref name=Vasudev2010>{{cite journal |vauthors=Vasudev A, Thomas A | title = 'Bipolar disorder' in the elderly: what's in a name? | journal = Maturitas | volume = 66 | issue = 3 | pages = 231–235 | date = July 2010 | pmid = 20307944 | doi = 10.1016/j.maturitas.2010.02.013 }}</ref> Older people with bipolar disorder experience cognitive changes, particularly in executive functions such as abstract thinking and switching cognitive sets, as well as concentrating for long periods and decision-making.<ref name=Forlenza16>{{cite journal |vauthors=Forlenza O, Valiengo L, Stella F |title=Mood disorders in the elderly: Prevalence, functional impact, and management challenges |journal=Neuropsychiatric Disease and Treatment |year=2016 |volume=12 |pages=2105–2114 |doi=10.2147/NDT.S94643|pmid=27601905 |pmc=5003566 |doi-access=free }}</ref>

== Prevention ==
Attempts at [[Medicine:Prevention of mental disorders|prevention of bipolar disorder]] have focused on stress (such as [[Medicine:Childhood trauma|childhood adversity]] or highly conflictual families) which, although not a diagnostically specific causal agent for bipolar, does place genetically and biologically vulnerable individuals at risk for a more severe course of illness.<ref>{{cite journal | vauthors = Miklowitz DJ, Chang KD | title = Prevention of bipolar disorder in at-risk children: theoretical assumptions and empirical foundations | journal = Development and Psychopathology | volume = 20 | issue = 3 | pages = 881–897 | date = Summer 2008 | pmid = 18606036 | pmc = 2504732 | doi = 10.1017/s0954579408000424 }}</ref> Longitudinal studies have indicated that full-blown manic stages are often preceded by a variety of prodromal clinical features, providing support for the occurrence of an at-risk state of the disorder when an early intervention might prevent its further development and/or improve its outcome.<ref>{{cite journal | vauthors = Vieta E, Salagre E, Grande I, Carvalho AF, Fernandes BS, Berk M, Birmaher B, Tohen M, Suppes T | display-authors = 6 | title = Early Intervention in Bipolar Disorder | journal = The American Journal of Psychiatry | volume = 175 | issue = 5 | pages = 411–426 | date = May 2018 | pmid = 29361850 | doi = 10.1176/appi.ajp.2017.17090972 | doi-access = free | hdl = 10536/DRO/DU:30106379 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Faedda GL, Baldessarini RJ, Marangoni C, Bechdolf A, Berk M, Birmaher B, Conus P, DelBello MP, Duffy AC, Hillegers MH, Pfennig A, Post RM, Preisig M, Ratheesh A, Salvatore P, Tohen M, Vázquez GH, Vieta E, Yatham LN, Youngstrom EA, Van Meter A, Correll CU | display-authors = 6 | title = An International Society of Bipolar Disorders task force report: Precursors and prodromes of bipolar disorder | journal = Bipolar Disorders | volume = 21 | issue = 8 | pages = 720–740 | date = December 2019 | pmid = 31479581 | doi = 10.1111/bdi.12831 | s2cid = 201829716 | hdl = 11343/286430 | hdl-access = free }}</ref>

== Management ==
{{Main|Medicine:Treatment of bipolar disorder}}

The aim of management is to treat acute episodes safely with medication and work with the patient in long-term maintenance to prevent further episodes and optimise function using a combination of  pharmacological and psychotherapeutic techniques.<ref name="Lancet2016" /> Hospitalization may be required especially with the manic episodes present in bipolar I. This can be voluntary or (local legislation permitting) [[Medicine:Involuntary commitment|involuntary]]. Long-term inpatient stays are now less common due to deinstitutionalization, although these can still occur.<ref name="BeckerKilian2006">{{cite journal |vauthors=Becker T, Kilian R | title = Psychiatric services for people with severe mental illness across western Europe: What can be generalized from current knowledge about differences in provision, costs and outcomes of mental health care? | journal = Acta Psychiatrica Scandinavica | volume = 113 | issue = 429 | pages = 9–16 | year = 2006 | pmid = 16445476 | doi = 10.1111/j.1600-0447.2005.00711.x | s2cid = 34615961 }}</ref> Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or an Assertive Community Treatment team, supported employment, [[Philosophy:Self-help groups for mental health|patient-led support groups]], and intensive outpatient programs. These are sometimes referred to as partial-inpatient programs.<ref>{{cite journal |vauthors=McGurk SR, Mueser KT, Feldman K, Wolfe R, Pascaris A | title = Cognitive Training for Supported Employment: 2–3 Year Outcomes of a Randomized Controlled Trial | journal = American Journal of Psychiatry | volume = 164 | issue = 3 | pages = 437–441 | year = 2007 | pmid = 17329468 | doi = 10.1176/appi.ajp.164.3.437 }}</ref> Compared to the general population, people with bipolar disorder are less likely to frequently engage in physical exercise. Exercise may have physical and mental benefits for people with bipolar disorder, but there is a lack of research.<ref>{{cite journal |last1=Sá Filho |first1=Alberto Souza |last2=Cheniaux |first2=Elie |last3=de Paula |first3=Carolina Cavalcante |last4=Murillo-Rodriguez |first4=Eric |last5=Teixeira |first5=Diogo |last6=Monteiro |first6=Diogo |last7=Cid |first7=Luis |last8=Yamamoto |first8=Tetsuya |last9=Telles-Correia |first9=Diogo |last10=Imperatori |first10=Claudio |last11=Budde |first11=Henning |last12=Machado |first12=Sergio |title=Exercise is medicine: a new perspective for health promotion in bipolar disorder |journal=Expert Review of Neurotherapeutics |date=1 November 2020 |volume=20 |issue=11 |pages=1099–1107 |doi=10.1080/14737175.2020.1807329|pmid=32762382 |hdl=10400.15/3006 |hdl-access=free }}</ref><ref>{{cite journal |last1=Goldstein |first1=Benjamin I. |last2=Baune |first2=Bernhard T. |last3=Bond |first3=David J. |last4=Chen |first4=Pao-Huan |last5=Eyler |first5=Lisa |last6=Fagiolini |first6=Andrea |last7=Gomes |first7=Fabiano |last8=Hajek |first8=Tomas |last9=Hatch |first9=Jessica |last10=McElroy |first10=Susan L. |last11=McIntyre |first11=Roger S. |last12=Prieto |first12=Miguel |last13=Sylvia |first13=Louisa G. |last14=Tsai |first14=Shang-Ying |last15=Kcomt |first15=Andrew |last16=Fiedorowicz |first16=Jess G. |title=Call to action regarding the vascular-bipolar link: A report from the Vascular Task Force of the International Society for Bipolar Disorders |journal=Bipolar Disorders |date=August 2020 |volume=22 |issue=5 |pages=440–460 |doi=10.1111/bdi.12921 |language=en |issn=1398-5647|doi-access=free |pmid=32356562 |pmc=7522687 |hdl=11343/251495 |hdl-access=free }}</ref><ref>{{cite journal |last1=Lin |first1=Kangguang |last2=Liu |first2=Tao |title=Chapter Seven - Exercise on bipolar disorder in humans |journal=International Review of Neurobiology |date=1 January 2019 |volume=147 |pages=189–198 |url=https://www.sciencedirect.com/science/article/abs/pii/S0074774219300479 |publisher=Academic Press|doi=10.1016/bs.irn.2019.07.001 |pmid=31607354 |s2cid=201161580 }}</ref>

=== Psychosocial ===
[[Medicine:Psychotherapy|Psychotherapy]] aims to assist a person with bipolar disorder in accepting and understanding their diagnosis, coping with various types of stress, improving their interpersonal relationships, and recognizing prodromal symptoms before full-blown recurrence.<ref name="Bobo2017"/> [[Medicine:Cognitive behavioral therapy|Cognitive behavioral therapy]] (CBT), [[Family therapy|family-focused therapy]], and [[Medicine:Psychoeducation|psychoeducation]] have the most evidence for efficacy in regard to relapse prevention, while [[Medicine:Interpersonal and social rhythm therapy|interpersonal and social rhythm therapy]] and cognitive-behavioral therapy appear the most effective in regard to residual depressive symptoms. Most studies have been based only on bipolar I, however, and treatment during the acute phase can be a particular challenge.<ref>{{cite journal |vauthors=Zaretsky AE, Rizvi S, Parikh SV | title = How well do psychosocial interventions work in bipolar disorder? | journal = Canadian Journal of Psychiatry| volume = 52 | issue = 1 | pages = 14–21 | year = 2007 | pmid = 17444074 | doi = 10.1177/070674370705200104 | doi-access = free }}</ref> Some clinicians emphasize the need to talk with individuals experiencing mania, to develop a [[Medicine:Therapeutic alliance|therapeutic alliance]] in support of [[Medicine:Recovery model|recovery]].<ref>{{cite journal |vauthors=Havens LL, Ghaemi SN | title = Existential despair and bipolar disorder: The therapeutic alliance as a mood stabilizer | journal = American Journal of Psychotherapy | volume = 59 | issue = 2 | pages = 137–147 | year = 2005 | pmid = 16170918 | doi = 10.1176/appi.psychotherapy.2005.59.2.137 | doi-access = free }}</ref>

=== Medication ===
[[File:Lithium2017a.jpg|thumb|Lithium is often used to treat bipolar disorder and has the best evidence for reducing suicide.]]

