The molecular bases of the suicidal brain

Suicide takes a heavy toll on society but can often be avoided through adequate treatment. However, societal normalities and taboos often make it difficult for individuals who experience suicidal ideation or aspects of suicidal behaviour to seek help before it is too late.Many factors contribute to suicidal behaviour and these can be globally classified as distal factors, which increase predisposition to suicide, and proximal factors, which precipitate a suicidal act.Distal factors comprise a family history of suicide, indicating a genetic predisposition, genetic variation between individuals and experiences of early-life adversity. Early-life adversity can result in stable changes to gene expression, which results in increased lifetime susceptibility to suicidal behaviour.Early-life adversity epigenetically regulates stress response systems and neuronal plasticity, which are associated with emotional and behavioural changes.Behavioural and emotional traits are known mediators of suicide risk, with impulsive aggressive and anxiety traits being intimately linked to suicidal behaviour.Proximal factors are associated with precipitation of the suicidal act and can be linked to changes in neurotransmitter levels, inflammation in the CNS and glial, notably astrocytic, dysfunction.