Which patient will feel down, which will be happy? The need to study the genetic disposition of emotional states

Abstract

Purpose: In quality-of-life (QL) research, the genetic susceptibility of negative and positive emotions is frequently ignored, taken for granted, or treated as noise. The objectives are to describe: (1) the major findings of studies addressing the heritable and environmental causes of variation in negative and positive emotional states and (2) the major biological pathways of and genetic variants involved in these emotional states.

Methods: Literature overview.

Results: The heritability estimates for anxiety and depression are 30-40%. Related traits as neuroticism and loneliness are also highly heritable. The hypothalamo-pituitary-adrenal axis is the 'final common pathway' for most depressive symptoms. The many findings of investigated genes are promising but not definitive. Heritability estimates of positive emotional states range between 40 and 50%. Life satisfaction and mental health share common genetic factors with optimism and self-esteem. The prefrontal cortex is a candidate brain area for positive emotional states. Biological and genetic research into positive emotional states is scarce.

Conclusion: Genetically informative studies may provide insights into a wide variety of complex questions that traditional QL studies cannot deliver. This insight in turn will help us to design more effective supportive programs that could moderate the outcomes of genetically based predispositions.

Fig. 1

Schematic illustration of the pathogenesis of depression (reprinted with permission from Bao et al., 2008 [13], p. 541). The schematic figure illustrates the impaired interaction among the decreased activity of vasopressin neurons (AVP) in the suprachiasmatic nucleus (SCN), the increased activity of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN), the increased release of adrenocorticotropin (ACTH) into the blood stream by the pituitary gland, and the increased release of cortisol by the adrenal gland. Normally, cortisol exerts a negative feedback effect to shut down the stress response when the threat has passed. In depressed patients, the cortisol feedback mechanism is deficient due to the presence of glucocorticoid resistance, which may be caused either by polymorphisms of the corticosteroid receptor or by early (intra-uterine or childhood) developmental disorders. Both, increased CRH and increased cortisol levels may induce mood disorders by their central effects. The increased cortisol levels also affect the vasopressin (AVP) neurons in the suprachiasmatic nucleus (SCN) as they subsequently fail to inhibit sufficiently the CRH neurons in the hypothalamic paraventricular nucleus (PVN). Such an impaired negative feedback mechanism may lead to a further increase in the activity of the HPA system [13]