Neurocognitive correlates of metabolic dysregulation in individuals with mood disorders: a systematic review and meta-analysis.

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition.

The EvalUation of goal-diRected activities to prOmote well-beIng and heAlth (EUROIA) scale: Psychometric evaluation with Confirmatory Factor Analysis.

OBJECTIVES: While state-based models of health-related quality of life (HRQL) are well-established in providing clinically relevant descriptions of HRQL status, they do not provide information on how to maintain or improve HRQL. The EvalUation of goal-diRected activities to prOmote well-beIng and heAlth (EUROIA), rooted in a novel process-based model of HRQL, measures goal-directed activities that are self-reported to promote HRQL as part of an individual's process of adapting to dynamic changes in health status. Our objectives were to condense and summarize the psychometric properties of the EUROIA by (i) defining and confirming its factor structure, (ii) evaluating its construct validity, and (iii) examining its internal consistency. METHODS: Principal component analysis was performed on the 18-item EUROIA to explore the underlying factor structure and condense the scale. Confirmatory factor analysis was conducted on the revised 14-item, 4-factor structure EUROIA instrument to evaluate the model fit. Data was obtained from adult participants with a diagnosis of chronic heart failure or advanced chronic kidney disease from 3 hospitals in Toronto, Canada. RESULTS: The revised 14-item EUROIA demonstrated 4 dimensions-Social Affiliation, fulfillment of Social Roles and Responsibilities, Self-Affirmation, and Eudaimonic Well-being-with a Cronbach's alpha of 0.83, representing good internal consistency. Our confirmatory factor analysis final model achieved good overall model fit: (χ2 / df = 1.80; Tucker-Lewis index = 0.90; comparative fit index = 0.93; standardized root-mean-square residual = 0.06; root-mean-square error of approximation = 0.06). All items exhibited a factor loading greater than λ > 0.4 and p < 0.001. CONCLUSION: The EUROIA holds clinical potential in its ability to provide informed feedback to patients on how they might maintain or modify their use of goal-directed activities to maintain and optimize perceived well-being.

Promising translatable pharmacological interventions for body weight management in individuals with severe mental illness - a narrative review.

INTRODUCTION: Psychotropic medications, especially antipsychotics, have been consistently shown to cause weight gain in individuals with severe mental illness (SMI), a population inherently challenged by poor physical health. Consequently, compared to the general population, this contributes to an increased cardiometabolic burden, including the risk of type 2 diabetes, dyslipidemia, and hypertension. Furthermore, comorbid obesity leads to treatment nonadherence, decreased quality of life, and increased risk of relapse, posing a challenge in the management of mental health. To address this, emerging agents investigated in the general population with potential to mitigate weight gain were explored to assess translatability to the SMI population. AREAS COVERED: A literature search was conducted including agents approved for the management of obesity in the general population, along with upcoming agents under investigation in phase III trials with weight loss properties. EXPERT OPINION: Metformin and topiramate along with lifestyle interventions are commonly prescribed for weight gain in individuals with SMI; however, their weight loss potential is modest at best. This review identified tirzepatide and cagrilintide-semaglutide among others as promising agents for adjunctive pharmacological management of weight gain.

Antipsychotic-Induced Weight Gain in Severe Mental Illness: Risk Factors and Special Considerations.

PURPOSE OF REVIEW: Weight gain is a disconcerting issue experienced by patients treated with antipsychotics (APs). This review summarizes current knowledge on the prevalence, etiology, and risk factors for antipsychotic-induced weight gain (AIWG), and evidence for interventions, including special considerations. RECENT FINDINGS: Predisposing risk factors for AIWG include lack of prior AP exposure, sex, and age. AP dose and duration of exposure are additional treatment-related factors that may contribute to this issue. Among current approaches to target AIWG, metformin has the most evidence to support its use, and this is increasingly reflected in clinical guidelines. While lifestyle approaches are recommended, cost-effectiveness and scalability represent limitations. More research is needed to identify newer treatment options and inform clinical recommendations for AIWG. Concerns around scope of practice in psychiatry to address AIWG and related comorbidities will require enhanced training opportunities and interdisciplinary collaborations, as well as updated position statements/practice guidelines emphasizing prevention.

