Tara Kenworthy

Autistic Traits in Children With and Without ADHD

OBJECTIVE: To assess the implications of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD) without a diagnosis of autism. METHODS: Participants were youth with (n = 242) and without (n = 227) ADHD and controls without ADHD in whom a diagnosis of autism was exclusionary. Assessment included measures of psychiatric, psychosocial, educational, and cognitive functioning. ATs were operationalized by using the withdrawn + social + thought problems T scores from the Child Behavior Checklist. RESULTS: A positive AT profile was significantly overrepresented among ADHD children versus controls (18% vs 0.87%; P < .001). ADHD children with the AT profile were significantly more impaired than control subjects in psychopathology, interpersonal, school, family, and cognitive domains. CONCLUSIONS: A substantial minority of ADHD children manifests ATs, and those exhibiting ATs have greater severity of illness and dysfunction.

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.

Mild Traumatic Brain Injury and Attention-Deficit Hyperactivity Disorder in Young Student Athletes.

Abstract A recent meta-analysis documented a significant statistical association between mild traumatic brain injury (mTBI) and attention deficit hyperactivity disorder (ADHD) (Adeyemo et al., 2014), but the direction of this effect was unclear. In this study, we hypothesized that ADHD would be an antecedent risk factor for mTBI. Participants were student athletes ages 12 to 25 who had sustained a mTBI and Controls of similar age and sex selected from studies of youth with and without ADHD. Subjects were assessed for symptoms of ADHD, concussion severity, and cognitive function. mTBI subjects had a significantly higher rate of ADHD than Controls, and in all cases the age of onset of ADHD was before mTBI onset. mTBI+ADHD subjects also had more severe concussion symptoms (fatigue and poor concentration) than mTBI-ADHD subjects. These results support ADHD as an antecedent risk factor for mTBI in student athletes and that its presence complicates the course of mTBI.

Further evidence that severe scores in the aggression/anxiety-depression/attention subscales of child behavior checklist (severe dysregulation profile) can screen for bipolar disorder symptomatology: a conditional probability analysis

BACKGROUND Previous work shows that children with high scores (2SD, combined score≥210) on the Attention Problems, Aggressive Behavior, and Anxious-Depressed (A-A-A) subscales of the Child Behavior Checklist (CBCL) are more likely than other children to meet criteria for bipolar (BP)-I disorder. However, the utility of this profile as a screening tool has remained unclear. METHODS We compared 140 patients with pediatric BP-I disorder, 83 with attention deficit hyperactivity disorder (ADHD), and 114 control subjects. We defined the CBCL-Severe Dysregulation profile as an aggregate cutoff score of ≥210 on the A-A-A scales. Patients were assessed with structured diagnostic interviews and functional measures. RESULTS Patients with BP-I disorder were significantly more likely than both control subjects (Odds Ratio [OR]: 173.2; 95% Confidence Interval [CI], 21.2 to 1413.8; P<0.001) and those with ADHD (OR: 14.6; 95% CI, 6.2 to 34.3; P<0.001) to have a positive CBCL-Severe Dysregulation profile. Receiver Operating Characteristics analyses showed that the area under the curve for this profile comparing children with BP-I disorder against control subjects and those with ADHD was 99% and 85%, respectively. The corresponding positive predictive values for this profile were 99% and 92% with false positive rates of <0.2% and 8% for the comparisons with control subjects and patients with ADHD, respectively. LIMITATIONS Non-clinician raters administered structured diagnostic interviews, and the sample was referred and largely Caucasian. CONCLUSIONS The CBCL-Severe Dysregulation profile can be useful as a screen for BP-I disorder in children in clinical practice.

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.

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.

