Risk factors and health consequences of obsessive-compulsive and chronic tic disorders

Abstract

Background: Obsessive-compulsive disorder (OCD) is a severe and heterogenous mental disorder characterized by intrusive thoughts, urges or images, followed by repetitive behaviors aimed to reduce the associated anxiety. Tic disorders are neurodevelopmental movement disorders consisting of recurring, involuntary, rapid, and sudden non-rhythmic motor movements or vocalizations. While OCD affects approximately 2% of the population and tic disorders affect about 1% of the population, a much smaller proportion of individuals seek help and come into contact with health services. Both disorders are associated with considerable distress and impairment. Little is known about the etiology and long-term health consequences of OCD and tic disorders. Tic-related OCD may constitute a biologically meaningful subtype of OCD but current evidence supporting this is incomplete.

Aims: The overarching aims of the studies in this thesis are: to synthesize the literature on potential environmental risk factors for OCD, to identify perinatal risk factors that may be in the causal pathway to OCD and tic disorders, to examine the validity of tic-related OCD as a potentially meaningful subtype of OCD, and to examine the risk of metabolic and cardiovascular disorders in individuals with OCD and tic disorders.

Methods: In study I we conducted a systematic review of potential environmental risk factors for OCD following the PRISMA guidelines. In studies II and III, we used population-based birth cohorts to estimate the risk of OCD and tic disorders in individuals with a range of perinatal events, including maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age, birth weight, Apgar score, and head circumference, compared to the unaffected general population. In study IV, we used a birth cohort to estimate the risk of OCD in relatives of individuals with OCD with and without comorbid tics, compared to relatives of unaffected individuals. In studies V and VI, we used total population cohorts to estimate the risk of metabolic and cardiovascular disorders in individuals with OCD or tic disorders, compared to the unaffected general population. Studies II, III, V, and VI applied sibling comparison designs to further control for shared familial confounding, and the role of other co-occurring psychiatric conditions was systematically evaluated. All studies adjusted for measured confounders.

Results: Including 128 studies of environmental risk factors for OCD, study I found that the methodological limitations of these studies precluded drawing strong conclusions. However, the systematic review identified several promising areas of potential risk factors, which could be considered as reasonable starting points for further research. Studies II and III found that several adverse perinatal events were associated with an increased risk of OCD and tic disorders, independent from measured confounders and unmeasured familial confounding. These perinatal events included breech presentation, cesarean section, preterm birth, low birth weight. Maternal smoking during pregnancy emerged as a potentially specific risk factor for OCD. A cumulative pattern was also found, whereby the greater the number of adverse perinatal events, the greater the risk for OCD and tic disorders. Study IV found that relatives of individuals with tic-related OCD are at higher risk of having OCD themselves than relatives of individuals with non-tic-related OCD, independent of age at first OCD diagnosis. The same pattern was not observed, when we created additional subgroups based on other neuropsychiatric comorbidities, like ADHD or autism spectrum disorders (ASD). The results confirm the hypothesis that individuals with history of tics constitute a particularly familial subtype of OCD. Studies V and VI found that both OCD and tic disorders are associated with increased risks of metabolic and cardiovascular disorders in general, and with obesity, type 2 diabetes mellitus, and circulatory system diseases in particular. The risks were considerably higher in individuals with tic disorders than in those with OCD, but were significantly reduced in the sibling comparisons.

Conclusions: Study I proposed a roadmap for future research of environmental risk factors for psychiatric disorders to improve upon the methodological limitations of previous studies. The road map emphasized using prospective longitudinal data at the population level, using standardized measures, and applying genetically informative study designs. Following the plan suggested in study I, studies II and III found a range of perinatal risk factors for OCD and tic disorders, independent of familial confounding. Dose-response associations were also observed for the number of adverse perinatal events, in that the greater the number of events, the greater the risk for either disorder. This cumulative effect provides some hope that, in the future, it may be possible to derive environmental risk scores for these disorders. Study IV found that tic-related OCD is a particularly familial subtype of OCD, supporting the validity of the DSM-5 tic-related OCD specifier. Identifying homogeneous subgroups of OCD may inform treatment selection, earlier detection, and future studies of OCD etiology, including ongoing gene-searching efforts. Studies V and VI found that OCD and tic disorders are associated with increased risks for metabolic and cardiovascular disorders, independent of shared familial confounding. The results emphasize the importance of monitoring the long-term physical health of individuals with OCD and tic disorders. These results further suggest that lifestyle interventions may be required alongside other standard evidence based treatments to reduce the risk of premature mortality in these patients.