Although obsessive compulsive disorder (OCD) is clearly known to have a strong genetic component, twin and family studies have consistently demonstrated a significant role for additional, non-genetic factors in the pathogenesis of the disease(Pauls, 2008). Despite this, only four studies have examined the potential contributions of various non-genetic factors in the development of OCD. In these studies, excessive maternal weight gain, hyperemesis of pregnancy, medication use during pregnancy, nuchal cord, hypoxia at birth, unspecified problems during pregnancy or in the perinatal period, and assisted delivery (forceps or Caesarean section) were associated in at least one study with increased risk of OCD(Geller et al., 2008, Grisham et al., 2011, Sampaio et al., 2009, Vasconcelos et al., 2007). In contrast, tobacco or illicit drug use during pregnancy, primiparity, low birthweight, hypertension or pre-eclampsia, and preterm birth were not found to be OCD risk factors. However, these studies had multiple limitations; all but one were retrospective, and the one prospective cohort study only examined a few variables. Therefore, there is a great need to examine a variety of candidate non-genetic OCD risk factors in a prospectively collected, population-based sample.

We have previously examined the relationship between pre- and perinatal risk factors for Tourette Syndrome (TS), a neurodevelopmental disorder that is etiologically and clinically related to OCD, in the ALSPAC cohort (Mathews, in press). We found that inadequate maternal weight gain during pregnancy, parity, and maternal alcohol and cannabis use were all associated with increased risk for TS or chronic tics (CT). Other pre/perinatal exposures that had previously been reported, most notably maternal prenatal smoking and low birth weight, were not associated with TS or CT in the ALSPAC cohort.

We propose to utilize the ALSPAC cohort to study non-genetic risk factors for OCD in a prospective manner, using the same approach used to study TS/CT, through the following specific aims:

Aim 1: Examine the association between previously reported prenatal and perinatal OCD risk factors and those previously found to be identified with TS/CT and the presence of OCD using a nested, case-control design within the longitudinal, prospective, population-based ALSPAC sample.

The ALSPAC study includes an assessment of obsessive compulsive symptoms and associated distress and impairment as a part of the Development and Well Being Assessment (DAWBA) parent interview. This self-report questionnaire was completed by ALSPAC mothers as part of the age 7, 10, and 14 questionnaires. We propose to use a definition of OCD that we have previously used in our work on examining perinatal risk factors for tic disorders; this definition corresponds to a DSM-IV-TR lifetime diagnosis of OCD. The presence of recurrent obsessions or compulsions (defined as a response of "sometimes" or "often" to one or more of the seven available questions about contamination, cleaning, checking, repeating, touching, arranging, or counting symptoms) at any of the three timepoints, is required for a diagnosis, along with sufficient severity and/or impairment to meet DSM-IV-TR criteria. This is defined as symptoms that were severe enough to take up at least an hour a day ("waste a lot of time",) cause significant distress ("upset a great deal"), or cause interference/impairment ("quite a lot" or "a great deal" answered to any of the five questions about interference (with family, friends, school, or hobbies). As is consistent with the DSM-IV-TR criteria, recognition that the symptoms are excessive is not required in children.

Exposures of interest will include prenatal and perinatal factors reported to be associated with either OCD or OCD symptom severity in at least one previous study, as well as those examined in our study of tic disorders, including birth weight, maternal weight gain, Apgar scores, paternal age, hyperemesis of pregnancy, increased maternal stress during pregnancy, maternal smoking, alcohol, illicit drug, and caffeine use, as well as obstetrical complications (such as forceps delivery and neonatal hypoxia).All children who do not meet OCD criteria (or subclinical OCD criteria, as defined by OCD symptoms with minimal impairment or distress), and do not have autism or intellectual disability will be included as controls.Both univariate analysis and multivariate analysis using logistic regression will be performed.We hypothesize that maternal smoking, paternal age and perhaps other environmental variables will be associated with the development of TS/CT in this population.

Aim 2: In the subgroup of ALSPAC subjects with OCD, examine the non-genetic risk factors identified in Aim 1 for association with co-occurring anxiety disorders, ADHD, and symptom severity.

In addition to the OCD assessments, ALSPAC subjects have been screened for DSM-IV diagnoses of other anxiety disorders (separation anxiety, social anxiety, and generalized anxiety), and ADHD at three different time points thus far (ages 7, 10 and 14). In this aim, we will evaluate each subject with OCD for the presence of additional co-occurring anxiety disorders and/or ADHD. We will then perform both univariate and multivariate analyses to test for an association between the presence of co-occurring disorders and the same previously reported prenatal and perinatal risk factors. We hypothesize that at least one of these variables will prove to be associated with OCD-associated comorbidities.

Table 1. Data requested for proposed ALSPAC study.

Concept

Specific Measure

Person

Source

Time Point(s)

Prenatal Risk Factors

Medications, smoking, alcohol, recreational drug use, family history, maternal/paternal age

Mother

Questionnaire

8 weeks gestation to 8 weeks post-partum

Prenatal Risk Factors

Hyperemesis

Mother

Questionnaire

8 weeks gestation to 8 weeks post-partum

Maternal stress

Life Events

Mother

Questionnaire

18 week gestation & 8 weeks post-partum

Perinatal events

Birthweight, Apgar scores, obstetrical complications

Mother

Obstetrical and neonatal record

Birth to 4 weeks

OCD

Checklist/screen for DSM-IV OCD criteria

Child-based

Questionnaire

Ages 7, 10, 14

ADHD

Checklist/screen for DSM-IV ADHD criteria

Child-based

Questionnaire

Ages 7, 10, 14

Anxiety disorders

Checklist/screen for separation anxiety, generalized anxiety, and social anxiety

Child-based

Questionnaire

Ages 7,10, 14

REFERENCES:

Geller, D. A., Wieland, N., Carey, K., Vivas, F., Petty, C. R., Johnson, J., Reichert, E., Pauls, D. & Biederman, J. (2008). Perinatal factors affecting expression of obsessive compulsive disorder in children and adolescents. J Child Adolesc Psychopharmacol 18, 373-9.

Grisham, J. R., Fullana, M. A., Mataix-Cols, D., Moffitt, T. E., Caspi, A. & Poulton, R. (2011). Risk factors prospectively associated with adult obsessive-compulsive symptom dimensions and obsessive-compulsive disorder. Psychol Med, 1-12.

Mathews, C. A., Scharf, J. M., Miller, L.L., Macdonald-Wallis, C., Lawlor, D.A., Ben-Shlomo, Y. (in press). Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorders in the ALSPAC cohort. Br J Psychiatry.

Pauls, D. L. (2008). The genetics of obsessive compulsive disorder: a review of the evidence. Am J Med Genet C Semin Med Genet 148C, 133-9.

Sampaio, A. S., Miguel, E. C., Borcato, S., Batistuzzo, M., Fossaluza, V., Geller, D. A. & Hounie, A. G. (2009). Perinatal risk factors and obsessive-compulsive spectrum disorders in patients with rheumatic fever. Gen Hosp Psychiatry 31, 288-91.

Vasconcelos, M. S., Sampaio, A. S., Hounie, A. G., Akkerman, F., Curi, M., Lopes, A. C. & Miguel, E. C. (2007). Prenatal, perinatal, and postnatal risk factors in obsessive-compulsive disorder. Biol Psychiatry 61, 301-7.