Danielle C. Cath

Factor structure, reliability and criterion validity of the Autism-Spectrum Quotient (AQ): A study in Dutch population and patient groups.

The factor structure of the Dutch translation of the Autism-Spectrum Quotient (AQ; a continuous, quantitative measure of autistic traits) was evaluated with confirmatory factor analyses in a large general population and student sample. The criterion validity of the AQ was examined in three matched patient groups (autism spectrum conditions (ASC), social anxiety disorder, and obsessive–compulsive disorder). A two factor model, consisting of a “Social interaction” factor and “Attention to detail” factor could be identified. The internal consistency and test–retest reliability of the AQ were satisfactory. High total AQ and factor scores were specific to ASC patients. Men scored higher than women and science students higher than non-science students. The Dutch translation of the AQ is a reliable instrument to assess autism spectrum conditions.

Twin Studies on Obsessive–Compulsive Disorder: A Review

Genetic factors have historically been thought of as important in the development of obsessive-compulsive disorder (OCD). For the estimation of the relative importance of genetic and environmental factors, twin studies are an obvious approach. Twin studies of OCD have a long history, starting in 1929. In this review, over 70 years of twin research of OCD is presented, using four different approaches that represent the steps in the twin research of OCD from past to present. These steps include (1) case-studies of twins with OCD from the old literature; (2) twin studies of OCD using Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria; (3) twin studies of OCD using a dimensional approach, comparing resemblances in monozygotic and dizygotic twins; and (4) twin studies of OCD using a dimensional approach, analyzing the data with Structural Equation Modeling. It is concluded that only the studies using the last method have convincingly shown that, in children, obsessive-compulsive (OC) symptoms are heritable, with genetic influences in the range of 45% to 65%. In adults, studies are suggestive for a genetic influence on OC symptoms, ranging from 27% to 47%, but a large twin study using a biometrical approach with continuous data is still needed to provide conclusive evidence. Strategies for future twin studies of OCD are discussed.

The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies

BACKGROUND Co-morbidity within anxiety disorders, and between anxiety disorders and depression, is common. According to the theory of Gray and McNaughton, this co-morbidity is caused by recursive interconnections linking the brain regions involved in fear, anxiety and panic and by heritable personality traits such as neuroticism. In other words, co-morbidity can be explained by one disorder being an epiphenomenon of the other and by a partly shared genetic etiology. The aim of this paper is to evaluate the theory of Gray and McNaughton using the results of genetic epidemiological studies. METHOD Twenty-three twin studies and 12 family studies on co-morbidity are reviewed. To compare the outcomes systematically, genetic and environmental correlations between disorders are calculated for the twin studies and the results from the family studies are summarized according to the method of Klein and Riso. RESULTS Twin studies show that co-morbidity within anxiety disorders and between anxiety disorders and depression is explained by a shared genetic vulnerability for both disorders. Some family studies support this conclusion, but others suggest that co-morbidity is due to one disorder being an epiphenomenon of the other. CONCLUSIONS Discrepancies between the twin and family studies seem partly due to differences in used methodology. The theory of Gray and McNaughton that neuroticism is a shared risk factor for anxiety and depression is supported. Further research should reveal the role of recursive interconnections linking brain regions. A model is proposed to simultaneously investigate the influence of neuroticism and recursive interconnections on co-morbidity.

Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome

In response to recent publicity regarding the potential use of deep brain stimulation (DBS) for reducing tic severity in Tourettes syndrome (TS), the Tourette Syndrome Association convened a group of TS and DBS experts to develop recommendations to guide the early use and potential clinical trials of DBS for TS and other tic disorders. The goals of these recommendations are to ensure that all surgical candidates are (1) fully informed about the risks, benefits, and alternative treatments available; (2) receive a comprehensive evaluation before surgery to ensure that DBS is clearly the appropriate clinical treatment choice; and (3) that early clinical experience will be documented publicly to facilitate rational decision‐making for both clinical care and future clinical trials.

Deep Brain Stimulation in Tourette's Syndrome: Two Targets?

In this report, we describe the effects of bilateral thalamic stimulation in one patient and of bilateral pallidal stimulation in another patient. Both patients suffered from intractable Tourette’s syndrome (TS). Any conservative treatment had failed or had been stopped because of unbearable side effects in the 2 patients. In both cases, there was no comorbidity except for associated behavioral symptoms (compulsions). Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro‐oralis internus) in one patient and in the posteroventral part of the globus pallidus internus (GPi) in the other patient. In both cases, deep brain stimulation (DBS) resulted in a substantial reduction of tics and compulsions. These data show that bilateral DBS of the thalamus as well as of the GPi can have a good effect on tics and behavioral symptoms in patients suffering from intractable TS.

