Association of Substance Use Disorders With Conversion From Schizotypal Disorder to Schizophrenia

Carsten Hjorthøj; Nikolai Albert; Merete Nordentoft

doi:10.1001/jamapsychiatry.2018.0568

Association of Substance Use Disorders With Conversion From Schizotypal Disorder to Schizophrenia

Carsten Hjorthøj, Nikolai Albert, Merete Nordentoft

Department of Clinical Medicine

10 Citations (Scopus)

Abstract

Importance: Understanding the role of substance use disorders in conversion from schizotypal disorder to schizophrenia may provide physicians and psychiatrists with important tools for prevention or early detection of schizophrenia.

Objective: To investigate whether substance use disorders, in particular cannabis use disorder, are associated with conversion to schizophrenia in individuals with schizotypal disorder.

Design, Setting, and Participants: This prospective cohort study included a population-based sample of all individuals born in Denmark from January 1, 1981, through August 10, 2014, with an incident diagnosis of schizotypal disorder and without a previous diagnosis of schizophrenia. Follow-up was completed on August 10, 2014, and data were analyzed from March 10, 2017, through February 15, 2018.

Exposures: Information on substance use disorders combined from 5 different registers.

Main Outcomes and Measures: Cox proportional hazards regression using time-varying information on substance use disorders and receipt of antipsychotics and adjusted for parental history of mental disorders, sex, birth year, and calendar year were used to estimate hazard ratios (HRs) and 95% CIs for conversion to schizophrenia.

Results: A total of 2539 participants with incident schizotypal disorder were identified (1448 men [57.0%] and 1091 women [43.0%]; mean [SD] age, 20.9 [4.4] years). After 2 years, 16.3% (95% CI, 14.8%-17.8%) experienced conversion to schizophrenia. After 20 years, the conversion rate was 33.1% (95% CI, 29.3%-37.3%) overall and 58.2% (95% CI, 44.8%-72.2%) among those with cannabis use disorders. In fully adjusted models, any substance use disorder was associated with conversion to schizophrenia (HR, 1.34; 95% CI, 1.11-1.63). When data were stratified by substance, cannabis use disorders (HR, 1.30; 95% CI, 1.01-1.68), amphetamine use disorders (HR, 1.90; 95% CI, 1.14-3.17), and opioid use disorders (HR, 2.74; 95% CI, 1.38-5.45) were associated with conversion to schizophrenia. These associations were not explained by concurrent use of antipsychotics, functional level before incident schizotypal disorder, or parental history of mental disorders.

Conclusions and Relevance: Substance use disorders, in particular cannabis, amphetamines, and opioids, may be associated with conversion from schizotypal disorder to schizophrenia. However, conversion rates are high even in those without substance use disorders, indicating a need for universal and substance-targeted prevention in individuals with schizotypal disorder.

Original language	English
Journal	JAMA Psychiatry
Volume	75
Issue number	7
Pages (from-to)	733-739
ISSN	2168-622X
DOIs	https://doi.org/10.1001/jamapsychiatry.2018.0568
Publication status	Published - Jul 2018

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@article{acd92702873a41879fe078fb27d0633a,

title = "Association of Substance Use Disorders With Conversion From Schizotypal Disorder to Schizophrenia",

abstract = "Importance: Understanding the role of substance use disorders in conversion from schizotypal disorder to schizophrenia may provide physicians and psychiatrists with important tools for prevention or early detection of schizophrenia.Objective: To investigate whether substance use disorders, in particular cannabis use disorder, are associated with conversion to schizophrenia in individuals with schizotypal disorder.Design, Setting, and Participants: This prospective cohort study included a population-based sample of all individuals born in Denmark from January 1, 1981, through August 10, 2014, with an incident diagnosis of schizotypal disorder and without a previous diagnosis of schizophrenia. Follow-up was completed on August 10, 2014, and data were analyzed from March 10, 2017, through February 15, 2018.Exposures: Information on substance use disorders combined from 5 different registers.Main Outcomes and Measures: Cox proportional hazards regression using time-varying information on substance use disorders and receipt of antipsychotics and adjusted for parental history of mental disorders, sex, birth year, and calendar year were used to estimate hazard ratios (HRs) and 95% CIs for conversion to schizophrenia.Results: A total of 2539 participants with incident schizotypal disorder were identified (1448 men [57.0%] and 1091 women [43.0%]; mean [SD] age, 20.9 [4.4] years). After 2 years, 16.3% (95% CI, 14.8%-17.8%) experienced conversion to schizophrenia. After 20 years, the conversion rate was 33.1% (95% CI, 29.3%-37.3%) overall and 58.2% (95% CI, 44.8%-72.2%) among those with cannabis use disorders. In fully adjusted models, any substance use disorder was associated with conversion to schizophrenia (HR, 1.34; 95% CI, 1.11-1.63). When data were stratified by substance, cannabis use disorders (HR, 1.30; 95% CI, 1.01-1.68), amphetamine use disorders (HR, 1.90; 95% CI, 1.14-3.17), and opioid use disorders (HR, 2.74; 95% CI, 1.38-5.45) were associated with conversion to schizophrenia. These associations were not explained by concurrent use of antipsychotics, functional level before incident schizotypal disorder, or parental history of mental disorders.Conclusions and Relevance: Substance use disorders, in particular cannabis, amphetamines, and opioids, may be associated with conversion from schizotypal disorder to schizophrenia. However, conversion rates are high even in those without substance use disorders, indicating a need for universal and substance-targeted prevention in individuals with schizotypal disorder.",

author = "Carsten Hjorth{\o}j and Nikolai Albert and Merete Nordentoft",

year = "2018",

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T1 - Association of Substance Use Disorders With Conversion From Schizotypal Disorder to Schizophrenia

