White matter microstructure shows sex differences in late childhood: Evidence from 6797 children.

Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging approaches. However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here, we rigorously characterized sex differences in white matter microstructure among over 6000 children from the Adolescent Brain Cognitive Development study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model-diffusion tensor imaging (DTI)-and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.

Cognitive control processes in behavior therapy for youth with Tourette's disorder.

BACKGROUND: Cognitive control processes are implicated in the behavioral treatment of Tourette's disorder (TD). However, the influence of these processes on treatment outcomes has received minimal attention. This study examined whether cognitive control processes and/or tic suppression predicted reductions in tic severity and treatment response to behavior therapy. METHOD: Fifty-three youth with TD or a pervasive tic disorder participated in a randomized wait list-controlled trial of behavior therapy. Following a baseline assessment to evaluate psychiatric diagnoses, tic severity, and cognitive control processes (e.g., response selection, inhibition, and suppression), youth were randomly assigned to receive eight sessions of behavior therapy (n = 23) or a wait list of equal duration (n = 28). Youth receiving immediate treatment completed a post-treatment assessment to determine improvement in tic severity. Meanwhile, youth in the wait list condition completed another assessment to re-evaluate tic severity and cognitive control processes, and subsequently received 8 sessions of behavior therapy followed by a post-treatment assessment to determine improvement. RESULTS: A multiple linear regression model found that pretreatment inhibition/switching on the Delis-Kaplan Executive Function System Color-Word Interference Test predicted reductions in tic severity after behavior therapy (ß = -.36, t = -2.35, p = .025, ƞ2 = .15). However, other cognitive control processes and tic suppression did not predict treatment response and/or reductions in tic severity. Small nonsignificant effects were observed in cognitive control processes after behavior therapy. CONCLUSION: Cognitive control processes may influence tic severity reductions in behavior therapy. Notably, even when other cognitive control processes are impaired and youth are initially unable to voluntarily suppress their tics, youth with TD can still benefit from behavior therapy. Findings offer implications for clinical practice and research for TD.

Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

BACKGROUND: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. OBJECTIVE: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT. METHODS: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature. RESULTS: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates. CONCLUSIONS: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Alpha modulation during working memory encoding predicts neurocognitive impairment in ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with working memory (WM) deficits. However, WM is a multiprocess construct that can be impaired through several pathways, leaving the source of WM impairments in ADHD unresolved. In this study, we aim to replicate, in an independent sample, previously reported deficits in component processes of WM deficits in ADHD and expand to consider their implications for neurocognitive outcomes. METHODS: In 119 children (7-14 years old, 85 with ADHD), we used electroencephalography measures to quantify component processes during performance of a spatial working memory task. We quantified stimulus encoding using alpha range (8-12 Hz) power; vigilance by the P2 event-related potential to cues; and WMmaintenance by occipital-alpha and frontal-theta (4-7 Hz) power. These measures were evaluated against metrics of executive function, ADHD symptoms, and academic achievement. RESULTS: Encoding alpha-power decreases and cue P2 amplitude were attenuated in ADHD, whereas occipital-alpha power during maintenance was significantly greater in ADHD, consistent with a compensatory response to weak encoding. Weak alpha modulation during encoding was associated with poorer reading comprehension and executive function, as well as enhanced ADHD symptoms. Previously reported effects in frontal-theta power failed to replicate. CONCLUSIONS: Stimulus encoding, a component process of WM coupled to alpha modulation, is impaired in ADHD, and, unlike WM maintenance or vigilance processes, has implications outside of the laboratory via a relationship with executive function, and, to a weaker extent, reading comprehension.

An exploration of concomitant psychiatric disorders in children with autism spectrum disorder.

OBJECTIVE: We explored patterns of concomitant psychiatric disorders in a large sample of treatment-seeking children and adolescents with autism spectrum disorder (ASD). METHODS: Participants were 658 children with ASD (age 3-17 years; mean = 7.2 years) in one of six federally-funded multisite randomized clinical trials (RCT) between 1999 and 2014. All children were referred for hyperactivity or irritability. Study designs varied, but all used the Child and Adolescent Symptom Inventory or Early Childhood Inventory to assess Attention Deficit Hyperactivity Disorder (ADHD), Oppositional-Defiant Disorder (ODD), Conduct Disorder (CD), Anxiety Disorders, and Mood Disorders. In addition, several measures in common were used to assess demographic and clinical characteristics. RESULTS: Of the 658 children, 73% were Caucasian and 59% had an IQ >70. The rates of concomitant disorders across studies were: ADHD 81%, ODD 46%, CD 12%, any anxiety disorder 42%, and any mood disorder 8%. Two or more psychiatric disorders were identified in 66% of the sample. Of those who met criteria for ADHD, 50% also met criteria for ODD and 46% for any anxiety disorder. Associations between types of concomitant disorders and a number of demographic and clinical characteristics are presented. CONCLUSION: In this well-characterized sample of treatment-seeking children with ASD, rates of concomitant psychiatric disorders were high and the presence of two or more co-occurring disorders was common. Findings highlight the importance of improving diagnostic practice in ASD and understanding possible mechanisms of comorbidity.

