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Background: Depressed patients have an increased incidence of pain. A pathophysiological connection between depression and pain is still not revealed. Immunological activation has been found in both depression and pain. There are few studies of pain and immune activation in patients with depression, without inflammatory and autoimmune disorders., Methods: This is a naturalistic follow-up study of 50 patients with a major depressive disorder (MDD) depressive episode, without any inflammatory or autoimmune conditions. We have previously reported on the relationship between depression and cytokine levels. In this study, we obtained data of depression, pain and cytokine levels before and after 12 weeks of depression treatment. All patients were medication-free at inclusion., Results: At inclusion three out of four patients experienced pain, and the pain scores correlated with the depression scores. After treatment, as depression was relieved, the pain scores dropped significantly and were no longer correlated to the depression scores. There were no correlations between pain scores and cytokine levels. Pain level at inclusion did not correlate with depression treatment outcome., Conclusion: Our findings indicate that pain is a feature of depression. Pain levels and cytokine values didn't correlate. Pain at inclusion did not predict depression treatment outcome.

The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection., Methods: We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP., Results: Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen's d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10)., Conclusions: These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates., (© 2020. The Author(s).)

Background: Several lines of evidence show that the immune system is implicated in the pathophysiology of major depressive disorder (MDD) and that treatment with antidepressants affects cytokine and C-reactive protein (CRP) levels. Few studies have investigated immune markers during non-pharmacological treatment. In this follow-up study, we investigated whether CRP and elevated plasma cytokine levels observed before treatment of an acute episode of MDD are normalized during non-pharmacological treatment., Methods: We obtained clinical assessments and blood for CRP and cytokine analysis from 50 unmedicated MDD patients, and cytokine levels from healthy controls. The patients received 'therapy as usual' for 12 weeks, and the assessments were then repeated. Of the 43 completers, 29 patients did not receive medication., Results: In the patients receiving treatment without antidepressants, the depressive symptoms and the plasma levels of eight cytokines (interleukin (IL)-1Ra, IL-5,-6,-8,-10, G-CSF, IFN-γ, and TNF-α) were significantly reduced (P = 0.002-0.048). The cytokine levels were no longer different from the controls. The plasma CRP level did not change., Conclusion: Cytokine plasma levels normalized during recovery from an acute depressive episode in MDD without antidepressant treatment. These findings may have implications for the understanding of the role of the immune system in depression and recovery from depression., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It has been suggested that the development of depressive symptoms as a result of cytokine therapy is attributable to cytokine-induced elevated activity of the kynurenine pathway. The few studies of this mechanism in patients with common major depressive disorder (MDD) have yielded inconsistent results. The aim of the present study was to identify markers of the kynurenine pathway in a clinical MDD sample with increased cytokine levels., Methods: Fifty medication-free MDD patients with a depressive episode and 34 healthy controls were included at baseline; the patients were followed for 12 weeks. Before initiating treatment, the patients were diagnosed and assessed for depressive symptoms and their blood was analyzed for tryptophan and its metabolites in the kynurenine pathway. The clinical assessments and metabolite measurements were repeated after 12 weeks of "treatment as usual"., Results: We did not find significant elevation of kynurenine plasma markers in patients with a depressive episode compared to healthy controls, despite elevated cytokine levels in the patients. Clinical depression scores were significantly reduced after 12 weeks, but no significant change in the plasma kynurenine pathway plasma markers was observed., Conclusion: The obtained results do not support the hypothesis that MDD depressive episodes are associated with elevated activity in the kynurenine pathway. This suggests that the pathophysiology underlying depressive episodes in common MDD differs from that of interferon induced depression. Our results warrant further study of the interplay between the kynurenine pathway and the cytokine activation patterns in these conditions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Cytokines are implicated in the pathophysiology of major depressive disorder (MDD). However, the pattern of alterations in cytokine levels is still unclear. The current study investigated the plasma levels of a range of cytokines in a follow-up design, with the aim of determining their involvement in depression., Methods: Fifty medication-free MDD patients with a depressive episode and 34 healthy controls were included at baseline; the patients were followed up after 12 weeks. Before initiating treatment, the patients were diagnosed and assessed for depressive symptoms and blood for cytokine analysis was obtained. The same clinical assessments and cytokine measurements were performed after 12 weeks of "treatment as usual.", Results: The cytokines interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-5, IL-6, IL-7, IL-8, IL-10, granulocyte