Anxiety and Disruptive Behavior Symptoms and Disorders in Preschool-Age Offspring of Parents With and Without Bipolar Disorder: Associations With Parental Comorbidity.

OBJECTIVE: We examined the relative contribution of parental bipolar disorder (BPD) and psychiatric comorbidities (disruptive behavior disorders [DBD] and anxiety disorders) in predicting psychiatric symptoms and disorders in 2-5-year-old offspring. METHODS: Participants were 60 families with a parent with BPD and 78 offspring and 70 comparison families in which neither parent had a mood disorder and 91 offspring. Parent and offspring diagnoses and symptoms were assessed using standardized diagnostic interviews and measures, with offspring assessors masked to parental diagnoses. RESULTS: Offspring of parents with BPD had significant elevations in behavioral, mood and anxiety disorders and symptoms. Both parental BPD and DBD contributed to elevations in child disruptive behavioral symptoms, whereas child anxiety symptoms were more strongly predicted by comorbid parental anxiety. Parental BPD was a stronger predictor than comorbid DBD of child DBDs. CONCLUSION: Some of the elevated risk for disorders in preschoolers is accounted for by parental comorbidity.

The Pediatric Accommodation Scale: Psychometric Evaluation of a Therapist-Report Format.

Anxiety disorders are the most common mental health problem in youth, and accommodation is prevalent among youth with anxiety disorders. The Pediatric Accommodation Scale (PAS) is an interview administered by trained evaluators and a parent-report form (PAS-PR) to assess accommodation and its impact. Both have strong psychometric properties including internal consistency, inter-rater reliability, and data supporting construct validity. The present study evaluates the Pediatric Accommodation Scale - Therapist Report (PAS-TR), a therapist-reported version of the PAS-PR. Participants were 90 youth enrolled in cognitive behavioral therapy for anxiety. Therapists completed the PAS-TR over 16 therapy sessions. Internal consistency at baseline, convergent validity, divergent validity, and parent-therapist agreement were evaluated. Results suggest that the PAS-TR has mixed psychometric qualities suggesting that while not strong prior to the initiation of treatment, the PAS-TR may be a useful measure for therapists to rate accommodation as treatment progresses. Implications for assessment, treatment, and research are discussed.

Accommodation of Anxiety in Youth with Autism Spectrum Disorder: Results from the TAASD Study.

Objective: Accommodation, or the ways in which families modify their routines and expectations in response to a child's anxiety, is common and interferes with anxiety treatment outcomes. However, little research has examined family accommodation among youth with autism spectrum disorder and anxiety. The current study aimed to (a) identify pre-treatment correlates of accommodation, (b) examine changes in accommodation after treatment, and (c) assess relationships between accommodation and post-treatment anxiety severity.Method: The sample consisted of 167 youth (mean age = 9.90 years; 79.6% male; 18% Latinx) with clinically significant anxiety and a diagnosis of autism spectrum disorder who were enrolled in a randomized clinical trial comparing two cognitive behavioral therapy interventions for anxiety and treatment-as-usual. Participants were evaluated for symptom severity and family accommodation at pre- and post-treatment.Results: Results indicated that clinician-rated anxiety severity and parent-rated externalizing behaviors and autism spectrum disorder severity significantly predicted pre-treatment accommodation. Accommodation significantly decreased from pre- to post-treatment and non-responders showed significantly higher accommodation at post-treatment compared to responders. Finally, youth with higher pre-treatment accommodation had higher post-treatment anxiety.Conclusions: Findings indicate that accommodation for anxiety is common among youth with autism spectrum disorder and anxiety. Furthermore, accommodation is implicated in treatment outcomes and should be targeted in treatment for youth with autism spectrum disorder and anxiety.

Beyond 16 Sessions: Extending Manualized Treatment of Anxious Youth.

Cognitive behavioral therapy (CBT) is well established as an efficacious treatment for anxious youth, yet a number of youth remain symptomatic after the 10-16 sessions of treatment stipulated by most CBT treatment manuals. While a significant minority do not respond, no study has examined the frequency and impact of additional therapy sessions. This study examined youth receiving outpatient therapy at an anxiety clinic who were offered the option to continue treatment after completing 16 sessions of manual-based CBT. Fifty-nine percent of participants chose to continue treatment, with an average of approximately 20 total sessions across participants. Therapist ratings demonstrated a significant overall improvement between session 16 and the final session. No pre-treatment measure of symptom severity differed between those who extended treatment and those who ended at session 16. Parent-rated anxiety differed between groups at session 16, as did the length of time between the pre-treatment assessment and week 16 assessments. Findings indicate that extending treatment is not uncommon, is typically limited to several additional sessions, and is associated with an increase in treatment gains. Current results suggest that two factors at session 16, parental perceptions of anxiety and time to complete 16 sessions, are influential and may be central to the decision to continue treatment past this point. Clinical implications and future directions are discussed.

Antidepressant Use in a 3- to 12-Year Follow-up of Anxious Youth: Results from the CAMELS Trial.

The current study explored whether patient characteristics predicted patterns of antidepressant use (i.e., never used, single episode of use, or two or more episodes) in a naturalistic follow-up. Participants in the child/adolescent multimodal (CAMS) extended long-term study. (n = 318) indicated medication use over the course of eight follow-up visits, 3-12 years after receiving treatment in CAMS. 40.6% of participants reported never using an antidepressant during follow-up, 41.4% reported a single episode of antidepressant use, and 18.0% reported multiple episodes of antidepressant use. Greater baseline anxiety severity marginally predicted a single episode of antidepressant use; baseline depression severity predicted multiple episodes of use. Reasons for discontinuing antidepressants included perceived ineffectiveness (31.8%), side effects (25.5%), and improvement in symptoms (18.5%). Exploratory analyses examined predictors of medication use. Findings suggest that antidepressant use is common among anxious youth, as is discontinuation of antidepressant use. Clinical implications and future directions are discussed.

