Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients.

In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes (‘normal’, ‘mixed’ and ‘impaired’) in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype.

Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype.

Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

Many studies have concluded that cannabis use disorder (CUD) negatively influences outcomes in first-episode psychosis (FEP). However, few have taken into account the impact of concurrent misuse of other substances.

This 2-year, prospective, longitudinal study of FEP patients, aged between 18 and 30 years, admitted to early intervention programs in Montreal, Quebec, Canada, examined the specific influence of different substance use disorders (SUD) (alcohol, cannabis, cocaine, amphetamines) on service utilization, symptomatic and functional outcomes in FEP.

Drugs and alcohol were associated with lower functioning, but drugs had a greater negative impact on most measures at 2-year follow-up. Half of CUD patients and more than 65% of cocaine or amphetamine abusers presented polysubstance use disorder (poly-SUD). The only group that deteriorated from years 1 to 2 (symptoms and functioning) were patients with persistent CUD alone. Outcome was worse in CUD than in the no-SUD group at 2 years. Cocaine, amphetamines and poly-SUD were associated with worse symptomatic and functional outcomes from the 1st year of treatment, persisting over time with higher service utilization (hospitalization).

The negative impact attributed to CUD in previous studies could be partly attributed to methodological flaws, like including polysubstance abusers among cannabis misusers. However, our investigation confirmed the negative effect of CUD on outcome. Attention should be paid to persistent cannabis misusers, since their condition seems to worsen over time, and to cocaine and amphetamine misusers, in view of their poorer outcome early during follow-up and high service utilization.