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

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.

Patients were rated on the Brief Psychiatric Rating Scale at study entry and after six weeks of standard antipsychotic medication treatment. Repeatable Battery for the Assessment of Neuropsychological Status as well as neurological soft signs and handedness (examined on the Neurological Evaluation Scale) was conducted along with the acquisition of high-resolution magnetic resonance imaging data from patients and control subjects. Images were analysed using cortical pattern matching.  We found widespread cerebral grey matter deficits in schizophrenia. Grey matter deficits in the right dorsolateral prefrontal cortex were the strongest predictor of diagnosis. Reduced regional grey matter correlated with more severe symptom expression in left and right posterior cingulate (BA23), right anterior cingulate (BA24), and left perirhinal cortex. Duration of illness (18.4 months [SD 29.1]) was highly correlated with age in patients (r=-0.69; p<0.01) and did not statistically differentiate from age-related effects on grey matter.

Our findings confirm that regional cerebral grey matter deficits are correlated with psychopathology and cognitive impairment in schizophrenia, thus supporting the notion of cerebral grey matter deficits as an intermediate phenotype of the disorder. Funded by the Schizophrenia Research Institute, Sydney, Australia and the World Bank.

Conference: ASC2013, MAPrc
Areas of Interest / Categories: ASC 2013, 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.

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.

Determinants of high smoking rates among people with psychosis living in a socially disadvantaged region in South Australia.

People suffering from psychiatric illness have alarmingly higher smoking rates than the general population, up to 80% in some cases. This has previously been attributed to measures of social disadvantage and poor economic well-being. This study aimed to identify factors associated with the high rates of tobacco smoking amongst people with psychosis living in a disadvantaged region in Adelaide, South Australia. We hypothesised that whilst tobacco use by people with psychosis living in this region was primarily associated with mental illness, smoking prevalence would be further increased by the disadvantaged conditions existing within this context. Data were collected from 402 people with psychosis aged 18-64 who resided in the Northern suburbs of Adelaide. Demographic data and lifestyle variables were assessed that may be accountable for smoking prevalence. 74% of men and 71% of women with psychosis were current smokers. Factors including unemployment, lower education, and receiving government welfare known to be associated with smoking in the general population, were more prevalent in the Northern region.

A healthy lifestyle intervention among people with psychotic disorders: Results from a RCT.

People with psychotic disorders have higher rates of CVD risk factors compared to the general community. To our knowledge, this is the first RCT of its kind. To determine the efficacy of a multi-component intervention (smoking, diet and activity) delivered face to face compared to a largely telephone delivered intervention (smoking) among smokers with psychotic disorders. Participants with psychotic disorders residing in the community and smoking =15 cigarettes/day (CPD) were randomly assigned to either condition.