Wednesday, October 6, 2010

Evidence That Familial Liability for Psychosis Is Expressed as Differential Sensitivity to Cannabis


The abstract of a paper posted online on October 4th by the journal Archives of General Psychiatry:

An Analysis of Patient-Sibling and Sibling-Control Pairs

By Genetic Risk and Outcome in Psychosis (GROUP) Investigators

Context

Individual differences in cannabis sensitivity may be associated with genetic risk for psychotic disorder.

Objectives

To demonstrate and replicate, using 2 conceptually different genetic epidemiological designs, that (familial) liability to psychosis is associated with sensitivity to cannabis.

Design, Setting, and Participants

Sibling-control and cross-sibling comparisons using samples of patients with a psychotic disorder (n = 1120), their siblings (n = 1057), and community controls (n = 590) in the Netherlands and Flanders.

Main Outcome Measures

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 (for siblings and patients). Cannabis use was assessed as current use (by urinalysis) and lifetime frequency of use (by Composite International Diagnostic Interview).

Results

In the sibling-control comparison, siblings displayed more than 15 times greater sensitivity to positive schizotypy associated with particularly current cannabis use by urinalysis (adjusted B = 0.197, P < .001) than controls (adjusted B = 0.013, P = .86) (P interaction = .04) and a similar difference in sensitivity to its effect on negative schizotypy (siblings: adjusted B = 0.120, P < .001; controls: B = –0.008, P = .87; P interaction = .03). Similarly, siblings exposed to cannabis resembled their patient relative nearly 10 times more closely in the positive psychotic dimension of the Community Assessment of Psychic Experiences (adjusted B = 0.278, P < .001) compared with nonexposed siblings (adjusted B = 0.025, P = .12) (P interaction < .001). No significant effect was apparent for the Community Assessment of Psychic Experiences negative domain, although the association was directionally similar (2 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).

Conclusions

Genetic risk for psychotic disorder may be expressed in part as sensitivity to the psychotomimetic effect of cannabis. Cannabis use may synergistically combine with preexisting psychosis liability to cause positive and negative symptoms of psychosis.

Author Affiliations:

René S. Kahn MD, PhD, Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands; Don H.Linszen MD, PhD, Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Jim van Os MD, PhD, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Centre, Maastricht, the Netherlands, and King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom; Durk Wiersma PhD, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Richard Bruggeman MD, PhD, Department of Psychiatry, University Medical Center Groningen, University of Groningen; Wiepke Cahn MD, PhD, Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht; Lieuwe de Haan MD, PhD, Department of Psychiatry, Academic Medical Centre, University of Amsterdam; Lydia Krabbendam PhD, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Centre; and Inez Myin-Germeys PhD, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Centre.

Posting of this abstract is for the purposes of research into psychosis and schizophrenia.

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