View source for Biology:Behavioral epigenetics

{{Short description|Study of epigenetics' influencing behavior}}
'''Behavioral epigenetics''' is the field of study examining the role of epigenetics in shaping [[Biology:Animal|animal]] and [[Biology:Human|human]] behavior.<ref name="Miller_2010"/>  It seeks to explain how nurture shapes nature,<ref name="Powledge_2011">{{cite journal | vauthors = Powledge T | title = Behavioral epigenetics: How nurture shapes nature | journal = BioScience | year = 2011 | volume = 61 | issue = 8 | pages = 588–592 | doi = 10.1525/bio.2011.61.8.4 | doi-access = free }}</ref> where nature refers to biological [[Biology:Heredity|heredity]]<ref name="Kail_2011">{{cite book | vauthors = Kail RV, Barnfield A | title = Children and Their Development, Second Canadian Edition with MyDevelopmentLab | publisher = Pearson Education Canada | location = Toronto | year = 2011 | isbn =978-0-13-255770-2 }}</ref> and nurture refers to virtually everything that occurs during the life-span (e.g., social-experience, diet and nutrition, and exposure to toxins).<ref name="Moore_2015">{{cite book | vauthors = Moore DS | title = The Developing Genome: An Introduction to Behavioral Epigenetics | date = 2015 | publisher = Oxford University Press | isbn = 978-0-19-992234-5 | edition = 1st }}</ref>  Behavioral epigenetics attempts to provide a framework for understanding how the expression of [[Biology:Gene|gene]]s is influenced by experiences and the environment<ref name="Champagne">{{cite journal | vauthors = Champagne FA, Mashoodh R | title = Genes in context: Gene-environment interplay and the origins of individual differences in behaviour | journal = Current Directions in Psychological Science | year = 2012 | volume = 18 | issue = 3 | pages = 127–131 | doi = 10.1111/j.1467-8721.2009.01622.x| s2cid = 18672157 }}</ref> to produce individual differences in behaviour,<ref name="Zhang_2010">{{cite journal | vauthors = Zhang TY, Meaney MJ | title = Epigenetics and the environmental regulation of the genome and its function | journal = Annual Review of Psychology | volume = 61 | pages = 439–66, C1-3 | year = 2010 | pmid = 19958180 | doi = 10.1146/annurev.psych.60.110707.163625 }}</ref> [[Cognition|cognition]],<ref name="Powledge_2011"/> [[Philosophy:Personality|personality]],<ref name="Bagot_2010">{{cite journal | vauthors = Bagot RC, Meaney MJ | title = Epigenetics and the biological basis of gene x environment interactions | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 49 | issue = 8 | pages = 752–71 | date = Aug 2010 | pmid = 20643310 | doi = 10.1016/j.jaac.2010.06.001 }}</ref> and [[Social:Mental health|mental health]].<ref name="pmid18197504">{{cite journal | vauthors = Stuffrein-Roberts S, Joyce PR, Kennedy MA | title = Role of epigenetics in mental disorders | journal = The Australian and New Zealand Journal of Psychiatry | volume = 42 | issue = 2 | pages = 97–107 | date = Feb 2008 | pmid = 18197504 | doi = 10.1080/00048670701787495 | s2cid = 36721906 | url = https://zenodo.org/record/3948906 }}</ref><ref name=McIlroy>{{cite journal | vauthors = Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L, Jia P, Assadzadeh A, Flanagan J, Schumacher A, Wang SC, Petronis A | title = Epigenomic profiling reveals DNA-methylation changes associated with major psychosis | journal = American Journal of Human Genetics | volume = 82 | issue = 3 | pages = 696–711 | date = Mar 2008 | pmid = 18319075 | pmc = 2427301 | doi = 10.1016/j.ajhg.2008.01.008 }}</ref>

Epigenetic [[Biology:Regulation of gene expression|gene regulation]] involves changes other than to the [[Biology:Nucleic acid sequence|sequence]] of [[Biology:DNA|DNA]] and includes changes to [[Biology:Histone|histone]]s (proteins around which DNA is wrapped) and [[Biology:DNA methylation|DNA methylation]].<ref>{{cite journal|title=Crime investigation through DNA methylation analysis: methods and applications in forensics | vauthors = Rana AK |date=24 January 2018 |journal=Egyptian Journal of Forensic Sciences |volume=8 |issue=1 |doi=10.1186/s41935-018-0042-1 |doi-access=free }}</ref><ref name="Moore_2015"/><ref name="pmid11498570">{{cite journal | vauthors = Pennisi E |  s2cid = 40236421 | title = Behind the scenes of gene expression | journal = Science | volume = 293 | issue = 5532 | pages = 1064–7 | date = Aug 2001 | pmid = 11498570 | doi = 10.1126/science.293.5532.1064 }}</ref>  These epigenetic changes can influence the growth of [[Biology:Neuron|neuron]]s in the developing brain<ref name="pmid20608952">{{cite journal | vauthors = Juliandi B, Abematsu M, Nakashima K | title = Epigenetic regulation in neural stem cell differentiation | journal = Development, Growth & Differentiation | volume = 52 | issue = 6 | pages = 493–504 | date = Aug 2010 | pmid = 20608952 | doi = 10.1111/j.1440-169X.2010.01175.x | s2cid = 28991168 | doi-access = free }}</ref> as well as modify the activity of neurons in the adult brain.<ref name="pmid20975758">{{cite journal | vauthors = Ma DK, Marchetto MC, Guo JU, Ming GL, Gage FH, Song H | title = Epigenetic choreographers of neurogenesis in the adult mammalian brain | journal = Nature Neuroscience | volume = 13 | issue = 11 | pages = 1338–44 | date = Nov 2010 | pmid = 20975758 | pmc = 3324277 | doi = 10.1038/nn.2672 }}</ref><ref name="pmid21395852">{{cite journal | vauthors = Sun J, Sun J, Ming GL, Song H | title = Epigenetic regulation of neurogenesis in the adult mammalian brain | journal = The European Journal of Neuroscience | volume = 33 | issue = 6 | pages = 1087–93 | date = Mar 2011 | pmid = 21395852 | pmc = 3076719 | doi = 10.1111/j.1460-9568.2011.07607.x }}</ref>  Together, these epigenetic changes in neuron structure and function can have a marked influence on an organism's behavior.<ref name="Miller_2010"/>

== Background ==
{{Main article|Biology:Epigenetics}}
In [[Biology:Biology|biology]], and specifically [[Biology:Genetics|genetics]], epigenetics is the study of heritable changes in [[Biology:Gene|gene]] activity which are ''not'' caused by changes in the [[Biology:DNA|DNA]] sequence; the term can also be used to describe the study of stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable.<ref name="pmid17522671">{{cite journal | vauthors = Bird A | title = Perceptions of epigenetics | journal = Nature | volume = 447 | issue = 7143 | pages = 396–8 | date = May 2007 | pmid = 17522671 | doi = 10.1038/nature05913 | bibcode = 2007Natur.447..396B | s2cid = 4357965 | doi-access = free }}</ref><ref>{{cite web |title=Overview of the Roadmap Epigenomics Project |url=http://www.roadmapepigenomics.org/overview |access-date=2013-12-15 |archive-date=2019-11-21 |archive-url=https://web.archive.org/web/20191121014029/http://www.roadmapepigenomics.org/overview |url-status=dead }}</ref>

Examples of mechanisms that produce such changes are [[Biology:DNA methylation|DNA methylation]]<ref name="pmid18940229">{{cite journal | vauthors = Mehler MF | title = Epigenetic principles and mechanisms underlying nervous system functions in health and disease | journal = Progress in Neurobiology | volume = 86 | issue = 4 | pages = 305–41 | date = Dec 2008 | pmid = 18940229 | pmc = 2636693 | doi = 10.1016/j.pneurobio.2008.10.001}}</ref> and histone modification,<ref name="Maze_2011"/> each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. 
[[Image:Epigenetic mechanisms.png|thumb|Modifications of the [[Biology:Epigenome|epigenome]] do not alter DNA.]]