Outcomes and clinical implications of intranasal insulin on cognition in humans: A systematic review and meta-analysis.

BACKGROUND: Aberrant brain insulin signaling has been posited to lie at the crossroads of several metabolic and cognitive disorders. Intranasal insulin (INI) is a non-invasive approach that allows investigation and modulation of insulin signaling in the brain while limiting peripheral side effects. OBJECTIVES: The objective of this systematic review and meta-analysis is to evaluate the effects of INI on cognition in diverse patient populations and healthy individuals. METHODS: MEDLINE, EMBASE, PsycINFO, and Cochrane CENTRAL were systematically searched from 2000 to July 2021. Eligible studies were randomized controlled trials that studied the effects of INI on cognition. Two independent reviewers determined study eligibility and extracted relevant descriptive and outcome data. RESULTS: Twenty-nine studies (pooled N = 1,726) in healthy individuals as well as those with Alzheimer's disease (AD)/mild cognitive impairment (MCI), mental health disorders, metabolic disorders, among others, were included in the quantitative meta-analysis. Patients with AD/MCI treated with INI were more likely to show an improvement in global cognition (SMD = 0.22, 95% CI: 0.05-0.38 p = <0.00001, N = 12 studies). Among studies with healthy individuals and other patient populations, no significant effects of INI were found for global cognition. CONCLUSIONS: This review demonstrates that INI may be associated with pro-cognitive benefits for global cognition, specifically for individuals with AD/MCI. Further studies are required to better understand the neurobiological mechanisms and differences in etiology to dissect the intrinsic and extrinsic factors contributing to the treatment response of INI.

Pharmacological Interventions for the Prevention of Antipsychotic-Induced Weight Gain in People With Schizophrenia: A Cochrane Systematic Review and Meta-Analysis.

Patients with schizophrenia are burdened by higher rates of obesity, cardiovascular disease and reduced life expectancy than the general population. In addition to illness, genetic and lifestyle factors, the associated weight gain and metabolic adverse effects of antipsychotic (AP) medications are known to exacerbate and accelerate these cardiometabolic problems significantly. Given the detrimental consequences of weight gain and other metabolic disturbances, there is an urgent need for safe and effective strategies to manage these issues as early on as possible. This review summarizes the literature of adjunctive pharmacological interventions aimed at preventing AP-induced weight gain.

Addressing Metabolic Comorbidity in Individuals With Intellectual and Developmental Disability on Antipsychotics: A Clinical Case Series.

PURPOSE/BACKGROUND: Individuals with intellectual and developmental disabilities (IDDs) are at increased risk for serious metabolic comorbidities, which is further exacerbated by the high rate of antipsychotic use in this population. There is currently a lack of literature on effective treatment options for antipsychotic-induced weight gain and metabolic abnormalities in IDD. This case series reports on the clinical use of metformin in patients with IDD on antipsychotics. METHODS/PROCEDURES: We conducted a retrospective review of patients in a novel clinical service at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada for adults with IDD experiencing antipsychotic-related weight gain and other metabolic aberrations. Charts were reviewed for weight and other metabolic outcome measures before and after commencing metformin treatment. FINDINGS/RESULTS: In 11 patients referred to this clinic, the mean weight loss while on metformin treatment was 11.1 kg, with over 50% of the sample achieving clinically meaningful weight loss of >7%. Additional adaptive changes were observed for fasting glucose, glycated hemoglobin, triglyceride, and high-density lipoprotein cholesterol levels. IMPLICATIONS/CONCLUSIONS: In line with its use in severe mental illness, metformin may be a safe, effective, and accessible treatment option for patients with IDD experiencing metabolic adverse effects of antipsychotic medication. Further research and randomized controlled trials are needed to examine the efficacy of metformin in this population.

