Biological and personality factors underlying major depression

Abstract

Research in recent years has revealed a large amount of biological correlates of depression. It has become increasingly clear that the initial hope that progress in the field of genetics would be able to unravel the genetic basis of the disease will not be fulfilled in the near future. Rather, depression is characterized by a complex interplay of many genes and associated biological systems, making the current findings difficult to interpret. This could be remedied by integrating the findings from gene-environment interactions with personality constructs. The latter could facilitate the classification of current findings and might represent a step toward theory-based research into the biological basis of depression etiology. Primary emotional systems are considered the emotional basis of human personality. They have a neurobiological basis in subcortical brain regions experimentally identified using deep brain stimulation studies and psychopharmacological challenge tests in animal models. The neural substrate of primary emotions allows for theory-driven investigations of the emotional consequences of stressful life events (SLEs) and their associations with biological systems associated with depression like the serotonin and the oxytocin system. This dissertation aims at collecting evidence for a comprehensive model of depression development comprising environmental, psychological and biological factors. Accordingly, the interplay between the 2D:4D (second digit to fourth digit) ratio a marker of prenatal androgen exposure, stressful life events, primary emotional systems, and methylation patterns of the serotonin and oxytocin systems was examined. This dissertation comprises five studies. In the first study, the associations between the 2D:4D ratio, sex and depression were investigated using a case-control design. The study showed no direct association between the 2D:4D ratio and depression. However, an absence of sex differences in the 2D:4D ratio of the right hands of patients as compared to controls was observed. The second and third study showed that SLEs were negatively associated with methylation status of the structural oxytocin gene. In addition, patients exhibited a significantly lower methylation status of the oxytocin gene as compared to matched controls. The fourth study provided evidence for the predictive value of the primary emotions SEEKING and SADNESS for first depression onset. Furthermore, methylation status of the serotonin transporter gene was positively associated with depression severity in women. The fifth study showed that SLEs and primary emotions explained a significant amount of variance in fear of a future SLE. The present dissertation provides evidence for associations between environmental, psychological as well as biological factors and depression. The consideration of primary emotions helps in the interpretation of associations between SLEs, epigenetic alterations and depression. Therefore, personality might bridge the gap between the environment and biological adaptions to the environment.