Atypical depression and non-atypical depression: Is HPA axis function a biomarker? A systematic review

Juruena, Mário F.; Bocharova, Mariia; Agustini, Bruno; Young, Allan H.

doi:10.1016/j.jad.2017.09.052

Cited by 247 publications

(158 citation statements)

References 91 publications

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“…Elevated G-CSF has been observed in patients with MDD (5) and glucocorticoids increase both G-CSF and neutrophil numbers (29). The hypercortisolemia observed in some MDD patients (30) may thus underpin the relative neutrophilia observed in MDD patients in our study.…”

Section: Neutrophil Abnormalities In Mddmentioning

confidence: 53%

Peripheral blood cell immunophenotyping reveals distinct subgroups of inflamed depression

Lynall

Turner

Bhatti

et al. 2019

Preprint

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One Sentence Summary: Two subgroups of depressed cases (about two-thirds of all 206 cases) were identified by peripheral blood biomarker evidence of distinctive cellular immunophenotypes, biased towards the myeloid or lymphoid lineages in different subgroups, but consistently associated with increased blood concentrations of inflammatory proteins and greater severity of depressive symptoms. Lynall et al. Blood cell count-defined subgroups of depression 3Abstract: Depression has been associated with increased inflammatory proteins but changes in circulating immune cells are less well defined. We used multi-parametric flow cytometry to investigate 14 subsets of peripheral blood cells in 206 cases of major depressive disorder (MDD) and 77 age-and sex-matched controls. There were significant case-control differences, by univariate and multivariate analysis: cases showed increased immune cell counts, especially neutrophils, CD4 + T cells and monocytes, and increased inflammatory proteins (C-reactive protein and interleukin-6).Within-group analysis demonstrated significant association between the severity of depressive symptoms and increased myeloid and CD4 + cell counts. MDD cases could be partitioned into two groups by forced binary clustering of cell counts: the inflamed depression group (N=81 out of 206; 39%) had increased monocyte, CD4 + and neutrophil counts, increased C-reactive protein (CRP) and interleukin 6 (IL-6), and was more depressed than the uninflamed majority of cases. Relaxing the presumption of a binary classification, data-driven clustering identified four subgroups of MDD cases: two of these subgroups (N=38 and N=100; 67% collectively) were associated with increased inflammatory proteins and more severe depression, but differed from each other in the relative weighting of myeloid and lymphoid cell counts. Case-control and within-group results were robust to statistical control for the potentially confounding effects of age, sex, BMI, recent infection status, and tobacco use. Peripheral blood immunophenotyping can be used to identify a candidate cellular biomarker of inflamed depression, and to further decompose that binary partition, suggesting that there is more than one mechanistic pathway underlying inflamed depression. Lynall et al. Blood cell count-defined subgroups of depression 4

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Section: Neutrophil Abnormalities In Mddmentioning

confidence: 53%

Peripheral blood cell immunophenotyping reveals distinct subgroups of inflamed depression

Lynall

Turner

Bhatti

et al. 2019

Preprint

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“…Reduced sucrose preference is thought to represent a rodent measure of anhedonia (a reduced ability to experience joy or pleasure), which is a core diagnostic criterion of MDD (Kupfer, Frank, & Phillips, ; Pizzagalli, ). The reductions in bodyweight and sucrose preference resulting from exogenous CORT resemble clinical aspects of MDD—particularly MDD with melancholic features, a subtype of depression characterized by severe anhedonia, weight loss, and a prominent association with excess cortisol (Gold, ; Juruena et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the degree of cortisol normalization in patients with Cushing syndrome after treatment is correlated with the degree of improvement in depressive symptoms (Pivonello et al., ; Starkman, ). Excess cortisol and disruption of its normal circadian rhythm are some of the most commonly observed clinical features in depressed patients (Juruena, Bocharova, Agustini, & Young, ; Pariante & Lightman, ). The enormous public health burden of MDD (Ferrari et al., ) and the widespread use of high‐dose glucocorticoid therapies in the US (Gray, Kogan, Marrocco, & McEwen, ) indicate that the identification and characterization of specific neural pathways underlying the associations between glucocorticoid abnormalities and depressive symptoms may have significant clinical impact.…”

Section: Introductionmentioning

confidence: 99%

Selective vulnerability of dorsal raphe‐medial prefrontal cortex projection neurons to corticosterone‐induced hypofunction