Medications are often prescribed to help improve symptoms of bipolar disorder. Medications approved for treating bipolar disorder including mood stabilizers, antipsychotics, and antidepressants. Sometimes a combination of medications may also be suggested.<ref name=Lancet2016/> The choice of medications may differ depending on the bipolar disorder episode type or if the person is experiencing unipolar or bipolar depression.<ref name="Lancet2016" /><ref name=":1" /> Other factors to consider when deciding on an appropriate treatment approach includes if the person has any comorbidities, their response to previous therapies, adverse effects, and the desire of the person to be treated.<ref name="Lancet2016" />

====Mood stabilizers====
Lithium and the [[Chemistry:Anticonvulsant|anticonvulsant]]s [[Chemistry:Carbamazepine|carbamazepine]], [[Chemistry:Lamotrigine|lamotrigine]], and valproic acid are classed as mood stabilizers due to their effect on the mood states in bipolar disorder.<ref name="Post2016"/> Lithium has the best overall evidence and is considered an effective treatment for acute manic episodes, preventing relapses, and bipolar depression.<ref name="Brown2013">{{cite journal|vauthors=Brown KM, Tracy DK|date=June 2013|title=Lithium: the pharmacodynamic actions of the amazing ion|journal=Therapeutic Advances in Psychopharmacology|volume=3|issue=3|pages=163–176|doi=10.1177/2045125312471963|pmc=3805456|pmid=24167688}}</ref><ref>{{cite journal|vauthors=McKnight RF, de La Motte de Broöns de Vauvert SJ, Chesney E, etal|date=June 2019|title=Lithium for acute mania|journal=Cochrane Database Syst Rev|volume=2019|issue=6 |pages=CD004048|doi=10.1002/14651858.CD004048.pub4|pmc=6544558|pmid=31152444|doi-access=free}}</ref> Lithium reduces the risk of suicide, self-harm, and death in people with bipolar disorder.<ref name="pmid23814104">{{cite journal|vauthors=Cipriani A, Hawton K, Stockton S, Geddes JR|date=June 2013|title=Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis|journal=BMJ|volume=346|pages=f3646|doi=10.1136/bmj.f3646|pmid=23814104|doi-access=free}}</ref> Lithium is preferred for long-term mood stabilization.<ref name="Geddestreatment">{{cite journal |vauthors=Geddes JR, Miklowitz DJ | title = Treatment of bipolar disorder | journal = Lancet | volume = 381 | issue = 9878 | pages = 1672–1682 | date = May 11, 2013 | pmid = 23663953 | doi = 10.1016/S0140-6736(13)60857-0 | pmc=3876031}}</ref> Lithium treatment is also associated with adverse effects and it has been shown to erode kidney and thyroid function over extended periods.<ref name=Lancet2016/> Valproate has become a commonly prescribed treatment and effectively treats manic episodes.<ref name="Macr02">{{cite journal | vauthors = Macritchie K, Geddes JR, Scott J, Haslam D, de Lima M, Goodwin G | issue = 1 | pages = CD004052 | year = 2003 | pmid = 12535506 | doi = 10.1002/14651858.CD004052 |title = Valproate for acute mood episodes in bipolar disorder | veditors = Reid K | journal = Cochrane Database of Systematic Reviews }}</ref> Carbamazepine is less effective in preventing relapse than lithium or valproate.<ref>{{cite journal |vauthors=Post RM, Ketter TA, Uhde T, Ballenger JC | title = Thirty years of clinical experience with carbamazepine in the treatment of bipolar illness: Principles and practice | journal = CNS Drugs | volume = 21 | issue = 1 | pages = 47–71 | year = 2007 | pmid = 17190529 | doi=10.2165/00023210-200721010-00005| s2cid = 105594 }}</ref><ref name="Rapoport2009">{{cite journal|vauthors=Rapoport SI, Basselin M, Kim HW, Rao JS |title=Bipolar disorder and mechanisms of action of mood stabilizers|journal=Brain Res Rev|volume=61|issue=2|pages=185–209|date=October 2009|pmid=19555719|pmc=2757443|doi=10.1016/j.brainresrev.2009.06.003}}</ref> Lamotrigine has some efficacy in treating depression, and this benefit is greatest in more severe depression.<ref>{{cite journal |vauthors=Geddes JR, Calabrese JR, Goodwin GM | title = Lamotrigine for treatment of bipolar depression: Independent meta-analysis and meta-regression of individual patient data from five randomised trials | journal = The British Journal of Psychiatry | volume = 194 | issue = 1 | pages = 4–9 | year = 2008 | pmid = 19118318 | doi = 10.1192/bjp.bp.107.048504 | doi-access = free }}</ref> Lamotrigine may have a similar effectiveness to lithium for treating bipolar disorder, however, there is evidence to suggest that lamotrigine is less effective at preventing recurrent mania episodes.<ref>{{cite journal |last1=Hashimoto |first1=Yasuhiko |last2=Kotake |first2=Kazumasa |last3=Watanabe |first3=Norio |last4=Fujiwara |first4=Takashi |last5=Sakamoto |first5=Shinji |date=2021-09-15 |title=Lamotrigine in the maintenance treatment of bipolar disorder |url= |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=9 |pages=CD013575 |doi=10.1002/14651858.CD013575.pub2 |issn=1469-493X |pmc=8440301 |pmid=34523118}}</ref> Lamotrigine treatment has been shown to be safer compared to lithium treatment, with less adverse effects. Valproate and carbamazepine are teratogenic and should be avoided as a treatment in women of childbearing age, but discontinuation of these medications during pregnancy is associated with a high risk of relapse.<ref name="Carvalho" /> The effectiveness of [[Biology:Topiramate|topiramate]] is unknown.<ref name="pmid16437453">{{cite journal | vauthors = Vasudev K, Macritchie K, Geddes J, Watson S, Young A  | journal = Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003384 | year = 2006 | pmid = 16437453 | doi = 10.1002/14651858.CD003384.pub2 | title= Topiramate for acute affective episodes in bipolar disorder | veditors = Young AH }}</ref> Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or more symptoms similar to that of [[Medicine:Schizoaffective disorder|schizoaffective disorder]].

Mood stabilizers are used for long-term maintenance but have not demonstrated the ability to quickly treat acute bipolar depression.<ref name="Post2016" />

====Antipsychotics====
[[Chemistry:Antipsychotic|Antipsychotic]] medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose.<ref name="Geddestreatment" /> Atypical antipsychotics are also indicated for bipolar depression refractory to treatment with mood stabilizers.<ref name="Post2016"/> [[Chemistry:Olanzapine|Olanzapine]] is effective in preventing relapses, although the supporting evidence is weaker than the evidence for lithium.<ref>{{cite journal | vauthors = Cipriani A, Rendell JM, Geddes J | title = Olanzapine in long-term treatment for bipolar disorder | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD004367 | date = January 2009 | pmid = 19160237 | doi = 10.1002/14651858.CD004367.pub2 | veditors = Cipriani A }}</ref> A 2006 review found that [[Chemistry:Haloperidol|haloperidol]] was an effective treatment for acute mania, limited data supported no difference in overall efficacy between haloperidol, [[Chemistry:Olanzapine|olanzapine]] or [[Chemistry:Risperidone|risperidone]], and that it could be less effective than [[Chemistry:Aripiprazole|aripiprazole]].<ref>{{cite journal | vauthors = Cipriani A, Rendell JM, Geddes JR | title = Haloperidol alone or in combination for acute mania | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD004362 | date = July 2006 | pmid = 16856043 | doi = 10.1002/14651858.CD004362.pub2 }}</ref>

====Antidepressants====
Antidepressants are not recommended for use alone in the treatment of bipolar disorder and do not provide any benefit over mood stabilizers.<ref name=Lancet2016/><ref name="PostGrad10">{{cite journal |vauthors=El-Mallakh RS, Elmaadawi AZ, Loganathan M, Lohano K, Gao Y | title = Bipolar disorder: an update | journal = Postgraduate Medicine | volume = 122 | issue = 4 | pages = 24–31 | date = July 2010 | pmid = 20675968 | doi = 10.3810/pgm.2010.07.2172 | s2cid = 43749362 }}</ref> Atypical antipsychotic medications (e.g., [[Chemistry:Aripiprazole|aripiprazole]]) are preferred over antidepressants to augment the effects of mood stabilizers due to the lack of efficacy of antidepressants in bipolar disorder.<ref name="Post2016"/> Treatment of bipolar disorder using antidepressants carries a risk of affective switches; where a person switches from depression to manic or hypomanic phases.<ref name="Carvalho" /> The risk of affective switches is higher in bipolar I depression; antidepressants are generally avoided in bipolar I disorder or only used with mood stabilizers when they are deemed necessary.<ref name="Carvalho" /> There is also a risk of accelerating cycling between phases when antidepressants are used in bipolar disorder.<ref name="Carvalho" />

==== Combined treatment approaches ====
[[Chemistry:Antipsychotic|Antipsychotic]]s and mood stabilizers used together are quicker and more effective at treating mania than either class of drug used alone. Some analyses indicate antipsychotics alone are also more effective at treating acute mania.<ref name="Lancet2016" />  A first-line treatment for depression in bipolar disorder is a combination of olanzapine and fluoxetine.<ref name=":1" />

