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

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

We adopted a placebo-controlled, double-blind, randomized, repeated within-subjects measures study design in which 19 healthy volunteers received either an intravenous saline infusion or a racemic mixture of ketamine (2 mg/ml) separated by at least 1 week. Eyes closed resting-state fMRI was acquired 20 minutes after infusion initiation to a target dose of 100 ng/ml. Participants were assessed for positive psychotic and dissociative symptoms on the Brief Psychotic Rating Scale (BPRS) and the Clinician Administered Dissociative States Scale (CADSS) respectively. Cortico-striato-thalamic functional connectivity was mapped using a comprehensive seeding (6 seeds per hemisphere) of dorsal and ventral striatal regions.

Compared to placebo, ketamine induced an increase in functional connectivity of the dorsal caudate with the thalamus and midbrain bilaterally. Ketamine caused additional increases in the functional connectivity of the ventral striatum (i.e. nucleus accumbens) and rostral ventromedial prefrontal cortex, an effect that was significantly correlated with higher change scores on the BPRS and the CADSS.  The findings are consistent with a role for the ventral cortico-striato-thalamic circuit in mediating psychotic symptoms possibly via enhanced subcortical glutamatergic tone and a concomitant disinhibition in the mesocortical and mesolimbic dopamine pathways. The thalamus may play a protective role by inhibiting dorsal striatal output preventing the overflow of sensory stimuli from reaching the cortex.

Speakers: Orwa Dandash
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.

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.

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.

Schizophrenia and neurodevelopment – Where do we stand today?

The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood or adolescent periods. The objective is to place schizophrenia neuropathology in a neurodevelopmental context. This requires solid, scrutinized evidence of changes occurring during normal development of the cerebral cortex. We review literature on the development of the prefrontal cortex and chart major molecular and cellular events on a similar time line. Whilst neurogenesis, neuronal migration and myelination undergo most dramatic changes prenatally, these processes also extend into adolescence.