Beng-Choon Ho, MRCPsych; Nancy C. Andreasen, MD, PhD; Steven Ziebell, BS; et al.
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Arch Gen Psychiatry. 2011;68(2):128-137. doi:10.1001/archgenpsychiatry.2010.199
Genetic Risk and Outcome in Psychosis (GROUP) Investigators
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Arch Gen Psychiatry. 2011;68(2):138-147. doi:10.1001/archgenpsychiatry.2010.132
ContextIndividual differences in cannabis sensitivity may be associated with genetic risk for psychotic disorder.ObjectivesTo demonstrate and replicate, using 2 conceptually different genetic epidemiological designs, that (familial) liability to psychosis is associated with sensitivity to cannabis.Design, Setting, and ParticipantsSibling-control and cross-sibling comparisons using samples of patients with a psychotic disorder (n聽=聽1120), their siblings (n聽=聽1057), and community controls (n聽=聽590) in the Netherlands and Flanders.Main Outcome MeasuresPositive and negative schizotypy using the Structured Interview for Schizotypy鈥揜evised (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).ResultsIn 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听=听0.197, P聽<聽.001) than controls (adjusted B听=听0.013, P聽=聽.86) (P interaction聽=聽.04) and a similar difference in sensitivity to its effect on negative schizotypy (siblings: adjusted B听=听0.120, P聽<聽.001; controls: B听=听鈭�0.008, P听=听.87; P interaction聽=聽.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听=听0.278, P聽<聽.001) compared with nonexposed siblings (adjusted B听=听0.025, P聽=聽.12) (P interaction聽<聽.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聽=聽.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).ConclusionsGenetic 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.
Ruud van Winkel, MD, MSc, PhD; Genetic Risk and Outcome of Psychosis (GROUP) Investigators
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Arch Gen Psychiatry. 2011;68(2):148-157. doi:10.1001/archgenpsychiatry.2010.152
ContextIndividual differences exist in sensitivity to the psychotomimetic effect of cannabis; the molecular genetic basis underlying differential sensitivity remains elusive.ObjectiveTo investigate whether selected schizophrenia candidate single-nucleotide polymorphisms (SNPs) moderate effects of cannabis use.DesignInteractions between recent cannabis use, determined by urinalysis results, and 152 SNPs in 42 candidate genes were examined in 740 unaffected siblings of 801 patients with psychosis to examine genetic moderation of the association between Structured Interview for Schizotypy鈥揜evised positive schizotypy and recent cannabis use (at-risk paradigm). The SNPs showing Bonferroni-adjusted association in the at-risk paradigm were used in a case-only analysis in the 801 patients, as well as in a case-sibling and case-control analysis (using 419 controls) focusing on genetic moderation of developmental effects of cannabis on later psychotic disorder.SettingThe Netherlands and Flanders, Belgium.ParticipantsEight hundred one patients with psychosis and their 740 unaffected siblings.Main Outcome MeasureSignificant interaction between any of the selected SNPs and cannabis in the at-risk paradigm, followed by selective case-only, case-sibling, and case-control analyses.ResultsIn the unaffected siblings, 16 SNPs in 12 genes showed significant interaction at P聽<聽.05, 3 of which survived correction for multiple testing (P聽<聽.0003), situated in AKT1 (rs2494732 and rs1130233) and LRRTM1 (rs673871). Follow-up analysis supported AKT1 rs2494732聽脳聽cannabis interaction in the case-only (尾聽=聽0.20; P聽=聽.007), case-sibling (interaction P聽=聽.040), and case-control (interaction P聽=聽.057) analyses, with individuals with C/C genotypes having an approximately 2-fold odds of being diagnosed with a psychotic disorder when having used cannabis. In the unaffected siblings, the AKT1聽脳聽cannabis interaction explained 2.2% additional variance in schizotypy in the whole sample and 19.0% additional variance in the exposed siblings with recent cannabis use.ConclusionsGenetic variation in AKT1 may mediate both short-term as well as longer-term effects on psychosis expression associated with use of cannabis, possibly through a mechanism of cannabinoid-regulated AKT1/GSK-3 signaling downstream of the dopamine D2 receptor.
Brian J. Mickey, MD, PhD; Zhifeng Zhou, PhD; Mary M. Heitzeg, PhD; et al.
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Arch Gen Psychiatry. 2011;68(2):158-166. doi:10.1001/archgenpsychiatry.2010.197
Henry J. Steadman, PhD; Allison Redlich, PhD; Lisa Callahan, PhD; et al.