DNA methylation turns a gene "off" – it results in the inability of genetic information to be read from DNA; removing the methyl tag can turn the gene back "on".<ref name="Reik_2007">{{cite journal | vauthors = Reik W | title = Stability and flexibility of epigenetic gene regulation in mammalian development | journal = Nature | volume = 447 | issue = 7143 | pages = 425–32 | date = May 2007 | pmid = 17522676 | doi = 10.1038/nature05918 | bibcode = 2007Natur.447..425R | s2cid = 11794102 }}</ref><ref name="Gottesman">{{cite journal | vauthors = Gottesman II, Hanson DR | title = Human development: biological and genetic processes | journal = Annual Review of Psychology | volume = 56 | pages = 263–86 | year = 2005 | pmid = 15709936 | doi = 10.1146/annurev.psych.56.091103.070208 }}</ref>

Histone modification changes the way that DNA is packaged into chromosomes. These changes impact how genes are expressed.<ref>{{Cite web|title=Histone modifications {{!}} Abcam|url=https://www.abcam.com/epigenetics/histone-modifications|access-date=2021-10-09|website=www.abcam.com}}</ref>

Epigenetics has a strong influence on the development of an organism and can alter the expression of individual traits.<ref name="pmid11498570"/>  Epigenetic changes occur not only in the developing fetus, but also in individuals throughout the human life-span.<ref name="Moore_2015"/><ref name="Campbell_2011">{{cite journal | vauthors = Campbell IC, Mill J, Uher R, Schmidt U | title = Eating disorders, gene-environment interactions and epigenetics | journal = Neuroscience and Biobehavioral Reviews | volume = 35 | issue = 3 | pages = 784–93 | date = Jan 2011 | pmid = 20888360 | doi = 10.1016/j.neubiorev.2010.09.012 | s2cid = 24599095 }}</ref>  Because some epigenetic modifications can be passed from one generation to the next,<ref name="Goto_1998">{{cite journal | vauthors = Goto T, Monk M | title = Regulation of X-chromosome inactivation in development in mice and humans | journal = Microbiology and Molecular Biology Reviews | volume = 62 | issue = 2 | pages = 362–78 | date = Jun 1998 | pmid = 9618446 | pmc = 98919 | doi = 10.1128/MMBR.62.2.362-378.1998}}</ref> subsequent generations may be affected by the epigenetic changes that took place in the parents.<ref name="Goto_1998"/>

== Discovery ==

The first documented example of epigenetics affecting behavior was provided by Michael Meaney and Moshe Szyf.<ref>{{cite journal | vauthors = Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ | title = Epigenetic programming by maternal behavior | journal = Nature Neuroscience | volume = 7 | issue = 8 | pages = 847–54 | date = August 2004 | pmid = 15220929 | doi = 10.1038/nn1276 | s2cid = 1649281 }}</ref> While working at McGill University in Montréal in 2004, they discovered that the type and amount of nurturing a mother rat provides in the early weeks of the rat's infancy determines how that rat responds to stress later in life.<ref name="Moore_2015"/> This stress sensitivity was linked to a [[Biology:Regulation of gene expression#Up-regulation and down-regulation|down-regulation]] in the expression of the [[Biology:Glucocorticoid receptor|glucocorticoid receptor]] in the brain.  In turn, this down-regulation was found to be a consequence of the extent of [[Biology:Methylation#Epigenetics|methylation]] in the [[Biology:Promoter (genetics)|promoter]] region of the glucocorticoid receptor [[Biology:Gene|gene]].<ref name="Miller_2010"/> Immediately after birth, Meaney and Szyf found that [[Chemistry:Methyl group|methyl group]]s repress the [[Biology:Glucocorticoid receptor|glucocorticoid receptor]] gene in all rat pups, making the gene unable to unwind from the histone in order to be transcribed, causing a decreased stress response. Nurturing behaviours from the mother rat were found to stimulate activation of stress signalling pathways that remove methyl groups from DNA. This releases the tightly wound gene, exposing it for transcription. The glucocorticoid gene is activated, resulting in lowered stress response. Rat pups that receive a less nurturing upbringing are more sensitive to stress throughout their life-span.

This pioneering work in rodents has been difficult to replicate in humans because of a general lack of availability of human brain tissue for measurement of epigenetic changes.<ref name="Miller_2010"/>

== Research into epigenetics in psychology ==

=== Anxiety and risk-taking ===
[[Image:TwinGirls.jpg|right|thumb|Monozygotic twins are identical twins. Twin studies help to reveal epigenetic differences related to various aspects of psychology.]]
In a small clinical study in humans published in 2008,<ref name="Kaminsky_2008"/> epigenetic differences were linked to differences in risk-taking and reactions to stress in [[Biology:Twin#Monozygotic ("identical") twins|monozygotic twins]].<ref name="Kaminsky_2008">{{cite journal | vauthors = Kaminsky Z, Petronis A, Wang SC, Levine B, Ghaffar O, Floden D, Feinstein A | title = Epigenetics of personality traits: an illustrative study of identical twins discordant for risk-taking behavior | journal = Twin Research and Human Genetics | volume = 11 | issue = 1 | pages = 1–11 | date = February 2008 | pmid = 18251670 | doi = 10.1375/twin.11.1.1 | s2cid = 32776461 | doi-access = free }}</ref>  The study identified twins with different life paths, wherein one twin displayed risk-taking behaviours, and the other displayed risk-averse behaviours.  Epigenetic differences in [[Biology:DNA methylation|DNA methylation]] of the CpG islands proximal to the DLX1 gene correlated with the differing behavior.<ref name="Kaminsky_2008"/>  The authors of the twin study noted that despite the associations between epigenetic markers and differences personality traits, epigenetics cannot predict complex decision-making processes like career selection.<ref name="Kaminsky_2008"/>

=== Stress ===
[[Image:Basic HPA Axis.jpeg|right|thumb|The [[Medicine:Hypothalamic–pituitary–adrenal axis|hypothalamic pituitary adrenal axis]] is involved in the human stress response.]]
Animal and human studies have found correlations between poor care during infancy and epigenetic changes that correlate with long-term impairments that result from neglect.<ref name=Masterpasqua>{{cite journal | vauthors =Masterpasqua F | title = Psychology and epigenetics | journal = Review of General Psychology | year = 2009 | volume = 13 | issue = 3 | pages = 194–201 | doi = 10.1037/a0016301| s2cid = 35879739 }}</ref><ref name="Szyf and McGowan">{{cite journal | vauthors = Szyf M, McGowan P, Meaney MJ | title = The social environment and the epigenome | journal = Environmental and Molecular Mutagenesis | volume = 49 | issue = 1 | pages = 46–60 | date = Jan 2008 | pmid = 18095330 | doi = 10.1002/em.20357 | s2cid = 18739871 | doi-access = free | bibcode = 2008EnvMM..49...46S }}</ref><ref name=Gonzalez-Pardo>{{cite journal | vauthors = González-Pardo H, Pérez Álvarez M | title = Epigenetics and its implications for Psychology | journal = Psicothema | volume = 25 | issue = 1 | pages = 3–12 | date = Feb 2013 | pmid = 23336536 | doi = 10.7334/psicothema2012.327 }}</ref>

Studies in rats have shown correlations between maternal care in terms of the parental licking of offspring and epigenetic changes.<ref name=Masterpasqua/> A high level of licking results in a long-term reduction in stress response as measured behaviorally and biochemically in elements of the hypothalamic-pituitary-adrenal axis (HPA).  Further, decreased DNA methylation of the [[Biology:Glucocorticoid receptor|glucocorticoid receptor]] gene were found in offspring that experienced a high level of licking; the glucorticoid receptor plays a key role in regulating the HPA.<ref name=Masterpasqua />  The opposite is found in offspring that experienced low levels of licking, and when pups are switched, the epigenetic changes are reversed. This research provides evidence for an underlying epigenetic mechanism.<ref name=Masterpasqua />  Further support comes from experiments with the same setup, using drugs that can increase or decrease methylation.<ref name="Szyf and McGowan"/>  Finally, epigenetic variations in parental care can be passed down from one generation to the next, from mother to female offspring. Female offspring who received increased parental care (i.e., high licking) became mothers who engaged in high licking and offspring who received less licking became mothers who engaged in less licking.<ref name=Masterpasqua />

In humans, a small clinical research study showed the relationship between prenatal exposure to maternal mood and genetic expression resulting in increased reactivity to stress in offspring.<ref name="Moore_2015"/> Three groups of infants were examined: those born to mothers medicated for depression with [[Chemistry:Selective serotonin reuptake inhibitor|serotonin reuptake inhibitors]]; those born to depressed mothers not being treated for depression; and those born to non-depressed mothers. Prenatal exposure to depressed/anxious mood was associated with increased DNA methylation at the glucocorticoid receptor gene and to increased HPA axis stress reactivity.<ref name=Masterpasqua />  The findings were independent of whether the mothers were being pharmaceutically treated for depression.<ref name=Masterpasqua />

Recent research has also shown the relationship of methylation of the maternal glucocorticoid receptor and maternal neural activity in response to mother-infant interactions on video.<ref>Schechter DS, Moser DA, Giacobino A, Stenz L, Gex-Fabry M, Adouan W, Cordero MI, Suardi F, Manini A, Sancho-Rossignol A, Merminod G, Aue T, Ansermet F, Dayer AG, Rusconi-Serpa S. (epub May 29, 2015)  Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure. Frontiers in Psychology. http://journal.frontiersin.org/article/10.3389/fpsyg.2015.00690/abstract</ref>  Longitudinal follow-up of those infants will be important to understand the impact of early caregiving in this high-risk population on child epigenetics and behavior.