Trichotillomania comorbidity in a sample enriched for familial obsessive-compulsive disorder.

BACKGROUND: This study addresses the strength of associations between trichotillomania (TTM) and other DSM-IV Axis I conditions in a large sample (n = 2606) enriched for familial obsessive-compulsive disorder (OCD), to inform TTM classification. METHODS: We identified participants with TTM in the Johns Hopkins OCD Family Study (153 families) and the OCD Collaborative Genetics Study, a six-site genetic linkage study of OCD (487 families). We used logistic regression (with generalized estimating equations) to assess the strength of associations between TTM and other DSM-IV disorders. RESULTS: TTM had excess comorbidity with a number of conditions from different DSM-IV chapters, including tic disorders, alcohol dependence, mood disorders, anxiety disorders, impulse-control disorders, and bulimia nervosa. However, association strengths (odds ratios) were highest for kleptomania (6.6), pyromania (5.8), OCD (5.6), skin picking disorder (4.4), bulimia nervosa (3.5), and pathological nail biting (3.4). CONCLUSIONS: TTM is comorbid with a number of psychiatric conditions besides OCD, and it is strongly associated with other conditions involving impaired impulse control. Though DSM-5 includes TTM as an OCD-related disorder, its comorbidity pattern also emphasizes the impulsive, appetitive aspects of this condition that may be relevant to classification.

Child and Adolescent Adherence With Cognitive Behavioral Therapy for Anxiety: Predictors and Associations With Outcomes.

Cognitive behavioral therapy (CBT) for anxiety disorders is effective, but nonadherence with treatment may reduce the benefits of CBT. This study examined (a) four baseline domains (i.e., demographic, youth clinical characteristics, therapy related, family/parent factors) as predictors of youth adherence with treatment and (b) the associations between youth adherence and treatment outcomes. Data were from 279 youth (7-17 years of age, 51.6% female; 79.6% White, 9% African American), with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) diagnoses of separation anxiety disorder, generalized anxiety disorder, and/or social phobia, who participated in CBT in the Child/Adolescent Anxiety Multimodal Study. Adherence was defined in three ways (session attendance, therapist-rated compliance, and homework completion). Multiple regressions revealed several significant predictors of youth adherence with CBT, but predictors varied according to the definition of adherence. The most robust predictors of greater adherence were living with both parents and fewer youth comorbid externalizing disorders. With respect to outcomes, therapist ratings of higher youth compliance with CBT predicted several indices of favorable outcome: lower anxiety severity, higher global functioning, and treatment responder status after 12 weeks of CBT. Number of sessions attended and homework completion did not predict treatment outcomes. Findings provide information about risks for youth nonadherence, which can inform treatment and highlight the importance of youth compliance with participating in therapy activities, rather than just attending sessions or completing homework assignments.

Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in children: A randomized, placebo-controlled crossover study.

BACKGROUND: Dopamine D2 receptor antagonists used to treat Tourette syndrome may have inadequate responses or intolerable side effects. We present results of a 4-week randomized, double-blind, placebo-controlled crossover study evaluating the safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in children and adolescents with Tourette syndrome. METHODS: Forty youth aged 7 to 17 years with Tourette syndrome and a Yale Global Tic Severity Scale - total tic score of ≥20 were enrolled and randomized to either ecopipam (50 mg/day for weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days, followed by a 2-week washout and then crossed to the alternative treatment for 30 days. Stimulants and tic-suppressing medications were excluded. The primary outcome measure was the total tic score. Secondary outcomes included obsessive compulsive and attention deficit/hyperactivity disorder scales. RESULTS: Relative to changes in placebo, reduction in total tic score was greater for ecopipam at 16 days (mean difference, -3.7; 95% CI, -6.5 to -0.9; P = 0.011) and 30 days (mean difference, -3.2; 95% CI, -6.1 to -0.3; P = 0.033). There were no weight gain, drug-induced dyskinesias, or changes in laboratory tests, electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of 40). Adverse events reported for both treatments were rated predominantly mild to moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo). CONCLUSIONS: Ecopipam reduced tics and was well tolerated. This placebo-controlled study of ecopipam supports further clinical trials in children and adolescents with Tourette syndrome. © 2018 International Parkinson and Movement Disorder Society.

Parsing heterogeneity in attention-deficit hyperactivity disorder using EEG-based subgroups.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition for which multiple efforts to characterize brain state differences are underway. The objective of this study was to identify distinct subgroups of resting electroencephalography (EEG) profiles among children with and without ADHD and subsequently provide extensive clinical characterization of the subgroups. METHODS: Latent class analysis was used with resting state EEG recorded from a large sample of 781 children with and without ADHD (N = 620 ADHD, N = 161 Control), aged 6-18 years old. Behavioral and cognitive characteristics of the latent classes were derived from semistructured diagnostic interviews, parent completed behavior rating scales, and cognitive test performance. RESULTS: A five-class solution was the best fit for the data, of which four classes had a defining spectral power elevation. The distribution of ADHD and control subjects was similar across classes suggesting there is no one resting state EEG profile for children with or without ADHD. Specific latent classes demonstrated distinct behavioral and cognitive profiles. Those with elevated slow-wave activity (i.e. delta and theta band) had higher levels of externalizing behaviors and cognitive deficits. Latent subgroups with elevated alpha and beta power had higher levels of internalizing behaviors, emotion dysregulation, and intact cognitive functioning. CONCLUSIONS: There is population-level heterogeneity in resting state EEG subgroups, which are associated with distinct behavioral and cognitive profiles. EEG measures may be more useful biomarkers of ADHD outcome or treatment response rather than diagnosis.

Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation.

RATIONALE: Epidemiological evidence indicates that exposures to fine particulate matter air pollution (PM2.5) contribute to global burden of disease, primarily as a result of increased risk of cardiovascular morbidity and mortality. However, mechanisms by which PM2.5 exposure induces cardiovascular injury remain unclear. PM2.5-induced endothelial dysfunction and systemic inflammation have been implicated, but direct evidence is lacking. OBJECTIVE: To examine whether acute exposure to PM2.5 is associated with endothelial injury and systemic inflammation. METHODS AND RESULTS: Blood was collected from healthy, nonsmoking, young adults during 3 study periods that included episodes of elevated PM2.5 levels. Microparticles and immune cells in blood were measured by flow cytometry, and plasma cytokine/growth factors were measured using multiplexing laser beads. PM2.5 exposure was associated with the elevated levels of endothelial microparticles (annexin V+/CD41-/CD31+), including subtypes expressing arterial-, venous-, and lung-specific markers, but not microparticles expressing CD62+. These changes were accompanied by suppressed circulating levels of proangiogenic growth factors (EGF [epidermal growth factor], sCD40L [soluble CD40 ligand], PDGF [platelet-derived growth factor], RANTES [regulated on activation, normal T-cell-expressed and secreted], GROα [growth-regulated protein α], and VEGF [vascular endothelial growth factor]), and an increase in the levels of antiangiogenic (TNFα [tumor necrosis factor α], IP-10 [interferon γ-induced protein 10]), and proinflammatory cytokines (MCP-1 [monocyte chemoattractant protein 1], MIP-1α/ß [macrophage inflammatory protein 1α/ß], IL-6 [interleukin 6], and IL-1ß [interleukin 1ß]), and markers of endothelial adhesion (sICAM-1 [soluble intercellular adhesion molecule 1] and sVCAM-1 [soluble vascular cellular adhesion molecule 1]). PM2.5 exposure was also associated with an inflammatory response characterized by elevated levels of circulating CD14+, CD16+, CD4+, and CD8+, but not CD19+ cells. CONCLUSIONS: Episodic PM2.5 exposures are associated with increased endothelial cell apoptosis, an antiangiogenic plasma profile, and elevated levels of circulating monocytes and T, but not B, lymphocytes. These changes could contribute to the pathogenic sequelae of atherogenesis and acute coronary events.

Self-reported executive function and hoarding in adults with obsessive-compulsive disorder.