Exposure with response prevention versus habit reversal in Tourettes’s syndrome: a controlled study

The intentional nature of tics provides the opportunity to apply behavioural interventions aimed at tic reduction through interruption of stimulus-response sequences. The aim of this study has been to evaluate the effect of exposure and response prevention (ER) versus habit reversal (HR) in 43 Tourettes syndrome (TS) patients. The three outcome measures were: the Yale Global Tic Severity Scale (YGTSS), 15-min tic frequency registrations monitored at the institute and 15-min home tic frequency registrations. Both treatment conditions resulted in statistically significant improvements on all outcome measures (p < 0.001). No significant differences were found between the treatment conditions on any of the outcome measures, although there was a tendency in favour of ER on the YGTSS (p = 0.05). These results suggest that, at least in the short term, TS tic symptoms can be treated effectively with both types of treatment.

Lifetime Prevalence, Age of Risk, and Genetic Relationships of Comorbid Psychiatric Disorders in Tourette Syndrome

IMPORTANCE Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (<200), and none has examined the ages of highest risk for each TS-associated comorbidity or their etiologic relationship to TS. OBJECTIVE To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional structured diagnostic interviews conducted between April 1, 1992, and December 31, 2008, of participants with TS (n = 1374) and TS-unaffected family members (n = 1142). MAIN OUTCOMES AND MEASURES Lifetime prevalence of comorbid DSM-IV-TR disorders, their heritabilities, ages of maximal risk, and associations with symptom severity, age at onset, and parental psychiatric history. RESULTS The lifetime prevalence of any psychiatric comorbidity among individuals with TS was 85.7%; 57.7% of the population had 2 or more psychiatric disorders. The mean (SD) number of lifetime comorbid diagnoses was 2.1 (1.6); the mean number was 0.9 (1.3) when obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) were excluded, and 72.1% of the individuals met the criteria for OCD or ADHD. Other disorders, including mood, anxiety, and disruptive behavior, each occurred in approximately 30% of the participants. The age of greatest risk for the onset of most comorbid psychiatric disorders was between 4 and 10 years, with the exception of eating and substance use disorders, which began in adolescence (interquartile range, 15-19 years for both). Tourette syndrome was associated with increased risk of anxiety (odds ratio [OR], 1.4; 95% CI, 1.0-1.9; P = .04) and decreased risk of substance use disorders (OR, 0.6; 95% CI, 0.3-0.9; P = .02) independent from comorbid OCD and ADHD; however, high rates of mood disorders among participants with TS (29.8%) may be accounted for by comorbid OCD (OR, 3.7; 95% CI, 2.9-4.8; P < .001). Parental history of ADHD was associated with a higher burden of non-OCD, non-ADHD comorbid psychiatric disorders (OR, 1.86; 95% CI, 1.32-2.61; P < .001). Genetic correlations between TS and mood (RhoG, 0.47), anxiety (RhoG, 0.35), and disruptive behavior disorders (RhoG, 0.48), may be accounted for by ADHD and, for mood disorders, by OCD. CONCLUSIONS AND RELEVANCE This study is, to our knowledge, the most comprehensive of its kind. It confirms the belief that psychiatric comorbidities are common among individuals with TS, demonstrates that most comorbidities begin early in life, and indicates that certain comorbidities may be mediated by the presence of comorbid OCD or ADHD. In addition, genetic analyses suggest that some comorbidities may be more biologically related to OCD and/or ADHD rather than to TS.

