Faculty Bibliography

Introduction: Over the course of the 20th century, there has been a sharp increase in the consumption of saturated fat and refined sugars. This so-called "western diet" (WD) has been extensively linked to biological alterations and associated functional deficits in the hippocampus of animals. However, the effects of a WD on the human hippocampus are less well-characterized. This preliminary study aimed to extend prior animal work by investigating the effects of a WD on hippocampal volume in children. Methods: Twenty-one healthy children (ages 5-9) completed a structural T1-weighted magnetic resonance imaging scan. Bilateral hippocampal volumes (as regions-of-interest) and bilateral amygdala volumes (as medial temporal lobe control regions-of-interest) were calculated. WD variables were derived from the parent-completed Youth/Adolescent Food Frequency Questionnaire. Specifically, variables were calculated as percent of daily calories consumed from sugars, fats, or a combination of these (WD). Results: While the relationships between overall WD consumption and bilateral hippocampal volumes were not significant, increased fat consumption was significantly related to decreased left hippocampal volume. Sugar consumption was not related to hippocampal size. Control region volumes were not related to any diet variables. Discussion: This study is the first to directly link diet-specifically fat consumption-to decreased left hippocampal volume in children. This extends previous work showing smaller left hippocampal volume related to obesity in pediatric samples. Though preliminary, findings represent an important step toward understanding the impact of diet on child brain development.

The anxiety-related attention bias (AB) has been studied for several decades as a clinically-relevant output of the dynamic and complex threat detection-response system. Despite research enthusiasm for the construct of AB, current theories and measurement approaches cannot adequately account for the growing body of mixed, contradictory, and null findings. Drawing on clinical, neuroscience, and animal models, we argue that the apparent complexity and contradictions in the empirical literature can be attributed to the field's failure to clearly conceptualize AB heterogeneity and the dearth of studies in AB that consider additional cognitive mechanisms in anxiety, particularly disruptions in threat-safety discrimination and cognitive control. We review existing research and propose a working model of AB heterogeneity positing that AB may be best conceptualized as multiple subtypes of dysregulated processing of and attention to threat anchored in individual differences in threat-safety discrimination and cognitive control. We review evidence for this working model and discuss how it can be used to advance knowledge of AB mechanisms and inform personalized prevention and intervention approaches.

Emotional lability and sensory sensitivity have been shown to contribute to the overall clinical picture in children with attention deficit hyperactivity disorder (ADHD; Dunn & Bennett, 2002; Sobanski et al., 2010). Further, both of these characteristics have been individually demonstrated to contribute to poorer quality of life, increased functional impairment, and poorer treatment response (Anastopoulos et al., 2010; Boterberg & Warreyn, 2016). However, to date, no study has evaluated the relationship among all three of these factors. The current study hypothesized that increased sensory sensitivity would moderate the relationship between hyperactive/impulsive symptoms of ADHD and emotional lability in youth. Results indicate that heightened sensory sensitivity strengthens the relationship between hyperactive/impulsive symptoms of ADHD and emotional lability in children with three or more clinically impairing ADHD symptoms. This dimensional approach was taken in accordance with growing evidence that even children with sub-threshold ADHD experience significant functional impairment and high rates of sensory sensitivity (Hong et al., 2014). These findings suggest that clinicians treating children with ADHD symptoms and emotional lability should consider assessing for sensory sensitivity as integration of multi-sensory techniques or referral to concurrent occupational therapy may significantly improve treatment outcomes and quality of life for these children and their families.

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC-ACC connectivity and hyperactivity, and between aMCC-precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.

OBJECTIVE:Children with ADHD frequently exhibit temper outbursts (TO). One related factor may be parental responses, such as harsh discipline and accommodation. This study tests the hypotheses that these responses will be associated with greater TO, and parental characteristics of higher anger and lower sense of competence, in children with ADHD. METHOD/METHODS:Participants included 79 5- to 9-year-old children with ADHD (77.22% boys). Regressions were used to determine the association between parental psychological factors and responses to TO while covarying for TO frequency, severity, and duration. RESULTS:Parental anger and sense of competence were not significantly related to any discipline responses after covarying for TO characteristics, although sense of competence predicted spanking at trend-level significance. Both parental anger and sense of competence significantly predicted accommodation over and above TO characteristics. CONCLUSION/CONCLUSIONS:Results underscore the importance of parental anger and sense of competency in predicting parental behavior, specifically parental accommodation.