== Cognition ==

=== Learning and memory ===
A 2010 review discussed the role of DNA methylation in memory formation and storage, but the precise mechanisms involving neuronal function, memory, and methylation reversal remained unclear at the time.<ref name="Day and Sweatt">{{cite journal | vauthors = Day JJ, Sweatt JD | title = DNA methylation and memory formation | journal = Nature Neuroscience | volume = 13 | issue = 11 | pages = 1319–23 | date = Nov 2010 | pmid = 20975755 | pmc = 3130618 | doi = 10.1038/nn.2666 }}</ref>

Further research investigated the molecular basis for [[Biology:Long-term memory|long-term memory]].  By 2015 it had become clear that long-term memory requires gene transcription activation and de novo protein synthesis.<ref name="pmid25475090">{{cite journal |vauthors=Alberini CM, Kandel ER |title=The regulation of transcription in memory consolidation |journal=Cold Spring Harb Perspect Biol |volume=7 |issue=1 |pages=a021741 |date=December 2014 |pmid=25475090 |pmc=4292167 |doi=10.1101/cshperspect.a021741 |url=}}</ref>  Long-term memory formation depends on both the activation of memory promoting genes and the inhibition of memory suppressor genes, and [[Biology:DNA methylation|DNA methylation]]/[[Biology:DNA demethylation|DNA demethylation]] was found to be a major mechanism for achieving this dual regulation.<ref name="pmid27634149">{{cite journal |vauthors=Oliveira AM |title=DNA methylation: a permissive mark in memory formation and maintenance |journal=Learn Mem |volume=23 |issue=10 |pages=587–93 |date=October 2016 |pmid=27634149 |pmc=5026210 |doi=10.1101/lm.042739.116 |url=}}</ref>

Rats with a new, strong long-term memory due to [[Philosophy:Fear conditioning|contextual fear conditioning]] have reduced expression of about 1,000 genes and increased expression of about 500 genes in the [[Biology:Hippocampus|hippocampus]] of the [[Biology:Brain|brain]] 24 hours after training, thus exhibiting modified expression of 9.17% of the rat hippocampal genome.  Reduced gene expressions were associated with methylations of those genes and hypomethylation was found for genes involved in synaptic transmission and neuronal differentiation.<ref name="pmid28620075">{{cite journal |vauthors=Duke CG, Kennedy AJ, Gavin CF, Day JJ, Sweatt JD |title=Experience-dependent epigenomic reorganization in the hippocampus |journal=Learn Mem |volume=24 |issue=7 |pages=278–288 |date=July 2017 |pmid=28620075 |pmc=5473107 |doi=10.1101/lm.045112.117 |url=}}</ref>

Further research into long-term memory has shed light on the molecular mechanisms by which methylation is created or removed, as reviewed in 2022.<ref name=Bernstein>{{cite journal |vauthors=Bernstein C |title=DNA Methylation and Establishing Memory |journal=Epigenet Insights |volume=15 |issue= |pages=25168657211072499 |date=2022 |pmid=35098021 |pmc=8793415 |doi=10.1177/25168657211072499 |url=}}</ref>  These mechanisms include, for instance, signal-responsive TOP2B-induced double-strand breaks in immediate early genes.  More than 100 DNA double-strand breaks occur, both in the hippocampus and in the medial prefrontal cortex (mPFC), in two peaks, at 10 minutes and at 30 minutes after contextual fear conditioning.<ref name=Stott>{{cite journal |vauthors=Stott RT, Kritsky O, Tsai LH |title=Profiling DNA break sites and transcriptional changes in response to contextual fear learning |journal=PLOS ONE |volume=16 |issue=7 |pages=e0249691 |date=2021 |pmid=34197463 |pmc=8248687 |doi=10.1371/journal.pone.0249691 |bibcode=2021PLoSO..1649691S |url=|doi-access=free }}</ref>  This appears to be earlier than the DNA methylations and demethylations of neuron DNA in the hippocampus that were measured at one hour and 24 hours after contextual fear conditioning.

The double strand breaks occur at known memory-related [[Biology:Immediate early gene|immediate early gene]]s (among other genes) in neurons after neuron activation.<ref name="pmid26052046">{{cite journal |vauthors=Madabhushi R, Gao F, Pfenning AR, Pan L, Yamakawa S, Seo J, Rueda R, Phan TX, Yamakawa H, Pao PC, Stott RT, Gjoneska E, Nott A, Cho S, Kellis M, Tsai LH |title=Activity-Induced DNA Breaks Govern the Expression of Neuronal Early-Response Genes |journal=Cell |volume=161 |issue=7 |pages=1592–605 |date=June 2015 |pmid=26052046 |pmc=4886855 |doi=10.1016/j.cell.2015.05.032 |url=}}</ref><ref name=Stott />  These double-strand breaks allow the genes to be transcribed and then translated into active proteins.

One [[Biology:Immediate early gene|immediate early gene]] newly transcribed after a double-strand break is [[Biology:EGR1|EGR1]].  EGR1 is an important [[Biology:Transcription factor|transcription factor]] in [[Memory|memory]] formation.  It has an essential role in [[Biology:Brain|brain]] [[Biology:Neuron|neuron]] [[Biology:Epigenetics|epigenetic]] reprogramming.  EGR1 recruits the [[Biology:Tet methylcytosine dioxygenase 1|TET1]] protein that initiates a pathway of [[Biology:DNA demethylation|DNA demethylation]].  Removing DNA methylation marks allows the activation of downstream genes (see [[Biology:Regulation of gene expression#Regulation of transcription in learning and memory|Regulation of gene expression]].  EGR1 brings TET1 to [[Biology:Promoter (genetics)|promoter]] sites of genes that need to be [[Biology:DNA demethylation|demethylated]] and activated (transcribed) during memory formation.<ref name=Sun>{{cite journal |vauthors=Sun Z, Xu X, He J, Murray A, Sun MA, Wei X, Wang X, McCoig E, Xie E, Jiang X, Li L, Zhu J, Chen J, Morozov A, Pickrell AM, Theus MH, Xie H |title=EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity |journal=Nat Commun |volume=10 |issue=1 |pages=3892 |date=August 2019 |pmid=31467272 |pmc=6715719 |doi=10.1038/s41467-019-11905-3 |bibcode=2019NatCo..10.3892S |url=}}</ref>  EGR-1, together with TET1, is employed in programming the distribution of [[Biology:DNA demethylation|DNA demethylation]] sites on brain DNA during memory formation and in long-term [[Biology:Neuroplasticity|neuronal plasticity]].<ref name=Sun />

[[Biology:DNA (cytosine-5)-methyltransferase 3A|DNMT3A2]] is another immediate early gene whose expression in neurons can be induced by sustained synaptic activity.<ref name="pmid22751036">{{cite journal |vauthors=Oliveira AM, Hemstedt TJ, Bading H |title=Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities |journal=Nat Neurosci |volume=15 |issue=8 |pages=1111–3 |date=July 2012 |pmid=22751036 |doi=10.1038/nn.3151 |s2cid=10590208 |url=}}</ref>  DNMTs bind to DNA and methylate cytosines at particular locations in the genome.  If this methylation is prevented by DNMT inhibitors, then memories do not form.<ref name="pmid28513272">{{cite journal |vauthors=Bayraktar G, Kreutz MR |title=Neuronal DNA Methyltransferases: Epigenetic Mediators between Synaptic Activity and Gene Expression? |journal=Neuroscientist |volume=24 |issue=2 |pages=171–185 |date=April 2018 |pmid=28513272 |pmc=5846851 |doi=10.1177/1073858417707457 |url=}}</ref>  If DNMT3A2 is over-expressed in the hippocampus of young adult mice it converts a weak learning experience into long-term memory and also enhances fear memory formation.<ref name="pmid27634149"/>

In another mechanism reviewed in 2022,<ref name=Bernstein /> the [[Biology:Messenger RNA|messenger RNA]]s of many genes that had been subjected to methylation-controlled increases or decreases are transported by neural granules ([[Biology:Messenger RNP|messenger RNP]]s) to the [[Dendritic spine|dendritic spine]]s. At these locations the messenger RNAs can be [[Biology:Translation|translated]] into the proteins that control signaling at [[Biology:Neuron|neuron]]al [[Biology:Synapse|synapse]]s.