AU - Hjorthøj, Carsten

AU - Albert, Nikolai

AU - Nordentoft, Merete

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N2 - Importance: Understanding the role of substance use disorders in conversion from schizotypal disorder to schizophrenia may provide physicians and psychiatrists with important tools for prevention or early detection of schizophrenia.Objective: To investigate whether substance use disorders, in particular cannabis use disorder, are associated with conversion to schizophrenia in individuals with schizotypal disorder.Design, Setting, and Participants: This prospective cohort study included a population-based sample of all individuals born in Denmark from January 1, 1981, through August 10, 2014, with an incident diagnosis of schizotypal disorder and without a previous diagnosis of schizophrenia. Follow-up was completed on August 10, 2014, and data were analyzed from March 10, 2017, through February 15, 2018.Exposures: Information on substance use disorders combined from 5 different registers.Main Outcomes and Measures: Cox proportional hazards regression using time-varying information on substance use disorders and receipt of antipsychotics and adjusted for parental history of mental disorders, sex, birth year, and calendar year were used to estimate hazard ratios (HRs) and 95% CIs for conversion to schizophrenia.Results: A total of 2539 participants with incident schizotypal disorder were identified (1448 men [57.0%] and 1091 women [43.0%]; mean [SD] age, 20.9 [4.4] years). After 2 years, 16.3% (95% CI, 14.8%-17.8%) experienced conversion to schizophrenia. After 20 years, the conversion rate was 33.1% (95% CI, 29.3%-37.3%) overall and 58.2% (95% CI, 44.8%-72.2%) among those with cannabis use disorders. In fully adjusted models, any substance use disorder was associated with conversion to schizophrenia (HR, 1.34; 95% CI, 1.11-1.63). When data were stratified by substance, cannabis use disorders (HR, 1.30; 95% CI, 1.01-1.68), amphetamine use disorders (HR, 1.90; 95% CI, 1.14-3.17), and opioid use disorders (HR, 2.74; 95% CI, 1.38-5.45) were associated with conversion to schizophrenia. These associations were not explained by concurrent use of antipsychotics, functional level before incident schizotypal disorder, or parental history of mental disorders.Conclusions and Relevance: Substance use disorders, in particular cannabis, amphetamines, and opioids, may be associated with conversion from schizotypal disorder to schizophrenia. However, conversion rates are high even in those without substance use disorders, indicating a need for universal and substance-targeted prevention in individuals with schizotypal disorder.

AB - Importance: Understanding the role of substance use disorders in conversion from schizotypal disorder to schizophrenia may provide physicians and psychiatrists with important tools for prevention or early detection of schizophrenia.Objective: To investigate whether substance use disorders, in particular cannabis use disorder, are associated with conversion to schizophrenia in individuals with schizotypal disorder.Design, Setting, and Participants: This prospective cohort study included a population-based sample of all individuals born in Denmark from January 1, 1981, through August 10, 2014, with an incident diagnosis of schizotypal disorder and without a previous diagnosis of schizophrenia. Follow-up was completed on August 10, 2014, and data were analyzed from March 10, 2017, through February 15, 2018.Exposures: Information on substance use disorders combined from 5 different registers.Main Outcomes and Measures: Cox proportional hazards regression using time-varying information on substance use disorders and receipt of antipsychotics and adjusted for parental history of mental disorders, sex, birth year, and calendar year were used to estimate hazard ratios (HRs) and 95% CIs for conversion to schizophrenia.Results: A total of 2539 participants with incident schizotypal disorder were identified (1448 men [57.0%] and 1091 women [43.0%]; mean [SD] age, 20.9 [4.4] years). After 2 years, 16.3% (95% CI, 14.8%-17.8%) experienced conversion to schizophrenia. After 20 years, the conversion rate was 33.1% (95% CI, 29.3%-37.3%) overall and 58.2% (95% CI, 44.8%-72.2%) among those with cannabis use disorders. In fully adjusted models, any substance use disorder was associated with conversion to schizophrenia (HR, 1.34; 95% CI, 1.11-1.63). When data were stratified by substance, cannabis use disorders (HR, 1.30; 95% CI, 1.01-1.68), amphetamine use disorders (HR, 1.90; 95% CI, 1.14-3.17), and opioid use disorders (HR, 2.74; 95% CI, 1.38-5.45) were associated with conversion to schizophrenia. These associations were not explained by concurrent use of antipsychotics, functional level before incident schizotypal disorder, or parental history of mental disorders.Conclusions and Relevance: Substance use disorders, in particular cannabis, amphetamines, and opioids, may be associated with conversion from schizotypal disorder to schizophrenia. However, conversion rates are high even in those without substance use disorders, indicating a need for universal and substance-targeted prevention in individuals with schizotypal disorder.

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DO - 10.1001/jamapsychiatry.2018.0568

M3 - Journal article

C2 - 29710317

SN - 2168-622X

VL - 75

SP - 733

EP - 739

JO - JAMA Psychiatry

JF - JAMA Psychiatry

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Association of Substance Use Disorders With Conversion From Schizotypal Disorder to Schizophrenia

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