The ALSPAC study includes two different assessments for the presence of tic disorders in the offspring cohort. The first is a screening question for "tics or twitches that he/she [the child] can't control" which is asked in nine of the mother-completed questionnaires between ages 18 months to 11 years. The second, more detailed, tic assessment occurs in the Age 13 mother-completed questionnaire, in which a section entitled "Tics and Unintended Habits" asks five different questions about specific motor and vocal tics (face/head, neck/shoulder/trunk, arms/hands/legs/feet, repeated simple noises/sounds, and repeated words/phrases) as well as two additional questions about the pattern and frequency of these repeated movements. If record linkage or abstracted medical data are available for a subset of the Age 13 children, we will examinethe validity of these two different assessments by correlating questionnaire responses to a clinical diagnosis of TS or CT. While the Age 13 questionnaire will likely be more specific in identifying TS cases, the serial screening questions from age 18 months to 11 years may be able to detect children with chronic tics (those whose mothers endorse the presence of tics in two or more questionnaires spaced greater than 1 year apart) for whom symptoms may have abated by age 13. Since ~7500 mothers completed the study through Age 13 and the prevalence of either TS or CT is approximately 1-2% in the general population, we expect to find 75-150 cases of TS/CT in the sample.

Exposures of interest will include prenatal and perinatal factors reported to be associated with either TS or tic severity in at least one previous study, including birth weight, Apgar scores, paternal age, hyperemesis of pregnancy, increased maternal stress during pregnancy, maternal smoking, alcohol, and caffeine use, as well as obstetrical complications (specifically forceps delivery and neonatal hypoxia). Three to five controls will be selected per case and will be matched based on gender, month and year of birth. 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 TS and/or CT, examine the non-genetic risk factors identified in Aim 1 for association with comorbid OCD and/or ADHD.

In addition to the above tic assessments, ALSPAC subjects have been screened for DSM-IV diagnoses of OCD and ADHD at three different time points thus far (ages 7, 10 and 14). In this aim, we will evaluate each subject with a chronic tic disorder (TS and/or CT) based on the criteria validated in Aim 1 for the presence of OCD and/or ADHD. We will then perform both univariate and multivariate analyses to test for an association between the presence of comorbid OCD and/or ADHD and the same previously reported prenatal and perinatal risk factors, focusing primarily on maternal smoking, alcohol and caffeine use during pregnancy as well as forceps delivery. We hypothesize that at least one of these variables will prove to be associated with TS-associated comorbidities, similar to the findings observed by Mathews and colleagues (Mathews et al., 2006).