Studies in rodents have found that the environment exerts an influence on epigenetic changes related to [[Cognition|cognition]], in terms of learning and memory;<ref name="Moore_2015"/> environmental enrichment correlated with increased histone acetylation, and verification by administering [[Biology:Histone deacetylase inhibitor|histone deacetylase inhibitor]]s induced sprouting of dendrites, an increased number of synapses, and reinstated learning behaviour and access to long-term memories.<ref name="Miller_2010">{{cite journal | vauthors = Miller G | title = Epigenetics. The seductive allure of behavioral epigenetics | journal = Science | volume = 329 | issue = 5987 | pages = 24–7 | date = Jul 2010 | pmid = 20595592 | doi = 10.1126/science.329.5987.24 | bibcode = 2010Sci...329...24M }}</ref><ref name="Fischer and Tsai">{{cite journal | vauthors = Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH | title = Recovery of learning and memory is associated with chromatin remodelling | journal = Nature | volume = 447 | issue = 7141 | pages = 178–82 | date = May 2007 | pmid = 17468743 | doi = 10.1038/nature05772 | bibcode = 2007Natur.447..178F | s2cid = 36395789 }}</ref>  Research has also linked learning and long-term memory formation to reversible epigenetic changes in the hippocampus and cortex in animals with normal-functioning, non-damaged brains.<ref name="Miller_2010" /><ref name=Gupat>{{cite journal | vauthors = Gupta S, Kim SY, Artis S, Molfese DL, Schumacher A, Sweatt JD, Paylor RE, Lubin FD | title = Histone methylation regulates memory formation | journal = The Journal of Neuroscience | volume = 30 | issue = 10 | pages = 3589–99 | date = Mar 2010 | pmid = 20219993 | pmc = 2859898 | doi = 10.1523/JNEUROSCI.3732-09.2010 }}</ref>  In human studies, post-mortem brains from Alzheimer's patients show increased histone de-acetylase levels.<ref name="Graff_2012">{{cite journal | vauthors = Gräff J, Rei D, Guan JS, Wang WY, Seo J, Hennig KM, Nieland TJ, Fass DM, Kao PF, Kahn M, Su SC, Samiei A, Joseph N, Haggarty SJ, Delalle I, Tsai LH | title = An epigenetic blockade of cognitive functions in the neurodegenerating brain | journal = Nature | volume = 483 | issue = 7388 | pages = 222–6 | date = Mar 2012 | pmid = 22388814 | pmc = 3498952 | doi = 10.1038/nature10849 | bibcode = 2012Natur.483..222G }}</ref><ref name=Peleg>{{cite journal | vauthors = Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, Agis-Balboa RC, Cota P, Wittnam JL, Gogol-Doering A, Opitz L, Salinas-Riester G, Dettenhofer M, Kang H, Farinelli L, Chen W, Fischer A | title = Altered histone acetylation is associated with age-dependent memory impairment in mice | journal = Science | volume = 328 | issue = 5979 | pages = 753–6 | date = May 2010 | pmid = 20448184 | doi = 10.1126/science.1186088 | bibcode = 2010Sci...328..753P | s2cid = 7370920 }}</ref>

== Psychopathology and mental health ==

=== Drug addiction ===
{{Psychostimulant addiction|Colorcode=yes|align=right}}
Environmental and epigenetic influences seem to work together to increase the risk of [[Medicine:Addiction|addiction]].<ref name="Wong_2011"/> For example, environmental stress has been shown to increase the risk of substance abuse.<ref name="Andersen and Teicher">{{cite journal | vauthors = Andersen SL, Teicher MH | title = Desperately driven and no brakes: developmental stress exposure and subsequent risk for substance abuse | journal = Neuroscience and Biobehavioral Reviews | volume = 33 | issue = 4 | pages = 516–24 | date = Apr 2009 | pmid = 18938197 | pmc = 2688959 | doi = 10.1016/j.neubiorev.2008.09.009 }}</ref> In an attempt to cope with stress, alcohol and drugs can be used as an escape.<ref name=Carver>{{cite book | vauthors = Carver C | chapter = Coping | veditors = Baum A, Contrada RJ | title = The Handbook of Stress Science: Biology, Psychology, and Health | publisher = Springer Publishing Company | location = New York | year = 2010 | pages = 223 | isbn = 978-0-8261-1471-6 }}</ref> Once substance abuse commences, however, epigenetic alterations may further exacerbate the biological and behavioural changes associated with addiction.<ref name="Wong_2011"/>

Even short-term substance abuse can produce long-lasting epigenetic changes in the brain of rodents,<ref name="Wong_2011"/> via DNA methylation and histone modification.<ref name="Maze_2011">{{cite journal | vauthors = Maze I, Nestler EJ | title = The epigenetic landscape of addiction | journal = Annals of the New York Academy of Sciences | volume = 1216 | issue = 1| pages = 99–113 | date = Jan 2011 | pmid = 21272014 | pmc = 3071632 | doi = 10.1111/j.1749-6632.2010.05893.x | bibcode = 2011NYASA1216...99M }}</ref> Epigenetic modifications have been observed in studies on rodents involving [[Chemistry:Ethanol|ethanol]], [[Chemistry:Nicotine|nicotine]], [[Biology:Cocaine|cocaine]], [[Chemistry:Amphetamine|amphetamine]], [[Chemistry:Methamphetamine|methamphetamine]] and opiates.<ref name="Moore_2015"/> Specifically, these epigenetic changes modify gene expression, which in turn increases the vulnerability of an individual to engage in repeated substance overdose in the future. In turn, increased substance abuse results in even greater epigenetic changes in various components of a rodent's [[Philosophy:Reward system|reward system]]<ref name="Wong_2011">{{cite journal | vauthors = Wong CC, Mill J, Fernandes C | title = Drugs and addiction: an introduction to epigenetics | journal = Addiction | volume = 106 | issue = 3 | pages = 480–9 | date = Mar 2011 | pmid = 21205049 | doi = 10.1111/j.1360-0443.2010.03321.x }}</ref> (e.g., in the [[Biology:Nucleus accumbens|nucleus accumbens]]<ref name="Renthal and Nestler">{{cite journal | vauthors = Renthal W, Nestler EJ | title = Epigenetic mechanisms in drug addiction | journal = Trends in Molecular Medicine | volume = 14 | issue = 8 | pages = 341–50 | date = Aug 2008 | pmid = 18635399 | pmc = 2753378 | doi = 10.1016/j.molmed.2008.06.004 }}</ref>). Hence, a cycle emerges whereby changes in areas of the [[Philosophy:Reward system|reward system]] contribute to the long-lasting neural and behavioural changes associated with the increased likelihood of addiction, the maintenance of addiction and relapse.<ref name="Wong_2011"/> In humans, alcohol consumption has been shown to produce epigenetic changes that contribute to the increased craving of alcohol. As such, epigenetic modifications may play a part in the progression from the controlled intake to the loss of control of alcohol consumption.<ref name=Naassila>{{cite journal | vauthors = Naassila M | title = Abstracts of ESBRA 2011, European Society for Biomedical Research on Alcoholism. Vienna, Austria. September 4–7, 2011 | journal = Alcohol and Alcoholism | volume = 46 | issue = Suppl 1 | pages = i1-63 | year = 2011 | pmid = 21863600 | doi = 10.1093/alcalc/agr085 | doi-access = free }}</ref>  These alterations may be long-term, as is evidenced in smokers who still possess nicotine-related epigenetic changes ten years after cessation.<ref name="Luanay et al">{{cite journal | vauthors = Launay JM, Del Pino M, Chironi G, Callebert J, Peoc'h K, Mégnien JL, Mallet J, Simon A, Rendu F | title = Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation | journal = PLOS ONE | volume = 4 | issue = 11 | pages = e7959 | year = 2009 | pmid = 19956754 | pmc = 2775922 | doi = 10.1371/journal.pone.0007959 | bibcode = 2009PLoSO...4.7959L | doi-access = free }}</ref>  Therefore, epigenetic modifications<ref name="Wong_2011"/> may account for some of the behavioural changes generally associated with addiction. These include: repetitive habits that increase the risk of disease, and personal and social problems; need for immediate [[Philosophy:Gratification|gratification]]; high rates of relapse following treatment; and, the feeling of loss of control.<ref name="Marlatt et al">{{cite journal | vauthors = Marlatt GA, Baer JS, Donovan DM, Kivlahan DR | title = Addictive behaviors: etiology and treatment | journal = Annual Review of Psychology | volume = 39 | pages = 223–52 | year = 1988 | pmid = 3278676 | doi = 10.1146/annurev.ps.39.020188.001255 }}</ref>

