Tourette syndrome in youth with and without obsessive compulsive disorder and attention deficit hyperactivity disorder.

Chronic tic disorders (TD) are consistently found to have high rates of comorbidity with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). The purpose of this study is to compare the severity of TD only to TD with comorbid OCD or ADHD based on severity of tics, measures of psychopathology and additional comorbid diagnoses. Baseline data from 158 youth with a chronic TD who participated in two longitudinal studies were examined. Fifty-three percent (N = 85) of the youth also met criteria for a diagnosis of OCD, 38.6 % (n = 61) met criteria for ADHD and 24.1 % (N = 38) met criteria for both. Measures of interest addressed severity of tics, symptoms of anxiety, depression, ADHD, psychosocial stress, global functioning and the presence of comorbid diagnoses. Youth with comorbid TD and OCD were characterized by more severe tics, increased levels of depressive and anxious symptoms, heightened psychosocial stress and poorer global functioning. Youth with comorbid TD and ADHD did not differ from those with TD alone on measures of tic severity, but experienced greater psychosocial stress and poorer global functioning. Subjects with comorbid TD and OCD had more internalizing disorders than those without OCD, while those with comorbid ADHD were more likely to meet criteria for oppositional defiant disorder. TD with OCD is a more severe subtype of TD than TD without OCD. TD with ADHD is associated with higher psychosocial stress and more externalizing behaviors. Further research is needed into the underlying relationships between these closely associated conditions.

Severe psychosocial stress and heavy cigarette smoking during pregnancy: an examination of the pre- and perinatal risk factors associated with ADHD and Tourette syndrome.

Attention-deficit/hyperactivity disorder (ADHD) is frequently diagnosed in children with Tourette syndrome (TS). The basis for this co-occurrence is uncertain. This study aimed to determine if specific pre- and perinatal risk factors, including heavy maternal smoking and severe psychosocial stress during pregnancy, were associated with one or both disorders, or neither. We compared maternal report data on pre- and perinatal risk factors on 222 children between the ages of 7 and 18 years including 45 individuals with TS alone, 52 individuals with ADHD alone, 60 individuals with condition of comorbid TS + ADHD, and 65 unaffected control children. Pre- and perinatal histories as well as psychiatric assessments were performed using standardized questionnaires and semi-structured interviews with the mothers and children. Logistic regression was used to determine the odds ratio for each variable of interest. Compared to the mothers of unaffected control children, the mothers of children with ADHD alone reported higher rates of heavy smoking (>10 cigarettes per day) during pregnancy and higher levels of severe psychosocial stress during pregnancy (OR = 13.5, p < 0.01 and OR = 6.8, p < 0.002, respectively). The TS + ADHD and the TS alone patients also had higher rates heavy maternal smoking and high levels of psychosocial stress compared to the control children, but these differences failed to reach statistical significance (heavy smoking: OR = 8.5, p < 0.052, OR = 4.6, p < 0.19, respectively; severe psychosocial stress: OR = 3.1, p < 0.07, OR = 2.6, p < 0.11, respectively). Heavy maternal smoking and severe levels psychosocial stress during pregnancy were independently associated with a diagnosis of ADHD. TS patients also had higher rates of these risk factors, but the ORs failed to reach statistical significance. Efforts are needed to reduce the frequency of these risk factors in high-risk populations. Future studies, using genetically sensitive designs, are also needed to sort out the causal pathways.

Consanguineous Iranian kindreds with severe Tourette syndrome.

The search for vulnerability genes for Tourette syndrome has been ongoing for nearly three decades. The contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. Homozygosity mapping has been successfully used to detect recessive loci within populations with high rates of consanguinity. Using this technique, even quite small inbred families can be informative due to autozygosity in which the two alleles at an autosomal locus are identical by descent (i.e., copies of a single ancestral gene). To explore the utility of this approach, we identified 12 consanguineous Iranian families. Remarkably, these families were seen with an unusual natural history characterized by the early onset of vocal tics and coprolalia and frequent comorbidity with obsessive-compulsive disorder. Genotyping the affected and unaffected members of these pedigrees has the potential to identify rare recessive contributions to this disorder.

