DECONSTRUCTING DEPRESSION

Background: Major depressive disorder (MDD) is expected to rise to the second most important cause of disability in the world by 2020. Owing to its prevalence, its chronic and recurrent nature and its frequent comorbidity with other chronic illnesses, depression may be the condition that is most responsible for decreases in health worldwide. Since there are few more important and less understood scientific topics touching, indeed too often hitting, most people in a modern society, the understanding, preventing, and treating of depression needs to be a global priority. Hence, my purpose when researching and writing this report has been threefold: 1.To inform the reader on major depressive disorder, a widespread and growing disease worldwide, not least in many high-income countries; 2.To foster the reader’s curiosity about psychiatric neuroscience, whether applied or basic, as well as about clinical research in biological psychiatry, in part by illustrating how closely these sciences are related; 3.To increase the reader’s respect for preclinical neuroscience by illuminating the close relationship between animal experiments and their “translational” clinical counterparts and consequences, suggesting how biological evolution connects MDD-related cell-biological phenomena across more than 500 million years of natural process development. Method: Surveying the recent scientific literature on MDD with the goal of being able to formulate where modern biological psychiatry stands on the issue of its causes, processes and future remedies. Presenting the outcome of this survey based on about 4000 research papers in a way that should be understandable by members of an educated lay public. Results: In a 530 A4 page report, research findings on the etiology, i.e., the study of disease causes, of MDD are discussed, providing some insight into important recent discoveries and unsolved critical issues. The pathological processes of chronic stress, both in early childhood and in adulthood, as well as of inflammation, are likely causative factors of two major, and quite different, forms of depression. Causative factors also include, e.g., recently discovered epigenetic phenomena in the gene – environment interaction processes related to MDD, as well as relationships between neural plasticity, adult neurogenesis, antidepressant drug action, and BDNF, a key brain nerve growth factor. The text comprises 43 chapters, distributed among 6 parts: Introduction, Part I: Introducing some abstract etiological hypotheses, Part II: Roles of plasticity in depression - The glial actors, Part III: Roles of plasticity in depression - The neuronal actors, Part IV: Stress, stress hormones and neuromodulators - Intriguers in depression, Part V: Psychoneuroimmunology and depression. Conclusions: If copyright issues related to proposed illustrations can be resolved, the report will be available either as a printed book or as an e-document, possibly in 2017.