ASC 2013

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.

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.

Serum epidermal growth factor levels are reduced in people with treatment resistant schizophrenia and modulated by clozapine treatment.

Up to 45% of patients with schizophrenia are treatment resistant to conventional drugs leaving clozapine as the only effective option. Its severe side-effects however limit it to a late stage option and the development of a biomarker to predict treatment response would be of high clinical utility. Our previous data demonstrate clozapine augments epidermal growth factor receptor (EGFR) signaling and hence we examined if EGF levels may be altered in treatment resistant schizophrenia (TRS) and are influenced by clozapine treatment. Study objectives: To determine if EGF levels are influenced by clozapine in TRS and can serve as a biomarker for clozapine response.

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.

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.

Increased gamma synchrony observed in First Episode Psychosis.

The synchronisation of gamma activity is a basic cortical process underlying a broad range of sensory and cognitive functions. Because of this, changes in gamma synchrony have been hypothesized to be central to the pathophysiology of the subtle alterations in function seen in psychotic disorders such as schizophrenia. In this study we report on the extent of changes found in gamma synchrony in a group of young people with their first episode of psychosis and the extent to which this was a marker of symptom profile, personality or cognitive dysfunction. One hundred and twenty four subjects, all assessed within 12 months of their presentation to mental health services with a psychotic disorder, were recruited from community and hospital services in Western Sydney. They were assessed using a structured clinical interview and a computerised battery of neurocognitive tests. Gamma synchrony was measured during an auditory oddball paradigm.

Overcoming non-adherence to treatment in schizophrenia – is it possible?

Adherence to treatment has important implications for patient outcome, from the outset of the disease. Discontinuation of medication is a major factor for relapse, and there is an increasing evidence showing a close relationship among the number of relapses and the lost of grey and white matter in the brain, which may contribute to the progressive deterioration observed in many patients with schizophrenia. Continuous pharmacological treatment combined with psychosocial treatments may improve the possibility of achieving functional recovery. However, a number of longitudinal studies show that the majority of schizophrenia patients are partially or non-adherent to medication. The reasons for non-adherence are complex and can be patient-, treatment- or environment/socially-related.

Maternal immune activation impacts on the kynurenine pathway in preadolescent offspring: Preventive effects of anti-inflammatory treatment.

Kynurenic acid (KYNA), a glia-derived metabolite of the kynurenine pathway (KP) of tryptophan degradation, is an antagonist at glutamate NMDA and a7 nicotinic acetylcholine receptors. Abnormalities in the KP have been described in patients with schizophrenia. Cyclo-oxygenese-2 (COX-2) inhibitors show considerable promise in treating early (but not late) stage schizophrenia and preclinical studies suggest that COX-2 inhibitors decrease KYNA in the brain.