Genetic Risk for Psychosis Expressed as Cannabis Sensitivity

Genetic risk for psychotic disorder might be expressed in part as sensitivity to the psychotomimetic effect of cannabis. And, cannabis use, combined with this preexisting risk, might cause positive and negative symptoms of psychosis, according to new research published online Oct. 4.

© Ron Hilton/iStockphoto.com

Previous studies have suggested that exposure to delta-9-tetrahydrocannabinol, the main psychotropic component of Cannabis sativa, induces psychotic symptoms in a substantial proportion of healthy controls. Also, prospective epidemiological studies indicate that cannabis use not only predicts onset of psychotic disorder but also is associated with subthreshold expression of psychosis either in the form of schizotypy or subclinical psychotic experiences.

Data for this study come from the Genetic Risk and Outcome in Psychosis (GROUP) trial, an ongoing longitudinal study in selected areas of the Netherlands and Belgium (Arch. Gen. Psychiatry 2010 Oct. 4 [doi:10.1001/archgenpsychiatry.2010.132]). The GROUP sample consists of 1,120 patients with nonaffective psychotic disorder, 1,057 siblings of these patients, 919 parents of patients and their siblings, and 590 unrelated controls.

Researchers used urinalysis to measure current substance abuse, sections of the Composite International Diagnostic Interview to assess long-term substance abuse, and an interview-based measure of schizotypy for the sibling–healthy control comparison. They performed sibling-control and cross-sibling comparisons using samples of patients with a psychotic disorder and community controls.

The main outcome measures were positive and negative schizotypy using the Structured Interview for Schizotypy–Revised for siblings and controls and self-reported positive and negative psychotic experiences using the Community Assessment of Psychic Experiences (CAPE) for siblings and patients.

Patients and their siblings more often used cannabis than did control subjects, and more often were male and nonwhite, the researchers found. Additional results showed that:

• Siblings of patients displayed more than 15 times greater sensitivity to positive schizotypy associated with particularly current cannabis use by urinalysis, and a similar difference in sensitivity to its effect on negative schizotypy.

• Siblings exposed to cannabis resembled their patient relative nearly 10 times more closely in the positive psychotic dimension of CAPE vs. nonexposed siblings.

• No significant effect was apparent for the negative domain of CAPE, although the association was directionally similar (two times more resemblance; P interaction = .17).

• Cross-sibling, cross-trait analyses suggested that the mechanism underlying these findings was moderation (familial risk increasing sensitivity to cannabis) rather than mediation (familial risk increasing use of cannabis).

“An important issue revealed by this study is that while the relative effect sizes of differential sensitivity were high, absolute effect sizes, for example, of cannabis on schizotypy in unaffected siblings, were small,” the researchers wrote. “It therefore follows that any study examining differential sensitivity will require a very large sample to demonstrate differences in sensitivity for an environmental risk factor between groups.”

Disclosures: The authors had no financial disclosures. The infrastructure for the GROUP study received funding from the Geestkracht program of the Netherlands Organisation for Health Research and Development, and from numerous universities and mental health care organizations in the Netherlands and Belgium. The analyses were supported by unrestricted grants from Janssen-Cilag, Eli Lilly and Co., AstraZeneca, and Lundbeck.

Genetic risk for psychotic disorder might be expressed in part as sensitivity to the psychotomimetic effect of cannabis. And, cannabis use, combined with this preexisting risk, might cause positive and negative symptoms of psychosis, according to new research published online Oct. 4.

© Ron Hilton/iStockphoto.com

Previous studies have suggested that exposure to delta-9-tetrahydrocannabinol, the main psychotropic component of Cannabis sativa, induces psychotic symptoms in a substantial proportion of healthy controls. Also, prospective epidemiological studies indicate that cannabis use not only predicts onset of psychotic disorder but also is associated with subthreshold expression of psychosis either in the form of schizotypy or subclinical psychotic experiences.

Data for this study come from the Genetic Risk and Outcome in Psychosis (GROUP) trial, an ongoing longitudinal study in selected areas of the Netherlands and Belgium (Arch. Gen. Psychiatry 2010 Oct. 4 [doi:10.1001/archgenpsychiatry.2010.132]). The GROUP sample consists of 1,120 patients with nonaffective psychotic disorder, 1,057 siblings of these patients, 919 parents of patients and their siblings, and 590 unrelated controls.

Researchers used urinalysis to measure current substance abuse, sections of the Composite International Diagnostic Interview to assess long-term substance abuse, and an interview-based measure of schizotypy for the sibling–healthy control comparison. They performed sibling-control and cross-sibling comparisons using samples of patients with a psychotic disorder and community controls.

