Deficits of social cognition in bipolar disorder: Systematic review and meta-analysis.

BACKGROUND: The association between impaired social cognition and bipolar disorder (BD) is well established. However, to our knowledge, there has not been a recent systematic review that characterizes disparate dimensions of social cognition in BD. Herein, this systematic review and meta-analysis aimed to synthesize the literature on core aspects of social cognition (i.e., Theory of Mind, emotion recognition, and social judgment) to identify potential areas of impairment. METHODS: Online databases (i.e., PubMed, Cochrane Libraries, PsycINFO) and Google Scholar were searched from inception to May 2021. Studies with populations ages ≥16 with DSM-IV or DSM-5 defined BD (I or II) either in a euthymic or symptomatic state were included. The risk of bias was measured using the ROBINS-1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively measured by synthesizing Hedge's g effect sizes through a random effects meta-analytic approach. RESULTS: A total of 29 studies were included in the final review (i.e., 12 studies on the Theory of Mind, 11 on emotion recognition, and 6 on social judgment). Overall, results demonstrated social cognition to be moderately impaired in individuals with BD (d = 0.59). The individual domains ranged in effect size (0.38 < d < 0.70), providing evidence for variation in impairment within social cognition. DISCUSSION: Individuals with BD exhibit clinically significant deficits in social cognition during euthymic and symptomatic states. Social cognition impairments in individuals with BD are an important therapeutic target for treatment discovery and development.

Association of current and remitted bipolar disorders with health-related quality of life: Findings from a nationally representative sample in the US.

BACKGROUND: The associations of current and remitted bipolar disorder (BD) with health-related quality of life (HRQOL) have been under-studied, and we aim to address these gaps. METHODS: The 2012-2013 National Epidemiological Survey on Alcohol and Related Conditions III (NESARC III) surveyed a nationally representative sample of non-institutionalized adults in the US. Using DSM-5 criteria, three groups were operationalized as: 1) adults who met criteria for BD in the past year (i.e., current BD; n = 566 unweighted); and 2) adults who met criteria for BD previously but not in the past year (i.e., BD in remission; n = 187); and 3) adults with no BD in their lifetime (n = 35,556). HRQOL and quality-adjusted life years (QALYs) were compared by these groups. Multivariable-adjusted regression analyses were used to adjust for and examine the role of covariates. RESULTS: Overall, 1.5 % of the study sample, representing 3.6 million adults nationwide, met criteria for current BD, and 0.5 %, representing 1.3 million adults, met criteria for BD in remission. Adults with current BD and BD in remission had lower mental HRQOL and QALYs, as compared to adults who never had BD. However, these differences were no longer significant when adjusted for behavioral co-morbidities (e.g., psychiatric and substance use disorders). CONCLUSION: Both current BD and BD in remission were adversely associated with HRQOL and QALYs, while these associations were not independent of behavioral co-morbidities. Because behavioral co-morbidities are common in individuals with current BD or those with BD in remission, they should be treated together to improve HRQOL.

Evaluating Anhedonia as a risk factor in suicidality: A meta-analysis.

Previous studies have evaluated the relationship between anhedonia and suicidality; however, to our knowledge, there has been no quantitative synthesis evaluating the foregoing association to date. Herein, this meta-analysis aims to provide a quantitative synthesis of the extant literature reporting on the association between levels of anhedonia across all dimensions (e.g., anticipatory, consummatory) amongst individuals endorsing suicidality. Online databases (i.e., PubMed, PsycINFO, Google Scholar) were searched from inception to 13 June 2022. Studies which assessed an aspect of suicidality (i.e., ideation, attempts) and a validated anhedonia scale were included. The risk of bias was assessed using the ROBINS-1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively synthesized using Pearson's r effect sizes via a random-effects meta-analysis. A total of 20 studies and 11,212 individuals were included in the final quantitative synthesis. Overall, results indicate that anhedonia has a significant and moderate correlation with suicidality in general and psychiatric populations (r = 0.31, p < 0.001 and r = 0.32, p < 0.001 respectively). Sub-analysis suggests a larger effect of anticipatory and consummatory interpersonal anhedonia (r = 0.40, p < 0.001). The identification of increased levels of anhedonia in individuals with suicidality indicates that anhedonia may be a core risk factor for suicidal ideation and behaviours. Future studies should endeavour to develop a comprehensive risk assessment encompassing all domains of anhedonia which can be utilized in a primary care setting as a potential prevention strategy for suicidal behaviours and outcomes.

