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Original Investigation |

Obsessive-Compulsive Disorder as a Risk Factor for Schizophrenia:  A Nationwide Study

Sandra M. Meier, PhD1,2; Liselotte Petersen, PhD1,2; Marianne G. Pedersen, MSc1,2; Mikkel C. B. Arendt, PhD3,4; Philip R. Nielsen, PhD, MSc1,2; Manuel Mattheisen, MD1,5; Ole Mors, MD, PhD1,6; Preben B. Mortensen, DrMedSc1,2
[+] Author Affiliations
1The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark
2National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
3Clinic for Anxiety Disorders, Aarhus University Hospital, Risskov, Denmark
4Department of Psychology and Behavioral Sciences, Aarhus University, Aarhus, Denmark
5Department of Biomedicine, Aarhus University, Aarhus, Denmark
6Research Department P, Aarhus University Hospital, Risskov, Denmark
JAMA Psychiatry. 2014;71(11):1215-1221. doi:10.1001/jamapsychiatry.2014.1011.
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Importance  Despite a remarkable co-occurrence of obsessive-compulsive disorder (OCD) and schizophrenia, little is known about the clinical and etiological relationship of these 2 disorders. Exploring the degree to which these disorders share etiological factors might provide useful implications for clinicians, researchers, and those with the disorders.

Objectives  To assess whether patients with OCD experience an enhanced risk of developing schizophrenia and schizophrenia spectrum disorders and to determine whether a family history of OCD constitutes a risk factor for schizophrenia and schizophrenia spectrum disorders.

Design, Setting, and Participants  Using individual data from longitudinal nationwide Danish registers, we conducted a prospective cohort study with 45 million person-years of follow-up. All survival analyses were adjusted for sex, age, calendar year, parental age, and place of residence at the time of birth. A total of 3 million people born between January 1, 1955, and November 30, 2006, were followed up from January 1, 1995, through December 31, 2012. During this period, 30 556 people developed schizophrenia or schizophrenia spectrum disorders.

Main Outcomes and Measures  The presence of a prior diagnosis of OCD and the risk of a first lifetime diagnosis of schizophrenia and a schizophrenia spectrum disorder assigned by a psychiatrist in a hospital, outpatient clinic, or emergency department setting. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals are used as measures of relative risk.

Results  The presence of prior diagnosis of OCD was associated with an increased risk of developing schizophrenia (IRR = 6.90; 95% CI, 6.25-7.60) and schizophrenia spectrum disorders (IRR = 5.77; 95% CI, 5.33-6.22) later in life. Similarly, offspring of parents diagnosed as having OCD had an increased risk of schizophrenia (IRR = 4.31; 95% CI, 2.72-6.43) and schizophrenia spectrum disorders (IRR = 3.10; 95% CI, 2.17-4.27). The results remained significant after adjusting for family history of psychiatric disorders and the patient’s psychiatric history.

Conclusions and Relevance  A diagnosis of OCD was associated with higher rates of schizophrenia and schizophrenia spectrum disorders. The observed increase in risk suggests that OCD, schizophrenia, and schizophrenia spectrum disorders probably lay on a common etiological pathway.

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Incidence Rate Ratios

Incidence rate ratios, with 95% confidence intervals (error bars), of schizophrenia and schizophrenia spectrum disorder in offspring of parents with schizophrenia, schizophrenia spectrum disorder, obsessive-compulsive disorder, and other psychiatric diagnosis.

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