A population-based family clustering study of tic-related obsessive-compulsive disorder

Gustaf Brander,Henrik Larsson,Christian Rück,Ralf Kuja-Halkola,Eva Serlachius,Paul Lichtenstein,David Mataix-Cols,Mina A Rosenqvist,Lorena Fernández De La Cruz,James J Crowley

doi:10.1038/s41380-019-0532-z

Abstract

In the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), obsessive-compulsive disorder (OCD) included a new “tic-related” specifier. However, strong evidence supporting tic-related OCD as a distinct subtype of OCD is lacking. This study investigated whether, at the population level, tic-related OCD has a stronger familial load than non-tic-related OCD. From a cohort of individuals born in Sweden between 1967 and 2007 (n = 4,085,367; 1257 with tic-related OCD and 20,975 with non-tic-related OCD), we identified all twins, full siblings, maternal and paternal half siblings, and cousins. Sex- and birth year-adjusted hazard ratios (aHR) were calculated to estimate the risk of OCD in relatives of individuals with OCD with and without comorbid tics, compared with relatives of unaffected individuals. We found that OCD is a familial disorder, regardless of comorbid tic disorder status. However, the risk of OCD in relatives of individuals with tic-related OCD was considerably greater than the risk of OCD in relatives of individuals with non-tic-related OCD (e.g., risk for full siblings: aHR = 10.63 [95% CI, 7.92–14.27] and aHR = 4.52 [95% CI, 4.06–5.02], respectively; p value for the difference < 0.0001). These differences remained when the groups were matched by age at first OCD diagnosis and after various sensitivity analyses. The observed familial patterns of OCD in relation to tics were not seen in relation to other neuropsychiatric comorbidities. Tic-related OCD is a particularly familial subtype of OCD. The results have important implications for ongoing gene-searching efforts.

Highlights

Obsessive-compulsive disorder (OCD) is a heterogeneous disorder [1,2,3]
Studies have reported a greater number of psychiatric comorbidities [27] and higher rates of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) [25] in this patient group
In order to confirm the robustness of our results, we accounted for possible differences in age at first OCD diagnosis and examined whether ADHD- and ASD-related OCD were more familial than OCD alone

Summary

1234567890();,: 1234567890();,: Introduction

Patients endorse the specifier if they have a current or past history of a tic disorder, not necessarily concurrent with their OCD These patients present with typical clinical characteristics: earlier age of OCD onset [9, 20, 21], greater proportion of males [5, 9, 22,23,24], higher rates of symmetry and sexual/ aggressive obsessions [9, 24, 25], and sensory phenomena preceding the compulsions [22, 26]. It is possible that the higher familiality of tic-related OCD reflects the fact that tic disorders themselves are highly heritable [35, 36] If this were correct, the co-occurrence of OCD with any other highly heritable neuropsychiatric disorder, such as ADHD or ASD, would result in familial subtypes. In order to confirm the robustness of our results, we accounted for possible differences in age at first OCD diagnosis and examined whether ADHD- and ASD-related OCD were more familial than OCD alone

Methods

Results

Discussion

Strengths and limitations

Conclusions

Compliance with ethical standards