The Role of Comorbid Depression in Youth Anxiety Treatment Outcomes.

Findings have been mixed regarding the relationship between comorbid depression and anxiety and treatment outcomes for anxious youth. The current study compared a sample of anxious youth with a comorbid depressive disorder (n = 20) and those without comorbid depression (n = 137). All participants received 16 weekly sessions of Coping Cat and completed measures assessing anxiety/depression severity, impairment, and functioning at pretreatment and posttreatment. Results indicated that anxiety-focused CBT is efficacious for anxious youth with and without comorbid depressive disorders, with a higher rate of symptom improvement for youth with comorbid depression during treatment. However, comorbid depression was associated with higher severity at baseline and after treatment. Thus, despite the higher rate of symptom improvement, anxious youth with comorbid depression may benefit from additional treatment to address remaining symptoms.

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

OBJECTIVE: Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. STUDY DESIGN: The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. RESULTS: No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. CONCLUSIONS: Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

ACCOMMODATION AND TREATMENT OF ANXIOUS YOUTH.

BACKGROUND: Parental accommodation refers to the ways in which a parent modifies their behavior to avoid or reduce the distress their child experiences. Parents of youth with anxiety disorders have been found to accommodate their child's anxiety in a variety of ways that contribute to the maintenance of the disorder. The current study evaluated the relationship between parental accommodation and the outcome of treatment for youth with anxiety. METHODS: Sixty-two youth (age 6-17) and their parents were evaluated for youth anxiety and parental accommodation before and after treatment. All youth received individual cognitive behavioral therapy (CBT). RESULTS: Parental accommodation was significantly reduced from before to after treatment. Reduction in parent-rated accommodation was significantly associated with the severity of youth's posttreatment anxiety, even when controlling for pretreatment youth anxiety. Level of pretreatment accommodation was significantly associated with treatment response. CONCLUSIONS: Findings indicate that parental accommodation is significantly reduced after individual youth CBT, and suggest that accommodation may be an important treatment focus. Clinical implications and future directions are discussed.

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression.

BACKGROUND: Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. METHODS: We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8-14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). RESULTS: At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. CONCLUSIONS: Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression.

The Treatment of Anxiety in Autism Spectrum Disorder (TAASD) Study: Rationale, Design and Methods.

This paper describes the rationale, design, and methods of the Treatment for Anxiety in Autism Spectrum Disorders study, a three-site randomized controlled trial investigating the relative efficacy of a modular CBT protocol for anxiety in ASD (Behavioral Interventions for Anxiety in Children with Autism) versus standard CBT for pediatric anxiety (the Coping Cat program) and a treatment-as-usual control. The trial is distinct in its scope, its direct comparison of active treatments for anxiety in ASD, and its comprehensive approach to assessing anxiety difficulties in youth with ASD. The trial will evaluate the relative benefits of CBT for children with ASD and investigate potential moderators (ASD severity, anxiety presentation, comorbidity) and mediators of treatment response, essential steps for future dissemination and implementation.

Functional and structural brain correlates of risk for major depression in children with familial depression.

Despite growing evidence for atypical amygdala function and structure in major depression, it remains uncertain as to whether these brain differences reflect the clinical state of depression or neurobiological traits that predispose individuals to major depression. We examined function and structure of the amygdala and associated areas in a group of unaffected children of depressed parents (at-risk group) and a group of children of parents without a history of major depression (control group). Compared to the control group, the at-risk group showed increased activation to fearful relative to neutral facial expressions in the amygdala and multiple cortical regions, and decreased activation to happy relative to neutral facial expressions in the anterior cingulate cortex and supramarginal gyrus. At-risk children also exhibited reduced amygdala volume. The extensive hyperactivation to negative facial expressions and hypoactivation to positive facial expressions in at-risk children are consistent with behavioral evidence that risk for major depression involves a bias to attend to negative information. These functional and structural brain differences between at-risk children and controls suggest that there are trait neurobiological underpinnings of risk for major depression.

Emotion regulation ability varies in relation to intrinsic functional brain architecture.

This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture.

Mild traumatic brain injury and ADHD: a systematic review of the literature and meta-analysis.

OBJECTIVE: This study investigated the association between mild traumatic brain injury (mTBI) and ADHD, which increases risk of injuries and accidents. METHOD: We conducted a systematic review and meta-analysis of studies that examined the relationship between mTBI and ADHD. RESULTS: Five studies, comprising 3,023 mTBI patients and 9,716 controls, fit our a priori inclusion and exclusion criteria. A meta-analysis found a significant association between ADHD and mTBI, which was significant when limited to studies that reported on ADHD subsequent to mTBI and when the direction of the association was not specified, but not for studies that reported mTBI subsequent to ADHD. Heterogeneity of effect size and publication biases were not evident. CONCLUSION: The literature documents a significant association between mTBI and ADHD. Further clarification of the relationship and direction of effect between mTBI and ADHD and treatment implications could have large clinical, scientific, and public health implications.

Brain differences between persistent and remitted attention deficit hyperactivity disorder.

Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions.