Familial Risk Plays a Moderate Role in Substance-Induced Psychotic Disorder

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Schizophrenia subsequent to substance-induced psychosis is likely a drug-precipitated disorder in highly vulnerable individuals, not a syndrome resulting from drug exposure.

Substance-induced psychotic disorder occurs in individuals with a high familial risk for drug and alcohol abuse and a moderate familial susceptibility to psychosis, according to the results of a Swedish study that were published in the American Journal of Psychiatry. The results suggest an interaction between substantial drug exposure and a genetic risk for psychosis.

Kenneth S. Kendler, MD, of the Virginia Institute for Psychiatric and Behavioral Genetics and the Department of Psychiatry, Virginia Commonwealth University in Richmond, and colleagues, used data from Swedish national medical registries to identify individuals with substance-induced psychotic disorder between 1997 and 2015 (n=7606) and followed them for a mean of 84 months. In addition, they analyzed data from medical, criminal, and pharmacy registries on first-degree through third-degree relatives to calculate familial risk scores for nonaffective psychosis, drug abuse, and alcohol use disorder. The investigators looked to clarify the etiology of substance-induced psychotic disorder and its progression to schizophrenia.

The data showed that individuals who developed substance-induced psychotic disorder had higher familial risk scores for drug abuse (+1.09) and alcohol use disorder (+0.98) and modest elevations for nonaffective psychosis (+0.35). The lowest risk for progression to schizophrenia was found in individuals who had alcohol-induced psychotic disorder and highest in individuals with cannabis-induced psychotic disorder. Other risk factors included early age at diagnosis of substance-induced psychotic disorder, male sex, and additional incidents of drug abuse, alcohol use disorder, and substance-induced psychotic disorder.

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The overall risk for progression to schizophrenia was 11.3%. While familial history of drug abuse and alcohol use disorder did not increase the risk for progression to schizophrenia, a familial history of nonaffective psychosis did.

The study was limited by its use of a purely Swedish database, which may reduce the ability to extrapolate these conclusions to other populations, and by the nature of obtaining data from registries.

“Substance-induced psychotic disorder appears to result from substantial drug exposure in individuals at high familial risk for substance abuse and moderately elevated familial risk for psychosis. Familial risk for psychosis, but not substance abuse, predicts progression from substance induced psychosis to schizophrenia,” the investigators concluded.


Kendler KS, Ohlsson H, Sundquist J, Sundquist K. Prediction of onset of substance-induced psychotic disorder and its progression to schizophrenia in a Swedish national sample. Am J Psychiatry [published online May 6, 2019]. doi:10.1176/appi.ajp.2019.18101217