Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs

Antipsychotics, Metabolic Adverse Effects, and Cognitive Function in Schizophrenia

Cognitive impairment is a core symptom domain of schizophrenia. The effect of antipsychotics, the cornerstone of treatment in schizophrenia, on this domain is not fully clear. There is some evidence suggesting that antipsychotics may partially improve cognitive function, and that this improvement may vary depending on the specific cognitive domain. However, this research is confounded by various factors, such as age, duration/stage of illness, medication adherence, and extrapyramidal side effects that complicate the relationship between antipsychotics and cognitive improvement. Furthermore, antipsychotics—particularly the second generation, or “atypical” antipsychotics—can induce serious metabolic side effects, such as obesity, dyslipidemia and type 2 diabetes, illnesses which themselves have been linked to impairments in cognition. Thus, the inter-relationships between cognition and metabolic side effects are complex, and this review aims to examine them in the context of schizophrenia and antipsychotic treatment. The review also speculates on potential mechanisms underlying cognitive functioning and metabolic risk in schizophrenia. We conclude that the available literature examining the inter-section of antipsychotics, cognition, and metabolic effects in schizophrenia is sparse, but suggests a relationship between metabolic comorbidity and worse cognitive function in patients with schizophrenia. Further research is required to determine if there is a causal connection between the well-recognized metabolic adverse effects of antipsychotics and cognitive deficits over the course of the illness of schizophrenia, as well as, to determine underlying mechanisms. In addition, findings from this review highlight the importance of monitoring metabolic disturbances in parallel with cognition, as well as, the importance of interventions to minimize metabolic abnormalities for both physical and cognitive health

Prevention strategies and modifiable risk factors for concussion:A systematic review and meta-analysis for the Female, woman and girl Athlete Injury pRevention (FAIR) consensus

Objective To examine prevention strategies and potential modifiable risk factors (MRFs) for sport-related concussion (SRC) and head impact/head acceleration event (HAE) outcomes in female, woman and/or girl athletes.Design Systematic review with meta-analyses and Grading of Recommendations, Assessment, Development and Evaluation.Data sources Medline, CINAHL, PsycINfo, SportDiscus, ERIC, CENTRAL and CDSR.Eligibility Primary data studies with comparison group(s) assessing the association of prevention interventions and/or MRFs for SRC or HAE with ≥1 female/woman/girl in each study group.Results Of the 108 included studies, 67 evaluated a SRC prevention strategy (equipment n=25, policy/rule n=21, training n=10, management n=11) and 41 evaluated potential MRFs (34 distinct MRFs across nine categories). In total, 40/108 (37%) studies (prevention 19/67; MRF 21/41) included female/woman/girl-specific estimates. Three meta-analyses were conducted: two SRC prevention strategies (headgear, eyewear) and one MRF (artificial turf vs grass) based on availability of female/woman/girl-only estimates and similar outcomes and exposure. Headgear was associated with 30% lower SRC rates in adolescent female/girl lacrosse and soccer (IRR=0.70, 95% CI 0.50 to 0.99; very-low certainty). Eyewear use was not protective for SRC (IRR=1.08, 95% CI 0.69 to 1.68; very-low certainty). SRC rates did not differ by artificial turf versus grass (IRR=0.95, 95% CI 0.62 to 1.45; very-low certainty).Conclusion We found limited evidence for prevention strategies and MRFs in female/woman/girl athletes except for very-low certainty evidence supporting headgear use in adolescent lacrosse and soccer. Future studies should consider the design, implementation and evaluation of SRC prevention strategies that target MRFs to guide safe practice recommendations specifically for female/woman/girl athletes

Gender- and/or sex-specific considerations for sport-related injury: a concept mapping approach for the Female, woman and/or girl Athlete Injury pRevention (FAIR) consensus

Objective: This study aimed to gather and represent experts’ perspectives on the gender- and/or sex-specific factors relevant to injury risk for female/woman/girl athletes. Methods: Mixed-methods concept mapping study. Sixty-six experts including cisgendered (1) athlete/coach/carers, (2) clinicians, (3) sports science/high-performance professional, (4) administrators and (5) researchers brainstormed statements to a prompt (‘What gender-specific and/or sex-specific factors do you think contribute to injury risk among female, woman and girl athletes?’) before thematically sorting and rating the statements/factors for importance and modifiability (5-point Likert scales). Results: Ten clusters were constructed from 101 unique statements/factors. The clusters (number of statements) include: (1) Inequitable organisational funding and support (n=17); (2) Athletes’ lack of, and access to, resources (n=7); (3) Lack of knowledge and expertise among support staff (n=6); (4) Lack of evidence for, and implementation of gender and sex-appropriate injury prevention (n=20); (5) Sex-related factors (n=14); (6) Gendered health (n=8); (7) Gendered expectations to conform to athletic ideals and norms (n=10); (8) Gendered harassment (interpersonal violence) and social biases (n=9); (9) Gendered sport environment (7); (10) Gendered communication (n=3). Lack of knowledge and expertise among support staff was deemed the most important and modifiable cluster to address gender- and/or sex-specific factors relevant to injury prevention for female/woman/girl athletes. Conclusion: Ten gender- and/or sex-specific clusters, ranging from organisational to biological considerations and societal influences, were defined that could impact female/woman/girl athlete injury risk factors. Advancing stronger evidence for gender and sex appropriate injury prevention is urgently needed