colony-stimulating factor (G-CSF), and interferon gamma (IFNγ) were significantly elevated (p=0.01-0.047) in depressed patients at baseline compared to healthy controls. After 12 weeks of treatment, the plasma levels of seven of these nine cytokines (IL-1Ra, IL-6, IL-7, IL-8, IL-10, G-CSF, and IFNγ had decreased significantly compared to baseline and did not differ from those in the healthy controls. The depressive symptoms were simultaneously significantly reduced. In addition, the reduction to normal cytokines levels occurred only in those who met the recovery criteria., Conclusion: A more general pattern of elevated cytokine levels is described herein relative to what has been described previously shown in MDD. Furthermore, recovery from depression was associated with reduction to normal levels of the majority of the measured cytokines. These results strongly support the notion that a complex network of cytokines is involved in the pathophysiology of MDD., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: We examined women with recurrent brief depression (RBD) with and without episodes of hypomania with an n-back working memory paradigm to assess how working memory load affects the neurological network corresponding to working memory for these groups., Method: Participants (n=33) were medication-free and mostly euthymic while performing a 1-back and a 2-back task in the fMRI scanner. Differential activation results between the tasks were assessed globally and within seven predefined regions of interest associated with working memory activation. The patient groups were compared with healthy women and matched for age, handedness, and length of education., Results: Poor task modulation was observed in both RBD groups in the prefrontal cortex (BA9) in the 1-back task and activation during the 2-back task, particularly in a subgroup with a history of brief hypomanic episodes (RBD-H) compared with the subgroup without such episodes (RBD-O). Task modulation in the right parahippocampal gyrus (BA27) distinguished the RBD-O group, and task modulation in the right insula clearly distinguished the RBD-H group., Limitations: Small sample size and recruitment of most patients through media that may induce a selection bias towards better-functioning subjects., Conclusion: The observed lack of deactivation within the right insula has also been reported in patients with bipolar I disorders. Activation differences in BA9 and the parahippocampal region between RBD patients with and without a history of hypomania suggest different functional hypersensitivity of early limbic regions and ability to sustain attention and working memory, respectively, possibly identifying functional differences between the two subgroups., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Clinical differences between independent and substance-induced (S-I) major depressive disorders (MDDs) in patients with substance use disorders (SUDs) are insufficiently studied., Methods: The catchment area sample consisted of 42 SUD patients with independent and/or S-I MDD (bipolar disorders excluded), admitted consecutively to addiction clinics or psychiatry departments (inpatient or outpatient) with no previous treatment history from specialized services. Assessments included the Psychiatric Research Interview for Substance and Mental Disorders (PRISM), the Structured Clinical Interview for DSM-IV, Axis II, Personality Disorders (SCID-II), the Inventory of Depressive Symptoms (IDS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Symptom Check List, 90 questions, revised (SCL-90-R)., Results: Of the 42 SUD patients, 48% had independent MDD episode(s) only, 24% had S-I MDD episode(s) only, and 28% had both independent and S-I MDD episodes. Insomnia, psychomotor agitation, concentration and decision problems, melancholic features, higher total MDD symptom count, longer time being depressed, higher mean score on the Montgomery-Asberg Depression Rating Scale, and shorter duration of SUDs characterized independent MDDs., Limitations: Small sample size with risk of type II error., Conclusions: Independent MDDs were more severe and had different qualities compared with S-I MDDs, suggesting important treatment implications. Longitudinal studies including larger samples and carefully addressing the association between SUD subtypes and MDD subtypes are needed to substantiate our findings., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: We compared the temperament and character profiles of 21 patients with bipolar II disorder, 40 patients with recurrent brief depression (RBD; at least monthly depressive episodes meeting the diagnostic criteria for major depressive episode except for duration that is less than 2 weeks, typically 2-3 days, without fixed relation to menstrual cycle) of which 21 had no history of hypomania and 19 had experienced hypomanic episodes, and 21 age- and sex-matched controls., Methods: Assessments included the Montgomery-Åsberg Depression Rating Scale, Hypomania Checklist, and Temperament and Character Inventory-125. Patients with cluster A and B personality disorders were excluded., Results: Bipolar II and RBD patients had higher harm avoidance (HA) and lower self-directedness (SD) compared with controls. Excluding panic disorder comorbidity effaced this difference in HA and SD (bipolar II only) and harm avoidance. No other differences were found., Conclusions: In this first study comparing personality profiles of patients with bipolar II vs RBD, when controlling for confounders, neither bipolar II nor RBD patients differed significantly from healthy controls. The lower SD scores among RBD patients may reflect sampling bias (a higher rate of Axis 2 cluster C disorders)., (Copyright © 2010 Elsevier Inc. All rights reserved.)