Evidence for relevant epigenetic changes came from human studies involving alcohol,<ref name="Bonsch et al">{{cite journal | vauthors = Bönsch D, Lenz B, Reulbach U, Kornhuber J, Bleich S | title = Homocysteine associated genomic DNA hypermethylation in patients with chronic alcoholism | journal = Journal of Neural Transmission | volume = 111 | issue = 12 | pages = 1611–6 | date = Dec 2004 | pmid = 15565495 | doi = 10.1007/s00702-004-0232-x | s2cid = 10692616 }}</ref> nicotine, and opiate abuse. Evidence for epigenetic changes stemming from amphetamine and cocaine abuse derives from animal studies. In animals, drug-related epigenetic changes in fathers have also been shown to negatively affect offspring in terms of poorer spatial [[Working memory|working memory]], decreased [[Philosophy:Attention|attention]] and decreased cerebral volume.<ref name="He et al">{{cite journal | vauthors = He F, Lidow IA, Lidow MS | title = Consequences of paternal cocaine exposure in mice | journal = Neurotoxicology and Teratology | volume = 28 | issue = 2 | pages = 198–209 | year = 2006 | pmid = 16458479 | doi = 10.1016/j.ntt.2005.12.003 }}</ref>

====Imprecise DNA repair can leave epigenetic scars====

[[Biology:DNA damage (naturally occurring)|DNA damage]] is increased in the brain of rodents by administration of the addictive substances [[Biology:Cocaine|cocaine]],<ref>{{cite journal | vauthors = de Souza MF, Gonçales TA, Steinmetz A, Moura DJ, Saffi J, Gomez R, Barros HM | title = Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions | journal = Clinical and Experimental Pharmacology & Physiology | volume = 41 | issue = 4 | pages = 265–269 | date = April 2014 | pmid = 24552452 | doi = 10.1111/1440-1681.12218 | s2cid = 20849951 }}</ref> [[Chemistry:Methamphetamine|methamphetamine]],<ref>{{cite journal | vauthors = Johnson Z, Venters J, Guarraci FA, Zewail-Foote M | title = Methamphetamine induces DNA damage in specific regions of the female rat brain | journal = Clinical and Experimental Pharmacology & Physiology | volume = 42 | issue = 6 | pages = 570–575 | date = June 2015 | pmid = 25867833 | doi = 10.1111/1440-1681.12404 | s2cid = 24182756 }}</ref><ref>{{cite journal | vauthors = Tokunaga I, Ishigami A, Kubo S, Gotohda T, Kitamura O | title = The peroxidative DNA damage and apoptosis in methamphetamine-treated rat brain | journal = The Journal of Medical Investigation | volume = 55 | issue = 3–4 | pages = 241–245 | date = August 2008 | pmid = 18797138 | doi = 10.2152/jmi.55.241 | doi-access = free }}</ref> [[Medicine:Alcoholism|alcohol]]<ref>{{cite journal | vauthors = Rulten SL, Hodder E, Ripley TL, Stephens DN, Mayne LV | title = Alcohol induces DNA damage and the Fanconi anemia D2 protein implicating FANCD2 in the DNA damage response pathways in brain | journal =  	Alcoholism: Clinical and Experimental Research | volume = 32 | issue = 7 | pages = 1186–1196 | date = July 2008 | pmid = 18482162 | doi = 10.1111/j.1530-0277.2008.00673.x | doi-access = free }}</ref> and [[Chemistry:Tobacco smoke|tobacco smoke]].<ref name="pmid28912356">{{cite journal | vauthors = Adhami N, Chen Y, Martins-Green M | title = Biomarkers of disease can be detected in mice as early as 4 weeks after initiation of exposure to third-hand smoke levels equivalent to those found in homes of smokers | journal = Clinical Science | location = London, England | volume = 131 | issue = 19 | pages = 2409–2426 | date = October 2017 | pmid = 28912356 | doi = 10.1042/CS20171053 | s2cid = 9167990 | doi-access = free }}</ref>  When such DNA damages are repaired, imprecise [[Biology:DNA repair|DNA repair]] may lead to persistent alterations such as [[Biology:DNA methylation|methylation of DNA]] or the acetylation or [[Biology:Histone methylation|methylation of histones]] at the sites of repair.<ref>{{cite journal | vauthors = Dabin J, Fortuny A, Polo SE | title = Epigenome Maintenance in Response to DNA Damage | journal = Molecular Cell | volume = 62 | issue = 5 | pages = 712–727 | date = June 2016 | pmid = 27259203 | pmc = 5476208 | doi = 10.1016/j.molcel.2016.04.006 }}</ref>  These alterations may be [[Biology:Epigenetics|epigenetic scars]] in the [[Biology:Chromatin|chromatin]] that contribute to the persistent epigenetic changes found in addiction.

=== Eating disorders and obesity ===
{{further|Biology:ΔFosB}}
Epigenetic changes may help to facilitate the development and maintenance of [[Medicine:Eating disorder|eating disorder]]s via influences in the early environment and throughout the life-span.<ref name="Campbell_2011"/> Pre-natal epigenetic changes due to maternal stress, behaviour and diet may later predispose offspring to persistent, increased anxiety and anxiety disorders. These anxiety issues can precipitate the onset of eating disorders and obesity, and persist even after recovery from the eating disorders.<ref name="pmid18213688">{{cite journal | vauthors = Raney TJ, Thornton LM, Berrettini W, Brandt H, Crawford S, Fichter MM, Halmi KA, Johnson C, Kaplan AS, LaVia M, Mitchell J, Rotondo A, Strober M, Woodside DB, Kaye WH, Bulik CM | title = Influence of overanxious disorder of childhood on the expression of anorexia nervosa | journal = The International Journal of Eating Disorders | volume = 41 | issue = 4 | pages = 326–32 | date = May 2008 | pmid = 18213688 | doi = 10.1002/eat.20508 | pmc = 8048416 }}</ref>

Epigenetic differences accumulating over the life-span may account for the incongruent differences in eating disorders observed in monozygotic twins. At puberty, sex hormones may exert epigenetic changes (via DNA methylation) on gene expression, thus accounting for higher rates of eating disorders in men as compared to women {{Citation needed|reason=A quick research on the web goes on the other direction|date=February 2023}}. Overall, epigenetics contribute to persistent, unregulated [[Philosophy:Self-control|self-control]] behaviours related to the urge to binge.<ref name="Campbell_2011"/>

=== Schizophrenia ===
{{further|Biology:Epigenetics of schizophrenia}}
Epigenetic changes including hypomethylation of glutamatergic genes (i.e., NMDA-receptor-subunit gene [[Biology:NMDA receptor|NR3B]] and the promoter of the AMPA-receptor-subunit gene GRIA2) in the post-mortem brains of people with schizophrenia are associated with increased levels of the neurotransmitter [[Chemistry:Glutamic acid|glutamate]].<ref name="Mostafavi-Abdolmaleky">{{cite book |veditors=Bronner F, Helmtrud I |title=Epigenetic Aspects of Chronic Diseases |publisher=Springer |location=Berlin |year=2011 |isbn=978-1-84882-643-4 |vauthors=Mostafavi-Abdolmaleky H, Glatt SJ, Tsuang MT |chapter=Epigenetics in Psychiatry |pages=163–174}}</ref>  Since glutamate is the most prevalent, fast, excitatory neurotransmitter, increased levels may result in the psychotic episodes related to [[Medicine:Schizophrenia|schizophrenia]]. Epigenetic changes affecting a greater number of genes have been detected in men with schizophrenia as compared to women with the illness.<ref name="Abdolmaleky_2005">{{cite journal |vauthors=Abdolmaleky HM, Thiagalingam S, Wilcox M |title=Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements, applications, and future scope |journal=American Journal of Pharmacogenomics |volume=5 |issue=3 |pages=149–60 |year=2005 |pmid=15952869 |doi=10.2165/00129785-200505030-00002|s2cid=16397510 }}</ref>

