Linking emotion to the social brain

Abstract

In 2006, research on the neurotransmitter serotonin and its transporter protein (5‐HTT) in the synaptic gap celebrated a series of anniversaries. Forty‐five years earlier, presynaptic neurotransmitter uptake was discovered (Hertting & Axelrod, 1961). Two decades later, 5‐HTT was first linked to depression (Langer et al , 1981), shortly after its identification as a target of antidepressant drugs (Raisman et al , 1979). The sequence of the transporter gene from rats was published 10 years after that (Blakely et al , 1991), which initiated an avalanche of molecular genetic studies on the regulation of emotionality. This research culminated in two reports revealing an association between variations of the 5‐HTT gene ( 5‐HTT and SLC6A4 ) and anxiety‐related traits as well as depression (Collier et al , 1996; Lesch et al , 1996). Since then, clinical studies have further supported the link between variants of 5‐HTT and disorders in the regulation of emotion. Although modest effect sizes—typical of non‐Mendelian traits—polygenic patterns of inheritance, epistatic and epigenetic interactions, and heterogeneity between studies confounded the results, 5‐HTT comprises a model molecule for studying gene–environment interactions in cognitive and psychiatric neuroscience. The demonstration in rhesus macaques that stress early in life uniquely reinforces links between variations of 5‐HTT , behaviour and psychopathology seems to herald in a new era of behavioural genetics. Moreover, the discovery that 5‐HTT is a susceptibility gene for depression is a first step towards explaining the molecular dimensions of personality and behaviour, identifying physiological pathways that lead to other disorders of cognitive function and emotion, and analysing the interactive effects of genes and environment in the development of disease. On the heels of these results from behavioural genetics, novel approaches including neurophysiology, neuropsychology and functional neuroimaging, as well as the inclusion of other phenotypes (such as higher cognitive functions, communication skills, social competence and longevity), have …