Joel Stoddard

The developmental psychopathology of irritability.

Chronic, severe irritability is common in childhood and is very impairing. Furthermore, childhood irritability predicts suicidality, social impairment, and depressive and anxiety disorders in adulthood. Focusing on both normative and pathologic development, we review the construct of irritability from its origins in aggression and disruptive behavior research to its contemporary relevance for affective psychopathology. We then describe two broad neurocognitive systems that show promise in differentiating irritable from nonirritable youths: aberrant processing of emotional stimuli and impaired context-sensitive regulation. We suggest behavioral, neurocognitive, and physiologic measures that may aid in studying severe irritability and assessing its therapeutics. Finally, we argue for therapeutic trials targeting severe irritability that address emotional aspects of irritability in addition to the associated disruptive behavior.

Sexual and Physical Abuse: A Comparison Between Lesbians and Their Heterosexual Sisters

The purpose of this study was to investigate similarities and differences in the incidence and patterns of abuse experienced by lesbians and their heterosexual sisters. In a matched sample of 324 lesbian/heterosexual sister pairs, the lesbians reported a greater incidence than their sisters of childhood physical and sexual abuse, as well as adult sexual abuse. Both groups identified male relatives as the most common perpetrator of both childhood physical and sexual abuse. Male relatives were most commonly identified as perpetrators of adult physical abuse and male strangers were most commonly identified as adult sexual abusers. Our results demonstrate that both sexual and physical abuse are common experiences for lesbian and heterosexual women; however, since the context of these experiences is different, each group will have special needs for services and treatment.

Irritability in child and adolescent anxiety disorders

Our objective was to compare self‐ and parent‐reported irritability in youths with anxiety disorders, healthy youths, and those with mood disorders characterized by irritability. Irritability is a common but relatively understudied psychiatric symptom in child and adolescent anxiety disorders. In anxious youths, little is known about the severity of irritability, its impact on functioning, or the effect of informant source on reports of irritability.

Aberrant amygdala intrinsic functional connectivity distinguishes youths with bipolar disorder from those with severe mood dysregulation

It remains unclear the degree to which youths with episodic mania (bipolar disorder; BD) vs. those with chronic, severe irritability (severe mood dysregulation, SMD) should be placed in similar or distinct diagnostic groups. Addressing this clinically meaningful question requires greater understanding of the neural alterations underlying both disorders. We evaluated resting state functional magnetic resonance imaging data of 53 youths (14 BD, 20 healthy volunteers (HV), and 19 SMD, ages 9-18.5 years). Seed regions of interest were the bilateral basolateral, superficial and centromedial amygdala, defined using the Juelich probabilistic atlas. We found a significant between-group difference in functional connectivity between the left basolateral amygdala and the medial aspect of the left frontal pole plus the posterior cingulate/precuneus. This finding was driven by hyperconnectivity among BD vs. HV or SMD youths. As with earlier data, these findings suggest that the pathophysiology of BD and SMD may differ.

Atypical development of the executive attention network in children with chromosome 22q11.2 deletion syndrome

Impairment in the executive control of attention has been found in youth with chromosome 22q11.2 deletion syndrome (22q11.2DS). However, how this impairment is modified by other factors, particularly age, is unknown. Forty-six typically developing and 53 children with 22q11.2DS were tested with the attention networks task (ANT) in this cross-sectional study. We used logarithmic transform and linear modeling to assess age effects on the executive index of the ANT. Mixed modeling accounted for between subject variability, age, handedness, catecholamine-O-transferase (COMT; codon 158) genotype, and gender on performance for all experimental conditions (cue × flanker) and their two-level interactions. Children with 22q11.2DS showed a relative, age-dependent executive index impairment but not orienting or alerting network index impairments. In factorial analysis, age was a major predictor of overall performance. There was a significant effect of the 22q11.2DS on overall performance. Of note, children with 22q11.2DS are specifically vulnerable to incongruent flanker interference, especially at younger ages. We did not find an overall effect of COMT genotype or handedness. Children with 22q11.2DS demonstrated age-related impairment in the executive control of attention. Future investigation will likely reveal that there are different developmental trajectories of executive attentional function likely related to the development of schizophrenia in 22q11.2DS.