Investigating the effects of antipsychotics on brain insulin action: Study protocol for a multi-modality magnetic resonance imaging (MRI) study in healthy controls.

Antipsychotics (APs) are the cornerstone of treatment for schizophrenia (SCZ) but are unfortunately associated with serious metabolic adverse effects including weight gain and type 2 diabetes. The pathophysiology of AP-induced metabolic dysfunction is largely undetermined. Brain insulin resistance has been posited to be at the cross-roads of many cognitive and metabolic disorders, and disruption of central insulin action has emerged as a possible explanatory mechanism underlying AP induced metabolic dysfunction. Previous studies suggest that change in neuroimaging-based parameters with intranasal insulin administration can be leveraged to investigate brain insulin resistance. In this proof-of-concept study, we will utilize neural signatures of insulin action in the brain to examine if APs disrupt brain insulin signaling. It is hypothesized that: 1) intranasal insulin (INI), but not intranasal placebo (INP), will change cerebral blood flow and resting state connectivity, as well as increase glutamate levels in the striatum and dorsolateral prefrontal cortex; 2) oral olanzapine (OLA), but not oral placebo (PL), will inhibit the effect of INI on these parameters. Thirty-two healthy volunteers will undergo a single blind, cross-over design, wherein all participants receive the following four treatment combinations, 2-6 weeks apart, in a random sequence: INP + PL, INP + OLA, INI + PL, and INI + OLA. Participants will undergo an MRI-based assay of brain insulin resistance 15 minutes after administering 160 IU INI or INP. The scanning protocol includes resting and task-based functional MRI, arterial spin labelling, and proton magnetic resonance spectroscopy. Demonstrating that OLA can acutely induce brain insulin resistance is clinically relevant to metabolic health in SCZ. Evidence of brain insulin resistance induced by acute AP dosing can inform the early use of adjunctive insulin sensitizers for the treatment of metabolic comorbidities associated with AP treatment in severe mental illness. Trial registration ClinicalTrials.gov Registration: NCT03741478.