The main outcome measures were positive and negative schizotypy using the Structured Interview for Schizotypy–Revised for siblings and controls and self-reported positive and negative psychotic experiences using the Community Assessment of Psychic Experiences (CAPE) for siblings and patients.

Patients and their siblings more often used cannabis than did control subjects, and more often were male and nonwhite, the researchers found. Additional results showed that:

• Siblings of patients displayed more than 15 times greater sensitivity to positive schizotypy associated with particularly current cannabis use by urinalysis, and a similar difference in sensitivity to its effect on negative schizotypy.

• Siblings exposed to cannabis resembled their patient relative nearly 10 times more closely in the positive psychotic dimension of CAPE vs. nonexposed siblings.

• No significant effect was apparent for the negative domain of CAPE, although the association was directionally similar (two times more resemblance; P interaction = .17).

• Cross-sibling, cross-trait analyses suggested that the mechanism underlying these findings was moderation (familial risk increasing sensitivity to cannabis) rather than mediation (familial risk increasing use of cannabis).

“An important issue revealed by this study is that while the relative effect sizes of differential sensitivity were high, absolute effect sizes, for example, of cannabis on schizotypy in unaffected siblings, were small,” the researchers wrote. “It therefore follows that any study examining differential sensitivity will require a very large sample to demonstrate differences in sensitivity for an environmental risk factor between groups.”

Disclosures: The authors had no financial disclosures. The infrastructure for the GROUP study received funding from the Geestkracht program of the Netherlands Organisation for Health Research and Development, and from numerous universities and mental health care organizations in the Netherlands and Belgium. The analyses were supported by unrestricted grants from Janssen-Cilag, Eli Lilly and Co., AstraZeneca, and Lundbeck.

Genetic risk for psychotic disorder might be expressed in part as sensitivity to the psychotomimetic effect of cannabis. And, cannabis use, combined with this preexisting risk, might cause positive and negative symptoms of psychosis, according to new research published online Oct. 4.

© Ron Hilton/iStockphoto.com

Previous studies have suggested that exposure to delta-9-tetrahydrocannabinol, the main psychotropic component of Cannabis sativa, induces psychotic symptoms in a substantial proportion of healthy controls. Also, prospective epidemiological studies indicate that cannabis use not only predicts onset of psychotic disorder but also is associated with subthreshold expression of psychosis either in the form of schizotypy or subclinical psychotic experiences.

Data for this study come from the Genetic Risk and Outcome in Psychosis (GROUP) trial, an ongoing longitudinal study in selected areas of the Netherlands and Belgium (Arch. Gen. Psychiatry 2010 Oct. 4 [doi:10.1001/archgenpsychiatry.2010.132]). The GROUP sample consists of 1,120 patients with nonaffective psychotic disorder, 1,057 siblings of these patients, 919 parents of patients and their siblings, and 590 unrelated controls.

Researchers used urinalysis to measure current substance abuse, sections of the Composite International Diagnostic Interview to assess long-term substance abuse, and an interview-based measure of schizotypy for the sibling–healthy control comparison. They performed sibling-control and cross-sibling comparisons using samples of patients with a psychotic disorder and community controls.

The main outcome measures were positive and negative schizotypy using the Structured Interview for Schizotypy–Revised for siblings and controls and self-reported positive and negative psychotic experiences using the Community Assessment of Psychic Experiences (CAPE) for siblings and patients.

Patients and their siblings more often used cannabis than did control subjects, and more often were male and nonwhite, the researchers found. Additional results showed that:

• Siblings of patients displayed more than 15 times greater sensitivity to positive schizotypy associated with particularly current cannabis use by urinalysis, and a similar difference in sensitivity to its effect on negative schizotypy.

• Siblings exposed to cannabis resembled their patient relative nearly 10 times more closely in the positive psychotic dimension of CAPE vs. nonexposed siblings.

• No significant effect was apparent for the negative domain of CAPE, although the association was directionally similar (two times more resemblance; P interaction = .17).

• Cross-sibling, cross-trait analyses suggested that the mechanism underlying these findings was moderation (familial risk increasing sensitivity to cannabis) rather than mediation (familial risk increasing use of cannabis).

“An important issue revealed by this study is that while the relative effect sizes of differential sensitivity were high, absolute effect sizes, for example, of cannabis on schizotypy in unaffected siblings, were small,” the researchers wrote. “It therefore follows that any study examining differential sensitivity will require a very large sample to demonstrate differences in sensitivity for an environmental risk factor between groups.”

Disclosures: The authors had no financial disclosures. The infrastructure for the GROUP study received funding from the Geestkracht program of the Netherlands Organisation for Health Research and Development, and from numerous universities and mental health care organizations in the Netherlands and Belgium. The analyses were supported by unrestricted grants from Janssen-Cilag, Eli Lilly and Co., AstraZeneca, and Lundbeck.