Objectives: Temper outbursts are frequently considered symptoms of irritability within the context of ODD, mood disorder, and anxiety disorder. However, even when chronic irritability is not present, they are associated with significant functional impairments. We will provide an overview of our research program that takes a multimodal approach to understanding severe temper outbursts in young children. Methods: We evaluated 216 boys and girls (ages 5-9 years; 73% boys) from diverse socioeconomic backgrounds who comprised three groups: 1) children with severe temper outbursts (STO; n = 80); 2) children with ADHD without outbursts (ADHD; n = 79); and 3) typically developing children (TDC; n = 57). Severe temper outbursts were defined as follows: 1) occurring at least three times per week; 2) lasting >10 minutes; 3) excessive for developmental level; and 4) causing significant impairment. Parents completed a semistructured diagnostic interview about their child and questionnaires about their child's behavior and emotion regulation skills. Children completed brief IQ and language screeners, questionnaires about their emotions and behavior, and tasks assessing frustration tolerance and emotion regulation. A number of these children (64 percent) successfully completed an MRI session that included resting-state, structural, and diffusion tension imaging scans. Results: Approximately 84 percent of the STO group received an ADHD diagnosis, 67 percent were diagnosed with ODD, 28 percent were diagnosed with an anxiety disorder, and 12 percent were diagnosed with a mood disorder. Few exhibited chronic irritabilities based on parent report. On an emotion regulation task, the STO group demonstrated deficits in regulating negative affect in response to frustration. Findings from the resting-state fMRI analyses suggest disruptions in dorsal anterior cingulate cortex (dACC) circuitry associated with tantrum severity. Tantrum severity was also related to cortical thickness of the dACC. Conclusions: Children with severe temper outbursts represent a highly impaired group, even when chronic irritability is not present. Evidence suggests an association between these outbursts and disruptions in dACC circuitry, a region implicated in the expression and regulation of frustration. Such findings have important implications for future conceptualization and treatment of young children with severe temper outbursts

Autism spectrum disorder (ASD) is exceptionally heterogeneous in both clinical and physiopathological presentations. Clinical variability applies to ASD-specific symptoms and frequent comorbid psychopathology such as emotional lability (EL). To date, the physiopathological underpinnings of the co-occurrence of EL and ASD are unknown. As a first step, we examined within-ASD inter-individual variability of EL and its neuronal correlates using resting-state functional magnetic resonance imaging (R-fMRI). We analyzed R-fMRI data from 58 children diagnosed with ASD (5-12 years) in relation to the Conners' Parent Rating Scale EL index. We performed both an a priori amygdala region-of-interest (ROI) analysis, and a multivariate unbiased whole-brain data-driven approach. While no significant brain-behavior relationships were identified regarding amygdala intrinsic functional connectivity (iFC), multivariate whole-brain analyses revealed an extended functional circuitry centered on two regions: middle frontal gyrus (MFG) and posterior insula (PI). Follow-up parametric and nonparametric ROI-analyses of these regions revealed relationships between EL and MFG- and PI-iFC with default, salience, and visual networks suggesting that higher-order cognitive and somatosensory processes are critical for emotion regulation in ASD. We did not detect evidence of amygdala iFC underpinning EL in ASD. However, exploratory whole-brain analyses identified large-scale networks that have been previously reported abnormal in ASD. Future studies should consider EL as a potential source of neuronal heterogeneity in ASD and focus on multinetwork interactions.

Disruptive mood dysregulation disorder (DMDD), a newcomer to psychiatric nosology, addresses the need for improved classification and treatment of children exhibiting chronic nonepisodic irritability and severe temper outbursts. In recent years, many of these children have been diagnosed with bipolar disorder, despite the lack of distinct mood episodes. This diagnostic practice has raised concerns, in part because of the escalating prescription of atypical antipsychotics. This article provides an overview of the limited literature on DMDD, including its history and relevant studies of assessment and treatment. A case study is included to illustrate key points, including diagnostic issues that clinicians may encounter when considering a diagnosis of DMDD.

OBJECTIVE: A substantial proportion of children with attention-deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits manifesting as chronic irritability, severe temper outbursts, and aggression. The amygdala is implicated in emotion regulation, but its connectivity and relation to emotion regulation in ADHD has yet to be explored. The purpose of this study was to examine the relationship between intrinsic functional connectivity (iFC) of amygdala circuits and emotion regulation deficits in youth with ADHD. METHOD: Bilateral amygdala iFC was examined using functional magnetic resonance imaging in 63 children with ADHD, aged 6 to 13 years. First, we examined the relationship between amygdala IFC and parent ratings of emotional lability (EL) in children with ADHD. Second, we compared amygdala iFC across subgroups of children with ADHD and high EL (n = 18), ADHD and low EL (n = 20), and typically developing children (TDC), all with low EL (n = 19). RESULTS: Higher EL ratings were associated with greater positive iFC between the amygdala and rostral anterior cingulate cortex in youth with ADHD. EL scores were also negatively associated with iFC between bilateral amygdala and posterior insula/superior temporal gyrus. Patterns of amygdala-cortical iFC in ADHD participants with low EL were not different from the comparison group, and the effect sizes for these comparisons were smaller than those for the trend-level differences observed between the high-EL and TDC groups. CONCLUSIONS: In children with ADHD and a range of EL, deficits in emotion regulation were associated with altered amygdala-cortical iFC. When comparing groups that differed on ADHD status but not EL, differences in amygdala iFC were small and nonsignificant, highlighting the specificity of this finding to emotional deficits, independent of other ADHD symptoms.