====Other drugs====
Short courses of benzodiazepines are used in addition to other medications for calming effect until mood stabilizing become effective.<ref>{{cite web|title=Benzodiazepines for Bipolar Disorder|url=http://www.webmd.com/bipolar-disorder/bipolar-benzodiazepines|publisher=WebMD.com|access-date=February 13, 2013|url-status=live|archive-url=https://web.archive.org/web/20130225080713/http://www.webmd.com/bipolar-disorder/bipolar-benzodiazepines|archive-date=February 25, 2013}}</ref> [[Biology:Electroconvulsive therapy|Electroconvulsive therapy]] (ECT) is an effective form of treatment for acute mood disturbances in those with bipolar disorder, especially when psychotic or [[Medicine:Catatonia|catatonic]] features are displayed. ECT is also recommended for use in pregnant women with bipolar disorder.<ref name=Lancet2016/> It is unclear if [[Chemistry:Ketamine|ketamine]] (a common general dissociative anesthetic used in surgery) is useful in bipolar disorder.<ref name=":1">{{cite journal | vauthors = Dean RL, Marquardt T, Hurducas C, Spyridi S, Barnes A, Smith R, Cowen PJ, McShane R, Hawton K, Malhi GS, Geddes J, Cipriani A | display-authors = 6 | title = Ketamine and other glutamate receptor modulators for depression in adults with bipolar disorder | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 10 | pages = CD011611 | date = October 2021 | pmid = 34623633 | pmc = 8499740 | doi = 10.1002/14651858.CD011611.pub3 }}</ref> [[Chemistry:Gabapentin|Gabapentin]] and [[Chemistry:Pregabalin|pregabalin]] are not proven to be effective for treating bipolar disorder.<ref>{{cite journal |date=2022-10-17 |title=Review finds little evidence to support gabapentinoid use in bipolar disorder or insomnia |url=https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_54173 |s2cid=252983016}}</ref><ref name=":12">{{cite journal | vauthors = Hong JS, Atkinson LZ, Al-Juffali N, Awad A, Geddes JR, Tunbridge EM, Harrison PJ, Cipriani A | display-authors = 6 | title = Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale | journal = Molecular Psychiatry | volume = 27 | issue = 3 | pages = 1339–1349 | date = March 2022 | pmid = 34819636 | pmc = 9095464 | doi = 10.1038/s41380-021-01386-6 }}</ref><ref>{{cite journal | vauthors = Ng QX, Han MX, Teoh SE, Yaow CY, Lim YL, Chee KT | title = A Systematic Review of the Clinical Use of Gabapentin and Pregabalin in Bipolar Disorder | journal = Pharmaceuticals | volume = 14 | issue = 9 | pages = 834 | date = August 2021 | pmid = 34577534 | pmc = 8469561 | doi = 10.3390/ph14090834 | doi-access = free }}</ref>

===Children===
Treating bipolar disorder in children involves medication and psychotherapy.<ref name=Lei2008>{{cite journal |vauthors=Leibenluft E, Rich BA | title = Pediatric Bipolar Disorder | journal = Annual Review of Clinical Psychology | volume = 4 | pages = 163–187 | year = 2008 | pmid = 17716034 | doi = 10.1146/annurev.clinpsy.4.022007.141216 | url = https://zenodo.org/record/1234949 }}</ref> The literature and research on the effects of psychosocial therapy on bipolar spectrum disorders are scarce, making it difficult to determine the efficacy of various therapies.<ref name=Fristad /> Mood stabilizers and [[Chemistry:Atypical antipsychotic|atypical antipsychotic]]s are commonly prescribed.<ref name=Lei2008 /> Among the former, [[Chemistry:Lithium (medication)|lithium]] is the only compound approved by the [[Organization:Food and Drug Administration|FDA]] for children.<ref name="pmid17195735">{{cite journal | vauthors = McClellan J, Kowatch R, Findling RL | title = Practice Parameter for the Assessment and Treatment of Children and Adolescents with Bipolar Disorder | journal = Journal of the American Academy of Child & Adolescent Psychiatry | volume = 46 | issue = 1 | pages = 107–125 | year = 2007 | pmid = 17195735 | doi = 10.1097/01.chi.0000242240.69678.c4 | others = Work Group on Quality Issues | s2cid = 689321 | doi-access = free }}</ref> Psychological treatment combines normally [[Medicine:Psychoeducation|education on the disease]], group therapy, and [[Medicine:Cognitive behavioral therapy|cognitive behavioral therapy]].<ref name=Lei2008 /> Long-term medication is often needed.<ref name=Lei2008 />

=== Resistance to treatment ===
The occurrence of poor response to treatment in has given support to the concept of resistance to treatment in bipolar disorder.<ref>{{cite journal | vauthors = Gitlin M | title = Treatment-resistant bipolar disorder | journal = Molecular Psychiatry | volume = 11 | issue = 3 | pages = 227–240 | date = March 2006 | pmid = 16432528 | doi = 10.1038/sj.mp.4001793 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hui Poon S, Sim K, Baldessarini RJ | title = Pharmacological Approaches for Treatment-resistant Bipolar Disorder | journal = Current Neuropharmacology | volume = 13 | issue = 5 | pages = 592–604 | date = 2015 | pmid = 26467409 | pmc = 4761631 | doi = 10.2174/1570159x13666150630171954 }}</ref> Guidelines to the definition of such treatment resistance and evidence-based options for its management were reviewed in 2020.<ref>{{cite journal | vauthors = Fountoulakis KN, Yatham LN, Grunze H, Vieta E, Young AH, Blier P, Tohen M, Kasper S, Moeller HJ | display-authors = 6 | title = The CINP Guidelines on the Definition and Evidence-Based Interventions for Treatment-Resistant Bipolar Disorder | journal = The International Journal of Neuropsychopharmacology | volume = 23 | issue = 4 | pages = 230–256 | date = April 2020 | pmid = 31802122 | pmc = 7177170 | doi = 10.1093/ijnp/pyz064 }}</ref>

=== Management of obesity ===
A large proportion (approximately 68%) of people who seek treatment for bipolar disorder are obese or overweight and managing obesity is important for reducing the risk of other health conditions that are associated with obesity.<ref name=":2">{{cite journal |last1=Tully |first1=Agnes |last2=Smyth |first2=Siobhan |last3=Conway |first3=Yvonne |last4=Geddes |first4=John |last5=Devane |first5=Declan |last6=Kelly |first6=John P. |last7=Jordan |first7=Fionnuala |date=2020-07-20 |title=Interventions for the management of obesity in people with bipolar disorder |url= |journal=The Cochrane Database of Systematic Reviews |volume=2020 |issue=7 |pages=CD013006 |doi=10.1002/14651858.CD013006.pub2 |issn=1469-493X |pmc=7386454 |pmid=32687629}}</ref> Management approaches include non-pharmacological, pharmacological, and surgical. Examples of non-pharmacological include dietary interventions, exercise, behavioral therapies, or combined approaches. Pharmacological approaches include weight-loss medications or changing medications already being prescribed.<ref>{{cite journal |title=Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline |journal=The Journal of Clinical Endocrinology and Metabolism |date=2015 |volume=100 |issue=5 |pages=2135–2136 |doi=10.1210/jc.2015-1782|pmid=25955325 |doi-access=free }}</ref> Some people with bipolar disorder who have obesity may also be eligible for bariatric surgery.<ref name=":2" />  The effectiveness of these various approaches to improving or managing obesity in people with bipolar disorder is not clear.<ref name=":2" />

== Prognosis ==
A lifelong condition with periods of partial or full recovery in between recurrent episodes of relapse,<ref name="Muneer2013" /><ref name="pmid18425912">{{cite journal | vauthors = Montgomery P, Richardson AJ | title = Omega-3 fatty acids for bipolar disorder | journal = Cochrane Database Syst Rev | issue = 2 | pages = CD005169 | date = April 2008 | pmid = 18425912 | doi = 10.1002/14651858.CD005169.pub2 }}</ref> bipolar disorder is considered to be a major health problem worldwide because of the increased rates of disability and premature mortality.<ref name="pmid18425912"/> It is also associated with co-occurring psychiatric and medical problems, higher rates of death from natural causes (e.g., [[Medicine:Coronary artery disease|cardiovascular disease]]), and high rates of initial under- or misdiagnosis, causing a delay in appropriate treatment and contributing to poorer prognoses.<ref name=BMJ2012 /><ref name="Bowden" /> When compared to the general population, people with bipolar disorder also have higher rates of other serious medical comorbidities including [[Medicine:Diabetes mellitus|diabetes mellitus]], respiratory diseases, [[Biology:HIV|HIV]], and [[Medicine:Hepatitis C|hepatitis C]] virus infection.<ref name="Cloutier2018"/> After a diagnosis is made, it remains difficult to achieve complete remission of all symptoms with the currently available psychiatric medications and symptoms often become progressively more severe over time.<ref name="Carvalho2015"/><ref name="Muneer2016">{{cite journal | vauthors = Muneer A | title = Staging Models in Bipolar Disorder: A Systematic Review of the Literature | journal = Clinical Psychopharmacology and Neuroscience | volume = 14 | issue = 2 | pages = 117–130 | date = May 2016 | pmid = 27121423 | pmc = 4857867 | doi = 10.9758/cpn.2016.14.2.117 }}</ref>

