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Available from: Athanasios Koukopoulos,
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    • "Further experiments employing pharmacological agents selective for each monoamine (e.g., one selective serotonin reuptake inhibitor and one norepinephrine reuptake inhibitor) may help to address this question. The other important biological feature that distinguishes melancholic versus non-melancholic depression is the sustained activation of the hypothalamic–pituitary–adrenal axis, which results in hypercortisolism and altered response to the dexamethasone suppression test (Roy et al., 1985; Parker et al., 2010). In keeping with this clinical evidence, MT 1 -/-mice showed both increased serum corticosterone levels during the dark/active phase and blunted physiological circadian diurnal fluctuation, confirming the disturbances of the hypothalamic–pituitary–adrenal activity. "
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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.
    The International Journal of Neuropsychopharmacology 01/2015; 18(3). DOI:10.1093/ijnp/pyu075 · 4.01 Impact Factor
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    • "There has been a long history of distinguishing disorders that involve depressed affect, particularly between disorders thought to be endogenous and those thought to be non-endogenous/ psychosocially based (Parker et al., 2010; Shorter, 2007). Several authors have suggested that major depression as currently defined in the DSM encompasses multiple distinct disorders (Kendler et al., 2013). "
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    ABSTRACT: Depression accompanied by somatic symptoms ("somatic" depression) has been found to differ from depression without the additional symptoms ("pure" depression) in their gender ratio, their association with measures of perceived gender inequality taken from both respondents and their parents, and in their response to pharmacological treatment. Further evidence of the distinction between the two syndromes might come from differential patterns of development. Data on the annual incidence of new cases of depression exhibited by a representative sample of respondents aged 12-19 came from the National household survey on drug use and health. Between early adolescence (ages 12-14) and late adolescence (ages 15-19), female respondents exhibited a much larger increase in somatic depression than in pure depression. Males did not exhibit the same pattern. These results further support the hypothesis that somatic and pure depressions are two distinct disorders.
    Psychiatry Research 07/2014; 220(1-2). DOI:10.1016/j.psychres.2014.07.054 · 2.47 Impact Factor
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    • "Delineation of depressive sub-types (melancholic versus non-melancholic depression) proceeded according to the clinical criteria presented by Parker et al. [34]. These criteria are based upon characteristic clinician rated scores (by trained psychiatrists in the current study) across a number of domains and include presenting clinical features (e.g. "
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    ABSTRACT: Cognitive disturbances in depression are pernicious and so contribute strongly to the burden of the disorder. Cognitive function has been traditionally studied by challenging subjects with modality-specific psychometric tasks and analysing performance using standard analysis of variance. Whilst informative, such an approach may miss deeper perceptual and inferential mechanisms that potentially unify apparently divergent emotional and cognitive deficits. Here, we sought to elucidate basic psychophysical processes underlying the detection of emotionally salient signals across individuals with melancholic and non-melancholic depression. Sixty participants completed an Affective Go/No-Go (AGN) task across negative, positive and neutral target stimuli blocks. We employed hierarchical Bayesian signal detection theory (SDT) to model psychometric performance across three equal groups of those with melancholic depression, those with a non-melancholic depression and healthy controls. This approach estimated likely response profiles (bias) and perceptual sensitivity (discriminability). Differences in the means of these measures speak to differences in the emotional signal detection between individuals across the groups, while differences in the variance reflect the heterogeneity of the groups themselves. Melancholic participants showed significantly decreased sensitivity to positive emotional stimuli compared to those in the non-melancholic group, and also had a significantly lower discriminability than healthy controls during the detection of neutral signals. The melancholic group also showed significantly higher variability in bias to both positive and negative emotionally salient material. Disturbances of emotional signal detection in melancholic depression appear dependent on emotional context, being biased during the detection of positive stimuli, consistent with a noisier representation of neutral stimuli. The greater heterogeneity of the bias across the melancholic group is consistent with a more labile disorder (i.e. variable across the day). Future work will aim to understand how these findings reflect specific individual differences (e.g. prior cognitive biases) and clarify whether such biases change dynamically during cognitive tasks as internal models of the sensorium are refined and updated in response to experience.
    BMC Psychiatry 04/2014; 14(1):122. DOI:10.1186/1471-244X-14-122 · 2.21 Impact Factor
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