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The Weight of Evidence: The Role of Metformin in Cardiometabolic Protection in Early Psychosis.

The Weight of Evidence: The Role of Metformin in Cardiometabolic Protection in Early Psychosis.

The relationship between weight gain and the treatment of first episode psychosis (FEP) with psychotropic medication is well established, with weight gain and increased cardiovascular risk as common sequelae. Such metabolic abnormalities create further disease burden and shorten the life expectancy of a population already dealing with mental illness. Antipsychotic-induced weight gain has been shown to commence within the first months of initiating treatment in drug-naïve youth, thus early intervention is necessary in order to attenuate the progression of metabolic abnormalities. Initial studies using metformin in this population have shown promising results.

This study aimed to examine the efficacy of initiating metformin in FEP youth (aged 15-25) who were engaged in treatment with the Early Psychosis Program (EPP) in Sydney, Australia, following clinically significant weight gain. Baseline anthropometric and fasting pathology measures (weight, BMI, waist circumference, BP and plasma glucose and lipids) were obtained in all EPP clients. Metformin was recommended to those who gained ≥ 7% of baseline weight. Findings were compared to data from those who were not prescribed metformin matched for age, sex and use of clozapine.

There was evidence that metformin either halted the deterioration of anthropometric measures and lowered blood pressure. There was no evidence that metformin decreased fasting blood sugars, which were at pre-diabetes threshold at the time of metformin initiation. Not all of the changes observed could be ascribed to metformin per se, as this was a naturalistic study in which patients were prescribed a range of antipsychotic medications. Conclusions: These findings suggest that large-scale clinical efficacy studies are warranted to augment the evidence-base provided by randomised controlled trials.

Speakers: Philip Ward
Conference: MAPrc
Areas of Interest / Categories: MAPrc 2014

MAPrc 2014

The effect of symptomatic improvement on gamma synchrony in psychosis: a pilot study.

Impaired functional connectivity, as measured by synchronous gamma activity, has been observed in both the early and chronic stages of schizophrenia, as well as in unaffected first-degree relatives. This suggests gamma synchrony may be a trait-like marker of psychosis susceptibility, and not just a state-dependant characteristic. To conduct a pilot study into the short-term temporal stability of gamma synchrony and its relationship to symptomatic improvement in young patients who have been treated for recent onset psychosis. 20 medicated subjects underwent both clinical (PANSS) and electrophysiological (auditory oddball task during EEG) evaluation at both baseline and 8 weeks follow-up.

The effect of symptomatic improvement on gamma synchrony in psychosis: a pilot study.

Impaired functional connectivity, as measured by synchronous gamma activity, has been observed in both the early and chronic stages of schizophrenia, as well as in unaffected first-degree relatives. This suggests gamma synchrony may be a trait-like marker of psychosis susceptibility, and not just a state-dependant characteristic. To conduct a pilot study into the short-term temporal stability of gamma synchrony and its relationship to symptomatic improvement in young patients who have been treated for recent onset psychosis. 20 medicated subjects underwent both clinical (PANSS) and electrophysiological (auditory oddball task during EEG) evaluation at both baseline and 8 weeks follow-up.

Cerebral cortical grey matter deficits in schizophrenia and their associations with ageing, psychopathology, cognition and treatment response.

The diagnosis of schizophrenia lacks a broadly accepted biological basis and its heterogeneity may well represent a group of disorders with different aetiologies. Even so, brain imaging can map and quantify structural brain abnormalities in vivo as an intermediate (or endo-) phenotype of the disorder. To identify the degree of regional grey matter deficits in relation to age, the severity of psychopathology and cognitive/ neurological impairment, and treatment response in schizophrenia. Eighteen schizophrenia patients (32.2 years [SD 14.3], meeting DSM-IV criteria were examined. Eighteen pair-wise age (±2 years) and gender-matched healthy volunteers (31.9 years [SD 14.3]) served as control group.

Keeping the Body in Mind: Exercise Physiology Services within a Community-based Early Psychosis Treatment Program

People with first episode psychosis (FEP) are prone to significant weight gain and metabolic abnormalities in the early stages of treatment putting them at significant risk of developing physical co-morbidities, including type-2 diabetes and metabolic syndrome. These co-morbidities reduce quality of life and life expectancy within this population. Despite known benefits of regular exercise including anxiolytic and anti-depressive effects, very low treatment adherence within FEP programs limits the effectiveness of exercise as a potential intervention. Determining the characteristics of FEP patients who frequently participate in a facilitated exercise program may assist in the development of strategies aimed at improving adherence. To determine the characteristics of frequent users of a facilitated exercise program.

Cardiometabolic risk indicators at 18-64 years in Australians with psychosis

Individuals with psychosis have an elevated risk for heart disease and are more likely to die prematurely from heart disease than the general population. The age at which cardiovascular risk indicators are first elevated relative to the general population is unknown. Mean waist circumference, BMI, blood pressure, fasting blood glucose, triglycerides, LDL, HDL and total cholesterol were plotted by age and sex in a representative sample of 1,642 individuals with psychosis (aged 18+) who were in contact with mental health services and 11,247 controls (aged 25+) from the general population. Correlations between risk indicators were compared between samples.

Role of intracellular mediators in clozapine induced ErbB1-ERK signalling in prefrontal cortical neurons: relevance to therapeutic efficacy.

Dysregulation of the epidermal growth factor (EGF) system, implicated in synaptic plasticity, long-term potentiation and dendritic spine connectivity has been linked to schizophrenia. For instance, in patient brain and blood low EGF levels resulting in compensatory up-regulation of the EGF receptor (ErbB1) is postulated to represent a hypofunctioning signalling state. Consistent with this hypothesis our preclinical in vitro and in vivo data demonstrate that the antipsychotic drug clozapine increases ErbB1 signalling via G-protein coupled receptor (GPCR) transactivation in prefrontal cortex and striatum1,2,3. The clozapine induced increase in ErbB1 signalling results in delayed activation of the extracellular signal regulated kinase (ERK) pathway with downstream activation of the transcription factors, p90RSK and c-Fos.

The effect of Ketamine on striatal functional connectivity as a model for risk for psychosis.

Ketamine is a potent antagonist of the N-methyld-aspartate receptor that induces positive psychotic symptoms in healthy individuals reminiscent of those seen in people with schizophrenia. Ketamine is believed to act by imposing a broad modulatory effect on brain networks, particularly cortico-striatothalamic circuitry. To investigate the effect of a sub-anaesthetic dose of ketamine on the resting-state functional connectivity of dorsal and ventral corticostriatal circuits, structures that have strongly been implicated in the emergence of psychotic symptoms, and to characterize the symptom correlates of putative changes in cortico-striato-thalamic functional connectivity induced by ketamine infusion.