Compliance with medications is one of the most significant factors that can decrease the rate and severity of relapse and have a positive impact on overall prognosis.<ref name=Jann/> However, the types of medications used in treating BD commonly cause side effects<ref name=Tsitsipa/> and more than 75% of individuals with BD inconsistently take their medications for various reasons.<ref name="Jann">{{cite journal | vauthors = Jann MW | title = Diagnosis and treatment of bipolar disorders in adults: a review of the evidence on pharmacologic treatments | journal = American Health & Drug Benefits | volume = 7 | issue = 9 | pages = 489–499 | date = December 2014 | pmid = 25610528 | pmc = 4296286 }}</ref> Of the various types of the disorder, rapid cycling (four or more episodes in one year) is associated with the worst prognosis due to higher rates of [[Medicine:Self-harm|self-harm]] and suicide.<ref name="Muneer2013"/> Individuals diagnosed with bipolar who have a family history of bipolar disorder are at a greater risk for more frequent manic/hypomanic episodes.<ref name=Maciukiewicz/> Early onset and psychotic features are also associated with worse outcomes,<ref>{{cite journal | vauthors = Kennedy KP, Cullen KR, DeYoung CG, Klimes-Dougan B | title = The genetics of early-onset bipolar disorder: A systematic review | journal = Journal of Affective Disorders | volume = 184 | pages = 1–12 | date = September 2015 | pmid = 26057335 | pmc = 5552237 | doi = 10.1016/j.jad.2015.05.017 }}</ref><ref>{{cite journal | vauthors = Serafini G, Pompili M, Borgwardt S, Houenou J, Geoffroy PA, Jardri R, Girardi P, Amore M | title = Brain changes in early-onset bipolar and unipolar depressive disorders: a systematic review in children and adolescents | journal = European Child & Adolescent Psychiatry | volume = 23 | issue = 11 | pages = 1023–1041 | date = November 2014 | pmid = 25212880 | doi = 10.1007/s00787-014-0614-z | s2cid = 24013921 }}</ref> as well as subtypes that are nonresponsive to lithium.<ref name=Muneer2016/>

Early recognition and intervention also improve prognosis as the symptoms in earlier stages are less severe and more responsive to treatment.<ref name=Muneer2016/> Onset after adolescence is connected to better prognoses for both genders, and being male is a protective factor against higher levels of depression. For women, better social functioning before developing bipolar disorder and being a parent are protective towards suicide attempts.<ref name="Maciukiewicz">{{cite journal |vauthors=Maciukiewicz M, Pawlak J, Kapelski P, Łabędzka M, Skibinska M, Zaremba D, Leszczynska-Rodziewicz A, Dmitrzak-Weglarz M, Hauser J |title=Can Psychological, Social and Demographical Factors Predict Clinical Characteristics Symptomatology of Bipolar Affective Disorder and Schizophrenia? |journal=Psychiatr Q |volume=87 |issue=3 |pages=501–513 |year=2016 |pmid=26646576 |pmc=4945684 |doi=10.1007/s11126-015-9405-z }}</ref>

=== Functioning ===
Changes in [[Cognition|cognitive]] processes and abilities are seen in mood disorders, with those of bipolar disorder being greater than those in major depressive disorder.<ref name="MacQueen2017">{{cite journal | vauthors = MacQueen GM, Memedovich KA | title = Cognitive dysfunction in major depression and bipolar disorder: Assessment and treatment options | journal = Psychiatry and Clinical Neurosciences | volume = 71 | issue = 1 | pages = 18–27 | date = January 2017 | pmid = 27685435 | doi = 10.1111/pcn.12463 | type = Review | doi-access = free }}</ref> These include reduced [[Philosophy:Attention|attention]]al and [[Philosophy:Executive functions|executive]] capabilities and impaired [[Memory|memory]].<ref name="Cipriani2017">{{cite journal | vauthors = Cipriani G, Danti S, Carlesi C, Cammisuli DM, Di Fiorino M | title = Bipolar Disorder and Cognitive Dysfunction: A Complex Link | journal = The Journal of Nervous and Mental Disease | volume = 205 | issue = 10 | pages = 743–756 | date = October 2017 | pmid = 28961594 | doi = 10.1097/NMD.0000000000000720 | s2cid = 22653449 | type = Review }}</ref> People with bipolar disorder often experience a decline in cognitive functioning during (or possibly before) their first episode, after which a certain degree of cognitive dysfunction typically becomes permanent, with more severe impairment during acute phases and moderate impairment during periods of remission. As a result, two-thirds of people with BD continue to experience impaired [[Social:Psychosocial|psychosocial functioning]] in between episodes even when their mood symptoms are in full remission. A similar pattern is seen in both BD-I and BD-II, but people with BD-II experience a lesser degree of impairment.<ref name="Tsitsipa">{{cite journal | vauthors = Tsitsipa E, Fountoulakis KN | title = The neurocognitive functioning in bipolar disorder: a systematic review of data | journal = Annals of General Psychiatry | volume = 14 | pages = 42 | date = December 1, 2015 | pmid = 26628905 | pmc = 4666163 | doi = 10.1186/s12991-015-0081-z | doi-access = free }}</ref>

When bipolar disorder occurs in children, it severely and adversely affects their psychosocial development.<ref name="Diler2019"/> Children and adolescents with bipolar disorder have higher rates of significant difficulties with substance use disorders, psychosis, academic difficulties, behavioral problems, social difficulties, and legal problems.<ref name="Diler2019"/>  Cognitive deficits typically increase over the course of the illness. Higher degrees of impairment correlate with the number of previous manic episodes and hospitalizations, and with the presence of psychotic symptoms.<ref name="Bortolato">{{cite journal | vauthors = Bortolato B, Miskowiak KW, Köhler CA, Vieta E, Carvalho AF | title = Cognitive dysfunction in bipolar disorder and schizophrenia: a systematic review of meta-analyses | journal = Neuropsychiatric Disease and Treatment | volume = 11 | pages = 3111–3125 | year = 2015 | pmid = 26719696 | pmc = 4689290 | doi = 10.2147/NDT.S76700 | doi-access = free }}</ref> Early intervention can slow the progression of cognitive impairment, while treatment at later stages can help reduce distress and negative consequences related to cognitive dysfunction.<ref name=Muneer2016/>

Despite the overly ambitious goals that are frequently part of manic episodes, symptoms of mania undermine the ability to achieve these goals and often interfere with an individual's social and occupational functioning. One-third of people with BD remain unemployed for one year following a hospitalization for mania.<ref>{{cite journal | vauthors = Johnson SL | title = Mania and dysregulation in goal pursuit: a review | journal = Clinical Psychology Review | volume = 25 | issue = 2 | pages = 241–262 | date = February 2005 | pmid = 15642648 | pmc = 2847498 | doi = 10.1016/j.cpr.2004.11.002 }}</ref> Depressive symptoms during and between episodes, which occur much more frequently for most people than hypomanic or manic symptoms over the course of illness, are associated with lower functional recovery in between episodes, including unemployment or underemployment for both BD-I and BD-II.<ref name=DSM5 /><ref name=Tse/> However, the course of illness (duration, age of onset, number of hospitalizations, and the presence or not of rapid cycling) and cognitive performance are the best predictors of employment outcomes in individuals with bipolar disorder, followed by symptoms of depression and years of education.<ref name=Tse>{{cite journal | vauthors = Tse S, Chan S, Ng KL, Yatham LN | title = Meta-analysis of predictors of favorable employment outcomes among individuals with bipolar disorder | journal = Bipolar Disorders | volume = 16 | issue = 3 | pages = 217–229 | date = May 2014 | pmid = 24219657 | doi = 10.1111/bdi.12148 | s2cid = 207065294 }}</ref>

=== Recovery and recurrence ===
A naturalistic study in 2003 by Tohen and coworkers from the first admission for mania or mixed episode (representing the hospitalized and therefore most severe cases) found that 50% achieved syndromal recovery (no longer meeting criteria for the diagnosis) within six weeks and 98% within two years. Within two years, 72% achieved symptomatic recovery (no symptoms at all) and 43% achieved functional recovery (regaining of prior occupational and residential status). However, 40% went on to experience a new episode of mania or depression within 2 years of syndromal recovery, and 19% switched phases without recovery.<ref>{{cite journal |vauthors=Tohen M, Zarate CA, Hennen J, Khalsa HM, Strakowski SM, Gebre-Medhin P, Salvatore P, Baldessarini RJ | s2cid = 30881311 | title = The McLean-Harvard First-Episode Mania Study: Prediction of recovery and first recurrence | journal = The American Journal of Psychiatry | volume = 160 | issue = 12 | pages = 2099–2107 | year = 2003 | pmid = 14638578 | doi = 10.1176/appi.ajp.160.12.2099 | hdl = 11381/1461461 }}</ref>

