The Genetics of Human Aggressive Behaviour

Abstract

Both genes and environment contribute to individual differences in aggression. Surveys of the pathways implicated in the physiological and neuronal processes involved highlight the potential role of genes regulating sexual differentiation, anxiety, stress response and neurotransmission. To date, however, association studies have provided little evidence of a substantially significant role for any single candidate gene in such pathways. This may be because genes function against a background in which other genetic and environmental factors are crucial. A series of recent studies, particularly concentrating on monoamine oxidase A , has emphasised the necessity of examining gene by environmental interactions if the contributions of individual loci are to be understood. These findings have major significance for the interpretation of data, both from individual gene and whole genome association studies. Functional imaging studies of genetic variants affecting serotonin pathways have also provided valuable insights into potential links between genes, brain and aggressive behaviour. Key Concepts: Aggression is an evolutionarily advantageous trait with input from one of the most primitive brain regions, the amygdala. There is significant disparity between aggressive behaviour in males and females. Genes and environment both influence aggressive behaviour and there is evidence that stressful life events can interact with specific genetic variants. DBH , COMT , adrenergic receptors, NET1 and SLC6A2 have been studied as possible candidate genes linking stress and aggression. In the serotonin system, genetic polymorphisms in MAOA , SLC6A4 , TPH1/2 and the serotonin receptor genes have been linked with aggression. Studies have shown a potential link between diet and its effects (e.g. on glucose levels) and aggression. Brain imaging studies are beginning to assist an interpretation of the links between genetic variation and aggression.

Population differentiation and behavioural association of the two ‘personality’ genesDRD4andSERTin dunnocks (Prunella modularis)

“…Therefore, our current results suggest that variation in the SERT promoter might influence dunnock male tendencies to be either monogamous or to form a cobreeding alliance with another male. Nevertheless, this finding must be considered with caution because the repeatability of mating status might represent a condition influenced by other behaviours that are linked with variation in SERT such as aggression (Craig & Halton ) or dominance (Miller‐Butterworth et al . ).…”

Vitamin D and the omega‐3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior

“…For example, the negative effects of tryptophan depletion on verbal memory are ameliorated in women who are treated with estrogen (201). Estrogen is likely to have positive effects on social behavior, as shown by the fact that women are less aggressive and commit fewer violent crimes and are less likely to commit suicide (78). Acute tryptophan depletion in women in the luteal phase of their menstrual cycle, when estrogen levels are low, causes them to be more aggressive than at other periods of the menstrual cycle when estrogen is more abundant (205).…”

“…Polymorphisms in the TPH2 gene and other serotoninrelated genes provide additional support that aberrant brain levels of serotonin are associated with increased susceptibility to ASD, ADHD, bipolar disorder, schizophrenia, and impulsive behavior, including aggression toward self and others (22, [69][70][71][72][73][74][75]. These polymorphisms are also associated with aggression, depression, and anxiety, which are all common psychologic abnormalities in these psychiatric disorders (76)(77)(78). Suicide is strongly linked to impulsive behavior and polymorphisms in tryptophan hydroxylase, and other serotonin-related pathways have been linked to increased suicide attempts (79,80).…”

Genetic variation in dopaminergic activity is associated with the risk for psychiatric side effects of levetiracetam

“…The most severe psychiatric complications of LEV encompass aggressive, hostile, and violent behavior. Aggression is a complex behavioral phenotype often classified as either instrumental‐proactive or reactive‐impulsive, with the former being goal‐directed and characterized by a lack of empathy and remorse and the latter resulting from a loss of inhibitory self‐control following anger outbursts (Craig & Halton, 2009). The behavioral phenotype typically observed in patients treated with LEV resembles reactive‐impulsive aggression (Helmstaedter et al., 2008).…”

“…Consequently, stage I had an a priori focus on SNPs located in genes encoding DBH (rs1611115), COMT (rs4680), MAOA (rs6323), and DRD2/ANKK1 (rs1800497, known as TAQ-1A polymorphism). MAOA and COMT also contribute to the degradation of the neurotransmitters norepinephrine (NE) and serotonin (5-HT), both of which have been linked to aggressive behavior (Craig & Halton, 2009). Therefore, to control for the specificity of the neurochemical pathway mediating increased susceptibility to the adverse psychotropic side effects of LEV, further analyses included aggression-related SNPs located in genes regulating noradrenergic and serotonergic signaling: NE transporter 1 (NET1, rs3785143), 5-HT1A receptor (HTR1A, rs6295), 5-HT2A receptor (HTR2A, rs6311), and tryptophan hydroxylase 1 (TPH1, rs1800532 and rs1799913).…”