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Abstract Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies’ findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond “total score” depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.

Background Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs). Aims We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms. Method This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n = 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or

Background Studies about brain structure in bipolar disorder have reported conflicting findings. These findings may be explained by the high degree of heterogeneity within bipolar disorder, especially if structural differences are mapped to single brain regions rather than networks. Aims We aim to complete a systematic review and meta-analysis to identify brain networks underlying structural abnormalities observed on T1-weighted magnetic resonance imaging scans in bipolar disorder across the lifespan. We also aim to explore how these brain networks are affected by sociodemographic and clinical heterogeneity in bipolar disorder. Method We will include case–control studies that focus on whole-brain analyses of structural differences between participants of any age with a standardised diagnosis of bipolar disorder and controls. The electronic databases Medline, PsycINFO and Web of Science will be searched. We will complete an activation likelihood estimation analysis and a novel coordinate-based network mapping approach to identify specific brain regions and brain circuits affected in bipolar disorder or relevant subgroups. Meta-regressions will examine the effect of sociodemographic and clinical variables on identified brain circuits. Conclusions Findings from this systematic review and meta-analysis will enhance understanding of the pathophysiology of bipolar disorder. The results will identify brain circuitry implicated in bipolar disorder, and how they may relate to relevant sociodemographic and clinical variables across the lifespan.

Abstract Background Evidence-based psychotherapies available to treat patients with bipolar disorders (BD) are limited. Dialectical behavior therapy (DBT) may target several common symptoms of BD. We conducted a systematic review on the efficacy of DBT for mood symptoms in patients with BD. The systematic search used key words related to DBT and BD in Medline, Embase, PsycInfo, CINAHL, and Cochrane Library databases from 1980 to April 1st, 2022. We included studies that enrolled patients with a BD I or II diagnosis (DSM or ICD), age 12 and older who received a DBT-based intervention. Studies reviewed were clinical trials including observational studies that reported at least one outcome related to BD mood symptoms or severity. We did not exclude based upon psychiatric or physical co-morbidity. Results We screened 848 abstracts and reviewed 28 full texts; 10 publications with 11 studies met our pre-determined eligibility criteria. All but one were feasibility pilot studies and most included participants in all mood states except for mania. The studies provided preliminary evidence suggesting these interventions may be effective for improving several core symptoms of BD. Overall, all the studies consistently supported that DBT-based interventions are feasible and acceptable for patients with BD. Conclusion DBT may be an effective treatment for BD; however, the confidence in this conclusion is limited by the small sample sizes, heterogeneity, and high risk of bias in all published trials. Larger well-designed RCTs are now required to establish the effectiveness of DBT in BD.

Background Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone. Aims To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone). Method In a 4-week, three-arm, ‘double dummy’ trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure. Results This trial will advance the understanding of psilocybin's mechanism of antidepressant action. Conclusions This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.

(1) Background: Approximately one-third of patients with bipolar disorder (BD) do not experience sustained remission with current treatments. Presently, astrocytes, i.e., glial cells that act as key regulators of neuroinflammation, have been a target for therapeutic development. Research regarding their role in the neuropathology of BD is limited. We conducted a scoping review on evidence linking astrocytes to the pathology of BD. (2) Methods: The search was conducted in MEDLINE for studies published from inception to August 2022. Studies of interest were data-extracted and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. (3) Results: Overall, 650 publications were identified, of which 122 full texts were evaluated and 12 included. Four were in vitro, seven were ex vivo, and one study was both in vitro and in vivo. In vitro investigations focused on plasma levels of neuroinflammatory biomarkers S100B and glial fibrillary acidic protein (GFAP). Ex vivo investigations were post-mortem brain studies assessing astrocytes in regions of interest (i.e., anterior cingulate cortex, dorsolateral prefrontal cortex) using phosphorylated GFAP and ASCT-1. The in vivo and in vitro study evaluated morphological and chemical variations of YKL-40 between cohorts. (4) Conclusions: Reports indicate an association between astrocyte dysfunction and BD although larger studies are required to validate this association.

Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The objectives of this scoping review were to synthesize evidence on the impact on mood symptoms of lipid lowering agents and anti-diabetics drugs, while also reviewing current knowledge on the association between mood disorders and dyslipidemia or hyperglycemia. We propose that metabolic dysfunction is prevalent in both MDD and BD and it may contribute to the development of these disorders through a variety of pathophysiological processes including inflammation, brain structural changes, hormonal alterations, neurotransmitter disruptions, alteration on brain cholesterol, central insulin resistance, and changes in gut microbiota. Current evidence is conflicting on the use of statins, polyunsaturated fatty acids, thiazolidinediones, glucagon-like peptide agonists, metformin, or insulin for the treatment of MDD and BD. Given the paucity of high-quality randomized controlled trials, additional studies are needed before any of these medications can be repurposed in routine clinical practice. Future trials need to enrich patient recruitment, include evaluations of mechanism of action, and explore differential effects on specific symptom domains such as anhedonia, suicidality, and cognition.

BackgroundPsychiatric inpatients often have limited access to psychotherapeutic education or skills for managing anxiety, a common transdiagnostic concern in severe and acute mental illness. COVID-19–related restrictions further limited access to therapy groups on inpatient psychiatric units. App-based interventions may improve access, but evidence supporting the feasibility of their use, acceptability, and effectiveness in psychiatric inpatient settings is limited. MindShift CBT is a free app based on cognitive behavioral therapy principles with evidence for alleviating anxiety symptoms in the outpatient setting. ObjectiveWe aimed to recruit 24 participants from an acute general psychiatric inpatient ward to a 1-month randomized control study assessing the feasibility and acceptability of providing patients with severe and acute mental illness access to the MindShift CBT app for help with managing anxiety symptoms. MethodsRecruitment, data collection, analysis, and interpretation were completed collaboratively by clinician and peer researchers. Inpatients were randomized to two conditions: treatment as usual (TAU) versus TAU plus use of the MindShift CBT app over 6 days. We collected demographic and quantitative data on acceptability and usability of the intervention. Symptoms of depression, anxiety, and psychological distress were measured in pre- and poststudy surveys for preliminary signals of efficacy. We conducted individual semistructured interviews with participants in the MindShift CBT app group at the end of their trial period, which were interpreted using a standardized protocol for thematic analysis. ResultsOver 4 weeks, 33 inpatients were referred to the study, 24 consented to participate, 20 were randomized, and 11 completed the study. Of the 9 randomized participants who did not complete the study, 7 were withdrawn because they were discharged or transferred prior to study completion, with a similar distribution among both conditions. Among the enrolled patients, 65% (13/20) were admitted for a psychotic disorder and no patient was admitted primarily for an anxiety disorder. The average length of stay was 20 days (SD 4.4; range 3-21) and 35% (7/20) of patients were involuntarily admitted to hospital. Small sample sizes limited accurate interpretation of the efficacy data. Themes emerging from qualitative interviews included acceptability and usability of the app, and patient agency associated with voluntary participation in research while admitted to hospital. ConclusionsOur study benefitted from collaboration between peer and clinician researchers. Due to rapid patient turnover in the acute inpatient setting, additional flexibility in recruitment and enrollment is needed to determine the efficacy of using app-based psychotherapy on an acute psychiatric ward. Despite the limited sample size, our study suggests that similar interventions may be feasible and acceptable for acutely unwell inpatients. Further study is needed to compare the efficacy of psychotherapeutic apps with existing standards of care in this setting. Trial RegistrationClinicalTrials.gov NCT04841603; https://clinicaltrials.gov/ct2/show/NCT04841603

Introduction The high placebo response in depression treatment trials is a major contributing factor for randomised control trial failure to establish efficacy of novel or repurposed treatments in treatment-resistant depression (TRD) and major depressive disorder in general. Though there have been a number of meta-analyses and primary research studies evaluating the placebo response in non-TRD, placebo response in TRD is poorly understood. It is important to understand the placebo response of TRD as treatments are only moderately effective and up to 1/3 of patients will experience TRD.Methods and analysis We will conduct a search of electronic databases (MEDLINE and PsychINFO) from inception to 24th January 2020 including randomised, placebo-controlled trials of pharmacological, somatic and psychological interventions for adults with TRD. TRD will be defined as a failure to respond to at least two interventions of adequate dose or duration. We will also search reference lists from review articles. We will perform several meta-analyses to quantify the placebo response for each treatment modality. Regression analysis will explore potential contributing demographic and clinical variables to the placebo response. We will use Cochrane risk of bias tool.Ethics and dissemination There is no research ethics board approval required. The dissemination plan is to publish results in a peer-reviewed academic journal.PROSPERO registration number 190 465.