Symptoms preceding a relapse (prodromal), especially those related to mania, can be reliably identified by people with bipolar disorder.<ref name="pmid12738039">{{cite journal |vauthors=Jackson A, Cavanagh J, Scott J | title = A systematic review of manic and depressive prodromes | journal = Journal of Affective Disorders | volume = 74 | issue = 3 | pages = 209–217 | year = 2003 | pmid = 12738039 | doi=10.1016/s0165-0327(02)00266-5}}</ref> There have been intents to teach patients coping strategies when noticing such symptoms with encouraging results.<ref name="pmid16125292">{{cite journal |vauthors=Lam D, Wong G | title = Prodromes, coping strategies and psychological interventions in bipolar disorders | journal = Clinical Psychology Review | volume = 25 | issue = 8 | pages = 1028–1042 | year = 2005 | pmid = 16125292 | doi = 10.1016/j.cpr.2005.06.005 }}</ref>

=== Suicide ===
Bipolar disorder can cause suicidal ideation that leads to [[Medicine:Suicide|suicide]] attempts. Individuals whose bipolar disorder begins with a depressive or mixed affective episode seem to have a poorer prognosis and an increased risk of suicide.<ref name="Baldessarini2013">{{cite journal |vauthors=Baldessarini RJ, Faedda GL, Offidani E, Vázquez GH, Marangoni C, Serra G, Tondo L | title = Antidepressant-associated mood-switching and transition from unipolar major depression to bipolar disorder: a review | journal = J Affect Disord | volume = 148 | issue = 1 | pages = 129–135 | date = May 2013 | pmid = 23219059 | doi = 10.1016/j.jad.2012.10.033 }}</ref> One out of two people with bipolar disorder attempt suicide at least once during their lifetime and many attempts are successfully completed.<ref name="Kerner2014" /> The annual average suicide rate is 0.4%-1.4%, which is 30 to 60 times greater than that of the general population.<ref name="Nierenberg 2023" /> The number of deaths from [[Medicine:Suicide|suicide]] in bipolar disorder is between 18 and 25 times higher [[Standardized mortality ratio|than would be expected]] in similarly aged people without bipolar disorder.<ref name="MortBio_2006">{{cite journal | vauthors = McIntyre RS, Soczynska JK, Konarski J | title = Bipolar Disorder: Defining Remission and Selecting Treatment. | journal = Psychiatric Times | date = October 2006 | volume = 23 | issue = 11 | pages = 46 |url=http://www.psychiatrictimes.com/article/showArticle.jhtml?articleId=193400986 |url-status=live |archive-url=https://web.archive.org/web/20070927223634/http://www.psychiatrictimes.com/article/showArticle.jhtml?articleId=193400986 |archive-date=September 27, 2007  }}</ref> The lifetime risk of suicide is much higher in those with bipolar disorder, with an estimated 34% of people attempting suicide and 15-20% dying by suicide.<ref name="Nierenberg 2023" />

Risk factors for suicide attempts and death from suicide in people with bipolar disorder include older age, prior suicide attempts, a depressive or mixed index episode (first episode), a manic index episode with psychotic symptoms, hopelessness or psychomotor agitation present during the episodes, co-existing anxiety disorder, a first degree relative with a mood disorder or suicide, interpersonal conflicts, occupational problems, bereavement or social isolation.<ref name="Carvalho" />

== Epidemiology ==

[[File:Bipolar disorder world map - DALY - WHO2004.svg|thumb|Burden of bipolar disorder around the world: [[disability-adjusted life year]]s per 100,000&nbsp;inhabitants in 2004
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Bipolar disorder is the sixth leading cause of disability worldwide and has a lifetime prevalence of about 1 to 3% in the general population.<ref name="Schmitt2014" /><ref name="Boland2013">{{cite journal | vauthors = Boland EM, Alloy LB | title = Sleep disturbance and cognitive deficits in bipolar disorder: toward an integrated examination of disorder maintenance and functional impairment | journal = Clinical Psychology Review | volume = 33 | issue = 1 | pages = 33–44 | date = February 2013 | pmid = 23123569 | pmc = 3534911 | doi = 10.1016/j.cpr.2012.10.001 }}</ref><ref>{{cite journal | vauthors = Moreira AL, Van Meter A, Genzlinger J, Youngstrom EA | title = Review and Meta-Analysis of Epidemiologic Studies of Adult Bipolar Disorder | journal = The Journal of Clinical Psychiatry | volume = 78 | issue = 9 | pages = e1259–e1269 |year = 2017 | pmid = 29188905 | doi = 10.4088/JCP.16r11165 | s2cid = 3763712 }}</ref> However, a reanalysis of data from the National Epidemiological Catchment Area survey in the United States suggested that 0.8% of the population experience a manic episode at least once (the diagnostic threshold for bipolar I) and a further 0.5% have a hypomanic episode (the diagnostic threshold for bipolar II or cyclothymia). Including sub-threshold diagnostic criteria, such as one or two symptoms over a short time-period, an additional 5.1% of the population, adding up to a total of 6.4%, were classified as having a bipolar spectrum disorder.<ref name="Judd_and_Akiskal_2003">{{cite journal | vauthors = Judd LL, Akiskal HS | title = The prevalence and disability of bipolar spectrum disorders in the US population: re-analysis of the ECA database taking into account subthreshold cases | journal = Journal of Affective Disorders | volume = 73 | issue = 1–2 | pages = 123–131 | date = January 2003 | pmid = 12507745 | doi = 10.1016/s0165-0327(02)00332-4 }}</ref> A more recent analysis of data from a second US [[Social:National Comorbidity Survey|National Comorbidity Survey]] found that 1% met lifetime prevalence criteria for bipolar I, 1.1% for bipolar II, and 2.4% for subthreshold symptoms.<ref>{{cite journal | vauthors = Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, Kessler RC | title = Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication | journal = Archives of General Psychiatry | volume = 64 | issue = 5 | pages = 543–552 | date = May 2007 | pmid = 17485606 | pmc = 1931566 | doi = 10.1001/archpsyc.64.5.543 }}</ref> Estimates vary about how many children and young adults have bipolar disorder.<ref name="Diler2019"/> These estimates range from 0.6 to 15% depending on differing settings, methods, and referral settings, raising suspicions of overdiagnosis.<ref name="Diler2019"/> One meta-analysis of bipolar disorder in young people worldwide estimated that about 1.8% of people between the ages of seven and 21 have bipolar disorder.<ref name="Diler2019"/> Similar to adults, bipolar disorder in children and adolescents is thought to occur at a similar frequency in boys and girls.<ref name="Diler2019"/>

There are conceptual and methodological limitations and variations in the findings. Prevalence studies of bipolar disorder are typically carried out by lay interviewers who follow fully structured/fixed interview schemes; responses to single items from such interviews may have limited validity. In addition, diagnoses (and therefore estimates of prevalence) vary depending on whether a categorical or spectrum approach is used. This consideration has led to concerns about the potential for both underdiagnosis and overdiagnosis.<ref>{{cite journal | vauthors = Phelps J |title=Bipolar Disorder: Particle or Wave? DSM Categories or Spectrum Dimensions? |journal=Psychiatric Times |year=2006 |url=http://www.psychiatrictimes.com/print.jhtml?articleID=191504355&url_prefix= |url-status=live |archive-url=https://web.archive.org/web/20071204014311/http://www.psychiatrictimes.com/print.jhtml?articleID=191504355&url_prefix= |archive-date=December 4, 2007  }}</ref>

The incidence of bipolar disorder is similar in men and women<ref name="Farren2012">{{cite journal | vauthors = Farren CK, Hill KP, Weiss RD | title = Bipolar disorder and alcohol use disorder: a review | journal = Current Psychiatry Reports | volume = 14 | issue = 6 | pages = 659–666 | date = December 2012 | pmid = 22983943 | pmc = 3730445 | doi = 10.1007/s11920-012-0320-9 }}</ref> as well as across different cultures and ethnic groups.<ref>{{cite journal | vauthors = Ferrari AJ, Baxter AJ, Whiteford HA | title = A systematic review of the global distribution and availability of prevalence data for bipolar disorder | journal = Journal of Affective Disorders | volume = 134 | issue = 1–3 | pages = 1–13 | date = November 2011 | pmid = 21131055 | doi = 10.1016/j.jad.2010.11.007 }}</ref> A 2000 study by the [[Organization:World Health Organization|World Health Organization]] found that prevalence and incidence of bipolar disorder are very similar across the world. Age-standardized prevalence per 100,000 ranged from 421.0 in South Asia to 481.7 in Africa and Europe for men and from 450.3 in Africa and Europe to 491.6 in Oceania for women. However, severity may differ widely across the globe. Disability-adjusted life year rates, for example, appear to be higher in developing countries, where medical coverage may be poorer and medication less available.<ref>{{cite web|title=Global burden of bipolar disorder in the year 2000|url=https://www.who.int/healthinfo/statistics/bod_bipolar.pdf|publisher=[[Organization:World Health Organization|World Health Organization]]| vauthors = Ayuso-Mateos JL |access-date=December 9, 2012|url-status=live|archive-url=https://web.archive.org/web/20130119132547/http://www.who.int/healthinfo/statistics/bod_bipolar.pdf |archive-date=January 19, 2013}}</ref> Within the United States, Asian Americans have significantly lower rates than their African American and European American counterparts.<ref name="kurasaki">{{cite book|title=Asian American Mental Health: Assessment Theories and Methods| vauthors = Kurasaki KS |year=2002|pages=14–15| publisher = Springer |url=https://books.google.com/books?id=-3sRIOeXfesC |isbn=9780306472688 }}</ref> In 2017, the [[Organization:Global Burden of Disease Study|Global Burden of Disease Study]] estimated there were 4.5 million new cases and a total of 45.5 million cases globally.<ref name=GBD2018>{{cite journal |vauthors=James SL, Abate D |title=Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 |journal=The Lancet |date=November 2018 |volume=392 |issue=10159 |pages=1789–1858 |doi=10.1016/S0140-6736(18)32279-7|pmid=30496104 |pmc=6227754 }}</ref>

