What Causes the Onset of Psychosis in Individuals at Clinical High Risk? A Meta-analysis of Risk and Protective Factors

Abstract

Twenty percent of individuals at clinical high risk for psychosis (CHR-P) develop the disorder within 2 years. Extensive research has explored the factors that differentiate those who develop psychosis and those who do not, but the results are conflicting. The current systematic review and meta-analysis comprehensively addresses the consistency and magnitude of evidence for non-purely genetic risk and protective factors associated with the risk of developing psychosis in CHR-P individuals. Random effects meta-analyses, standardized mean difference (SMD) and odds ratio (OR) were used, in combination with an established stratification of evidence that assesses the association of each factor and the onset of psychotic disorders (from class I, convincing evidence to class IV weak evidence), while controlling for several types of biases. A total of 128 original controlled studies relating to 26 factors were retrieved. No factors showed class I-convincing evidence. Two further factors were associated with class II-highly suggestive evidence: attenuated positive psychotic symptoms (SMD = 0.348, 95% CI: 0.280, 0.415) and global functioning (SMD = −0.291, 95% CI: −0.370, −0.211). There was class III-suggestive evidence for negative psychotic symptoms (SMD = 0.393, 95% CI: 0.317, 0.469). There was either class IV-weak or no evidence for all other factors. Our findings suggest that despite the large number of putative risk factors investigated in the literature, only attenuated positive psychotic symptoms, global functioning, and negative psychotic symptoms show suggestive evidence or greater for association with transition to psychosis. The current findings may inform the refinement of clinical prediction models and precision medicine in this field.

Progression from being at-risk to psychosis: next steps

“…Thus, this dynamic model appeared to be a better method for prediction of transition to psychosis in CHR. The second paper is one of the first and largest meta-analysis of both risk and protective factors that might predict transition 47 . Reviewing 128 studies and 26 potential risk factors, the authors identified the most robust risk factors for psychosis against different types of biases 48 , classifying the levels of evidence of the association as convincing (Class I), highly suggestive (Class II), suggestive (Class III) and not met or weak (Class IV).…”

Prenatal and perinatal risk and protective factors for psychosis: a systematic review and meta-analysis

“…Since that time, prospective studies have established the long-term consequences of pre-and perinatal hazards on exposed infants 24,25 . These, and also umbrella reviews 26 (meta-analyses of meta-analyses) have revealed that numerous pre-and perinatal risk factors are associated not only with psychosis but with a range of cognitive and neurological abnormalities as well as other psychiatric and neurodevelopmental disorders [27][28][29][30][31][32] ; neuroimaging studies have demonstrated that when such infants reach adulthood they show an excess of brain structural and dopaminergic abnormalities reminiscent of those found in patients with schizophrenia 25,33 .…”

Clinical High Risk Psychosis: Issues of Diagnostics and Therapy

“…Имеются данные о том, что не только АПС, но и первичные негативные симптомы, возникающие на доманифестных этапах эндогенного процесса [17,35,36], ассоциированы с риском манифестации психоза [37]. Установлено, что они встречаются у 85% пациентов из группы КВР-П [38].…”