Perspectives on Depression: A synthesis of biological and behavioural findings

Abstract

Introduction: Depression is a complex and widespread phenomenon, with few effective treatments that may be universally applied. Although a great deal of research has been reported on various aspects of depression from the perspectives of the different disciplines of general psychiatry, genetics, neuroscience, endocrinology, immunology, pharmacology, psychology, behaviour analysis and evolutionary theory, there is no extant synthesis of those data that is recent or comprehensive in its coverage. This thesis therefore reviewed the literatures from these nine areas, focussing principally from a neurobiological perspective, and drew the findings from that review into a comprehensive model of the way in which depression develops and why it occurs. Method: Working from a selection of authoritative texts, plus cross-referencing and weekly checks of over 20 major journals that reported data on depression during the period 2000 to 2010, plus online electronic searches via four search engines, more than 100 review chapters and over 3,500 journal articles on depression were found across the disciplines mentioned above. From these, a subset of 768 sources was identified as holding information directly pertinent to the focus of this thesis. These sources were then reviewed and summarised in discrete sections of this thesis. From these summaries, a new model of depression was developed which encompassed the wider literature. Results & Conclusion: Commencing with genetic bases for depression (gender, predisposition to melancholic depression) and two major indicators of the organism's exaggerated responsivity to environmental threat (the 5-HTTLPR polymorphism, methylation of several key genes involved in the HPA axis function) which cause increases in the activity of the Hypothalamus-Pituitary-Adrenal (HPA) axis, the model developed in this thesis considers the effects of that HPA axis hyperactivation and resultant elevated circulating cortisol.