Randomized Sham Controlled Double-blind Trial of Repetitive Transcranial Magnetic Stimulation for Adults With Severe Tourette Syndrome.

BACKGROUND: A small proportion of individuals with Tourette syndrome (TS) have a lifelong course of illness that fails to respond to conventional treatments. Open label studies have suggested that low frequency (1-Hz) repetitive transcranial magnetic stimulation (rTMS) targeting the supplementary motor area (SMA) may be effective in reducing tic severity. OBJECTIVE/HYPOTHESIS: To examine the efficacy of rTMS over the SMA for TS in a randomized double-blind sham-controlled trial (RCT). METHODS: We conducted a two-site RCT-rTMS with 20 adults with severe TS for 3 weeks. Treatment consisted of 15 sessions (1-Hz; 30 min; 1800 pulses per day) of active or sham rTMS at 110% of the motor threshold over the SMA. A subsequent 3 week course of active rTMS treatment was offered. RESULTS: Of the 20 patients (16 males; mean age of 33.7 ± 12.2 years), 9 received active and 11 received sham rTMS. After 3 weeks, patients receiving active rTMS showed on average a 17.3% reduction in the YGTSS total tic score compared to a 13.2% reduction in those receiving sham rTMS, resulting in no statistically significant reduction in tic severity (P = 0.27). An additional 3 week open label active treatment for those patients (n = 7) initially randomized to active rTMS resulted in a significant overall 29.7% reduction in tic severity compared to baseline (P = 0.04). CONCLUSION: This RCT did not demonstrate efficacy of 3-week SMA-targeted low frequency rTMS in the treatment of severe adult TS. Further studies using longer or alternative stimulation protocols are warranted.

Lessons Learned from Open-label Deep Brain Stimulation for Tourette Syndrome: Eight Cases over 7 Years.

BACKGROUND: Deep brain stimulation (DBS) remains an experimental but promising treatment for patients with severe refractory Gilles de la Tourette syndrome (TS). Controversial issues include the selection of patients (age and clinical presentation), the choice of brain targets to obtain optimal patient-specific outcomes, and the risk of surgery- and stimulation-related serious adverse events. METHODS: This report describes our open-label experience with eight patients with severe refractory malignant TS treated with DBS. The electrodes were placed in the midline thalamic nuclei or globus pallidus, pars internus, or both. Tics were clinically assessed in all patients pre- and postoperatively using the Modified Rush Video Protocol and the Yale Global Tic Severity Scale (YGTSS). RESULTS: Although three patients had marked postoperative improvement in their tics (>50% improvement on the YGTSS), the majority did not reach this level of clinical improvement. Two patients had to have their DBS leads removed (one because of postoperative infection and another because of lack of benefit). DISCUSSION: Our clinical experience supports the urgent need for more data and refinements in interventions and outcome measurements for severe, malignant, and medication-refractory TS. Because TS is not an etiologically homogenous clinical entity, the inclusion criteria for DBS patients and the choice of brain targets will require more refinement.

Adverse effects of heavy prenatal maternal smoking on attentional control in children with ADHD.

OBJECTIVE: Exposure to heavy maternal cigarette smoking in pregnancy and severe maternal psychosocial stress during pregnancy appear to be important risk factors for the development of ADHD. This study aimed to determine whether these perinatal risk factors were associated with neuropsychological deficits commonly seen in ADHD. METHOD: We examined the effect of these two risk factors on measures of attentional control, motor inhibition, visual-motor integration, and fine motor coordination in a group of 81 children with ADHD, aged from 8 to 18 years. The neuropsychological battery included the Connors' Continuous Performance Test (CPT), the Stroop Color-Word Interference Test, the Beery Visual-Motor Integration Test, and the Purdue Pegboard Test. RESULTS: Heavy maternal smoking during pregnancy was associated with slower reaction times (p < .002), and reaction time variability (p < .007) on the CPT. CONCLUSIONS: This study suggests a persistent negative effect of heavy prenatal maternal smoking on attentional control in children with ADHD. Future studies should examine the neurobiological basis and determine the degree to which inherited genetic susceptibility factors contribute to this finding.