The potential role of appetite in predicting weight changes during treatment with olanzapine

Background Clinically significant weight gain has been reported during treatment with atypical antipsychotics. It has been suggested that weight changes in patients treated with olanzapine may be associated with increased appetite. Methods Data were used from adult patients for whom both appetite and weight data were available from 4 prospective, 12- to 24-week clinical trials. Patients' appetites were assessed with Eating Behavior Assessment (EBA, Study 1), Platypus Appetite Rating Scale (PARS, Study 2), Eating Inventory (EI, Study 3), Food Craving Inventory (FCI, Study 3), and Eating Attitude Scale (EAS, Study 4). Results In Studies 1 (EBA) and 4 (EAS), patients who reported overall score increases on appetite scales, indicating an increase in appetite, experienced the greatest overall weight gains. However, in Studies 2 (PARS) and 3 (EI, FCI), patients who reported overall score increases on appetite scales did not experience greater weight changes than patients not reporting score increases. Early weight changes (2-4 weeks) were more positively correlated with overall weight changes than early or overall score changes on any utilized appetite assessment scale. No additional information was gained by adding early appetite change to early weight change in correlation to overall weight change. Conclusions Early weight changes may be a more useful predictor for long-term weight changes than early score changes on appetite assessment scales

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

Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat

This study aims to investigate whether orexigenic antipsychotic drugs may induce dyslipidemia and glucose disturbances in female rats through direct perturbation of metabolically active peripheral tissues, independent of prior weight gain. Methods In the current study, we examined whether a single intraperitoneal injection of clozapine or olanzapine induced metabolic disturbances in adult female outbred Sprague–Dawley rats. Serum glucose and lipid parameters were measured during time-course experiments up to 48 h. Real-time quantitative PCR was used to measure specific transcriptional alterations in lipid and carbohydrate metabolism in adipose tissue depots or in the liver. Results Our results demonstrated that acute administration of clozapine or olanzapine induced a rapid, robust elevation of free fatty acids and glucose in serum, followed by hepatic accumulation of lipids evident after 12–24 h. These metabolic disturbances were associated with biphasic patterns of gluconeogenic and lipid-related gene expression in the liver and in white adipose tissue depots. Conclusion Our results support that clozapine and olanzapine are associated with primary effects on carbohydrate and lipid metabolism associated with transcriptional changes in metabolically active peripheral tissues prior to the development of drug-induced weight gain

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

SKJUTNINGARNA BAKOM NYHETSRUBRIKERNA : En kvantitativ studie om orsakerna bakom det regionala skjutvapenvåldet

Gun violence has become a well-discussed subject within the political debate about crime. Frequent shootings in criminal environments have become a major issue distinguishing Sweden from other countries. This paper presents a quantitative study on how several social factors may influence the shooting rate at a regional level. Using data from the SOM Institute at the University of Gothenburg and SVT this study aims to provide a deeper understanding of gun violence in Sweden, regionally. Previous research suggests that there is an ongoing violent spiral and areas with a high number of crimes has different levels of trust in the police and deficient socioeconomic standards, such as low levels of education and financial difficulties, often induce crime rates. Regression analysis was used to examine how trust in the police, educational level, average income and year may affect the regional shooting rates over the years 2018, 2019 and 2020. Moreover, the theoretical framework of this study is mainly the social disorganization theory and routine activity theory. The result suggests that there are no statistically significant correlations between any of the hypothesized factors and the regional shooting rate, contradictory to what previous research implies. Finally, this study concludes that even though no statistically significant relationships were found on a regional level, geographical correlations may occur if smaller units such as socially vulnerable areas were to be examined. Limitations and recommendations for future studies on gun violence are discussed.

SKJUTNINGARNA BAKOM NYHETSRUBRIKERNA : En kvantitativ studie om orsakerna bakom det regionala skjutvapenvåldet

Gun violence has become a well-discussed subject within the political debate about crime. Frequent shootings in criminal environments have become a major issue distinguishing Sweden from other countries. This paper presents a quantitative study on how several social factors may influence the shooting rate at a regional level. Using data from the SOM Institute at the University of Gothenburg and SVT this study aims to provide a deeper understanding of gun violence in Sweden, regionally. Previous research suggests that there is an ongoing violent spiral and areas with a high number of crimes has different levels of trust in the police and deficient socioeconomic standards, such as low levels of education and financial difficulties, often induce crime rates. Regression analysis was used to examine how trust in the police, educational level, average income and year may affect the regional shooting rates over the years 2018, 2019 and 2020. Moreover, the theoretical framework of this study is mainly the social disorganization theory and routine activity theory. The result suggests that there are no statistically significant correlations between any of the hypothesized factors and the regional shooting rate, contradictory to what previous research implies. Finally, this study concludes that even though no statistically significant relationships were found on a regional level, geographical correlations may occur if smaller units such as socially vulnerable areas were to be examined. Limitations and recommendations for future studies on gun violence are discussed.

The Complex Relationship between Antipsychotic-Induced Weight Gain and Therapeutic Benefits: A Systematic Review and Implications for Treatment

Background: Antipsychotic-induced weight gain (AIWG) and other adverse metabolic effects represent serious side effects faced by many patients with psychosis that can lead to numerous comorbidities and which reduce the lifespan. While the pathophysiology of AIWG remains poorly understood, numerous studies have reported a positive association between AIWG and the therapeutic benefit of antipsychotic medications.Objectives: To review the literature to (1) determine if AIWG is consistently associated with therapeutic benefit and (2) investigate which variables may mediate such an association.Data Sources: MEDLINE, Google Scholar, Cochrane Database and PsycINFO databases were searched for articles containing all the following exploded MESH terms: schizophrenia [AND] antipsychotic agents/neuroleptics [AND] (weight gain [OR] lipids [OR] insulin [OR] leptin) [AND] treatment outcome. Results were limited to full-text, English journal articles.Results: Our literature search uncovered 31 independent studies which investigated an AIWG-therapeutic benefit association with a total of 6063 enrolled individuals diagnosed with schizophrenia or another serious mental illness receiving antipsychotic medications. Twenty-two studies found a positive association while, 10 studies found no association and one study reported a negative association. Study variables including medication compliance, sex, ethnicity, or prior antipsychotic exposure did not appear to consistently affect the AIWG-therapeutic benefit relationship. In contrast, there was some evidence that controlling for baseline BMI/psychopathology, duration of treatment and specific agent studied [i.e., olanzapine (OLZ) or clozapine (CLZ)] strengthened the relationship between AIWG and therapeutic benefit.Limitations: There were limitations of the reviewed studies in that many had small sample sizes, and/or were retrospective. The heterogeneity of the studies also made comparisons difficult and publication bias was not controlled for.Conclusions: An AIWG-therapeutic benefit association may exist and is most likely to be observed in OLZ and CLZ-treated patients. The clinical meaningfulness of this association remains unclear and weight gain and other metabolic comorbidities should be identified and treated to the same targets as the general population. Further research should continue to explore the links between therapeutic benefit and metabolic health with emphasis on both pre-clinical work and well-designed prospective clinical trials examining metabolic parameters associated, but also occurring independently to AIWG