Pharmacological interventions for prevention of weight gain in people with schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain is an extremely common problem in people with schizophrenia and is associated with increased morbidity and mortality. Adjunctive pharmacological interventions may be necessary to help manage antipsychotic-induced weight gain. This review splits and updates a previous Cochrane Review that focused on both pharmacological and behavioural approaches to this problem. OBJECTIVES: To determine the effectiveness of pharmacological interventions for preventing antipsychotic-induced weight gain in people with schizophrenia. SEARCH METHODS: The Cochrane Schizophrenia Information Specialist searched Cochrane Schizophrenia's Register of Trials on 10 February 2021. There are no language, date, document type, or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that examined any adjunctive pharmacological intervention for preventing weight gain in people with schizophrenia or schizophrenia-like illnesses who use antipsychotic medications. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed the quality of included studies. For continuous outcomes, we combined mean differences (MD) in endpoint and change data in the analysis. For dichotomous outcomes, we calculated risk ratios (RR). We assessed risk of bias for included studies and used GRADE to judge certainty of evidence and create summary of findings tables. The primary outcomes for this review were clinically important change in weight, clinically important change in body mass index (BMI), leaving the study early, compliance with treatment, and frequency of nausea. The included studies rarely reported these outcomes, so, post hoc, we added two new outcomes, average endpoint/change in weight and average endpoint/change in BMI. MAIN RESULTS: Seventeen RCTs, with a total of 1388 participants, met the inclusion criteria for the review. Five studies investigated metformin, three topiramate, three H2 antagonists, three monoamine modulators, and one each investigated monoamine modulators plus betahistine, melatonin and samidorphan. The comparator in all studies was placebo or no treatment (i.e. standard care alone). We synthesised all studies in a quantitative meta-analysis. Most studies inadequately reported their methods of allocation concealment and blinding of participants and personnel. The resulting risk of bias and often small sample sizes limited the overall certainty of the evidence. Only one reboxetine study reported the primary outcome, number of participants with clinically important change in weight. Fewer people in the treatment condition experienced weight gains of more than 5% and more than 7% of their bodyweight than those in the placebo group (> 5% weight gain RR 0.27, 95% confidence interval (CI) 0.11 to 0.65; 1 study, 43 participants; > 7% weight gain RR 0.24, 95% CI 0.07 to 0.83; 1 study, 43 participants; very low-certainty evidence). No studies reported the primary outcomes, 'clinically important change in BMI', or 'compliance with treatment'. However, several studies reported 'average endpoint/change in body weight' or 'average endpoint/change in BMI'. Metformin may be effective in preventing weight gain (MD -4.03 kg, 95% CI -5.78 to -2.28; 4 studies, 131 participants; low-certainty evidence); and BMI increase (MD -1.63 kg/m2, 95% CI -2.96 to -0.29; 5 studies, 227 participants; low-certainty evidence). Other agents that may be slightly effective in preventing weight gain include H2 antagonists such as nizatidine, famotidine and ranitidine (MD -1.32 kg, 95% CI -2.09 to -0.56; 3 studies, 248 participants; low-certainty evidence) and monoamine modulators such as reboxetine and fluoxetine (weight: MD -1.89 kg, 95% CI -3.31 to -0.47; 3 studies, 103 participants; low-certainty evidence; BMI: MD -0.66 kg/m2, 95% CI -1.05 to -0.26; 3 studies, 103 participants; low-certainty evidence). Topiramate did not appear effective in preventing weight gain (MD -4.82 kg, 95% CI -9.99 to 0.35; 3 studies, 168 participants; very low-certainty evidence). For all agents, there was no difference between groups in terms of individuals leaving the study or reports of nausea. However, the results of these outcomes are uncertain given the very low-certainty evidence. AUTHORS' CONCLUSIONS: There is low-certainty evidence to suggest that metformin may be effective in preventing weight gain. Interpretation of this result and those for other agents, is limited by the small number of studies, small sample size, and short study duration. In future, we need studies that are adequately powered and with longer treatment durations to further evaluate the efficacy and safety of interventions for managing weight gain.

The metabolic adverse effects of antipsychotic use in individuals with intellectual and/or developmental disability: A systematic review and meta-analysis.

OBJECTIVE: Individuals with intellectual and/or developmental disability (IDD) are often prescribed antipsychotics (APs). However, despite their known propensity to cause metabolic adverse effects, including weight gain, diabetes, and increased risk of cardiovascular events, there is currently a limited body of literature describing the metabolic consequences of AP use in this population. METHODS: We searched MEDLINE, EMBASE, PsychINFO, CENTRAL, and CINAHL databases to identify all randomized trials that reported on the metabolic effects of APs in individuals with IDD. Random effects meta-analyses were used to examine weight gain as both a continuous and dichotomous outcome. RESULTS: Eighteen randomized trials met our inclusion criteria with a total of 1376 patients across a variety of IDDs. AP use was associated with significantly greater weight gain compared with placebo (Continuous: mean difference = 1.10 kg, [0.79, 1.40], p < 0.00001, I2  = 54%; Dichotomous: odds ratio = 3.94, [2.15, 7.23], p < 0.00001, I2  = 0). Sub-group analysis revealed no significant effect of AP type. Data regarding the effects of APs on other metabolic outcomes were limited. CONCLUSION: This review (PROSPERO # CRD42021255558) demonstrates that AP use is associated with significant weight gain among patients with IDD. Concerningly, most reported studies were in children and adolescents, which sets up an already vulnerable population for adverse medical sequalae at an early age. There was also a lack of long-term studies in adults with IDD. Further studies are required to better understand how AP use affects metabolic parameters in this group of individuals.

Metformin for the prevention of clozapine-induced weight gain: A retrospective naturalistic cohort study.

