Exploring causal mechanisms of psychosis risk

Abstract

Robust epidemiological evidence of risk and protective factors for psychosis is essential to inform preventive interventions. Previous evidence syntheses have classified these risk and protective factors according to their strength of association with psychosis. In this critical review we appraise the distinct and overlapping mechanisms of 25 key environmental risk factors for psychosis, and link these to mechanistic pathways that may contribute to neurochemical alterations hypothesised to underlie psychotic symptoms. We then discuss the implications of our findings for future research, specifically considering interactions between factors, exploring universal and subgroup-specific factors, improving understanding of temporality and risk dynamics, standardising operationalisation and measurement of risk and protective factors, and developing preventive interventions targeting risk and protective factors.

Keywords: Dopamine; Glutamate; Neurobiology; Neurodevelopment; Prevention; Psychosis; Risk factors.

Fig. 1

Summary figure illustrating a hypothetical potential trajectory to psychosis onset. This represents a single potential causal pie of many and may not represent an accurate portrayal of disorder progression, with included risk factors, pathways and their effects being purely illustrative. In this example, the mother of this individual experienced obstetric complications during pregnancy leading to neurodevelopmental abnormalities and inflammatory priming, increasing psychosis risk but not enough to lead to psychosis onset. Psychosocial stress led to another increase in psychosis risk before cannabis use led to further increased risk. The resultant changes led to the onset of attenuated psychotic symptoms, drop in global functioning and CHR-P onset. Further psychosocial stress increases risk and resulted in transition to psychosis. This hypothetical causal pathway is one of many potential trajectories to psychosis onset.