Social Environment and Genetics as Determinants of Depression Occurrence and Its Chronicity: A Longitudinal Survey
Abstract: Depressive disorders are a set of heterogeneous disorders who se common characteristics are sadness and lack of interest, but varying regarding other symptoms, response to treatment and probability of recurrence and chronicity. They are a serious public health problem due to high prevalence and disability burden . Dep ression has a multifactorial causality with several genetic, behavioral and environmental factors playing a putative causal role . Thus, the aim of this thesis wa s to elucidate the interwoven effects of some environmental stressors, individual’s characteristics and some genetic factors on the occurrence and the course of depressive disorders. T he subjects were drawn from the PART study (In Swedish: Psykisk hälsa, A rbete och RelaTioner), a longitudinal study with three waves between 1998 and 2010, focused on mental health, work and relations among adult people residing in the Stockholm County, Sweden . In S tudies I and III, the relationship between polymorphisms in C OMT and serotonin transporter genes and depressive disorders were explored using a case - control approach. Ge ne x environment interaction effect s on depression risk were addressed focusing on COMT gene, childhood adversit ies and stressful life event s in Stu dy I ; and focusing on serotonin transporter gene and objective life events (i.e. loss/separation ) in Study III. Significant interactions were found between COMT and family problems during childhood and between serotonin transporter and partner’s loss/ separ ation. In Study II, the association between the psychosocial work environment and depression was scrutinized in a follow - up design of people employed in the same job over three - years . T he results showed a strong relationship between inadequate social climate and major depression among women three - years later , while there were no certain effects for the remaining exposure variables. Among men, the findings were controversial : high job demands and inadequate skill discretion appeared as protective factor s against depression ; thus, more studies using a similar approach are warranted. In Study IV, the complex inter - relationships among personal characteristics and circumstances over different life periods , and their effects on the chronicity of depression , were explored in a follow - up study of depressed subjects over ten years . It was analyzed using structural equation modeling (SEM). The resulting model revealed two main mechanisms anchored on personality traits: an internalizing pathway and an externalized /adversity pathway ; which are in line with studies about the onset of depression. The effort in this doctoral thesis consisted in putting together some pieces of a big puzzle. It is necessary to develop integrative models from different disciplines (e.g. genetics, neurosciences and epidemiology) in order to elucidate the complex mechanisms behind the depressive disorders.
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