Population studies have established a strong association linking schizophrenia in children born to older fathers.<ref name="Malaspina_2001">{{cite journal | vauthors = Malaspina D, Harlap S, Fennig S, Heiman D, Nahon D, Feldman D, Susser ES | title = Advancing paternal age and the risk of schizophrenia | journal = Archives of General Psychiatry | volume = 58 | issue = 4 | pages = 361–7 | date = Apr 2001 | pmid = 11296097 | doi = 10.1001/archpsyc.58.4.361 | doi-access = free }}</ref><ref name="Rutten_2009"/> Specifically, children born to fathers over the age of 35 years are up to three times more likely to develop schizophrenia.<ref name="Rutten_2009"/> Epigenetic dysfunction in human male sperm cells, affecting numerous genes, have been shown to increase with age. This provides a possible explanation for increased rates of the disease in men.<ref name="Abdolmaleky_2005"/><ref name="Rutten_2009">{{cite journal | vauthors = Rutten BP, Mill J | title = Epigenetic mediation of environmental influences in major psychotic disorders | journal = Schizophrenia Bulletin | volume = 35 | issue = 6 | pages = 1045–56 | date = Nov 2009 | pmid = 19783603 | pmc = 2762629 | doi = 10.1093/schbul/sbp104 }}</ref>{{Failed verification|date=September 2012}} To this end, toxins<ref name="Abdolmaleky_2005"/><ref name="Rutten_2009"/> (e.g., air pollutants) have been shown to increase epigenetic differentiation. Animals exposed to ambient air from [[Engineering:Steel mill|steel mill]]s and [[Engineering:Highway|highway]]s show drastic epigenetic changes that persist after removal from the exposure.<ref name="Yauk_2008">{{cite journal | vauthors = Yauk C, Polyzos A, Rowan-Carroll A, Somers CM, Godschalk RW, Van Schooten FJ, Berndt ML, Pogribny IP, Koturbash I, Williams A, Douglas GR, Kovalchuk O | title = Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 2 | pages = 605–10 | date = Jan 2008 | pmid = 18195365 | pmc = 2206583 | doi = 10.1073/pnas.0705896105 | bibcode = 2008PNAS..105..605Y | doi-access = free }}</ref> Therefore, similar epigenetic changes in older human fathers are likely.<ref name="Rutten_2009"/> Schizophrenia studies provide evidence that the [[Philosophy:Nature versus nurture|nature versus nurture]] debate in the field of [[Philosophy:Psychopathology|psychopathology]] should be re-evaluated to accommodate the concept that genes and the environment work in tandem. As such, many other environmental factors (e.g., nutritional deficiencies and [[Biology:Cannabis (drug)|cannabis]] use) have been proposed to increase the susceptibility of psychotic disorders like schizophrenia via epigenetics.<ref name="Rutten_2009"/>

=== Bipolar disorder ===

Evidence for [[Biology:Epigenetics of bipolar disorder|epigenetic modifications for bipolar disorder]] is unclear.<ref name="McGowan_2008">{{cite journal | vauthors = McGowan PO, Kato T | title = Epigenetics in mood disorders | journal = Environmental Health and Preventive Medicine | volume = 13 | issue = 1 | pages = 16–24 | date = Jan 2008 | pmid = 19568875 | pmc = 2698240 | doi = 10.1007/s12199-007-0002-0 | bibcode = 2008EHPM...13...16M }}</ref> One study found hypomethylation of a gene promoter of a [[Biology:Frontal lobe|prefrontal lobe]] enzyme (i.e., membrane-bound catechol-O-methyl transferase, or COMT) in post-mortem brain samples from individuals with bipolar disorder. COMT is an enzyme that metabolizes [[Biology:Dopamine|dopamine]] in the [[Biology:Synapse|synapse]]. These findings suggest that the hypomethylation of the [[Biology:Promoter (genetics)|promoter]] results in over-expression of the enzyme. In turn, this results in increased degradation of dopamine levels in the brain. These findings provide evidence that epigenetic modification in the prefrontal lobe is a risk factor for bipolar disorder.<ref name="Abdolmaleky_2006">{{cite journal | vauthors = Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F, Smith CL, Shafa R, Aeali B, Carnevale J, Pan H, Papageorgis P, Ponte JF, Sivaraman V, Tsuang MT, Thiagalingam S | title = Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder | journal = Human Molecular Genetics | volume = 15 | issue = 21 | pages = 3132–45 | date = Nov 2006 | pmid = 16984965 | pmc = 2799943 | doi = 10.1093/hmg/ddl253 }}</ref> However, a second study found no epigenetic differences in post-mortem brains from bipolar individuals.<ref name="Dempster_2006">{{cite journal | vauthors = Dempster EL, Mill J, Craig IW, Collier DA | title = The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression | journal = BMC Medical Genetics | volume = 7 | pages = 10 | year = 2006 | pmid = 16483362 | pmc = 1456954 | doi = 10.1186/1471-2350-7-10 | doi-access = free }}</ref>

=== Major depressive disorder===
The causes of major depressive disorder (MDD) are poorly understood from a [[Biology:Neuroscience|neuroscience]] perspective.<ref name="Massart">{{cite journal | vauthors = Massart R, Mongeau R, Lanfumey L | title = Beyond the monoaminergic hypothesis: neuroplasticity and epigenetic changes in a transgenic mouse model of depression | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 367 | issue = 1601 | pages = 2485–94 | date = Sep 2012 | pmid = 22826347 | pmc = 3405682 | doi = 10.1098/rstb.2012.0212 }}</ref>  The epigenetic changes leading to changes in glucocorticoid receptor expression and its effect on the HPA stress system discussed above, have also been applied to attempts to understand MDD.<ref name="Pariante">{{cite journal | vauthors = Pariante CM, Lightman SL | title = The HPA axis in major depression: classical theories and new developments | journal = Trends in Neurosciences | volume = 31 | issue = 9 | pages = 464–8 | date = Sep 2008 | pmid = 18675469 | doi = 10.1016/j.tins.2008.06.006 | s2cid = 13308611 }}</ref>

Much of the work in animal models has focused on the indirect downregulation of brain derived neurotrophic factor (BDNF) by over-activation of the stress axis.<ref name="Tsankova">{{cite journal | vauthors = Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ | title = Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action | journal = Nature Neuroscience | volume = 9 | issue = 4 | pages = 519–25 | date = Apr 2006 | pmid = 16501568 | doi = 10.1038/nn1659 | s2cid = 21547891 }}</ref><ref name="Gray">{{cite journal | vauthors = Gray JD, Milner TA, McEwen BS | title = Dynamic plasticity: the role of glucocorticoids, brain-derived neurotrophic factor and other trophic factors | journal = Neuroscience | volume = 239 | pages = 214–27 | date = Jun 2013 | pmid = 22922121 | doi = 10.1016/j.neuroscience.2012.08.034 | pmc = 3743657 }}</ref>  Studies in various rodent models of depression, often involving induction of stress, have found direct epigenetic modulation of BDNF as well.<ref name="Hunter">{{cite journal | vauthors = Hunter RG | title = Epigenetic effects of stress and corticosteroids in the brain | journal = Frontiers in Cellular Neuroscience | volume = 6 | pages = 18 | year = 2012 | pmid = 22529779 | doi = 10.3389/fncel.2012.00018 | pmc=3329877| doi-access = free }}</ref>

