The gut microbiota as a contributing factor to antipsychotic-induced weight gain and metabolic dysfunction

Schizophrenia represents one of the world’s most devastating illnesses due to its often lifelong course and debilitating nature. The treatment of schizophrenia has vastly improved over recent decades with the discovery of several antipsychotic compounds; however these drugs are not without adverse effects that must be addressed to maximize their therapeutic value. Newer, atypical, antipsychotics are associated with a compilation of serious metabolic side effects including weight gain, insulin resistance, fat deposition, glucose dysregulation and ensuing co-morbidities such as type II diabetes mellitus. The mechanisms underlying these side effects remain to be fully elucidated and adequate interventions are lacking. Further understanding of the factors that contribute these side effects is therefore required in order to develop effective adjunctive therapies and to potentially design antipsychotic drugs in the future with reduced impact on the metabolic health of patients. We investigated if the gut microbiota represented a novel mechanism contributing to the metabolic dysfunction associated with atypical antipsychotics. The gut microbiota comprises the bacteria that exist symbiotically within the gastrointestinal tract, and has been shown in recent years to be involved in several aspects of energy balance and metabolism. We have demonstrated that administration of certain antipsychotics in the rat results in an altered microbiota profile and, moreover, that the microbiota is required for the full scale of metabolic dysfunction to occur. We have further shown that specific antibiotics can attenuate certain aspects of olanzapine and risperidone–induced metabolic dysfunction, in particular fat deposition and adipose tissue inflammation. Mechanisms underlying this novel link appear to involve energy utilization via expression of lipogenic genes as well as reduced inflammatory tone. Taken together, these data indicate that the gut microbiota is an important factor involved in the myriad of metabolic complications associated with antipsychotic therapy. Furthermore, these data support the future investigation of microbial-based therapeutics for not only antipsychotic-induced weight gain but also for tackling the global obesity epidemic.

Taking neuroleptic medications as embodied experience : a hermeneutic phenomenological study

This hermeneutic phenomenological study focuses on the question: What is it like to take neuroleptic medications for schizophrenia, and what is the meaning of this experience?

Burden of care and general health in families of patients with schizophrenia

Background: De-institutionalization of psychiatric patients has led to a greater emphasis on family management in the community, and family members are often overwhelmed by the demands that caring for a patient with schizophrenia involves. Most studies of family burden in schizophrenia have taken place in developed countries. The current study examined family burden and its correlates in a regional area of a medium income country in South America. Method: Sixty-five relatives of patients with schizophrenia who were attending a public mental health out-patient service in the province of Arica, Chile, were assessed on Spanish versions of the Zarit Caregiver Burden Scale and SF-36 Health Survey (SF-36). Results: Average levels of burden were very high, particularly for mothers, carers with less education, carers of younger patients and carers of patients with more hospitalisations in the previous 3 years. Kinship and number of recent hospitalisations retained unique predictive variance in a multiple regression. Burden was the strongest predictor of SF-36 subscales, and the prediction from burden remained significant after entry of other potential predictors. Conclusions: In common with families in developed countries, family members of schizophrenia patients in regional Chile reported high levels of burden and related functional and health impact. The study highlighted the support needs of carers in contexts with high rates of poverty and limited health and community resources.

An examination of the utility of the AUDIT in people with schizophrenia

Objective: To examine the reliability and validity of the Alcohol Use Disorders Identification Test (AUDIT) compared to a structured diagnostic interview, the Composite international Diagnostic Interview (CIDI; 12-month version) in psychiatric patients with a diagnosis of schizophrenia. Method: Patients (N = 71, 53 men) were interviewed using the CIDI (Alcohol Misuse Section; 12-month version) and then completed the AUDIT. Results: The CIDI identified 32.4% of the sample as having an alcohol use disorder. Of these, 5 (7.0%) met diagnostic criteria for harmful use of alcohol, 1 (1.4%) met diagnostic criteria for alcohol abuse and 17 (23.9%) met diagnostic criteria for alcohol dependence. The AUDIT was found to have good internal reliability (coefficient = 0.85). An AUDIT cutoff of greater than or equal to 8 had a sensitivity of 87% and specificity of 90% in detecting CIDI-diagnosed alcohol disorders. All items except Item 9 contributed significantly to discriminant validity. Conclusions: The findings replicate and extend previous findings of high rates of alcohol use disorders in people with severe mental illness. The AUDIT was found to be reliable and valid in this sample and can be used with confidence as a screening instrument for alcohol use disorders in people with schizophrenia.

Event-related potential (ERP) correlates of impaired visuospatial memory in schizophrenia

Previous studies have reported that patients with schizophrenia demonstrate impaired performance during working memory (WM) tasks. The current study aimed to determine whether WM impairments in schizophrenia are accompanied by reduced slow wave (SW) activity during on-line maintenance of mnemonic information. Event-related potentials were obtained from patients with schizophrenia and well controls as they performed a visuospatial delayed response task. On 50% of trials, a distractor stimulus was introduced during the delay. Compared with controls, patients with schizophrenia produced less SW memory negativity, particularly over the right hemisphere, together with reduced frontal enhancement of SW memory negativity in response to distraction. The results indicate that patients with schizophrenia generate less maintenance phase neuronal activity during WM performance, especially under conditions of distraction.