Can unipolar and bipolar pediatric major depression be differentiated from each other? A systematic review of cross-sectional studies examining differences in unipolar and bipolar depression

INTRODUCTION While pediatric mania and depression can be distinguished from each other, differentiating between unipolar major depressive disorder (unipolar MDD) and bipolar major depression (bipolar MDD) poses unique clinical and therapeutic challenges. Our aim was to examine the current body of knowledge on whether unipolar MDD and bipolar MDD in youth could be distinguished from one another in terms of clinical features and correlates. METHODS A systematic literature search was conducted on studies assessing the clinical characteristics and correlates of unipolar MDD and bipolar MDD in youth. RESULTS Four scientific papers that met our priori inclusion and exclusion criteria were identified. These papers reported that bipolar MDD is distinct from unipolar MDD in its higher levels of depression severity, associated impairment, psychiatric co-morbidity with oppositional defiant disorder, conduct disorder and anxiety disorders, and family history of mood and disruptive behavior disorders in first-degree relatives. LIMITATIONS Though we examined a sizeable and diverse sample, we were only able to identify four cross sectional informative studies in our review. Therefore, our conclusions should be viewed as preliminary. CONCLUSIONS These findings can aid clinicians in differentiating the two forms of MDD in youth.

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.

Glutamatergic dysregulation in pediatric psychiatric disorders: a systematic review of the magnetic resonance spectroscopy literature.

OBJECTIVE As the major excitatory neurotransmitter in the brain, glutamate plays a critical role in normal brain function; thus, its dysregulation could lead to psychopathology in youth. A growing body of literature has investigated the role of glutamate in the pathophysiology of childhood psychiatric disorders through magnetic resonance spectroscopy (MRS). The aim of this study was to review the existing literature to gauge the specificity of such findings. DATA SOURCES PubMed was searched for all scientific, peer-reviewed articles published in English that included MRS measurements of glutamatergic metabolites in pediatric psychiatric populations through August 14, 2013. STUDY SELECTION 50 articles were included in this review. These studies included measurements of glutamate or related metabolites with MRS in children with psychiatric disorders. DATA EXTRACTION All relevant data (eg, population; number, sex, and age of subjects; method of comparison; treatment history; MRS Tesla; brain regions of interest; glutamatergic findings; other findings; and comorbidities) were extracted from the included articles. The direction and significance of glutamate dysregulation and brain region(s) examined were used to compare the studies. RESULTS Most consistently, increases in glutamatergic metabolites were found in the anterior cingulate cortex (ACC) and other regions in youth with attention-deficit/hyperactivity disorder (ADHD). Limited data suggested increases in glutamatergic metabolites in youth with autism spectrum disorders, emotional dysregulation, and high risk for schizophrenia and decreases in youth with major depression, bipolar disorder, and obsessive-compulsive disorder. There was limited but consistent evidence for normalization of glutamatergic levels with treatment, particularly in bipolar disorder and ADHD. CONCLUSIONS A relatively small number of studies have examined the role of glutamatergic dysregulation in pediatric psychiatric disorders. Some consistencies can be found, but interpretation of the data is limited by differences in methodology, including age of subjects, severity of current symptoms, treatment, and scanning parameters.

A Systematic Evaluation of the QTc Interval and Antidepressants in Youth: An Electronic Health Record Study.

Objective: The US Food and Drug Administration announced that citalopram was associated with dose-related prolongation of the QTc interval in adults. This study aimed to assess how antidepressants affect QTc intervals in children. The authors hypothesized that some antidepressants would show an association with QTc prolongation. Methods: An electronic medical record review was conducted of children aged 5 to 18 years in the Partners Healthcare system with at least 1 prescription of an antidepressant or methadone between February 1990 and August 2011. The authors extracted lifetime diagnoses and QTc interval of patients who had received an electrocardiogram 14 to 90 days after antidepressant or methadone prescription (N = 297). The mean QTc per medication was calculated as compared with the mean of all QTc measurements across medications. The number of patients taking medications who had QTc values in normal, borderline, abnormal, or high were also calculated. Results: Mean QTc values for all medications were in the normal range. The highest mean QTc was in patients on escitalopram (436 milliseconds). The mean QTc for sertraline (416 milliseconds) was significantly lower than all other drugs measured (t(331) = −2.21, p < .05). After controlling for confounding effects, none of the differences in mean QTc compared with other study drugs reached statistical significance. The greatest percentages of abnormal and high QTc values were found among patients taking paroxetine (18.8%), followed by escitalopram (15.4%). None of the children had documented ventricular arrhythmia. Conclusion: The results suggest that most antidepressants are not associated with prolonged QTc at doses typically prescribed for children.