Atypical Functional Brain Activation During a Multiple Object Tracking Task in Girls With Turner Syndrome: Neurocorrelates of Reduced Spatiotemporal Resolution

Turner syndrome is associated with spatial and numerical cognitive impairments. We hypothesized that these nonverbal cognitive impairments result from limits in spatial and temporal processing, particularly as it affects attention. To examine spatiotemporal attention in girls with Turner syndrome versus typically developing controls, we used a multiple object tracking task during functional magnetic resonance (fMRI) imaging. Participants actively tracked a target among six distracters or passively viewed the animations. Neural activation in girls with Turner syndrome during object tracking overlapped with but was dissimilar to the canonical frontoparietal network evident in typically developing controls and included greater limbic activity. Task performance and atypical functional activation indicate anomalous development of cortical and subcortical temporal and spatial processing circuits in girls with Turner syndrome.

Angry-happy interpretations of ambiguous faces in social anxiety disorder.

Social Anxiety Disorder (SAD) is characterized by a tendency to interpret ambiguous social cues as negative. Here we tested whether interpretation of ambiguous faces differs between participants with SAD and non-anxious controls. Twenty-seven individuals with SAD and 21 non-anxious control participants completed an emotion recognition task in which they judged ambiguous morphed faces as happy or angry. Participants with SAD judged a higher proportion of the faces as angry compared to non-anxious participants, and were slower to judge faces as angry compared to happy, while no such reaction time bias manifested in the control group. Finally, happy judgments were slower in the SAD group compared to the control group, while angry judgments were faster in the SAD group compared to the control group. These findings provide evidence for a negative bias in resolving emotional ambiguity in facial expressions among individuals with SAD.

Early-Childhood Social Reticence Predicts Brain Function in Preadolescent Youths During Distinct Forms of Peer Evaluation:

Social reticence is expressed as shy, anxiously avoidant behavior in early childhood. With development, overt signs of social reticence may diminish but could still manifest themselves in neural responses to peers. We obtained measures of social reticence across 2 to 7 years of age. At age 11, preadolescents previously characterized as high (n = 30) or low (n = 23) in social reticence completed a novel functional-MRI-based peer-interaction task that quantifies neural responses to the anticipation and receipt of distinct forms of social evaluation. High (but not low) social reticence in early childhood predicted greater activity in dorsal anterior cingulate cortex and left and right insula, brain regions implicated in processing salience and distress, when participants anticipated unpredictable compared with predictable feedback. High social reticence was also associated with negative functional connectivity between insula and ventromedial prefrontal cortex, a region commonly implicated in affect regulation. Finally, among participants with high social reticence, negative evaluation was associated with increased amygdala activity, but only during feedback from unpredictable peers.

Aberrant intrinsic functional connectivity within and between corticostriatal and temporal-parietal networks in adults and youth with bipolar disorder

BACKGROUND Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic and striatal areas. METHOD We collected resting-state functional magnetic resonance imaging (fMRI) data from youths and adults (ages 10-50 years) with BD (n = 39) and healthy volunteers (HV; n = 78). We identified brain regions with aberrant intrinsic functional connectivity in BD by first comparing voxel-wise mean global connectivity and then conducting correlation analyses. We used k-means clustering and multidimensional scaling to organize all detected regions into networks. RESULTS Across the brain, we detected areas of dysconnectivity in both youths and adults with BD relative to HV. There were no significant age-group × diagnosis interactions. When organized by interregional connectivity, the areas of dysconnectivity in patients with BD comprised two networks: one of temporal and parietal areas involved in late stages of visual processing, and one of corticostriatal areas involved in attention, cognitive control and response generation. CONCLUSIONS These data suggest that two networks show abnormal intrinsic functional connectivity in BD. Regions in these networks have been implicated previously in BD. We observed similar dysconnectivity in youths and adults with BD. These findings provide guidance for refining models of network-based dysfunction in BD.

Impaired multiple object tracking in children with chromosome 22q11.2 deletion syndrome.

BackgroundChromosome 22q11.2 Deletion Syndrome (22q11.2DS) occurs in approximately 1:4,000 live births with a complex and variable presentation that includes medical, socioemotional and psychological symptoms with intellectual impairment. Cognitive impairments in spatiotemporal and visuospatial attention have also been reported. However, maintenance of selective attention to dynamic and interacting objects has not been systematically investigated in children with 22q11.2DS.MethodsWe used a multiple object tracking task to assay capacity and resolution performance of children with 22q11.2DS aged 7 to 14 years versus age-matched typically developing (TD) peers.ResultsChildren with 22q11.2DS but not TD children demonstrated impaired performance when task demands increased due to an increase in the number of targets presented, but not from an increase in object speed. Task performance in children with 22q11.2DS was also unrelated to intelligence or measures of attention deficit hyperactivity disorder.ConclusionsThese findings suggest that children with 22q11.2DS may be particularly susceptible to dynamic crowding of objects with increasing cognitive demands related to monitoring multiple targets reflecting a reduced acuity in spatiotemporal cognitive representation.