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Arch Gen Psychiatry. 2011;68(2):167-172. doi:10.1001/archgenpsychiatry.2010.134
ContextMental health courts are growing in popularity as a form of jail diversion for justice system鈥搃nvolved people with serious mental illness. This is the first prospective multisite study on mental health courts with treatment and control groups.ObjectivesTo determine if participation in a mental health court is associated with more favorable criminal justice outcomes than processing through the regular criminal court system and to identify defendants for whom mental health courts produce the most favorable criminal justice outcomes.DesignLongitudinal study.SettingFour mental health courts in San Francisco County, CA, Santa Clara County, CA, Hennepin County (Minneapolis), MN, and Marion County (Indianapolis), IN.ParticipantsA total 447 persons in the mental health court (MHC) and 600 treatment-as-usual (TAU) controls.InterventionEighteen months of pre-entry and postentry data for 4 jurisdictions. All subjects were interviewed at baseline, and 70% were interviewed at 6 months. Objective outcome data were obtained on all subjects from Federal Bureau of Investigation arrest records, jails, prisons, and community treatment providers.Main Outcome MeasuresAnnualized rearrest rates, number of rearrests, and postentry incarceration days.ResultsThe MHC and TAU samples are similar on the major outcome measures in the pre-entry 18-month period. In the 18 months following treatment, defined as entry into mental health court, the MHC group has a lower annualized rearrest rate, fewer post鈥�18-month arrests, and fewer post鈥�18-month incarceration days than the TAU group. The MHC graduates had lower rearrest rates than participants whose participation was terminated both during MHC supervision and after supervision ended. Factors associated with better outcomes among the MHC participants include lower pre鈥�18-month arrests and incarceration days, treatment at baseline, not using illegal substances, and a diagnosis of bipolar disorder rather than schizophrenia or depression.ConclusionsMental health courts meet the public safety objectives of lowering posttreatment arrest rates and days of incarceration. Both clinical and criminal justice factors are associated with better public safety outcomes for MHC participants.
Carol S. North, MD, MPE; Christopher L. Ringwalt, DrPH; Dana Downs, MSW; et al.
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Arch Gen Psychiatry. 2011;68(2):173-180. doi:10.1001/archgenpsychiatry.2010.131
ContextAlthough several studies have suggested that alcohol use may increase after disasters, it is unclear whether any apparent postdisaster increases regularly translate into new cases of alcohol use disorders.ObjectiveTo determine the relationship of predisaster and postdisaster prevalence of alcohol use disorders and to examine the incidence of alcohol use disorders in relation to disasters.DesignData from 10 disasters, studied within the first few postdisaster months and at 1 to 3 years postdisaster, were merged and examined.ParticipantsSix hundred ninety-seven directly exposed survivors of 10 disasters.MeasuresThe Diagnostic Interview Schedule for DSM-III-R provided lifetime diagnoses of alcohol abuse and dependence, and onset and recency questions allowed a determination of whether the disorder had been present either prior to or following the event, or both.ResultsWhile the postdisaster prevalence of alcohol use disorders was 19%, only 0.3% of the sample developed an acute new postdisaster alcohol use disorder. Most of those in recovery, however, consumed alcohol after the disaster (83%) and coped with their emotions by drinking alcohol (22%). Those with a postdisaster alcohol use disorder were more than 4 times as likely as those without to cope with their disaster-related emotions by drinking alcohol (40% vs 9%).ConclusionsThe vast majority of postdisaster alcohol use disorders represented the continuation or recurrence of preexisting problems. Findings suggest that those in recovery as well as those who drink to cope with their emotions represent groups warranting potential concern for postdisaster mental health intervention. Further research is needed to clarify the clinical significance of changes in alcohol use after disasters.
Benjamin B. Lahey, PhD; Carol A. Van Hulle, PhD; Amber L. Singh, PhD; et al.
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Arch Gen Psychiatry. 2011;68(2):181-189. doi:10.1001/archgenpsychiatry.2010.192
Helen C. Kales, MD; Kara Zivin, PhD; Hyungjin Myra Kim, ScD; et al.
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Arch Gen Psychiatry. 2011;68(2):190-197. doi:10.1001/archgenpsychiatry.2010.200
Aristotle N. Voineskos, MD, PhD, FRCPC; Jason P. Lerch, PhD; Daniel Felsky, BSc; et al.
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Arch Gen Psychiatry. 2011;68(2):198-206. doi:10.1001/archgenpsychiatry.2010.194
Brit-Maren M. Schjeide, BS; Cathrin Schnack, PhD; Jean-Charles Lambert, PhD; et al.
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Arch Gen Psychiatry. 2011;68(2):207-213. doi:10.1001/archgenpsychiatry.2010.196
Scott Y. H. Kim, MD, PhD; Jason H. Karlawish, MD; H. Myra Kim, ScD; et al.
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Arch Gen Psychiatry. 2011;68(2):214-219. doi:10.1001/archgenpsychiatry.2010.191