Symptom Overlap between Autism Spectrum Disorder, Generalized Social Anxiety Disorder and Obsessive-Compulsive Disorder in Adults: A Preliminary Case-Controlled Study

Background: Obsessive-compulsive disorder (OCD) and social anxiety disorder (SAD) frequently co-occur in persons with autism spectrum disorder (ASD). We studied which features distinguish ‘pure’ anxiety disordered patients from those with co-morbid ASD. Method: In a case-controlled design in which groups were matched for age, sex and educational level, patients with OCD or SAD and co-morbid ASD were compared with patients with ‘pure’ (i.e. without ASD) OCD, with ‘pure’ SAD and a control group, using the Autism Questionnaire (AQ), Yale-Brown Obsessive-Compulsive Scales, Liebowitz Social Anxiety Scale, Beck Anxiety Inventory and questions on egodystonia of OC behaviors. Results: No between patient group differences were found on social or general anxiety measures. The AQ subscales communication problems and lack of imagination discriminated best between patients with comorbid ASD and the other groups, ASD patients showing elevated scores, whereas the other patient groups scored equal to controls. On the AQ social skill subscale all patient groups showed elevated scores. On OC symptom severity, pure OCD patients showed highest scores, whereas comorbid ASD subjects scored intermediate between controls and the pure OCD group, the differences being explained by lower obsession severity in the ASD group. There were no differences between the pure OCD and comorbid ASD groups on egodystonia. Conclusion: Patients with comorbid ASD differ from patients with pure OCD and SAD on autism-related problem behaviors, but there is also overlap between groups, possibly reflecting overlapping etiologies. Despite the relatively small sample size, these data strongly suggest that specific autism symptom domains should be assessed to pick up autism-related problems in OCD and SAD patients, and subsequently fine-tune treatment programs for these patients.

UPDATED META-ANALYSIS OF CLASSICAL FEAR CONDITIONING IN THE ANXIETY DISORDERS

The aim of the current study was twofold: (1) to systematically examine differences in fear conditioning between anxiety patients and healthy controls using meta‐analytic methods, and (2) to examine the extent to which study characteristics may account for the variability in findings across studies. Forty‐four studies (published between 1920 and 2013) with data on 963 anxiety disordered patients and 1,222 control subjects were obtained through PubMed and PsycINFO, as well as from a previous meta‐analysis on fear conditioning (Lissek et al. ). Results demonstrated robustly increased fear responses to conditioned safety cues (CS−) in anxiety patients compared to controls during acquisition. This effect may represent an impaired ability to inhibit fear in the presence of safety cues (CS−) and/or may signify an increased tendency in anxiety disordered patients to generalize fear responses to safe stimuli resembling the conditioned danger cue (CS+). In contrast, during extinction, patients show stronger fear responses to the CS+ and a trend toward increased discrimination learning (differentiation between the CS+ and CS−) compared to controls, indicating delayed and/or reduced extinction of fear in anxiety patients. Finally, none of the included study characteristics, such as the type of fear measure (subjective vs. psychophysiological index of fear), could account significantly for the variance in effect sizes across studies. Further research is needed to investigate the predictive value of fear extinction on treatment outcome, as extinction processes are thought to underlie the beneficial effects of exposure treatment in anxiety disorders.

Presupplementary Motor Area Hyperactivity During Response Inhibition: A Candidate Endophenotype of Obsessive-Compulsive Disorder

OBJECTIVE Endophenotype studies of obsessive-compulsive disorder (OCD) may uncover heritable traits that are related to genetic susceptibility to OCD. Deficient response inhibition is a promising endophenotype of OCD, although its functional neural correlates have not been extensively studied. The authors sought to determine the functional neural correlates of response inhibition in a large sample of medication-free OCD patients and their unaffected siblings. METHOD Forty-one OCD patients, 17 of their siblings, and 37 matched healthy comparison subjects performed a stop-signal task during 3-T functional MRI. The stop-signal reaction time provided a behavioral measure of response inhibition. The neural correlates of response inhibition were assessed in a region-of-interest analysis that included the presupplementary motor area, inferior frontal gyrus, subthalamic nucleus, and inferior parietal cortex. RESULTS Patients with OCD had greater stop-signal reaction times relative to healthy comparison subjects. The numerical stop-signal reaction time difference between siblings and comparison subjects failed to reach significance. Both patients with OCD and their siblings showed greater activity in the left presupplementary motor area during successful inhibition relative to comparison subjects. Relative to both the comparison subjects and the siblings, patients with OCD showed decreased activity in the right inferior parietal cortex and inferior frontal gyrus. In patients and siblings, presupplementary motor area activity correlated negatively with stop-signal reaction time. CONCLUSIONS These findings suggest that presupplementary motor area hyperactivity is a neurocognitive endophenotype of OCD that is possibly related to inefficient neural processing within the presupplementary motor area itself. Patients with OCD further showed a state-dependent deficit in recruiting right inferior parietal cortex and inferior frontal gyrus, which may contribute to their inhibition deficit.