Familial Clustering of Immune-Mediated Diseases in Children with Abrupt-Onset Obsessive Compulsive Disorder

To the Editor:

We read with interest your June 2019 publication regarding the multi-site questionnaire study by Westwell-Roper et al. (2019). The authors reported increased rates of immune-mediated comorbidities among first-degree relatives of patients with obsessive compulsive disorder (OCD). The authors pointed out that their study was limited by the lack of healthy control data, and they asked for a replication study. We, therefore, analyzed our family history data from patients with abrupt-onset OCD and healthy controls to supplement their findings.

In our multidisciplinary pediatric acute-onset neuropsychiatric syndrome (PANS) clinic, we see children in our community who present with abrupt-onset OCD, including those meeting the diagnostic criteria of PANS (Frankovich et al. 2015). We also recruit healthy children of the same age range, from the same community, for research studies. Patients' and healthy controls' families complete an intake questionnaire that queries family history of immune-mediated diseases and psychiatric disorders. Our study included 244 consecutive patients who presented with abrupt-onset OCD in childhood, and 121 healthy controls who had minimal to no psychiatric symptoms, from September 2012 through June 2019. We excluded six adopted children with unclear family history. We abstracted family history data from intake questionnaires, and described our findings. This study was approved by the Stanford IRB, and all patients and healthy controls were consented.

Our study patients had a mean age of symptom onset at 8.6 (standard deviation [SD] 3.6) years and a mean age of clinic presentation at 10.6 (SD 4.2) years; 61% were males and 78% were white; mean Children's Yale-Brown Obsessive Compulsive Scale at initial clinic presentation was 17.3 (SD 10.0). Healthy controls presented to us at older age (mean 12.4, SD 4.4 years), and a lower proportion (52%) was white. Otherwise, patient and healthy controls were demographically similar. We found OCD more prevalent in siblings and parents of our patients than those of healthy controls (Table 1). As well, siblings and parents of patients reported more immune-mediated diseases than those of healthy controls with statistical significance after adjusting for race and age at clinic presentation (adjusted odds ratio 2.80, 95% confidence interval 1.64–4.76, p < 0.001). The sample size was not big enough for stratification analysis by family history of OCD.

Epidemiologic studies from Sweden and North America have consistently shown familial clustering of immune-mediated diseases in patients with OCD and tic disorders (Murphy et al. 2010; Mataix-Cols et al. 2018; Westwell-Roper et al. 2019). Our findings of an increased risk of having immune-mediated disorders in first-degree relatives of our patients with early abrupt-onset OCD are in line with those of Westwell-Roper et al. (2019) in the general OCD population. When seeing patients with both abrupt-onset OCD and idiopathic OCD, clinicians should carefully evaluate families for immune disorders. Long-term follow-up studies of the impact of positive family history of immune diseases on patients' treatment responses and disease trajectories will be of great interest.