Efficacy, safety, and tolerability of ulotaront (SEP-363856, a trace amine-associated receptor 1 agonist) for the treatment of schizophrenia and other mental disorders: a systematic review of preclinical and clinical trials.

INTRODUCTION: Schizophrenia is a mental illness that can disrupt emotions, perceptions, and cognition and reduce quality of life. The classical approach to treat schizophrenia is to use typical and atypical antipsychotics; however, limitations include low efficacy in mitigating negative symptoms and cognitive dysfunctions and a range of adverse effects. Evidence has accumulated on trace amine-associated receptor 1 (TAAR1) as a novel therapeutic target for treating schizophrenia. This systematic review investigates the available evidence on a TAAR1 agonist, ulotaront, as a treatment for schizophrenia. METHODS: A systematic search was conducted on PubMed/MEDLINE and Ovid databases for English-published articles from inception to 18 December 2022. The literature focusing on the association between ulotaront and schizophrenia was evaluated based on an inclusion/exclusion criterion. Selected studies were assessed for the risk of bias, using the Cochrane Collaboration tool, and summarized in a table to generate discussion topics. RESULTS: Three clinical, two comparative, and five preclinical studies examining ulotaront's pharmacology, tolerability and safety, and/or efficacy were identified. Results indicate that ulotaront has a differing adverse effect profile from other antipsychotics, may mitigate metabolic-related adverse effects commonly associated with antipsychotics, and may be effective for treating positive and negative symptoms. CONCLUSIONS: Findings from the available literature present ulotaront as a potential and promising alternative treatment method for schizophrenia. Despite this, our results were limited due to the lack of clinical trials on ulotaront's long-term efficacy and mechanisms of action. Future research should focus on these limitations to elucidate ulotaront's efficacy and safety for the treatment of schizophrenia and other mental disorders with similar pathophysiology.

Olanzapine and samidorphan combination treatment: A systematic review.

INTRODUCTION: The overarching aim of this review is to synthesize the efficacy, tolerability, and weight-mitigation effects of the olanzapine/samidorphan (OLZ/SAM) combination treatment in adults with schizophrenia and bipolar disorder-I. METHODS: A systematic search of PubMed, Web of Science, Embase, and The Cochrane Library was conducted on August 15th, 2021. Studies were included if they investigated the use of OLZ/SAM treatment in patients with schizophrenia or bipolar disorder-I, and reported the clinical outcomes: efficacy, change in weight or waist circumference, tolerability, pharmacokinetics, or change in metabolic parameters. A narrative synthesis was undertaken of the data. RESULTS: Eight studies met the inclusion criteria. All identified studies were conducted in adults with schizophrenia. Compared to OLZ-monotherapy, OLZ/SAM was associated with decreased odds of developing clinically significant (>10%) weight gain (OR=0.50, 95% CI:0.31,0.80; p= 0.003) and increase in waist circumference (risk difference = -17.1% 95% CI:-26.3,-7.8) from baseline measurements respectively. In another study, OLZ was 2.7 times more associated with clinically significant weight gain as compared to OLZ/SAM (OR=2.73, 95% CI:1.11, 6.67; p = 0.023). The clinical efficacy of OLZ/SAM remained similar to OLZ with improved tolerability in both short- and long-term studies with no significantly altered pharmacokinetic properties of the constituent agents. CONCLUSION: OLZ/SAM-treatment is associated with mitigated weight-gain liability when compared to OLZ-monotherapy in adults with schizophrenia. Additional studies are needed to ascertain patient acceptability, appropriate selection and sequencing of OLZ/SAM in the treatment algorithms for adults with schizophrenia (and BD-I), as well as to determine cost-effectiveness and long-term metabolic effects.

Immune response to vaccination in adults with mental disorders: A systematic review.

BACKGROUND: Mental disorders are associated with immune dysregulation as measured by serum levels of biological markers of immunity. Adults with mental disorders have also been reported to have attenuated post vaccine immune response. The COVID-19 pandemic has invited the need to determine whether individuals with mental disorders exhibit differential immune response following the administration of vaccines for other infections. METHODS: A systematic search of MEDLINE, Embase, Cochrane, and PsycInfo was conducted from inception to May 2021 investigating vaccine response in persons with mental disorders, as measured by biological markers of immunity (i.e., antibodies, cytokines). RESULTS: Thirteen articles were identified which evaluated vaccine efficacy in persons with mental disorders. Individuals with major depressive disorder (MDD) or schizophrenia revealed attenuated immune response to vaccination, or no statistical difference compared to control subjects. Individuals with anorexia nervosa or post-traumatic stress disorder (PTSD) displayed no attenuated post-vaccination antibody level. Individuals with insomnia displayed lower levels of antibodies after vaccination, whereas individuals with obstructive sleep apnea (OSA) displayed no difference in vaccine response compared to control subjects. LIMITATIONS: The limitations of this review include the relatively few articles included (n = 13) and small sample sizes (less than thirty subjects) in the majority of articles. CONCLUSION: Vaccine response in adults with a mental disorder remains inconclusive. Notwithstanding the heterogeneity and relatively small number of studies, available evidence does suggest attenuated immune response across disparate vaccinations. Future research is required to confirm vaccine efficacy in persons with mental disorders, especially regarding immune responses to COVID-19 vaccination.

