<p id="d601924e164">Converging evidence suggests that psychosis emerges from the complex
genetic and environmental factors. Stressful life events (SLEs) play a prominent role
in combination with coping strategies and with a dysfunctional hypothalamus-pituitary-adrenal
axis (HPAA). It has been proposed that the framework of schizotypy might help disentangle
the interaction between genetic and environmental factors in the pathogenesis of psychosis.
Similarly, 22q11.2 deletion syndrome (22q11DS) is considered as a genetic model of
psychosis vulnerability. However, SLE and coping strategies remain largely unexplored
in 22q11DS. Moreover, the HPAA has not been systematically investigated in this population.
Here, we explored the correlation between SLE, emotional coping strategies, schizotypal
personality traits, subthreshold psychotic symptoms in a sample of 43 healthy controls
(HCs) compared with 59 individuals with 22q11DS. In the latter, we also explored the
correlation with pituitary volume as estimated from structural magnetic resonance
imaging. We found that SLE and negative coping strategies were correlated with schizotypal
personality traits in both HCs and 22q11DS, and with psychotic symptoms in the 22q11DS
group only, whereas reduced pituitary volume correlated with general psychopathology.
Moreover, dysfunctional coping mediated the effect of SLE on schizotypal personality
traits and psychotic symptoms in 22q11DS. Our findings recapitulate evidence in nonsyndromic
patients and confirm the central role of stress and coping in the pathogenesis of
psychosis. More broadly, they highlight the importance of environmental factors in
the pathway to psychosis in 22q11DS, suggesting a strong rationale for the implementation
of stress and particularly coping-oriented interventions in this population.