BACKGROUND: Hoarding behavior may distinguish a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Little is known about the relationship between executive dysfunction and hoarding in individuals with OCD. METHODS: The study sample included 431 adults diagnosed with DSM-IV OCD. Participants were assessed by clinicians for Axis I disorders, personality disorders, indecision, and hoarding. Executive functioning domains were evaluated using a self-report instrument, the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). We compared scores on these domains in the 143 hoarding and 288 non-hoarding participants, separately in men and women. We used logistic regression to evaluate relationships between executive function scores and hoarding, and correlation and linear regression analyses to evaluate relationships between executive function scores and hoarding severity, in women. RESULTS: In men, the hoarding group had a significantly higher mean score than the non-hoarding group only on the shift dimension. In contrast, in women, the hoarding group had higher mean scores on the shift scale and all metacognition dimensions, i.e., those that assess the ability to systematically solve problems via planning and organization. The relationships in women between hoarding and scores on initiating tasks, planning/organizing, organization of materials, and the metacognition index were independent of other clinical features. Furthermore, the severity of hoarding in women correlated most strongly with metacognition dimensions. CONCLUSIONS: Self-reported deficits in planning and organization are associated with the occurrence and severity of hoarding in women, but not men, with OCD. This may have implications for elucidating the etiology of, and developing effective treatments for, hoarding in OCD.

Mediators of Treatment Outcomes for Anxious Children and Adolescents: The Role of Somatic Symptoms.

Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors are effective treatments for pediatric anxiety disorders. However, the mechanisms of these treatments are unknown. Previous research indicated that somatic symptoms are reduced following treatment, but it is unclear if their reductions are merely a consequence of treatment gains. This study examined reductions in somatic symptoms as a potential mediator of the relationship between treatment and anxiety outcomes. Participants were 488 anxious youth ages 7-17 (M = 10.7), 50.4% male, 78.9% Caucasian, enrolled in Child/Adolescent Anxiety Multimodal Study, a large randomized control trial comparing 12-week treatments of CBT, sertraline, a combination of CBT and sertraline, and a pill placebo. Causal mediation models were tested in R using data from baseline, 8-, and 12-week evaluations. Somatic symptoms were assessed using the Panic/Somatic subscale from the Screen for Child Anxiety Related Emotional Disorders. Youth outcomes were assessed using the Pediatric Anxiety Rating Scale and Children's Global Assessment Scale. Reductions in somatic symptoms mediated improvement in anxiety symptoms and global functioning for those in the sertraline-only condition based on parent report. Conditions involving CBT and data based on child reported somatic symptoms did not show a mediation effect. Findings indicate that reductions in somatic symptoms may be a mediator of improvements for treatments including pharmacotherapy and not CBT. Although the overall efficacy of sertraline and CBT for anxiety may be similar, the treatments appear to function via different mechanisms.

The Interplay of Familial and Individual Risk in Predicting Clinical Improvements in Pediatric Anxiety Disorders.

Bioecological models of developmental psychopathology underscore the role of familial experiences of adversity and children's individual-level characteristics in heightening risk for pediatric anxiety through direct, combined, and interactive effects. To date, much of the existing research dedicated to pediatric anxiety disorders has largely been examined in bioecological models of diathesis-stress using community samples. This study extends our understanding of children's differential responsiveness to familial adversity by examining the diathesis-stress interaction of cumulative risk and children's individual-level vulnerabilities (negative affectivity and coping efficacy) within a clinic-referred treatment study for pediatric anxiety disorders. A cumulative risk index assessing exposure to familial adversity (e.g., socioeconomic status [SES], parent psychiatric illness) and self-reported measures of children's negative affectivity and coping efficacy were each measured at the intake of a randomized controlled clinical trial for the treatment of pediatric anxiety disorders (N = 488; 7-17 years of age). Trajectories of interviewer-rated anxiety symptoms were assessed across 12 weeks of treatment at baseline, 4 weeks, 8 weeks, and 12 weeks. Consistent with models of temperamental risk for mental health problems, negative affectivity predicted higher anxiety symptoms at intake. A significant diathesis-stress interaction between cumulative risk and coping efficacy emerged, as high risk and perceptions of lower coping efficacy attenuated declines in anxiety across 12 weeks. These patterns did not differ across treatment conditions. The results indicate that for youth experiencing high levels of stress, additional treatment efforts targeting familial stressors and coping efficacy may be important in maximizing treatment outcomes.

The Effect of Neurocognitive Function on Math Computation in Pediatric ADHD: Moderating Influences of Anxious Perfectionism and Gender.