== History ==
{{Main|Medicine:History of bipolar disorder}}

[[File:Emil Kraepelin 1926.jpg|alt=|thumb|right|German psychiatrist Emil Kraepelin first distinguished between manic–depressive illness and "dementia praecox" (now known as schizophrenia) in the late 19th century.]]
In the early 1800s, French psychiatrist Jean-Étienne Dominique Esquirol's lypemania, one of his affective monomanias, was the first elaboration on what was to become modern depression.<ref>{{cite journal | author = Borch-Jacobsen M | title = Which came first, the condition or the drug? | journal = London Review of Books | volume = 32 | issue = 19 | pages = 31–33 | date = October 2010 | url = http://www.lrb.co.uk/v32/n19/mikkel-borch-jacobsen/which-came-first-the-condition-or-the-drug | quote = at the beginning of the 19th century with Esquirol's 'affective monomanias' (notably 'lypemania', the first elaboration of what was to become our modern depression) | url-status=live | archive-url = https://web.archive.org/web/20150313201452/http://www.lrb.co.uk/v32/n19/mikkel-borch-jacobsen/which-came-first-the-condition-or-the-drug | archive-date = March 13, 2015 | df = mdy-all }}</ref> The basis of the current conceptualization of bipolar illness can be traced back to the 1850s. In 1850, Jean-Pierre Falret described "circular insanity" (''{{Lang|fr|la folie circulaire}}'', {{IPA-fr|la fɔli siʁ.ky.lɛʁ}}); the lecture was summarized in 1851 in the ''{{Lang|fr|Gazette des hôpitaux}}'' ("Hospital Gazette").<ref name=Shorter2005>{{cite book|author=Edward Shorter|title=A Historical Dictionary of Psychiatry|url=https://books.google.com/books?id=M49pEDoEpl0C&pg=PA165|year=2005|place=New York|publisher=Oxford University Press|isbn=978-0-19-517668-1|pages=165–166}}</ref> Three years later, in 1854, Jules-Gabriel-François Baillarger (1809–1890) described to the French Imperial Académie Nationale de Médecine a biphasic mental illness causing recurrent oscillations between mania and melancholia, which he termed {{Lang|fr|la folie à double forme}} ({{IPA-fr|la fɔli a dubl fɔʀm}}, "madness in double form").<ref name=Shorter2005/><ref>{{cite journal |author=Pichot P. |title=150e anniversaire de la Folie Circulaire |trans-title=Circular insanity, 150 years on |journal = Bulletin de l'Académie Nationale de Médecine |volume=188 |issue=2 |pages=275–284 |year=2004 |pmid = 15506718 |language=fr|doi=10.1016/S0001-4079(19)33801-4 |doi-access=free }}</ref> Baillarger's original paper, "{{Lang|fr|De la folie à double forme|italic=no}}", appeared in the medical journal ''Annales médico-psychologiques'' (''Medico-psychological annals'') in 1854.<ref name=Shorter2005/>

These concepts were developed by the German psychiatrist [[Biography:Emil Kraepelin|Emil Kraepelin]] (1856–1926), who, using Kahlbaum's concept of cyclothymia,{{sfn|Millon|1996|p=290}} categorized and studied the natural course of untreated bipolar patients. He coined the term ''manic depressive psychosis'', after noting that periods of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals where the patient was able to function normally.<ref>{{cite journal | vauthors = Kraepelin E |year=1921|title=Manic–depressive Insanity and Paranoia|journal=The Indian Medical Gazette|volume=56|issue=4|pages=156–157|isbn= 978-0-405-07441-7|pmc=5166213}}</ref>

The term "manic–depressive ''reaction''" appeared in the first version of the DSM in 1952, influenced by the legacy of Adolf Meyer.{{sfn|Goodwin|Jamison|2007| loc=Chapter 1}} Subtyping into "unipolar" depressive disorders and bipolar disorders has its origin in Karl Kleist's concept – since 1911 – of unipolar and bipolar affective disorders, which was used by Karl Leonhard in 1957 to differentiate between unipolar and bipolar disorder in depression.<ref name="Angst-2001" >{{cite journal | vauthors = Angst J, Marneros A | title = Bipolarity from ancient to modern times: conception, birth and rebirth | journal = J Affect Disord | volume = 67 | issue = 1–3 | pages = 3–19 | date = December 2001 | pmid = 11869749 | doi = 10.1016/s0165-0327(01)00429-3 }}</ref> These subtypes have been regarded as separate conditions since publication of the DSM-III. The subtypes bipolar II and rapid cycling have been included since the DSM-IV, based on work from the 1970s by David Dunner, [[Biography:Elliot S. Gershon|Elliot Gershon]], Frederick Goodwin, Ronald Fieve, and [[Biography:Joseph L. Fleiss|Joseph Fleiss]].<ref>[https://books.google.com/books?id=6-IfJ6dYy2cC Bipolar Depression: Molecular Neurobiology, Clinical Diagnosis and Pharmacotherapy] {{webarchive|url=https://web.archive.org/web/20160507061659/https://books.google.com/books?id=6-IfJ6dYy2cC |date=May 7, 2016 }} Carlos A. Zarate Jr., Husseini K. Manji, Springer Science & Business Media, April 16, 2009</ref><ref>{{cite journal | doi = 10.1192/apt.bp.107.004903 | volume=16 | title=The course of bipolar disorder | year=2010 | journal=Advances in Psychiatric Treatment | pages=318–328 | author=Saunders KE| issue=5 | doi-access=free }}</ref><ref name="Ban">[http://d.plnk.co/ACNP/50th/Transcripts/David%20Dunner%20by%20Thomas%20A.%20Ban.doc David L. Dunner interviewed by Thomas A. Ban] {{webarchive|url=https://web.archive.org/web/20130521160737/http://d.plnk.co/ACNP/50th/Transcripts/David%20Dunner%20by%20Thomas%20A.%20Ban.doc |date=May 21, 2013 }} for the ANCP, Waikoloa, Hawaii, December 13, 2001</ref>
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== Society and culture ==
[[File:Rosemary Clooney Allan Warren.jpg|alt=|thumb|Singer Rosemary Clooney's public revelation of bipolar disorder made her an early celebrity spokesperson for mental illness.<ref>{{cite web|title=More Than a Girl Singer|url=https://www.cancertodaymag.org/Pages/Fall2014/Singer-Rosemary-Clooney-Lung-Cancer-Treatment-Advancements.aspx|website=cancertodaymag.org|access-date=18 May 2018}}</ref>]]

===Cost===
The {{wipe|United States}} spent approximately $202.1 billion on people diagnosed with bipolar I disorder (excluding other subtypes of bipolar disorder and undiagnosed people) in 2015.<ref name="Cloutier2018">{{cite journal | vauthors = Cloutier M, Greene M, Guerin A, Touya M, Wu E | title = The economic burden of bipolar I disorder in the United States in 2015 | journal = Journal of Affective Disorders | volume = 226 | pages = 45–51 | date = January 2018 | pmid = 28961441 | doi = 10.1016/j.jad.2017.09.011 | doi-access = free | type = Review }}</ref> One analysis estimated that the {{wipe|United Kingdom}} spent approximately £5.2 billion on the disorder in 2007.<ref name="Abdul2014">{{cite journal | vauthors = Abdul Pari AA, Simon J, Wolstenholme J, Geddes JR, Goodwin GM | title = Economic evaluations in bipolar disorder: a systematic review and critical appraisal | journal = Bipolar Disorders | volume = 16 | issue = 6 | pages = 557–582 | date = September 2014 | pmid = 24917477 | doi = 10.1111/bdi.12213 | type = Review | s2cid = 5450333 }}</ref><ref name="McCrone2008">{{cite web | vauthors = McCrone P, Dhanasiri S, Patel A, Knapp M, Lawton-Smith S |title=PAYING THE PRICE The cost of mental health care in England to 2026 |url= https://www.kingsfund.org.uk/sites/default/files/Paying-the-Price-the-cost-of-mental-health-care-England-2026-McCrone-Dhanasiri-Patel-Knapp-Lawton-Smith-Kings-Fund-May-2008_0.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://www.kingsfund.org.uk/sites/default/files/Paying-the-Price-the-cost-of-mental-health-care-England-2026-McCrone-Dhanasiri-Patel-Knapp-Lawton-Smith-Kings-Fund-May-2008_0.pdf |archive-date=2022-10-09 |url-status=live |website=kingsfund.org |publisher=The King's Fund}}</ref> In addition to the economic costs, bipolar disorder is a leading cause of disability and lost productivity worldwide.<ref name="Ferrari2016"/> People with bipolar disorder are generally more disabled, have a lower level of functioning, longer duration of illness, and increased rates of work absenteeism and decreased productivity when compared to people experiencing other mental health disorders.<ref name="Kleine2014">{{cite journal | vauthors = Kleine-Budde K, Touil E, Moock J, Bramesfeld A, Kawohl W, Rössler W | title = Cost of illness for bipolar disorder: a systematic review of the economic burden | journal = Bipolar Disorders | volume = 16 | issue = 4 | pages = 337–353 | date = June 2014 | pmid = 24372893 | doi = 10.1111/bdi.12165 | type = Review | s2cid = 25742003 }}</ref> The decrease in the productivity seen in those who care for people with bipolar disorder also significantly contributes to these costs.<ref name="Miller2014">{{cite journal | vauthors = Miller S, Dell'Osso B, Ketter TA | title = The prevalence and burden of bipolar depression | journal = Journal of Affective Disorders | volume = 169 | issue = Supplement 1 | pages = S3-11 | date = December 2014 | pmid = 25533912 | doi = 10.1016/S0165-0327(14)70003-5 | type = Review | doi-access = free | hdl = 2434/265329 | hdl-access = free }}</ref>

