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Brain Behav Immun. 2018 Mar;69:603-617. doi: 10.1016/j.bbi.2017.10.012. Epub 2017 Oct 16.

Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and ultimate functions.

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Department of Biology, University of Turku, FIN-20014 Turku, Finland; Turku Brain and Mind Center, University of Turku, FIN-20014 Turku, Finland. Electronic address:
English, Drama and Writing Studies, University of Auckland, 1010 Auckland, New Zealand; School of Psychology, University of Auckland, 1010 Auckland, New Zealand.
Institute of Ecology and Earth Sciences, University of Tartu, 51014 Tartu, Estonia; Department of Zoology and Animal Ecology, University of Latvia, 1004 Riga, Latvia.
Department of Psychiatry, University of Turku and Turku University Hospital, FIN-20014 Turku, Finland; Turku Brain and Mind Center, University of Turku, FIN-20014 Turku, Finland.


Major depressive disorder constitutes one of the leading causes of disability worldwide. However, it is not a unitary disease-it is a heterogeneous syndrome, with patients differing remarkably in symptom profile, pathophysiology and treatment responsiveness. Previous attempts to subtype major depressive disorder have showed limited clinical applicability. We present a classification of major depressive disorder episodes based on the proximate mechanisms that led to the original mood change that caused the depressive episode. We identify discrete depression subtypes that are induced by: 1) infection, 2) long-term stress, 3) loneliness, 4) traumatic experience, 5) hierarchy conflict, 6) grief, 7) romantic rejection, 8) postpartum events, 9) the season, 10) chemicals, 11) somatic diseases and 12) starvation. We further examine the ultimate functions of these subtypes and show that not all types of mood changes that trigger depression are adaptive. Instead, some are clearly maladaptive and some are byproducts of other adaptations. In modern societies, low mood after adverse life events may turn into a pathological depressive state. Modern lifestyle increases susceptibility to inflammatory dysregulation and chronic stress, both of which increase the amount of proinflammatory cytokines in peripheral blood, leading to low mood and sickness behaviour. Proinflammatory cytokines may aggravate the previously adaptive short-term mood changes to a chronic maladaptive depressive state by preventing the normalization of mood after adverse life events. Subtyping depression enables an effective and intelligent long-term treatment of patients in each subtype by treating the underlying causes of depression.


Depression; Epidemiology; Evolutionary psychopathology; Inflammation; Modernization; Obesity; Proinflammatory cytokines


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