Behavioral epigenetics

In biology, and specifically genetics, epigenetics is the study of heritable changes in gene activity which are not caused by changes in the 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. Genetic activity can be influenced by environmental factors, as well as parenting styles, diet and even social interactions. Examples of mechanisms that produce such changes are DNA methylation and histone modification, Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. 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". Histone modification changes the way that DNA is packaged into chromosomes. These changes impact how genes are expressed.{{ Epigenetic changes occur not only in the developing fetus, but also in individuals throughout the human life-span. == Discovery ==

The first documented example of epigenetics affecting behavior was provided by Michael Meaney and Moshe Szyf. 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. This stress sensitivity was linked to a down-regulation in the expression of the glucocorticoid receptor in the brain. In turn, this down-regulation was found to be a consequence of the extent of methylation in the promoter region of the glucocorticoid receptor gene. Immediately after birth, Meaney and Szyf found that methyl groups repress the 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. == 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. Further research investigated the molecular basis for long-term memory. By 2015 it had become clear that long-term memory requires gene transcription activation and de novo protein synthesis. Long-term memory formation depends on both the activation of memory promoting genes and the inhibition of memory suppressor genes, and DNA methylation/DNA demethylation was found to be a major mechanism for achieving this dual regulation. Rats with a new, strong long-term memory due to contextual fear conditioning have reduced expression of about 1,000 genes and increased expression of about 500 genes in the hippocampus of the 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. Further research into long-term memory has shed light on the molecular mechanisms by which methylation is created or removed, as reviewed in 2022. 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. 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 immediate early genes (among other genes) in neurons after neuron activation. EGR-1, together with TET1, is employed in programming the distribution of DNA demethylation sites on brain DNA during memory formation and in long-term neuronal plasticity. 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. 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. 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. In human studies, post-mortem brains from patients with Alzheimer's dementia show high levels of histone de-acetylase. == Psychopathology and mental health ==

Anxiety and risk-taking are identical twins. Twin studies help to reveal epigenetic differences related to various aspects of psychology. Due to the stress that can be placed on individuals can increase levels of anxiety and the way the epigenetics are responding in relation to the individual. Epigenetics investigate how alterations upon environment and behavior can affect the way in which genes operate. Within research, it's know that majority of epigenetic modifications identified have been involved with anxiety-like phenotypes that involve genes that regulate the hypothalamic-pituitary adrenal axis which results to the way our bodies respond to stress that we endure as people. Epigenetics is altered by many influences, whether it be genetic and or environmental. Within the prenatal times it is evident that through changes of DNA methylation, that maternal and pre-maternal distress have been connected to modifications in the fetal HPA axis. This demonstrates that the link between our development, stress and anxiety a mother can feel during this time creates a linkage in the response of how the epigenetic may be altered in the response of the HPA axis. Linkage of the impacts of childhood trauma in connection with epigenetic and anxiety, in that there is a change in DNA methylation process, increasing the chances of neuroendocrine damage to likely occur. In relation, the neuroendocrine damage induces the state of depression, making it mentally unstable for a person to possibly perform their daily activities. The Brain-derived neurotropic factor (BDNF) is known to change its state because of epigenetic mechanisms and contributes to the alters within the development process necessary for the brain of us individuals. Alterations within the epigenetic process can be treated using different types clinical procedures, by targeting specific changes and the treating them with the proper sort of care. Studies in rats have shown correlations between maternal care in terms of the parental licking of offspring and epigenetic changes. In an attempt to cope with stress, alcohol and drugs can be used as an escape. Once substance abuse commences, however, epigenetic alterations may further exacerbate the biological and behavioural changes associated with addiction. Epigenetic modifications have been observed in studies on rodents involving ethanol, nicotine, cocaine, amphetamine, methamphetamine and opiates. (e.g., in the nucleus accumbens). Hence, a cycle emerges whereby changes in areas of the reward system contribute to the long-lasting neural and behavioural changes associated with the increased likelihood of addiction, the maintenance of addiction and relapse. These alterations may be long-term, as is evidenced in smokers who still possess nicotine-related epigenetic changes ten years after cessation. Therefore, epigenetic modifications Evidence for relevant epigenetic changes came from human studies involving alcohol, 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, decreased attention and decreased cerebral volume. Eating disorders and obesity Epigenetic changes may help to facilitate the development and maintenance of eating disorders via influences in the early environment and throughout the life-span. 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 . Overall, epigenetics contribute to persistent, unregulated self-control behaviours related to the urge to binge. Since glutamate is the most prevalent, fast, excitatory neurotransmitter, increased levels may result in the psychotic episodes related to schizophrenia. Epigenetic changes affecting a greater number of genes have been detected in men with schizophrenia as compared to women with the illness. Population studies have established a strong association linking schizophrenia in children born to older fathers. To this end, toxins Therefore, similar epigenetic changes in older human fathers are likely. One study found hypomethylation of a gene promoter of a 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 dopamine in the synapse. These findings suggest that the hypomethylation of the 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. However, a second study found no epigenetic differences in post-mortem brains from bipolar individuals. Major depressive disorder The causes of major depressive disorder (MDD) are poorly understood from a neuroscience perspective. 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. 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. Studies in various rodent models of depression, often involving induction of stress, have found direct epigenetic modulation of BDNF as well. Psychopathy Epigenetics may be relevant to aspects of psychopathic behaviour through methylation and histone modification. These processes are heritable but can also be influenced by environmental factors such as smoking and abuse. Epigenetics may be one of the mechanisms through which the environment can impact the expression of the genome. Studies have also linked methylation of genes associated with nicotine and alcohol dependence in women, ADHD, and drug abuse. 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. == 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. Knocking down the DNMT3 in the larvae changed the worker to queen-like phenotype. 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. == Limitations and future direction ==

Many researchers contribute information to the Human Epigenome Consortium. The aim of future research is to reprogram epigenetic changes to help with addiction, mental illness, age related changes, In actuality, many genes and interactions between them likely contribute to individual differences in personality, behaviour and health. 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. Limited access to human brain tissue poses a challenge to conducting human research. some researchers caution about the extrapolation of animal studies to humans. Lack of resources has also limited the number of intergenerational studies. Therefore, advancing longitudinal and multigenerational, experience-dependent studies will be critical to further understanding the role of epigenetics in psychology. == See also ==