Psychosis onset typically occurs during adolescence or early adulthood, coinciding with the latest stage of brain maturation. Alterations in brain functional connectivity (FC) accompany the emergence of psychiatric symptoms and cognitive impairments. Thus, age-related FC changes may be informative regarding psychosis onset.

We defined neurotypical age-related FC trajectories and hypothesized that FC of individuals at familial and clinical high risk (HR) for psychosis deviates from FC of neurotypical controls (NC).

We analyzed two independent cohorts, of (a) 356 early adult NC (yNC; age=22±2y, m:f=149:207), and 127 mature adult NC (aNC; age=38±7y, m:f=79:48), and (b) 92 yNC (age=22±2y, m:f=34:58), 33 aNC (age=36±6y, m:f=21:12), 38 early HR adults (age=20±3y, m:f=18:20). We acquired fMRI data from multiple scans (resting-state, working memory, episodic memory, and implicit emotion processing). FC was obtained by computing Pearson’s correlations between time-courses of every independent component (IC) defined by an Independent Component Analysis approach (NeuroMark). Age-varying components of interest (yNC/aNC differences on FC based on linear mixed effect regressions) were tested for differences between HR and yNC through the Wilcoxon rank-sum test.

showed age-related FC differences (yNC/aNC) in a set of 17 IC pairs (pFDR<0.05). HR showed increased FC within a network including dorsolateral and medial prefrontal cortices, and sensorimotor cortex, while decreased FC between cerebellum and the parietal and visual cortices, compared with yNC (pFDR<0.05). HR showed no significant difference compared with aNC (pFDR>0.05).

This study tested FC alterations associated with the risk for psychosis and highlighted the relationship between psychosis and potentially altered brain functional processes.

No significant relationships.

Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.

The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).

Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.

Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.

Gender differences in symptomatology in chronic schizophrenia and first episode psychosis patients have often been reported. However, little is known about gender differences in those at risk of psychotic disorders. This study investigated gender differences in symptomatology, drug use, comorbidity (i.e. substance use, affective and anxiety disorders) and global functioning in patients with an at-risk mental state (ARMS) for psychosis.

The sample consisted of 336 ARMS patients (159 women) from the prodromal work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI; 11 centers). Clinical symptoms, drug use, comorbidity and functioning were assessed at first presentation to an early detection center using structured interviews.

In unadjusted analyses, men were found to have significantly higher rates of negative symptoms and current cannabis use while women showed higher rates of general psychopathology and more often displayed comorbid affective and anxiety disorders. No gender differences were found for global functioning. The results generally did not change when corrected for possible cofounders (e.g. cannabis use). However, most differences did not withstand correction for multiple testing.

Findings indicate that gender differences in symptomatology and comorbidity in ARMS are similar to those seen in overt psychosis and in healthy controls. However, observed differences are small and would only be reliably detected in studies with high statistical power. Moreover, such small effects would likely not be clinically meaningful.