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    ABSTRACT: Melancholic depression, described also as endogenous depression, is a mood disorder with distinctive specific psychopathological features and biological homogeneity, including anhedonia, circadian variation of mood, psychomotor activation, weight loss, diurnal cortisol changes, and sleep disturbances. Although several hypotheses have been proposed, the etiology of this disorder is still unknown. Behavioral, electrophysiological and biochemical approaches were used to characterize the emotional phenotype, serotonergic and noradrenergic electrical activity, and corticosterone in melatonin MT1 receptor knockout mice and their wild type counterparts, during both light and dark phases. Melatonin MT1 receptor knockout mice have decreased mobility in the forced swim and tail suspension tests as well as decreased sucrose consumption, mostly during the dark/inactive phase. These mood variations are reversed by chronic treatment with the tricyclic antidepressant desipramine. In addition, MT1 receptor knockout mice exhibit psychomotor disturbances, higher serum levels of corticosterone the dark phase, and a blunted circadian variation of corticosterone levels. In vivo electrophysiological recordings show a decreased burst-firing activity of locus coeruleus norepinephrine neurons during the dark phase. The circadian physiological variation in the spontaneous firing activity of high-firing neuronal subpopulations of both norepinephrine neurons and dorsal raphe serotonin neurons are abolished in MT1 knockout mice. These data demonstrate that melatonin MT1 receptor knockout mice recapitulate several behavioral and neurobiological circadian changes of human melancholic depression and, for the first time, suggest that the MT1 receptor may be implicated in the pathogenesis of melancholic depression and is a potential pharmacological target for this mental condition. © The Author 2015. Published by Oxford University Press on behalf of CINP.
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    ABSTRACT: The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 defines mental disorders as syndromes and also introduced disorder "specifiers" with the aim of providing increased diagnostic specificity by defining more homogeneous subgroups of those with the disorder and who share certain features. While the majority of specifiers in DSM-5 define a specific aspect of the disorder such as age at onset or severity, some define syndromes that appear to meet the DSM-5 definition of a mental disorder. Specifically, melancholia is positioned in DSM-5 as a major depressive disorder (non-coded) specifier, while catatonia is listed as both a disorder secondary to a medical condition and as a specifier associated with other mental disorders such as schizophrenia, major depressive disorder, and bipolar disorder. Despite decades of research supporting melancholia's status as a categorical "disorder" (a higher-order construct than a specifier), failure to provide convincing support for its disorder status has contributed to its current positioning in DSM-5. As DSM-5 has similar symptom criteria for major depression and for its melancholia specifier, research seeking to differentiate melancholic and non-melancholic depression according to DSM-5 criteria will have limited capacity to demonstrate "melancholia" as a separate disorder and risks melancholia continuing to be reified as a low-order specifier and thus clinical marginalization. There have been few advances in catatonia research in recent years with its positioning largely relying on opinion and clinical observation rather than on empirical studies.
    Current Psychiatry Reports 01/2015; 17(1):536. DOI:10.1007/s11920-014-0536-y · 3.05 Impact Factor
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    ABSTRACT: Studies on major depressive disorder (MDD) show that the degree of correlation between the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) varies widely. We aimed to determine whether this discrepancy reflects specific functional abnormalities in the frontotemporal cortex. Mildly depressed or euthymic patients with MDD (n=52), including 21 patients with MDD with the discrepancy, i.e., those with low HAMD17 scores (≤13) but high BDI-II scores (>28), and 31 patients without the discrepancy, i.e., those with low HAMD17 scores and low BDI-II scores (≤28), participated in the study along with 48 control subjects. Regional changes of oxygenated hemoglobin (oxy-Hb) levels during a verbal fluency task (VFT) were monitored using a 52-channel near-infrared spectroscopy (NIRS) device. In the frontotemporal regions, mean oxy-Hb changes induced by the VFT were significantly smaller in patients with MDD than in control subjects. In 5 channels within frontal regions, the increase in mean oxy-Hb levels was significantly greater in MDD patients with the BDI-HAMD discrepancy than in those without the discrepancy. In 6 channels within the frontal region of the patients with MDD, significant positive correlations were observed between mean oxy-Hb changes and BDI total scores (ρ=0.38-0.59; P<0.05, false discovery rate corrected). Our findings required replication in severely depressed patients, particularly those with melancholia. The distinct pattern of activation of the prefrontal cortex suggests that MDD with the BDI-HAMD discrepancy is pathophysiologically different from MDD without the discrepancy. Copyright © 2014 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 11/2014; 174C:165-172. DOI:10.1016/j.jad.2014.11.020 · 3.71 Impact Factor

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May 19, 2014