OBJECTIVE: Clozapine is presently the sole antipsychotic with an indication for treatment-resistant Schizophrenia, but is associated with significant weight gain and other metabolic aberrations. This retrospective chart review aimed to evaluate the effectiveness of adjunctive metformin in preventing clozapine-induced weight gain. METHODS: We conducted a retrospective chart review of patients newly initiated on clozapine at the Centre for Addiction and Mental Health in Canada, from November 2014 to April 2021. Our primary outcome was body weight at 6 and 12 months after clozapine initiation. Other metabolic parameters served as secondary outcomes. RESULTS: Among 396 patients (males: 71.5%, mean age: 42.8 years) initiated on clozapine, 69 were on metformin or prescribed it ≤3 months after clozapine initiation. The clozapine+metformin group demonstrated less weight gain compared with the clozapine-only group at 6 months (clozapine+metformin: -0.15 kg [SE = 1.08] vs. clozapine-only: 2.99 kg, SE = 0.54) and 12 months after clozapine initiation (clozapine+metformin: -0.67 kg, SE = 1.22 vs. clozapine-only: 4.72 kg, SE = 0.67). Adaptive changes were also observed for fasting glucose (F = 3.10, p = 0.046) and triglycerides (F = 8.56, p < 0.001) in the clozapine+metformin group compared with clozapine only. CONCLUSION: In this large retrospective naturalistic cohort study, co-prescription of clozapine and metformin was associated with less weight gain and related metabolic dysfunction at 6 and 12 months after initiation versus clozapine alone. These findings provide evidence for the effectiveness of metformin in preventing clozapine-induced weight gain; larger randomized controlled trials are needed to confirm these results.

Getting Into the Zone: A Pilot Study of Autonomic-Cardiac Modulation and Flow State During Piano Performance.

Background: Music performance anxiety is a common experience among elite and professional musicians and impedes performers from achieving flow state, or a state of focused, sustained engagement that promotes optimal performance. Objective: The aim of this study was to use heart rate variability (HRV) to determine the psychophysiological underpinnings of optimal music performance. Methods: We assessed HRV to study how autonomic-cardiac modulation was associated with flow during piano performance. Twenty-two pianists (15-22 years) with at least a Grade 8 Royal Conservatory of Music certification prepared two standardized pieces and a self-selected piece. Performer heart rate data were measured with a Polar 800 watch in 5-min periods immediately before performances, during performances and post-performance. HRV was employed to assess autonomic modulation of cardiac intervals. HRV indices of sympathetic and parasympathetic modulation of the heart were analyzed in 2.5-min segments to monitor short-term autonomic adjustments using the Kubios HRV Software. Flow state was measured using the 36-item Flow State Scale (FSS). Relationships were analyzed using zero-order correlations and multiple linear regressions. Results: Our sample consisted of 22 RCM Grade 8 certified pianists. Participants achieved the highest level of flow during performance of the Bach piece. Decreased HRV was observed during performance, as indicated by a significant drop in total power. Flow state was positively associated with High Frequency (HF) power during the pre-performance phase, and inversely associated with Low Frequency (LF) power during performance. Conclusion: Inverse association of flow with LF-HRV during performance affirms the importance of vagal-HR modulation for achievement of flow state. Increased HF-HRV and reduced LF-HRV immediately prior to performance suggests that flow state may be shaped as much by physiological preparation during pre-performance as it is by physiologic responses during performance. Further research is required to validate the correlation between autonomic modulation of the heart and flow state. Evidence of this correlation between autonomic modulation of the heart and achievement of flow state may pave the way for further research on enhancing musical performance and targeting MPA through HRV-based interventions.

Gut microbiome in schizophrenia and antipsychotic-induced metabolic alterations: a scoping review.

Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a 'chamber of secrets', particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.

Non-invasive neuromodulation of dorsolateral prefrontal cortex to reduce craving in alcohol use disorder: A meta-analysis.