Prouty

Chandler

Gao

et al. 2019

Eur J of Neuroscience

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Glucocorticoid hormones and serotonin (5‐HT) are strongly associated with the development and treatment of depression, respectively. Glucocorticoids regulate the function of serotonergic neurons in the dorsal raphe nucleus (DR), which are the major source of 5‐HT to the forebrain. DR 5‐HT neurons are electrophysiologically heterogeneous, though whether this phenotypic variation aligns with specific brain functions or neuropsychiatric disease states is largely unknown. The goal of this work was to determine if chronic exogenous glucocorticoid administration differentially affects the electrophysiological profile of DR neurons implicated in the regulation of emotion versus visual sensation by comparing properties of cells projecting to medial prefrontal cortex (mPFC) versus lateral geniculate nucleus (LGN). Following retrograde tracer injection into mPFC or LGN, male Sprague‐Dawley rats received daily injections of corticosterone (CORT) for 21 days, after which whole‐cell patch clamp recordings were made from retrogradely labeled DR neurons. CORT‐treatment significantly increased the action potential half‐width of LGN‐projecting DR neurons, but did not significantly affect the firing frequency or excitatory postsynaptic currents of these cells. CORT‐treatment significantly reduced the input resistance, evoked firing frequency, and spontaneous excitatory postsynaptic current frequency of mPFC‐projecting DR neurons, indicating a concurrent reduction of both intrinsic excitability and excitatory drive. Our results suggest that the serotonergic regulation of cognitive and emotional networks in the mPFC may be more sensitive to the effects of glucocorticoid excess than visual sensory circuits in the LGN and that reduced 5‐HT transmission in the mPFC may underlie the association between glucocorticoid excess and depression.

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“…Dexamethasone non-suppression can be considered the "intermediate phenotype" of human depression of melancholic type (Juruena et al, 2017). In addition to the HPA axis disturbances, hyper-responsiveness under stress of the serotonergic system has been noted (Froger et al, 2004;Linthorst et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders

Matrov

Kaart

Lanfumey

et al. 2019

Behavioural Brain Research

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The psychopathology of depression is highly complex and the outcome of studies on animal models is divergent. In order to find brain regions that could be metabolically distinctively active across a variety of mouse depression models and to compare the interconnectivity of brain regions of wild-type and such genetically modified mice, histochemical mapping of oxidative metabolism was performed by the measurement of cytochrome oxidase activity. We included mice with the heterozygous knockout of the vesicular glutamate transporter (VGLUT1 −/+ ), full knockout of the cannabinoid 1 receptor (CB1 −/− ), an anti-sense knockdown of the glucocorticoid receptor (GRi) and overexpression of the human 5-hydroxytryptamine transporter (h5-HTT). Altogether 76 mouse brains were studied to measure oxidative metabolism in one hundred brain regions, and the obtained dataset was submitted to a variety of machine learning algorithms and multidimensional scaling. Overall, the top brain regions having the largest contribution to classification into depression model were the lateroanterior hypothalamic nucleus, the anterior part of the basomedial amygdaloid nucleus, claustrum, the suprachiasmatic nucleus, the ventromedial hypothalamic nucleus, and the anterior hypothalamic area. In terms of the patterns of interregional relationship between wild-type and genetically modified mice there was little overall difference, while the most deviating brain regions were cortical amygdala and ventrolateral and ventral posteromedial thalamic nuclei. The GRi mice that most clearly differed from their controls exhibited deviation of connectivity for a number of brain regions, such as ventrolateral thalamic nucleus, the intermediate part of the lateral septal nucleus, the anteriodorsal part of the medial amygdaloid nucleus, the medial division of the central amygdaloid nucleus, ventral pallidum, nucleus of the vertical limb of the diagonal band, anteroventral parts of the thalamic nucleus and parts of the bed nucleus of the stria terminalis. Conclusively, the GRi mouse model was characterized by changes in the functional connectivity of the extended amygdala and stress response circuits. Cytochrome oxidase histochemistry cortex, CA1 field CA1 of hippocampus, CA2 field CA2 of hippocampus, CA3 field CA3 of hippocampus, FrA frontal association cortex, GP globus pallidus, IL infralimbic cortex, IPR interpeduncular nucleus rostral subnucleus, Lent lateral entorhinal cortex, LHb lateral habenular nucleus, LH lateral hypothalamic area, LO lateral orbital cortex, LPAG lateral periaqueductal gray, LPO lateral preoptic area, LSI lateral septal nucleus intermediate part, LA lateroanterior hypothalamic nucleus, LC locus coeruleus, MeAD medial amygdaloid nucleus anterior dorsal, MHb medial habenular nucleus, MM medial mammillary nucleus medial part, MO medial orbital cortex, MPA medial preoptic area, MPOM medial preoptic nucleus medial part, MS medial septal nucleus, MnPO median preoptic nucleus, MnR median raphe nucleus, MDL mediodorsal thalamic nucleus lateral pa...

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Atypical depression and non-atypical depression: Is HPA axis function a biomarker? A systematic review

Cited by 247 publications

References 91 publications

Peripheral blood cell immunophenotyping reveals distinct subgroups of inflamed depression

Peripheral blood cell immunophenotyping reveals distinct subgroups of inflamed depression

Selective vulnerability of dorsal raphe‐medial prefrontal cortex projection neurons to corticosterone‐induced hypofunction

Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders

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