===Advocacy===
There are widespread issues with [[Social:Social stigma|social stigma]], stereotypes, and prejudice against individuals with a diagnosis of bipolar disorder.<ref name=Elgie2007>{{cite journal | author = Elgie R. Morselli PL | title = Social functioning in bipolar patients: the perception and perspective of patients, relatives and advocacy organizations – a review | journal = Bipolar Disorders | volume = 9 | issue = 1–2 | pages = 144–157 | date = Feb–Mar 2007 | pmid = 17391357 | doi = 10.1111/j.1399-5618.2007.00339.x | doi-access = free }}</ref> In 2000, actress Carrie Fisher went public with her bipolar disorder diagnosis.<ref>{{cite web |last=Stephens |first=Stephanie |date=2015-01-01 |title=Our Leading Lady, Carrie Fisher |url=https://www.bphope.com/our-leading-lady-carrie-fisher/ |access-date=2023-09-27 |website=bpHope.com |language=en-US}}</ref><ref>{{cite web |last=Howard |first=Jacqueline |date=2016-12-27 |title=Carrie Fisher was a champion for mental health, too |url=https://www.cnn.com/2016/12/27/health/mental-health-carrie-fisher/index.html |access-date=2023-09-27 |website=CNN |language=en}}</ref> She became one of the most well-recognized advocates for people with bipolar disorder in the public eye and fiercely advocated to eliminate the stigma surrounding mental illnesses, including bipolar disorder.<ref name="WilerUSAToday">{{cite web | vauthors = Wiler S |title=Carrie Fisher was a mental health hero. Her advocacy was as important as her acting. |url=https://www.usatoday.com/story/opinion/2019/07/26/carrie-fisher-champion-mental-health-awareness-column/1820161001/ |work=USA Today}}</ref> Stephen Fried, who has written extensively on the topic, noted that Fisher helped to draw attention to the disorder's chronicity, relapsing nature, and that bipolar disorder relapses do not indicate a lack of discipline or moral shortcomings.<ref name="WilerUSAToday"/> Since being diagnosed at age 37, actor [[Biography:Stephen Fry|Stephen Fry]] has pushed to raise awareness of the condition, with his 2006 documentary ''Stephen Fry: The Secret Life of the Manic Depressive''.<ref>{{cite web |url=https://www.bbc.co.uk/health/tv_and_radio/secretlife_index.shtml |title=The Secret Life of the Manic Depressive |publisher=BBC |year=2006 |access-date=February 20, 2007 |archive-url=https://web.archive.org/web/20061118045848/http://www.bbc.co.uk/health/tv_and_radio/secretlife_index.shtml |archive-date=November 18, 2006 |url-status=live  }}</ref><ref>{{cite news | vauthors = Barr S |title=Stephen Fry discusses mental health and battle with bipolar disorder: 'I'm not going to kid myself that it's cured' |url=https://www.independent.co.uk/life-style/health-and-families/stephen-fry-mental-health-bipolar-disorder-fearne-cotton-podcast-happy-place-a8274051.html |access-date=March 10, 2020 |work=The Independent |date=March 26, 2018}}</ref> In an effort to ease the social stigma associated with bipolar disorder, the orchestra conductor Ronald Braunstein cofounded the ME/2 Orchestra with his wife Caroline Whiddon in 2011. Braunstein was diagnosed with bipolar disorder in 1985 and his concerts with the ME/2 Orchestra were conceived in order to create a welcoming performance environment for his musical colleagues, while also raising public awareness about mental illness.<ref>{{cite news | vauthors = Gram D | date=December 27, 2013 | title=For this orchestra, playing music is therapeutic | work=The Boston Globe | url=https://www.bostonglobe.com/arts/theater-art/2013/12/27/mentally-ill-and-their-supporters-fill-vermont-orchestra/WIeh9mIp9GzPampyIXwtLM/story.html | access-date=March 7, 2019 | archive-url=https://web.archive.org/web/20190414112300/https://www.bostonglobe.com/arts/theater-art/2013/12/27/mentally-ill-and-their-supporters-fill-vermont-orchestra/WIeh9mIp9GzPampyIXwtLM/story.html | archive-date=April 14, 2019 | url-status=dead }}</ref><ref>{{cite news|first1=Franz | last1=Strasser |first2=David | last2=Botti | date= January 7, 2013|title=Conductor with bipolar disorder on music and mental illness | work= BBC News|url=https://www.bbc.com/news/magazine-20732070}}</ref>

===Notable cases===
Numerous authors have written about bipolar disorder and many successful people have openly discussed their experience with it. [[Biography:Kay Redfield Jamison|Kay Redfield Jamison]], a clinical psychologist and professor of psychiatry at the Johns Hopkins University School of Medicine, profiled her own bipolar disorder in her memoir ''An Unquiet Mind'' (1995).{{sfn|Jamison|1995}} It is likely that Grigory Potemkin, Russian statesman and alleged husband of Catherine the Great, suffered from some kind of bipolar disorder.<ref>{{cite book|url=https://books.google.com/books?id=9crS6557gVgC&q=manic&pg=PA169|title = Potemkin: Catherine the Great's Imperial Partner|isbn = 9781400077175|last1 = Montefiore|first1 = Simon Sebag|year = 2005| publisher=Vintage Books }}</ref> Several celebrities have also publicly shared that they have bipolar disorder; in addition to Carrie Fisher and [[Biography:Stephen Fry|Stephen Fry]] these include Catherine Zeta-Jones, Mariah Carey, Kanye West,<ref>{{cite web|author1=Michele R. Berman |author2=Mark S. Boguski |title=Understanding Kanye West's Bipolar Disorder |date=July 15, 2020 |url=https://www.medpagetoday.com/popmedicine/celebritydiagnosis/87581 |url-status=live |archive-url=https://web.archive.org/web/20210607232802/https://www.medpagetoday.com/popmedicine/celebritydiagnosis/87581 |archive-date=June 7, 2021 |access-date=August 1, 2021}}</ref> Jane Pauley, Demi Lovato,<ref name="WilerUSAToday"/> Selena Gomez,<ref name="Naftulin 2020">{{cite web | vauthors = Naftulin J | title=Selena Gomez opened up about the challenges of being in lockdown after her bipolar diagnosis | website=Insider | date=2020-08-07 | url=https://www.insider.com/selena-gomez-bipolar-disorder-diagnosis-pandemic-mental-health-2020-8 | access-date=2020-12-06}}</ref> and Russell Brand.<ref>{{cite magazine |url=https://www.harpersbazaar.com/uk/beauty/mind-body/a33519731/bipolar-disorder-why-we-need-to-keep-talking/ |title=Bipolar disorder: why we need to keep talking about it after the headlines fade | vauthors = Newall S |date=5 August 2020 |magazine=Harper's Bazaar |access-date=14 January 2022}}</ref>

===Media portrayals===
Several dramatic works have portrayed characters with traits suggestive of the diagnosis which have been the subject of discussion by psychiatrists and film experts alike.

