12 Another morphometrical study corroborates the finding that short-allele carriers show decreased volume in the affective division of the anterior cingulate and decreased gray matter density in its pre-genual region. 12 These authors conclude that 5-HTT induced variation in anatomy and function of an amygdala-cingulate feedback circuit that is critical for emotional states and implied a genetic susceptibility for depression. 4, 10, 11, 12, 13 A morphometrical study of this genetic association reports reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala. In particular-with remarkable consistency-a body of neuroscientific research shows increased amygdala activation to negative emotional stimuli among carriers of short alleles.

This process is shown in Figure 1.įunctional variation in the serotonin transporter gene is increasingly understood to exert strong influence on parts of the brain regulated by serotonergic neurotransmission. In turn, more serotonin is reintroduced into the pre-synaptic cell.

6, 7, 8, 9 The long polymorphism thus results in increased gene expression and more serotonin transporters in the cell membrane. Consequently, the long variant produces significantly more 5-HTT mRNA and protein. The ‘long’ (528 bp) and ‘short’ (484 bp) polymorphism produces the same protein, but the long allele is associated with an approximately three times higher basal activity than the shorter allele. The 5-HTT gene contains a 44-bp variable-number tandem repeat polymorphism in the promoter region (5-HTTLPR) that is believed to be responsible for variation in transcriptional efficiency. The serotonin transporter gene has been studied extensively, and much is known about the way different versions of this gene influence serotonergic neurotransmission which, in turn, is found to influence personality and mental health. Most serotonin is recycled after use and the serotonin transporter allows serotonergic neurons to restock. The 5-HTT gene (locus symbol SLC6A4) codes for the serotonin transporters (5-HTT or SERT) that are placed in the cell wall and reabsorb the neurotransmitter serotonin from the synaptic cleft. Functional variation in the promotor region of the serotonin transporter gene ( 5-HTTLPR) is a promising candidate for better understanding the individual heterogeneity in subjective well-being. 2, 3 However, twin studies do not identify which genes might be involved. An important finding from this literature is that people tend to have a ‘baseline’ or ‘set point’ happiness level 1 that shows persistent strength over time, and twin studies indicate that up to 50% of the variance in happiness between individuals can be attributed to genetic influences. Research on subjective well-being has produced valuable insights into the sources of individual happiness.

Transporter 5