Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia.

The neurobiological effects of clozapine are under characterised. We examined the effects clozapine treatment on subcortical volume and cortical thickness and investigated whether macrostructural changes were linked to alterations in glutamate or N-acetylaspartate (NAA). Data were acquired in 24 patients with treatment-resistant schizophrenia before and 12 weeks after switching to clozapine. During clozapine treatment we observed reductions in caudate and putamen volume, lateral ventricle enlargement (P < 0.001), and reductions in thickness of the left inferior temporal cortex, left caudal middle frontal cortex, and the right temporal pole. Reductions in right caudate volume were associated with local reductions in NAA (P = 0.002). None of the morphometric changes were associated with changes in glutamate levels. These results indicate that clozapine treatment is associated with subcortical volume loss and cortical thinning and that at least some of these effects are linked to changes in neuronal or metabolic integrity.

Changes in Brain Glutamate on Switching to Clozapine in Treatment-Resistant Schizophrenia.

It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P = .01) but not in the ACC (n = 24, F = 0.02, P = .59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r = .42, P = .04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment.

Facilitating the Delivery of Cognitive Remediation in First-Episode Psychosis: Pilot Study of a Home-Delivered Web-Based Intervention.

We explored the adherence to a home-delivered, computer-based, cognitive remediation protocol in a first-episode psychosis outpatient cohort. Seventeen patients underwent a cognitive training protocol for 6 months using an online platform accessible from their home under the supervision of a qualified neuropsychologist. Neuropsychological, psychopathological, and functional data were collected at baseline and postintervention, whereas qualitative appraisal of the intervention was assessed monthly. Overall, participants' evaluation of the program was positive. This was reflected in a good adherence rate with 12 (70%) of 17 patients completing 80% of the prescribed sessions. Exploratory analysis revealed significant improvements in sustained attention (p = 0.020) and verbal memory (p = 0.018). A decrease in negative symptoms and an improvement on the Clinical Global Impression were also found (p = 0.009). We believe these are encouraging results to further explore the adopted delivery approach, which could facilitate access to cognitive training earlier and to a larger group of patients.

Disorder, not just state of risk: meta-analysis of functioning and quality of life in people at high risk of psychosis.

BACKGROUND: The nosology of the psychosis high-risk state is controversial. Traditionally conceived as an 'at risk' state for the development of psychotic disorders, it is also conceptualised as a clinical syndrome associated with functional impairment. AIMS: To investigate meta-analytically the functional status of patients at high clinical risk for psychosis and its association with longitudinal outcomes. METHOD: Three meta-analyses compared level of functioning (n = 3012) and quality of life (QoL) (n = 945) between a high-risk group, a healthy control group and group with psychosis, and baseline functioning in people in the high-risk group who did or did not have a transition to psychosis at follow-up (n = 654). RESULTS: People at high risk had a large impairment in functioning (P<0.001) and worse QoL (P = 0.001) than the healthy control group, but only small to moderately better functioning (P = 0.012) and similar QoL (P = 0.958) compared with the psychosis group. Among the high-risk group, those who did not develop psychosis reported better functioning (P = 0.001) than those who did. CONCLUSIONS: Our results indicate that the high-risk state is characterised by consistent and large impairments of functioning and reduction in QoL similar to those in other coded psychiatric disorders.