In ''Mr. Jones'' (1993), (Richard Gere) swings from a manic episode into a depressive phase and back again, spending time in a psychiatric hospital and displaying many of the features of the syndrome.{{sfn|Robinson|2003|pp=78–81}} In ''The Mosquito Coast'' (1986), Allie Fox (Harrison Ford) displays some features including recklessness, grandiosity, increased goal-directed activity and mood lability, as well as some [[Medicine:Paranoia|paranoia]].{{sfn|Robinson|2003|pp=84–85}} Psychiatrists have suggested that Willy Loman, the main character in [[Biography:Arthur Miller|Arthur Miller]]'s classic play ''Death of a Salesman'', has bipolar disorder.<ref>{{cite news| vauthors = McKinley J |title=Get That Man Some Prozac; If the Dramatic Tension Is All in His Head|url=https://www.nytimes.com/1999/02/28/weekinreview/ideas-trends-get-that-man-some-prozac-if-the-dramatic-tension-is-all-in-his-head.html|access-date=March 3, 2012|newspaper=The New York Times|date=February 28, 1999|url-status=live |archive-url= https://web.archive.org/web/20120101024850/http://www.nytimes.com/1999/02/28/weekinreview/ideas-trends-get-that-man-some-prozac-if-the-dramatic-tension-is-all-in-his-head.html |archive-date=January 1, 2012}}</ref>

The 2009 drama ''90210'' featured a character, Silver, who was diagnosed with bipolar disorder.<ref>{{cite web|url=http://www.bpkids.org/90210 |archive-url=https://archive.today/20120803024403/http://www.bpkids.org/90210 |url-status=dead |archive-date=August 3, 2012 |title=Child and Adolescent Bipolar Foundation special 90210 website |publisher=CABF |year=2009 |access-date=April 7, 2009 }}</ref> Stacey Slater, a character from the BBC soap ''EastEnders'', has been diagnosed with the disorder. The storyline was developed as part of the BBC's Headroom campaign.<ref>{{cite web|url=https://www.bbc.co.uk/pressoffice/pressreleases/stories/2009/05_may/14/stacey.shtml|title=EastEnders' Stacey faces bipolar disorder|publisher=BBC Press Office|date=May 14, 2009|access-date=May 28, 2009|url-status=live|archive-url=https://web.archive.org/web/20090518033958/http://www.bbc.co.uk/pressoffice/pressreleases/stories/2009/05_may/14/stacey.shtml|archive-date=May 18, 2009}}</ref> The Channel 4 soap ''Brookside'' had earlier featured a story about bipolar disorder when the character Jimmy Corkhill was diagnosed with the condition.<ref name="Echo14May2003">{{cite news|url= http://www.thefreelibrary.com/The+Brookie+boys+who+shone+at+soap+awards+show%3B+TONIGHT+the+nation...-a0101743730|title= The Brookie boys who shone at soap awards show|work= Liverpool Echo|publisher= Mirror Group Newspapers| vauthors = Tinniswood R |date= May 14, 2003|access-date=April 26, 2014}}</ref> 2011 Showtime's political thriller drama ''Homeland'' protagonist Carrie Mathison has bipolar disorder, which she has kept secret since her school days.<ref name="pilot">{{cite episode|title=Pilot|episode-link=Homeland (season 1)#ep1|series=Homeland|series-link=Homeland|network=Showtime|airdate=October 2, 2011|season=1|number=1}}</ref> The 2014 ABC medical drama, ''Black Box'', featured a world-renowned neuroscientist with bipolar disorder.<ref>{{cite web|url=http://abc.go.com/shows/black-box/cast/catherine-black|title=Catherine Black by Kelly Reilly |publisher=American Broadcasting Company|archive-url=https://web.archive.org/web/20140523174651/http://abc.go.com/shows/black-box/cast/catherine-black |archive-date=May 23, 2014|access-date=May 22, 2014}}</ref>
In the TV series ''Dave'', the eponymous main character, played by Lil Dicky as a fictionalized version of himself, is an aspiring rapper. Lil Dicky's real-life hype man GaTa also plays himself. In one episode, after being off his medication and having an episode, GaTa tearfully confesses to having bipolar disorder. GaTa has bipolar disorder in real life but, like his character in the show, he is able to manage it with medication.<ref>{{cite web |title=How a white rapper's sidekick became a breakout sitcom star — and TV's unlikeliest role model |url=https://www.latimes.com/entertainment-arts/music/story/2020-04-15/gata-dave-lil-dicky |website=Los Angeles Times|date=April 15, 2020 }}</ref>

===Creativity===
A link between mental illness and professional success or creativity has been suggested, including in accounts by [[Biography:Socrates|Socrates]], [[Biography:Seneca the Younger|Seneca the Younger]], and [[Biography:Cesare Lombroso|Cesare Lombroso]]. Despite prominence in popular culture, the link between creativity and bipolar has not been rigorously studied. This area of study also is likely affected by [[Confirmation bias|confirmation bias]]. Some evidence suggests that some heritable component of bipolar disorder overlaps with heritable components of creativity. [[Biology:Proband|Proband]]s of people with bipolar disorder are more likely to be professionally successful, as well as to demonstrate temperamental traits similar to bipolar disorder. Furthermore, while studies of the frequency of bipolar disorder in creative population samples have been conflicting, full-blown bipolar disorder in creative samples is rare.<ref>{{cite book | vauthors = Akiskal H, Akiskal K | veditors = Lakshmi Y |title=Bipolar Disorder: Clinical and Neurobiological Foundations |pages=83–89 |publisher=Wiley |chapter=The Genius-Insanity Debate: Focus on Bipolarity, Temperament, Creativity and Leadership|doi=10.1002/9780470661277.ch9 |isbn = 9780470661277|year=2010 }}</ref>

==Research==
Research directions for bipolar disorder in children include optimizing treatments, increasing the knowledge of the genetic and neurobiological basis of the pediatric disorder and improving diagnostic criteria.<ref name=Lei2008 /> Some treatment research suggests that [[Social:Psychosocial|psychosocial]] interventions that involve the family, psychoeducation, and skills building (through therapies such as [[Medicine:Cognitive behavioral therapy|CBT]], [[Social:Dialectical behavior therapy|DBT]], and [[Medicine:Interpersonal and social rhythm therapy|IPSRT]]) can benefit in addition to pharmacotherapy.<ref name="Fristad">{{cite journal | vauthors = Fristad MA, MacPherson HA | title = Evidence-based psychosocial treatments for child and adolescent bipolar spectrum disorders | journal = Journal of Clinical Child and Adolescent Psychology | volume = 43 | issue = 3 | pages = 339–355 |year = 2014 | pmid = 23927375 | pmc = 3844106 | doi = 10.1080/15374416.2013.822309 }}</ref>

==See also==
* List of people with bipolar disorder
* [[Biology:Outline of bipolar disorder|Outline of bipolar disorder]]
* [[Medicine:Bipolar I disorder|Bipolar I disorder]]
* [[Medicine:Bipolar II disorder|Bipolar II disorder]]
* Bipolar NOS
* [[Medicine:Cyclothymia|Cyclothymia]]
* Bipolar disorders research
* [[Medicine:Borderline personality disorder|Borderline personality disorder]]
* [[Philosophy:Emotional dysregulation|Emotional dysregulation]]
* Mood (psychology)
* [[Philosophy:Mood swing|Mood swing]]
* [[Organization:International Society for Bipolar Disorders|International Society for Bipolar Disorders]]

== Explanatory notes ==
{{notelist}}

== Citations ==
{{Reflist}}

==Cited texts==
{{refbegin}}
* {{cite book | vauthors = Brown MR, Basso MR |year=2004 |title=Focus on Bipolar Disorder Research |publisher=Nova Science Publishers |isbn=978-1-59454-059-2 }}
* {{cite book | vauthors = Goodwin FK, Jamison KR |year=2007 |title=Manic–depressive illness: bipolar disorders and recurrent depression |publisher=Oxford University Press |isbn=978-0-19-513579-4 |edition=2nd.|url=https://books.google.com/books?id=rnr_OxfcqDcC |oclc=70929267 |access-date=April 2, 2016}}
* {{cite book | vauthors = Jamison KR |year=1995 |title=An Unquiet Mind: A Memoir of Moods and Madness |location=New York |publisher=Knopf |isbn=978-0-330-34651-1 }}
* {{cite book | vauthors = Millon T |year=1996 |title=Disorders of Personality: DSM-IV-TM and Beyond |location=New York |publisher=John Wiley and Sons |isbn=978-0-471-01186-6 }}
* {{cite book | vauthors = Robinson DJ |year= 2003 |title=Reel Psychiatry: Movie Portrayals of Psychiatric Conditions |location=Port Huron, Michigan |publisher=Rapid Psychler Press |isbn=978-1-894328-07-4 }}
{{refend}}

== Further reading ==
{{Library resources box}}
{{refbegin}}
* {{cite journal | vauthors = Goldstein BI, Birmaher B, Carlson GA, DelBello MP, Findling RL, Fristad M, Kowatch RA, Miklowitz DJ, Nery FG, Perez-Algorta G, Van Meter A, Zeni CP, Correll CU, Kim HW, Wozniak J, Chang KD, Hillegers M, Youngstrom EA | display-authors = 6 | title = The International Society for Bipolar Disorders Task Force report on pediatric bipolar disorder: Knowledge to date and directions for future research | journal = Bipolar Disorders | volume = 19 | issue = 7 | pages = 524–543 | date = November 2017 | pmid = 28944987 | pmc = 5716873 | doi = 10.1111/bdi.12556 }}
{{refend}}

== External links ==

{{Medical condition classification and resources
| DiseasesDB = 7812
| ICD11 = {{ICD11|6A60}}, {{ICD11|6A61}}
| ICD10 = {{ICD10|F31}}
| ICD9 = {{ICD9|296.0}}, {{ICD9|296.1}}, {{ICD9|296.4}}, {{ICD9|296.5}}, {{ICD9|296.6}}, {{ICD9|296.7}}, {{ICD9|296.8}}
| ICDO =
| OMIM = 125480
| OMIM_mult = {{OMIM|309200||none}}
| MedlinePlus = 000926
| eMedicineSubj = med
| eMedicineTopic = 229
| MeshID = D001714
}}
{{Mental and behavioral disorders|selected = mood}}
{{Mood disorders|state=expanded}}

[[Category:Bipolar disorder| ]]
[[Category:Mood disorders]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Bipolar disorder}}