An etiological approach to psychosis: potential benefits for treatment, research and prevention.

Current treatment of psychosis focuses on antipsychotic medication, and rarely addresses the factors that have contributed to the onset and persistence of the disorder. We suggest that the most useful way of facilitating treatment, research and prevention is to identify the causal risk factors to which psychotic patients have been exposed. Operating on a background of genetic vulnerability, the main types of environmental risk factors for psychosis comprise impaired neurodevelopment, substance abuse, and social adversity. In most patients with psychosis, striatal dopamine dysfunction, often mediated by disrupted gamma-aminobutyric acid (GABA)ergic and glutamatergic signaling in the hippocampus, appears to be the final common pathway from those distal risk factors to positive symptoms. There are clinical and biological differences among individuals who develop psychosis following exposure to the different risk factors. For example, those with impaired neurodevelopment are more likely to show minor physical anomalies or soft neurological signs, cognitive deficits, and brain structural abnormalities. Individualized interventions need to be offered to those patients who have been exposed to particular risk factors. For example, in addition to antipsychotic medication, patients who continue to use cannabis should be offered cognitive behavioral/motivational therapy to decrease their substance consumption, while patients who were exposed to child abuse could be offered trauma-based therapy, and antidepressants as appropriate. Of course, many patients have been exposed to more than one type of risk factor. Such patients deserve therapeutic action directed to each of those risk pathways. In addition to promoting individualized treatment, attention to etiology could benefit research, allowing the study of psychological and biological characteristics of patients whose psychosis appears to have resulted predominantly from one particular risk factor, and could open the door to universal and selective preventive strategies to decrease psychosis incidence through reducing exposure to risk factors.