Introduction: While several pharmacological and behavioral treatments are available for alcohol use disorder (AUD), they may not be effective for all patients. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of rTMS and tDCS for craving in AUD. Methods: EMBASE, Cochrane Library, PsycINFO, and PubMed databases were searched for original, peer-reviewed research articles in the English language published between January 2000 and January 2022. Randomized controlled trials (RCTs) reporting changes in alcohol craving among patients with AUD were selected. Random-effects meta-analysis was employed to pool data. Results: Changes in alcohol craving were extracted from 15 RCTs. Six studies assessed the efficacy of rTMS while nine studies examined tDCS. Results demonstrated that in comparison to sham stimulation, active rTMS to the DLPFC yields small but significant reductions in alcohol craving (standardized mean difference [SMD] = -0.27, p = .03). However, DLPFC stimulation via tDCS was not superior to sham stimulation in producing changes in alcohol craving (SMD = -0.08, p = .59). Conclusions: Our meta-analysis suggests that rTMS may be superior to tDCS in reducing alcohol craving in patients with AUD. However, additional research is needed to identify optimal stimulation parameters for both non-invasive neuromodulatory techniques in AUD.

Metabolic adverse effects of off-label use of second-generation antipsychotics in the adult population: a systematic review and meta-analysis.

Prescription rates of second-generation antipsychotics (SGAs) are rapidly increasing for non-indicated (i.e., off-label) usage. SGAs used for approved indications are associated with significant metabolic adverse effects, including weight gain. The objective of this systematic review and meta-analysis is to evaluate the metabolic adverse effects of SGA use for off-label management of psychiatric illnesses in the adult population. We performed a systematic database search to identify randomized controlled trials (RCTs) that reported on weight and other metabolic outcomes with off-label use of SGAs among adults. Thirty-eight RCTs met inclusion criteria for this review; 35 of these studies, with a total of 4930 patients, were included in the quantitative meta-analysis. Patients treated with olanzapine, risperidone, and quetiapine were more likely to report weight gain as a side effect and experience clinically significant (≥7%) weight gain compared to those treated with a placebo. Among studies that reported weight as a continuous outcome, olanzapine was associated with significantly greater weight gain across all disorders (mean difference (MD) = 3.24 kg, 95% CI: 2.57-3.90 p = 0.001, N = 12 studies). Similar trends were noted with quetiapine and risperidone. A meta-regression analysis revealed a positive dose-response association between olanzapine dose and weight gain (regression coefficient: 0.36, p = 0.001). This review demonstrates that off-label use of SGAs, and particularly olanzapine, is associated with significant weight gain among adult patients. Our findings are concerning given the widespread off-label use of SGAs. Further studies are required to better understand the effects of off-label SGA use on other metabolic parameters. The study was registered with the PROSPERO international database of prospectively registered systematic reviews (PROSPERO #143186).

Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health.

Schizophrenia (SCZ) is a psychiatric disorder characterized by a wide range of positive, negative and cognitive symptoms, along with an increased risk of metabolic syndrome and cardiovascular disease that contribute to a 15-20-year reduced life expectancy. Autonomic dysfunction, in the form of increased sympathetic activity and decreased parasympathetic activity, is postulated to be implicated in SCZ and its treatment. The aim of this narrative review is to view SCZ through an autonomic lens and synthesize the evidence relating autonomic dysfunction to different domains of SCZ. Using various methods of assessing autonomic activity, autonomic dysfunction was found to be associated with multiple aspects of SCZ pathophysiology, including symptom severity, cognitive impairment, and the development of cardiometabolic comorbidities, such as metabolic syndrome and high BMI. The strongest association of low heart rate variability was noted among patients on antipsychotic treatment with high-affinity muscarinic antagonism (i.e., clozapine, olanzapine and quetiapine). The review will also suggest ways in which studying autonomic dysfunction can help reduce morbidity and mortality associated with SCZ and its treatment.