Predictors of math achievement in attention-deficit/hyperactivity disorder (ADHD) are not well-known. To address this gap in the literature, we examined individual differences in neurocognitive functioning domains on math computation in a cross-sectional sample of youth with ADHD. Gender and anxiety symptoms were explored as potential moderators. The sample consisted of 281 youth (aged 8-15 years) diagnosed with ADHD. Neurocognitive tasks assessed auditory-verbal working memory, visuospatial working memory, and processing speed. Auditory-verbal working memory speed significantly predicted math computation. A three-way interaction revealed that at low levels of anxious perfectionism, slower processing speed predicted poorer math computation for boys compared to girls. These findings indicate the uniquely predictive values of auditory-verbal working memory and processing speed on math computation, and their differential moderation. These findings provide preliminary support that gender and anxious perfectionism may influence the relationship between neurocognitive functioning and academic achievement.

Development and validation of an item response theory-based Social Responsiveness Scale short form.

BACKGROUND: Research and practice in autism spectrum disorder (ASD) rely on quantitative measures, such as the Social Responsiveness Scale (SRS), for characterization and diagnosis. Like many ASD diagnostic measures, SRS scores are influenced by factors unrelated to ASD core features. This study further interrogates the psychometric properties of the SRS using item response theory (IRT), and demonstrates a strategy to create a psychometrically sound short form by applying IRT results. METHODS: Social Responsiveness Scale analyses were conducted on a large sample (N = 21,426) of youth from four ASD databases. Items were subjected to item factor analyses and evaluation of item bias by gender, age, expressive language level, behavior problems, and nonverbal IQ. RESULTS: Item selection based on item psychometric properties, DIF analyses, and substantive validity produced a reduced item SRS short form that was unidimensional in structure, highly reliable (α = .96), and free of gender, age, expressive language, behavior problems, and nonverbal IQ influence. The short form also showed strong relationships with established measures of autism symptom severity (ADOS, ADI-R, Vineland). Degree of association between all measures varied as a function of expressive language. CONCLUSIONS: Results identified specific SRS items that are more vulnerable to non-ASD-related traits. The resultant 16-item SRS short form may possess superior psychometric properties compared to the original scale and emerge as a more precise measure of ASD core symptom severity, facilitating research and practice. Future research using IRT is needed to further refine existing measures of autism symptomatology.

Parental bonding and hoarding in obsessive-compulsive disorder.

BACKGROUND: Hoarding behavior may indicate a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Empirical evidence supports a relationship between hoarding and emotional over-attachment to objects. However, little is known about the relationship between hoarding and parental attachment in OCD. METHOD: The study sample included 894 adults diagnosed with DSM-IV OCD who had participated in family and genetic studies of OCD. Participants were assessed for Axis I disorders, personality disorders, and general personality dimensions. The Parental Bonding Instrument (PBI) was used to assess dimensions of perceived parental rearing (care, overprotection, and control). We compared parental PBI scores in the 334 hoarding and 560 non-hoarding participants, separately in men and women. We used logistic regression to evaluate the relationship between parenting scores and hoarding in women, adjusting for other clinical features associated with hoarding. RESULTS: In men, there were no significant differences between hoarding and non-hoarding groups in maternal or paternal parenting scores. In women, the hoarding group had a lower mean score on maternal care (23.4 vs. 25.7, p<0.01); a higher mean score on maternal protection (9.4 vs. 7.7, p<0.001); and a higher mean score on maternal control (7.0 vs. 6.2, p<0.05), compared to the non-hoarding group. The magnitude of the relationships between maternal bonding dimensions and hoarding in women did not change after adjustment for other clinical features. Women who reported low maternal care/high maternal protection had significantly greater odds of hoarding compared to women with high maternal care/low maternal protection (OR=2.54, 95% CI=1.60-4.02, p<0.001). CONCLUSIONS: Perceived poor maternal care, maternal overprotection, and maternal overcontrol are associated with hoarding in women with OCD. Parenting dimensions are not related to hoarding in men. These findings provide further support for a hoarding subtype of OCD and for sex-specific differences in etiologic pathways for hoarding in OCD.

An investigation of doubt in obsessive-compulsive disorder.

