Associations between short-chain fatty acid levels and mood disorder symptoms: a systematic review.

Background: Available evidence points to a possible role of Short Chain Fatty Acids (SCFAs) in mood disorders. This is the first systematic review to map the associations between SCFA levels and mood disorder symptoms.Methods: Following the PRISMA guidelines, the databases PubMed, Embase, and PsycINFO were searched for studies that assessed SCFA levels in human populations with mood disorder symptoms, or animal models of mood disorder. Risk of bias was assessed by the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) checklist.Results: 19 studies were included and could be divided into animal (n=8) and human studies (n=11), with the animal studies including 166 animals and 100 controls, and the human studies including 662 participants and 330 controls. The studies were characterized by heterogeneity and methodological challenges on multiple parameters, limiting the validity and transferability of findings. Notably, only two of the clinical studies assessed the presence of mood disorder with diagnostic criteria, and no studies of mania or bipolar disorder met the inclusion criteria.Discussion: Despite significant methodological limitations, associations between SCFA levels and depressive symptoms were reported in most of the studies. However, the direction of these associations and the specific SCFAs identified varied. The quantification of SCFA levels in mood disorders is an emerging yet sparsely studied research field. Although there is some evidence suggesting a link between SCFAs and depressive symptoms, the directionality of effects and mechanisms are unclear and the relation to manic symptoms is uninvestigated.

Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders: A randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Persistent cognitive impairment is frequent across bipolar disorder (BD) and major depressive disorder (MDD), highlighting an urgent need for pro-cognitive treatments. AIM: This study investigated effects of erythropoietin (EPO) on cognitive impairment and dorsal prefrontal cortex (dPFC) activity in affective disorders. METHODS: In this randomized, double-blinded, placebo-controlled trial, cognitively impaired patients with remitted BD or MDD received 1 weekly recombinant human EPO (40,000 IU/mL) or saline infusion for a 12-week period. Assessments were conducted at baseline, after 2 weeks of treatment (week 3), immediately after treatment (week 13) and at 6-months follow-up. Participants underwent functional MRI during performance on a n-back working memory (WM) task at baseline and week 3, and for a subgroup 6 weeks post-treatment (week 18). The primary outcome was a cognitive composite score at week 13, whereas secondary outcomes comprised sustained attention and functioning. WM-related dPFC activity was a tertiary outcome. RESULTS: Data were analysed for 101 of the 103 included patients (EPO, n = 58; saline, n = 43). There were no effects of EPO over saline on any cognitive or functional outcomes or on WM-related dPFC activity. CONCLUSIONS: The absence of treatment-related changes in cognition and neural activity was unexpected and contrasts with multiple previous preclinical and clinical studies. It is possible that the lack of effects resulted from a recent change in the manufacturing process for EPO. Nevertheless, the findings support the validity of dPFC target engagement as a biomarker model for pro-cognitive effects, according to which treatments that do not improve cognition should not modulate dPFC activity. TRIAL REGISTRATIONS: EudraCT no.: 2016-004023-24; ClinicalTrials.gov identifier: NCT03315897.

Electroencephalographic Parameters Differentiating Melancholic Depression, Non-melancholic Depression, and Healthy Controls. A Systematic Review.

Introduction: The objective of this systematic review was to investigate whether electroencephalographic parameters can serve as a tool to distinguish between melancholic depression, non-melancholic depression, and healthy controls in adults. Methods: A systematic review comprising an extensive literature search conducted in PubMed, Embase, Google Scholar, and PsycINFO in August 2020 with monthly updates until November 1st, 2020. In addition, we performed a citation search and scanned reference lists. Clinical trials that performed an EEG-based examination on an adult patient group diagnosed with melancholic unipolar depression and compared with a control group of non-melancholic unipolar depression and/or healthy controls were eligible. Risk of bias was assessed by the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) checklist. Results: A total of 24 studies, all case-control design, met the inclusion criteria and could be divided into three subgroups: Resting state studies (n = 5), sleep EEG studies (n = 10), and event-related potentials (ERP) studies (n = 9). Within each subgroup, studies were characterized by marked variability on almost all levels, preventing pooling of data, and many studies were subject to weighty methodological problems. However, the main part of the studies identified one or several EEG parameters that differentiated the groups. Conclusions: Multiple EEG modalities showed an ability to distinguish melancholic patients from non-melancholic patients and/or healthy controls. The considerable heterogeneity across studies and the frequent methodological difficulties at the individual study level were the main limitations to this work. Also, the underlying premise of shifting diagnostic paradigms may have resulted in an inhomogeneous patient population. Systematic Review Registration: Registered in the PROSPERO registry on August 8th, 2020, registration number CRD42020197472.