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.

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.

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.

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.

The nosology of the psychosis high-risk (HR) state is highly controversial. Traditionally conceived as an 'atrisk" state for the development of psychotic disorders, it is also conceptualized as a clinical syndrome associated with functional impairment and disability. In this meta-analysis quality of life (QoL) in HR were compared to healthy controls (HC) and psychotic patients (PS). We performed a systematic search of studies published until 2013 selecting cross-sectional studies addressing QoL in HR. Raw scores, demographic data were extracted by two independent authors. We performed the meta-analyses comparing QoL data between HR, HC and PS 945 subjects : mean age 23, 40% female). The analysis found HR subjects experience a significantly worse QoL than healthy controls (Hedges' g=-1.824, 95% CI from-2.853 to-0.795, p=0.001, 4 studies included), while no difference with psychotic subjects was found (Hedges' g=0.017, 95% CI from-0.636 to 0.671, p=0.958, 3 studies included). Despite the high heterogeneity (l 2 =95,18%) the effect size of each study comparing HR and healthy controls was significant and coherent in the direction of the effect. Our results indicate that the HR state is characterised by consistent and large reduction in QoL, a clinical indicator for functional disruption: these impairments would call not only for prevention of a future transition to psychosis, but also for treatment of the current disorder.

Subjective quality of life in subjects at risk for a first episode of psychosis: a comparison with first episode schizophrenia patients and healthy controls.