The efficacy and safety of adjunctive intranasal esketamine treatment in major depressive disorder: a systematic review and meta-analysis.

INTRODUCTION: Intranasal (IN) esketamine represents an innovative treatment for individuals with treatment resistant depression and depression with suicidal ideation and behavior. Herein, we synthesize extant long-term studies (≥ 4 weeks) regarding this treatment. RESEARCH DESIGN AND METHODS: The interventional studies of IN esketamine in patients with depression having a study period of at least four weeks were included for our synthesis. A meta-analysis was undertaken for the efficacy and safety parameters of adjunctive IN esketamine vs IN placebo with an oral antidepressant. The data excluded from meta-analysis were synthesized narratively. RESULTS: After pooling data from seven randomized controlled trials, treatment with adjunctive IN esketamine vs IN placebo was safe overall, and more effective at decreasing depressive symptoms (d = -0.239; 95%CI = -0.335,-0.142;p < 0.0001), with higher response (RR = 1.221; 95% CI = 1.055,1.428; p = 0.017) and remission (RR = 1.366; 95% CI = 1.182,1.578; p < 0.0001) rates. The year-long trials showed that treatment with adjunctive IN esketamine led to lower relapse rates with no considerable long-term side effects. CONCLUSION: Intranasal esketamine was demonstrated to be safe, well tolerated, and rapidly effective in individuals with treatment resistant depression, suicidal ideation, and suicidal behavior.

Hallucinogen persisting perceptual disorder: a scoping review covering frequency, risk factors, prevention, and treatment.

INTRODUCTION: Hallucinogen persisting perception disorder (HPPD) affects a subset of persons who use hallucinogens and is defined as the repeated experience of hallucinations and other perceptual disturbances as a result of prior intoxications. As select hallucinogens are under development for the treatment of selectmental disorders, there is a need to better characterize this disorder. AREAS COVERED: A scoping review of the literature on HPPD was completed from inception to July 2021. Topics covered in the review herein include treatments for HPPD, prevalence or incidence data on HPPD among different classes of hallucinogens, risk factors for HPPD, and data pertaining to the pathophysiology of HPPD. EXPERT OPINION: Hallucinogen persisting perception disorder appears to be an uncommon yet serious event associated with prior hallucinogen exposure. The renewed interest in psychedelics as potential treatment options for select mental disorders, especially agents with hallucinogenic potential, provides the impetus to characterize HPPD in its frequency, risk and protective factors, key characteristics, as well as other clinical and treatment-related factors.

Evaluating cognitive function in unaffected relatives of individuals with bipolar disorders: A meta-analysis.

BACKGROUND: Available studies have evaluated cognition in the unaffected relatives of bipolar disorder patients; however, to our knowledge, there has been no quantitative analysis evaluating the foregoing association. Herein, this meta-analysis aims to provide a quantitative synthesis of the extant literature reporting on the association between performance in cognitive domains (i.e., executive function, attention, learning and memory or global cognition) amongst unaffected individuals of probands with bipolar disorders. METHODS: Online databases (i.e., PubMed, PsycINFO) and Google Scholar were searched from inception to 20 September 2021. Studies with unaffected, first-degree relatives of individuals with DSM-IV or DSM-5 defined bipolar disorders were included. The risk of bias was assessed using the ROBINS-1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively synthesized using Cohen's d effect sizes via a random-effects meta-analytic approach on JASP. RESULTS: A total of 15 studies were included in the final review. Overall, results indicate that cognitive performance across all domains is moderately impaired in unaffected relatives of individuals with bipolar disorders (d = 0.488). Sub-analysis suggests there is a higher level of impairment in executive functioning (d = 0.612). DISCUSSION: The identification of cognitive deficits in unaffected relatives of probands with bipolar disorders indicates that cognitive impairment is endophenotypic and a core disturbance in persons with bipolar disorders; future studies should endeavour to target cognition as a potential pre-emptive and prevention strategy of bipolar disorders.