Event-related potential correlates of theory of mind in schizophrenia

Theory of mind (ToM) is the knowledge that other people have minds, thoughts, beliefs and values different from our own. Patients with schizophrenia are generally thought to be impaired at tasks requiring this ability. Frith (1992) has proposed that specific signs and symptoms of schizophrenia are associated with dysfunction in ToM ability. The purpose of the present study was to investigate the role of thought disorder in theory of mind and to tease out the electrophysiological correlates of this phenomenon. Participants partook in an intention attribution task, during which event-related potentials (ERPs) were recorded. Patients with high ratings of thought disorder performed worse than those with low thought disorder and significantly worse than normal subjects. ERP results were unexpected as no differences were detected for ERPs on frontal sites. A significant difference in the P600 component was observed on Pz. Possible explanations for parietal activation are discussed

The diabetogenic effects of atypical antipsychotic medication: an animal model

In the schizophrenia population, the increased prevalence of atypical antipsychotic use has been paralleled by an increase in reported incidence of obesity, type 2 diabetes, diabetic ketoacidosis and other metabolic abnormalities. These side effects contribute additional health risks to a population that is already burdened by issues of increased morbidity and mortality. We have developed an animal model to evaluate a number of variables relating to antipsychotic treatment and disruptions in metabolism. Investigating measures of insulin sensitivity, and secretion we assessed the chronic versus acute effects of atypical antipsychotic treatment, the differential effect of various antipsychotics, and a neural component by which the atypical antipsychotics induce glucose dysregulation. Chronic administration of olanzapine resulted in a decrease in insulin sensitivity. This insulin resistance was also observed with acute administration of olanzapine. Clozapine and risperidone induced insulin resistance, while ziprasidone and haloperidol did not change insulin sensitivity. We report novel data that show olanzapine and clozapine can have an immediate and significant impact on pancreatic beta cell function. We also initiated experiments to help uncover the pathways mediating antipsychotic-induced glucose dysregulation. Our results show that ICV injections of olanzapine affect both insulin sensitivity and secretion. Our acute data challenge prior notions that weight gain is the primary side effect of treatment with atypical antipsychotic medication and that the host of metabolic problems observed are merely a result of this increased adiposity. We highlight the significant risk to homeostatic glucoregulatory mechanisms in the acute phase of treatment with atypicals reiterating the need for clinicians to monitor metabolic status from the earliest stages of pharmacotherapy.Ph.D

T231. QUALITY OF LIFE IN ANTIPSYCHOTIC-NAïVE YOUTH: EXPLORING THE INTERPLAY WITH METABOLIC SIDE-EFFECTS

Abstract Background This observational, exploratory pilot study aims to understand changes in clinical presentation and quality of life (QoL) in antipsychotic-naïve youth. Outcomes for these first-episode psychosis patients will be explored in the context metabolic changes during their first three months of treatment. Methods Participants (n = 10) aged 14–29 years were followed throughout their first three months of treatment with an antipsychotic medication (of physician’s/patient’s choice). Participants were evaluated on metabolic indices including weight, waist circumference, and BMI, as well as QoL [Pediatric Quality of Life Index (PedsQL) and PedsQL General Well-Being Scale] and clinical presentation [Clinical Global Impression (CGI) scale]. Descriptive statistics and nonparametric tests were conducted to compare significant changes across these variables. Results Significant changes in metabolic indices were observed over the first three months of treatment, as measured in weight gain (p = 0.02), increased waist circumference (p = 0.02) and increased BMI (p = 0.01). Physicians rated clinical improvement in participants, CGI score (p = 0.03). However, patient-rated QoL remained unchanged within all subcategories, including psychosocial (p = 0.52) and general well-being (p = 0.35). Discussion It appears that antipsychotic-related metabolic side effects may not impede upon early clinical improvement or impact QoL. In addition, there does not appear to be a relationship between clinical presentation and QoL as our small sample show QoL remains neutral or positive. Taken together, these findings suggest that clinical presentation and metabolic side effects may not be influential in early psychosis. From a clinical perspective, these early pilot data add to the literature highlighting the significant, early, antipsychotic-induced metabolic side effects in youth, and also encouraging clinicians to attend to the interplay between treatment and related QoL. This study is limited by its small sample size and naturalistic treatment allocation. These participants will be followed longitudinally to monitor development of adverse metabolic outcomes as well as changes in QoL in later stages of treatment/illness. The field must to understand how treatment and management of metabolic side effects can be augmented to promote clinical improvement and QoL, given the prevalence of adolescent patients who eventually wish to discontinue antipsychotic drugs because of metabolic side effects. </jats:sec