BACKGROUND: Clinicians have long considered doubt to be a fundamental characteristic of obsessive-compulsive disorder (OCD). However, the clinical relevance of doubt in OCD has not been addressed. METHODS: Participants included 1182 adults with OCD who had participated in family and genetic studies of OCD. We used a clinical measure of the severity of doubt, categorized as none, mild, moderate, severe, or extreme. We evaluated the relationship between doubt and OCD clinical features, Axis I disorders, personality and personality disorder dimensions, impairment, and treatment response. RESULTS: The severity of doubt was inversely related to the age at onset of OCD symptoms. Doubt was strongly related to the number of checking symptoms and, to a lesser extent, to the numbers of contamination/cleaning and hoarding symptoms. Doubt also was related to the lifetime prevalence of recurrent major depression and generalized anxiety disorder; to the numbers of avoidant, dependent, and obsessive-compulsive personality disorder traits; and to neuroticism and introversion. Moreover, doubt was strongly associated with global impairment and poor response to cognitive behavioral treatment (CBT), even adjusting for OCD severity and other correlates of doubt. CONCLUSIONS: Doubt is associated with important clinical features of OCD, including impairment and cognitive-behavioral treatment response.

Autonomic arousal in anxious and typically developing youth during a stressor involving error feedback.

Anxiety has been proposed to influence psychophysiological reactivity in children and adolescents. However, the extant empirical literature has not always found physiological reactivity to be associated with anxiety in youth. Further, most investigations have not examined psychophysiological reactivity in real time over the course of acute stress. To test the impact of anxiety disorder status on autonomic arousal in youth, we compared youth with primary anxiety disorders (N = 24) to typically developing (TD) youth (N = 22) on heart rate (HR), heart rate variability (HRV), and respiratory sinus arrhythmia (RSA) during an acute stressor in which youth received error-related feedback. We also conducted exploratory analyses on youth performance during the task. Youth ages 9-17 participated in the arithmetic portion of the Trier Social Stress Test for Children (Buske-Kirschbaum et al., Psychosom 59:419-426, 1997), during which time they received consecutive, standardized feedback that they made calculation errors. Results indicated that, compared to their TD counterparts, the anxious group demonstrated elevated HR and suppressed HRV during initial provision of error feedback and during the recovery period. No group differences were found for RSA. Additionally, overall TD youth made a greater proportion of errors than anxious youth. Clinically, these findings may provide preliminary support for anxious youth exhibiting physiological reactivity in response to receipt of error-related feedback, and may have implications for understanding biological processes during stress. This work underscores the need for further study of when and how anxiety may influence autonomic reactivity over the course of stress.

Distinguishing Fear Versus Distress Symptomatology in Pediatric OCD.

Prior research has identified OCD subtypes or "clusters" of symptoms that differentially relate to clinical features of the disorder. Given the high comorbidity between OCD and anxiety, OCD symptom clusters may more broadly associate with fear and/or distress internalizing constructs. This study examines fear and distress dimensions, including physical concerns (fear), separation anxiety (fear), perfectionism (distress), and anxious coping (distress), as predictors of previously empirically-derived OCD symptom clusters in a sample of 215 youth diagnosed with primary OCD (ages 7-17, mean age = 12.25). Self-reported separation fears predicted membership in Cluster 1 (aggressive, sexual, religious, somatic obsessions, and checking compulsions) while somatic/autonomic fears predicted membership in Cluster 2 (symmetry obsessions and ordering, counting, repeating compulsions). Results highlight the diversity of pediatric OCD symptoms and their differential association with fear, suggesting the need to carefully assess both OCD and global fear constructs that might be directly targeted in treatment.

The diffusion tensor imaging (DTI) component of the NIH MRI study of normal brain development (PedsDTI).

The NIH MRI Study of normal brain development sought to characterize typical brain development in a population of infants, toddlers, children and adolescents/young adults, covering the socio-economic and ethnic diversity of the population of the United States. The study began in 1999 with data collection commencing in 2001 and concluding in 2007. The study was designed with the final goal of providing a controlled-access database; open to qualified researchers and clinicians, which could serve as a powerful tool for elucidating typical brain development and identifying deviations associated with brain-based disorders and diseases, and as a resource for developing computational methods and image processing tools. This paper focuses on the DTI component of the NIH MRI study of normal brain development. In this work, we describe the DTI data acquisition protocols, data processing steps, quality assessment procedures, and data included in the database, along with database access requirements. For more details, visit http://www.pediatricmri.nih.gov. This longitudinal DTI dataset includes raw and processed diffusion data from 498 low resolution (3 mm) DTI datasets from 274 unique subjects, and 193 high resolution (2.5 mm) DTI datasets from 152 unique subjects. Subjects range in age from 10 days (from date of birth) through 22 years. Additionally, a set of age-specific DTI templates are included. This forms one component of the larger NIH MRI study of normal brain development which also includes T1-, T2-, proton density-weighted, and proton magnetic resonance spectroscopy (MRS) imaging data, and demographic, clinical and behavioral data.