"First-episode psychosis: Structural covariance deficits in salience network correlate with symptoms severity".

BACKGROUND: Patterns of coordinated variations of gray matter (GM) morphology across individuals are promising indicators of disease. However, it remains unclear if they can help characterize first-episode psychosis (FEP) and symptoms' severity. METHODS: Sixty-seven FEP and 67 matched healthy controls (HC) were assessed with structural MRI to evaluate the existence of distributed GM structural covariance patterns associated to brain areas belonging to salience network. Voxel-based morphometry (VBM) and structural covariance differences, investigated with salience network seed-based Partial Least Square, were applied to explore differences between groups. GM density associations with Raven's intelligent quotient (IQ) and Positive and Negative Syndrome Scale (PANSS) scores were investigated. RESULTS: Univariate VBM results gave trend without significant GM differences across groups. GM and IQ correlated positively in both groups: in FEP, mostly in hippocampus, insula, and fronto-temporal structures, while in HC mostly in amygdala, thalamus and fronto-temporal regions. GM and PANSS scores correlated negatively in FEP, with widespread clusters located in limbic regions. Multivariate analysis showed strong and opposite structural GM covariance with salience network for FEP and HC. Moreover, structural covariance of the salience network in FEP correlated negatively with severity of clinical symptoms. CONCLUSION: Our study provides evidence supporting the insular dysfunction model of psychosis. Reduced structural GM covariance of the salience network, with its association to symptom's severity, appears a promising morphometry feature for FEP detection.

Immune and metabolic alterations in first episode psychosis (FEP) patients.

The molecular underpinnings associated to first episode psychosis (FEP) remains to be elucidated, but compelling evidence supported an association of FEP with blood alterations in biomarkers related to immune system, growth factors and metabolism regulators. Many of these studies have not been already confirmed in larger samples or have not considered the FEP diagnostic subgroups. In order to identify biochemical signatures of FEP, the serum levels of the growth factors BDNF and VEGF, the immune regulators IL-1RA, IL-6, IL-10 and IL-17, RANTES/CCL5, MIP-1b/CCL4, IL-8 and the metabolic regulators C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1, resistin and visfatin were analysed in 260 subjects collected in the GET UP project. The results indicated an increase of MIP-1b/CCL4, VEGF, IL-6 and PAI-1, while IL-17, ghrelin, glucagon and GLP-1 were decreased in the whole sample of FEP patients (p < 0.01 for all markers except for PAI-1 p < 0.05). No differences were evidenced for these markers among the diagnostic groups that constitute the FEP sample, whereas IL-8 is increased only in patients with a diagnosis of affective psychosis. The principal component analysis (PCA) and variable importance analysis (VIA) indicated that MIP-1b/CCL4, ghrelin, glucagon, VEGF and GLP-1 were the variables mostly altered in FEP patients. On the contrary, none of the analysed markers nor a combination of them can discriminate between FEP diagnostic subgroups. These data evidence a profile of immune and metabolic alterations in FEP patients, providing new information on the molecular mechanism associated to the psychosis onset for the development of preventive strategies and innovative treatment targets.

Feasibility and Effectiveness of a Multi-Element Psychosocial Intervention for First-Episode Psychosis: Results From the Cluster-Randomized Controlled GET UP PIANO Trial in a Catchment Area of 10 Million Inhabitants.

Integrated multi-element psychosocial interventions have been suggested to improve the outcomes of first-episode psychosis (FEP) patients, but they have been studied primarily in experimental settings and in nonepidemiologically representative samples. Thus, we performed a cluster-randomized controlled trial, comparing an integrated multi-element psychosocial intervention, comprising cognitive behavioral therapy, family intervention, and case management, with treatment as usual (TAU) for FEP patients in 117 community mental health centers (CMHCs) in a large area of northern Italy (10 million inhabitants). The randomized units (clusters) were the CMHCs, and the units of observation the patients (and, when available, their family members). The primary hypotheses were that add-on multicomponent intervention: (1) results in greater improvements in symptoms, as assessed with positive and negative syndrome scale and (2) reduces in-hospital stay, based on days of hospitalization over the 9-month follow-up. Four hundred and forty-four FEP patients received the intervention or TAU and were assessed at baseline and 9 months. Based on the retention rates of patients (and families) in the experimental arm, multi-element psychosocial interventions can be implemented in routine mental health services. Regarding primary outcomes, patients in the experimental arm showed greater reductions in overall symptom severity, while no difference could be found for days of hospitalization. Among the secondary outcomes, greater improvements were detected in the experimental arm for global functioning, emotional well-being, and subjective burden of delusions. No difference could be found for service disengagement and subjective burden of auditory hallucinations. These findings support feasibility and effectiveness of early interventions for psychosis in generalist mental health services.