===Psychopathy===

Epigenetics may be relevant to aspects of psychopathic behaviour through methylation and histone modification.<ref name="pmid19005036">{{cite journal | vauthors = Jiang Y, Langley B, Lubin FD, Renthal W, Wood MA, Yasui DH, Kumar A, Nestler EJ, Akbarian S, Beckel-Mitchener AC | title = Epigenetics in the nervous system | journal = The Journal of Neuroscience | volume = 28 | issue = 46 | pages = 11753–9 | date = Nov 2008 | pmid = 19005036 | pmc = 3844836 | doi = 10.1523/JNEUROSCI.3797-08.2008 }}</ref>  These processes are heritable but can also be influenced by environmental factors such as smoking and abuse.<ref name="pmid19777560">{{cite journal | vauthors = Philibert RA, Beach SR, Gunter TD, Brody GH, Madan A, Gerrard M | title = The effect of smoking on MAOA promoter methylation in DNA prepared from lymphoblasts and whole blood | journal = American Journal of Medical Genetics Part B | volume = 153B | issue = 2 | pages = 619–28 | date = Mar 2010 | pmid = 19777560 | pmc = 3694401 | doi = 10.1002/ajmg.b.31031 }}</ref>  Epigenetics may be one of the mechanisms through which the environment can impact the expression of the genome.<ref name="pmid17987668">{{cite journal | vauthors = Philibert RA, Sandhu H, Hollenbeck N, Gunter T, Adams W, Madan A | title = The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies | journal = American Journal of Medical Genetics Part B | volume = 147B | issue = 5 | pages = 543–9 | date = Jul 2008 | pmid = 17987668 | pmc = 3643119 | doi = 10.1002/ajmg.b.30657 }}</ref>  Studies have also linked methylation of genes associated with nicotine and alcohol dependence in women, ADHD, and drug abuse.<ref name="pmid18454435">{{cite journal | vauthors = Philibert RA, Gunter TD, Beach SR, Brody GH, Madan A | title = MAOA methylation is associated with nicotine and alcohol dependence in women | journal = American Journal of Medical Genetics Part B | volume = 147B | issue = 5 | pages = 565–70 | date = Jul 2008 | pmid = 18454435 | pmc = 3685146 | doi = 10.1002/ajmg.b.30778 }}</ref><ref name="pmid20875476">{{cite journal | vauthors = Bodnar RJ | title = Endogenous opiates and behavior: 2009 | journal = Peptides | volume = 31 | issue = 12 | pages = 2325–59 | date = Dec 2010 | pmid = 20875476 | pmc = 2693002 | doi = 10.1016/j.peptides.2010.09.016 }}</ref><ref name="pmid18492038">{{cite journal | vauthors = Mill J, Petronis A | title = Pre- and peri-natal environmental risks for attention-deficit hyperactivity disorder (ADHD): the potential role of epigenetic processes in mediating susceptibility | journal = Journal of Child Psychology and Psychiatry, and Allied Disciplines | volume = 49 | issue = 10 | pages = 1020–30 | date = Oct 2008 | pmid = 18492038 | doi = 10.1111/j.1469-7610.2008.01909.x }}</ref> It is probable that epigenetic regulation as well as methylation profiling will play an increasingly important role in the study of the play between the environment and genetics of psychopaths.<ref name="pmid20422643">{{cite journal | vauthors = Gunter TD, Vaughn MG, Philibert RA | title = Behavioral genetics in antisocial spectrum disorders and psychopathy: a review of the recent literature | journal = Behavioral Sciences & the Law | volume = 28 | issue = 2 | pages = 148–73 | year = 2010 | pmid = 20422643 | doi = 10.1002/bsl.923 }}</ref>

=== Suicide ===

A study of the brains of 24 who died by suicide, 12 of whom had a history of child abuse and 12 who did not, found decreased levels of [[Biology:Glucocorticoid receptor|glucocorticoid receptor]] in victims of child abuse and associated epigenetic changes.<ref name="McGowan_2009">{{cite journal | vauthors = McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ | title = Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse | journal = Nature Neuroscience | volume = 12 | issue = 3 | pages = 342–8 | date = Mar 2009 | pmid = 19234457 | pmc = 2944040 | doi = 10.1038/nn.2270 }}</ref>

== Social insects ==
Several studies have indicated DNA cytosine methylation linked to the social behavior of insects, such as honeybees and ants. In honeybees, when nurse bee switched from her in-hive tasks to out foraging, cytosine methylation marks are changing. When a forager bee was reversed to do nurse duties, the cytosine methylation marks were also reversed.<ref name="Herb_2012">{{cite journal | vauthors = Herb BR, Wolschin F, Hansen KD, Aryee MJ, Langmead B, Irizarry R, Amdam GV, Feinberg AP | title = Reversible switching between epigenetic states in honeybee behavioral subcastes | journal = Nature Neuroscience | volume = 15 | issue = 10 | pages = 1371–3 | date = Oct 2012 | pmid = 22983211 | doi = 10.1038/nn.3218 | pmc=3518384}}</ref> Knocking down the DNMT3 in the larvae changed the worker to queen-like phenotype.<ref name="Kucharski_2008">{{cite journal | vauthors = Kucharski R, Maleszka J, Foret S, Maleszka R | s2cid = 955740 | title = Nutritional control of reproductive status in honeybees via DNA methylation | journal = Science | volume = 319 | issue = 5871 | pages = 1827–30 | date = Mar 2008 | pmid = 18339900 | doi = 10.1126/science.1153069 | bibcode = 2008Sci...319.1827K }}</ref> Queen and worker are two distinguish castes with different morphology, behavior, and physiology. Studies in DNMT3 silencing also indicated DNA methylation may regulate gene alternative splicing and pre-mRNA maturation.<ref name="Li-Byarlay_2013">{{cite journal | vauthors = Li-Byarlay H, Li Y, Stroud H, Feng S, Newman TC, Kaneda M, Hou KK, Worley KC, Elsik CG, Wickline SA, Jacobsen SE, Ma J, Robinson GE | title = RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 31 | pages = 12750–5 | date = Jul 2013 | pmid = 23852726 | doi = 10.1073/pnas.1310735110 | pmc=3732956| bibcode = 2013PNAS..11012750L | doi-access = free }}</ref>

== Limitations and future direction ==
Many researchers contribute information to the [[Organization:International Human Epigenome Consortium|Human Epigenome Consortium]].<ref name="Albert_2010">{{cite journal | vauthors = Albert PR | title = Epigenetics in mental illness: hope or hype? | journal = Journal of Psychiatry & Neuroscience | volume = 35 | issue = 6 | pages = 366–8 | date = Nov 2010 | pmid = 20964959 | pmc = 2964366 | doi = 10.1503/jpn.100148 }}</ref> The aim of future research is to reprogram epigenetic changes to help with addiction, mental illness, age related changes,<ref name="Powledge_2011" /> memory decline, and other issues.<ref name="Miller_2010" /> However, the sheer volume of consortium-based data makes analysis difficult.<ref name="Powledge_2011" /> Most studies also focus on one gene.<ref name=McCaffery>{{cite book | vauthors = McCaffery JM | chapter = Genetic epidemiology of stress and gene by stress interaction |veditors=Baum A, Contrada RJ | title = The Handbook of Stress Science: Biology, Psychology, and Health | publisher = Springer Publishing Company | location = New York | year = 2010 | pages = 78–85 | isbn = 978-0-8261-1471-6 }}</ref>  In actuality, many genes and interactions between them likely contribute to individual differences in personality, behaviour and health.<ref name="Kalant_2010">{{cite journal | vauthors = Kalant H | title = What neurobiology cannot tell us about addiction | journal = Addiction | volume = 105 | issue = 5 | pages = 780–9 | date = May 2010 | pmid = 19919596 | doi = 10.1111/j.1360-0443.2009.02739.x }}</ref> As social scientists often work with many variables, determining the number of affected genes also poses methodological challenges. More collaboration between medical researchers, geneticists and social scientists has been advocated to increase knowledge in this field of study.<ref name = "Guo_2010">{{cite book | vauthors = Guo G | chapter = Family influences on children's well being: potential roles of molecular genetics and epigenetics |veditors=Landale N, Booth A, McHale S | title = Biosocial Foundations of Family Processes (National Symposium on Family Issues) | publisher = Springer | location = Berlin | year = 2010 | pages = 181–204 | isbn = 978-1-4419-7360-3 }}</ref>
 
Limited access to human brain tissue poses a challenge to conducting human research.<ref name="Powledge_2011" /> Not yet knowing if epigenetic changes in the blood and (non-brain) tissues parallel modifications in the brain, places even greater reliance on brain research.<ref name="Albert_2010"/> Although some epigenetic studies have translated findings from animals to humans,<ref name="McGowan_2009"/> a some researchers caution about the extrapolation of animal studies to humans.<ref name="Miller_2010" /> One view notes that when animal studies do not consider how the subcellular and cellular components, organs and the entire individual interact with the influences of the environment, results are too reductive to explain behaviour.<ref name="Kalant_2010" />

Some researchers note that epigenetic perspectives will likely be incorporated into pharmacological treatments.<ref name="pmid18197504" /> Others caution that more research is necessary as drugs are known to modify the activity of multiple genes and may, therefore, cause serious side effects.<ref name="Miller_2010" /> However, the ultimate goal is to find patterns of epigenetic changes that can be targeted to treat mental illness, and reverse the effects of childhood stressors, for example. If such treatable patterns eventually become well-established, the inability to access brains in living humans to identify them poses an obstacle to pharmacological treatment.<ref name="Albert_2010"/> Future research may also focus on epigenetic changes that mediate the impact of psychotherapy on personality and behaviour.<ref name=Masterpasqua />

