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

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

Investigating the Gut Microbiome, Metabolomic Signatures, and Metabolic Dysfunction in Antipsychotic Naïve Patients

Antipsychotics (APs) are the treatment cornerstone for psychotic spectrum disorders (PSDs) but have severe metabolic side-effects. Gut microbiome (GMB) and metabolomic profiling may explain these. This thesis comprises two 12-week studies. In study one, 6 AP-naïve (cases) and 6 healthy participants (HCs) completed baseline GMB and metabolic assessments, repeated at 6 and 12 weeks for cases. At baseline, alpha diversity and genera level differences were found between groups. Over the three months of AP treatment, genera changes were observed and a positive correlation between triglycerides and Actinobacteria change was noted. In study two, 24 cases and 5 HCs completed metabolomic and metabolic assessments. Cases had lower acylcarnitine levels and differences in fatty acids compared to HCs. Baseline aspartic acid was higher for cases who gained weight. The GMB and metabolome may provide biomarkers for PSDs, intrinsic metabolic abnormalities, and help predict/monitor AP induced metabolic side-effects.M.Sc

“If you're offered help, take it”: A qualitative study examining bariatric patients' experience of telephone‐based

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167098/1/cob12431_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167098/2/cob12431.pd

The clozapine to norclozapine ratio: a narrative review of the clinical utility to minimize metabolic risk and enhance clozapine efficacy

Introduction: Clozapine remains the most effective antipsychotic for treatment-refractory schizophrenia. However, 40% of the patients respond insufficiently to clozapine. Clozapine's effects, both beneficial and adverse, have been proposed to be partially attributable to its main metabolite, N-desmethylclozapine (NDMC). However, the relation of the clozapine to norclozapine ratio (CLZ:NDMC; optimally defined as 2) to clinical response and metabolic outcomes is not clear. Areas covered: This narrative review comprehensively examines the clinical utility of the CLZ:NDMC ratio to reduce metabolic risk and increase treatment efficacy. The association of the CLZ:NDMC ratio with changes in psychopathology, cognitive functioning, and cardiometabolic burden will be explored, as well as adjunctive treatments and their effects. Expert opinion: The literature suggests a positive association between the CLZ:NDMC ratio and better cardiometabolic outcomes. Conversely, the CLZ:NDMC ratio appears inversely associated with better cognitive functioning but less consistently with other psychiatric domains. The CLZ:NDMC ratio may be useful for predicting and monitoring cardiometabolic adverse effects and optimizing potential cognitive benefits of clozapine. Future studies are required to replicate these findings, which if substantiated, would encourage examination of adjunctive treatments aiming to alter the CLZ:NDMC ratio to best meet the needs of the individual patient, thereby broadening clozapine's clinical utility

Evaluating recovery colleges: a co-created scoping review

Recovery Colleges (RCs) are education-based centres providing information, networking, and skills development for managing mental health, well-being, and daily living. A central principle is co-creation involving people with lived experience of mental health/illness and/or addictions (MHA). Identified gaps are RCs evaluations and information about whether such evaluations are co-created. We describe a co-created scoping review of how RCs are evaluated in the published and grey literature. Also assessed were: the frameworks, designs, and analyses used; the themes/outcomes reported; the trustworthiness of the evidence; and whether the evaluations are co-created. We followed Arksey and O’Malley’s methodology with one important modification: “Consultation” was re-conceptualised as “co-creator engagement” and was the first, foundational step rather than the last, optional one. Seventy-nine percent of the 43 included evaluations were peer-reviewed, 21% grey literature. These evaluations represented 33 RCs located in the UK (58%), Australia (15%), Canada (9%), Ireland (9%), the USA (6%), and Italy (3%). Our findings depict a developing field that is exploring a mix of evaluative approaches. However, few evaluations appeared to be co-created. Although most studies referenced co-design/co-production, few described how much or how meaningfully people with lived experience were involved in the evaluation.</p