Working memory correlates of three symptom clusters in schizophrenia

Examined whether discrete working memory deficits underlie positive, negative and disorganised symptoms of schizophrenia. 52 outpatients (mean age 37.5 yrs) with schizophrenia were studied using items drawn from the Positive and Negative Syndrome Scale (PANSS). Linear regression and correlational analyses were conducted to examine whether symptom dimension scores were related to performance on several tests of working memory function. Severity of negative symptoms correlated with reduced production of words during a verbal fluency task, impaired ability to hold letter and number sequences on-line and manipulate them simultaneously, reduced performance during a dual task, and compromised visuospatial working memory under distraction-free conditions. Severity of disorganisation symptoms correlated with impaired visuospatial working memory under conditions of distraction, failure of inhibition during a verbal fluency task, perseverative responding on a test of set-shifting ability, and impaired ability to judge the veracity of simple declarative statements. The present study provides evidence that the positive, negative and disorganised symptom dimensions of the PANSS constitute independent clusters, associated with unique patterns of working memory impairment.

Further evidence for a deficit in switching attention in schizophrenia

In this study, sustained, selective, divided, and switching attention, and reloading of working memory were investigated in schizophrenia by using a newly developed Visual Attention Battery (VAB). Twenty-four outpatients with schizophrenia and 24 control participants were studied using the VAB. Performance on VAB components was correlated with performance of standard tests. Patients with schizophrenia were significantly impaired on VAB tasks that required switching of attention and reloading of working memory but had normal performance on tasks involving sustained attention or attention to multiple stimulus features. Switching attention and reloading of working memory were highly correlated with Trails (B - A) score for patients. The decline in performance on the switching-attention task in patients with schizophrenia met criteria for a differential deficit in switching attention. Future research should examine the neurophysiological basis of the switching deficit and its sensitivity and specificity to schizophrenia.

An intervention for substance abuse in schizophrenia

Describes a cognitive-behavioral intervention for alcohol and cannabis abuse with schizophrenic patients. The intervention integrates substance abuse treatment with other aspects of psychosis management, including assessment, use of anti-psychotic medication, and training in coping skills.

Application of cognitive-behavioural family intervention for schizophrenia in multidisciplinary teams : what can the matter be?

Surveyed 45 therapists who had participated in a family intervention for schizophrenia training program to examine the difficulties they had encountered, their recall of the intervention strategies, and the extent that they thought the approach had become integrated in their everyday work. Between 6 mo and 3 yrs after the family training, Ss reported the number of families they had systematically treated, and the difficulties they had encountered. Allowance of time to undertake the intervention, afterhours scheduling, and illness or holidays presented particular difficulties. Only 4% reported that their knowledge of behavioral techniques was a problem, but in a written test most therapists did not display minimum recall of the material of cognitive therapy, social skills training, or behavioral strategies. The study demonstrated significant problems in disseminating cognitive-behavioral approaches to multidisciplinary settings.

Recent developments in expressed emotion and schizophrenia.

Reviews outcome studies on the course of schizophrenia as predicted by expressed emotion (EE) and considers methodological issues. The nature of EE and the mechanism for the predictive results are explored. EE probably determines relapse through its effect on emotions and symptom control. A stress-vulnerability model of relapse is advanced that incorporates biological factors and cycles of mutual influence between symptomatic behavior, life events, and EE. A social interaction model of schizophrenia may help to alleviate concerns that EE represents an attempt to blame families for schizophrenic relapse. Aversive types of behavior in patients and their relatives are seen as understandable reactions to stress that are moderated by social perceptions and coping skills. Families have made positive achievements, including the provision of noninvasive support.

Low-fat oxidation may be a factor in obesity among men with schizophrenia

Objective: Obesity associated with atypical antipsychotic medications is an important clinical issue for people with schizophrenia. The purpose of this project was to determine whether there were any differences in resting energy expenditure (REE) and respiratory quotient (RQ) between men with schizophrenia and controls. Method: Thirty-one men with schizophrenia were individually matched for age and relative body weight with healthy, sedentary controls. Deuterium dilution was used to determine total body water and subsequently fat-free mass (FFM). Indirect calorimetry using a Deltatrac metabolic cart was used to determine REE and RQ. Results: When corrected for FFM, there was no significant difference in REE between the groups. However, fasting RQ was significantly higher in the men with schizophrenia than the controls. Conclusion: Men with schizophrenia oxidised proportionally less fat and more carbohydrate under resting conditions than healthy controls. These differences in substrate utilisation at rest may be an important consideration in obesity in this clinical group.

Schizophrenia : an overview and practical handbook

Schizophrenia is a serious mental disorder currently undergoing a renaissance of scientific interest. This book summarizes current knowledge and details some of the recent developments. Divided into three sections, it presents an overview of the disorder, including its features, social impact and aetiology; reviews methods of assessing the symptoms and disabilities of schizophrenia and examining the sufferer's social environment; and discusses a range of interventions, from pharmacological treatment to skill training for individuals and families. Issues that arise in planning services for sufferers and their families are also reviewed. All of the chapters focus on clinical practice and many include guides to assessment and practice. This handbook should be particularly useful in training health professionals in psychiatric/mental health services and general practice. It also aims to offer practitioners and researchers a comprehensive update on schizophrenia that is both easy to read and practical in its focus.