Most epigenetic research is correlational; it merely establishes associations. More experimental research is necessary to help establish causation.<ref name="pmid21908516">{{cite journal | vauthors = Dempster EL, Pidsley R, Schalkwyk LC, Owens S, Georgiades A, Kane F, Kalidindi S, Picchioni M, Kravariti E, Toulopoulou T, Murray RM, Mill J | title = Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder | journal = Human Molecular Genetics | volume = 20 | issue = 24 | pages = 4786–96 | date = Dec 2011 | pmid = 21908516 | pmc = 3221539 | doi = 10.1093/hmg/ddr416 }}</ref> Lack of resources has also limited the number of intergenerational studies.<ref name="Powledge_2011" /> Therefore, advancing longitudinal<ref name="Guo_2010" /> and multigenerational, experience-dependent studies will be critical to further understanding the role of epigenetics in psychology.<ref name="Champagne" />

== See also ==
* Behavioral genetics
* [[Social:Behavioral neuroscience|Behavioral neuroscience]]
* [[Biology:Epigenetics of anxiety and stress-related disorders|Epigenetics of anxiety and stress-related disorders]]
* Evolutionary neuroscience
* [[Biology:Neuroscience|Neuroscience]]
* [[Social:Personality psychology|Personality psychology]]

== References ==
{{Reflist|33em}}
;Image legend
{{reflist|group=Color legend}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Lester BM, Tronick E, Nestler E, Abel T, Kosofsky B, Kuzawa CW, Marsit CJ, Maze I, Meaney MJ, Monteggia LM, Reul JM, Skuse DH, Sweatt JD, Wood MA | title = Behavioral epigenetics | journal = Annals of the New York Academy of Sciences | volume = 1226 | issue = 1| pages = 14–33 | date = May 2011 | pmid = 21615751 | doi = 10.1111/j.1749-6632.2011.06037.x | bibcode = 2011NYASA1226...14L | pmc = 3783959 }}
* {{cite journal | vauthors = Champagne FA, Rissman EF | title = Behavioral epigenetics: a new frontier in the study of hormones and behavior | journal = Hormones and Behavior | volume = 59 | issue = 3 | pages = 277–8 | date = Mar 2011 | pmid = 21419246 | doi = 10.1016/j.yhbeh.2011.02.011 | s2cid = 17285061 }}
* {{cite journal | vauthors = Nelson ED, Monteggia LM | title = Epigenetics in the mature mammalian brain: effects on behavior and synaptic transmission | journal = Neurobiology of Learning and Memory | volume = 96 | issue = 1 | pages = 53–60 | date = Jul 2011 | pmid = 21396474 | pmc = 3463371 | doi = 10.1016/j.nlm.2011.02.015 }}
* {{cite journal | vauthors = Plazas-Mayorca MD, Vrana KE | title = Proteomic investigation of epigenetics in neuropsychiatric disorders: a missing link between genetics and behavior? | journal = Journal of Proteome Research | volume = 10 | issue = 1 | pages = 58–65 | date = Jan 2011 | pmid = 20735116 | pmc = 3017635 | doi = 10.1021/pr100463y }}
* {{cite journal | vauthors = Curley JP, Jensen CL, Mashoodh R, Champagne FA | title = Social influences on neurobiology and behavior: epigenetic effects during development | journal = Psychoneuroendocrinology | volume = 36 | issue = 3 | pages = 352–71 | date = Apr 2011 | pmid = 20650569 | pmc = 2980807 | doi = 10.1016/j.psyneuen.2010.06.005 }}
* {{cite journal | vauthors = Crews D | title = Epigenetic modifications of brain and behavior: theory and practice | journal = Hormones and Behavior | volume = 59 | issue = 3 | pages = 393–8 | date = Mar 2011 | pmid = 20633562 | pmc = 3401366 | doi = 10.1016/j.yhbeh.2010.07.001 }}
* {{cite journal | vauthors = Mann JJ, Currier DM | title = Stress, genetics and epigenetic effects on the neurobiology of suicidal behavior and depression | journal = European Psychiatry | volume = 25 | issue = 5 | pages = 268–71 | date = Jun 2010 | pmid = 20451357 | pmc = 2896004 | doi = 10.1016/j.eurpsy.2010.01.009 }}
* {{cite journal | vauthors = Crews D | title = Epigenetics, brain, behavior, and the environment | journal = Hormones | volume = 9 | issue = 1 | pages = 41–50 | year = 2010 | pmid = 20363720 | doi = 10.14310/horm.2002.1251 | doi-access = free }}
* {{cite journal | vauthors = Malvaez M, Barrett RM, Wood MA, Sanchis-Segura C | title = Epigenetic mechanisms underlying extinction of memory and drug-seeking behavior | journal = Mammalian Genome | volume = 20 | issue = 9–10 | pages = 612–23 | year = 2009 | pmid = 19789849 | pmc = 3157916 | doi = 10.1007/s00335-009-9224-3 }}
* {{cite journal | vauthors = Nicolaïdis S | title = Prenatal imprinting of postnatal specific appetites and feeding behavior | journal = Metabolism | volume = 57 |issue = Suppl 2 | pages = S22-6 | date = Oct 2008 | pmid = 18803961 | doi = 10.1016/j.metabol.2008.07.004 }}
* {{cite journal | vauthors = McGowan PO, Meaney MJ, Szyf M | title = Diet and the epigenetic (re)programming of phenotypic differences in behavior | journal = Brain Research | volume = 1237 | pages = 12–24 | date = Oct 2008 | pmid = 18694740 | pmc = 2951010 | doi = 10.1016/j.brainres.2008.07.074 }}
* {{cite journal | vauthors = Szyf M, Weaver I, Meaney M | title = Maternal care, the epigenome and phenotypic differences in behavior | journal = Reproductive Toxicology | volume = 24 | issue = 1 | pages = 9–19 | date = Jul 2007 | pmid = 17561370 | doi = 10.1016/j.reprotox.2007.05.001 }}
* {{cite journal | vauthors = Bonasio R, Zhang G, Ye C, Mutti NS, Fang X, Qin N, Donahue G, Yang P, Li Q, Li C, Zhang P, Huang Z, Berger SL, Reinberg D, Wang J, Liebig J | title = Genomic comparison of the ants Camponotus floridanus and Harpegnathos saltator | journal = Science | volume = 329 | issue = 5995 | pages = 1068–71 | date = Aug 2010 | pmid = 20798317 | doi = 10.1126/science.1192428 | bibcode = 2010Sci...329.1068B | pmc = 3772619 }}
{{refend}}

== External links ==
{{refbegin}}
* {{cite web | url = http://www.cbc.ca/video/news/audioplayer.html?clipid=2161607978 | title = The Fingerprints of Poverty | vauthors = McDonald B | year = 2011 | work = Quirks & Quarks |publisher=CBC Radio |quote=Audio interview with Moshe Szyf, a professor of Pharmacology and Therapeutics at McGill University, discusses how epigenetic changes are related to differences in socioeconomic status. }}
* {{cite web | url = http://www.doctoroz.com/videos/control-your-pregnancy | title = Control Your Pregnancy | vauthors = Oz M | year = 2011 | work = The Dr. Oz Show | quote = Video explaining how epigenetics can affect the unborn fetus. }}
* {{cite web|url=http://www.scivee.tv/node/20905 |title=Epigenetic Landscapes |vauthors=Paylor B |year=2010 |quote=This video addresses how, in principle, accumulated epigenetic changes may result in personality differences in identical twins. This video was made by a Ph.D. candidate in experimental medicine and award winning filmmaker Ben Paylor. |url-status=dead |archive-url=https://web.archive.org/web/20131215182353/http://www.scivee.tv/node/20905 |archive-date=2013-12-15 }} page text. 
* {{cite magazine | url = http://www.scientificamerican.com/article.cfm?id=epigenetics-explained | title = Epigenetics Explained (Animation) | vauthors = Rusting R | date = November 2011 | magazine = Scientific American | quote = A series of diagrams explaining how epigenetic marks affect genetic expression. }}
{{refend}}

{{Psychology|state = collapsed}}
{{Neuroscience|state = collapsed}}
{{Evolutionary psychology}}

[[Category:Epigenetics]]
[[Category:Neuroscience]]
[[Category:Behavioural genetics]]

{{Sourceattribution|Behavioral epigenetics}}