Faculty Bibliography
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29
Parenting and childhood irritability: Negative emotion socialization and parental control moderate the development of irritability
Irritability, characterized by anger in response to frustration, is normative in childhood. While children typically show a decline in irritability from toddlerhood to school age, elevated irritability throughout childhood may predict later psychopathology. The current study (n = 78) examined associations between trajectories of irritability in early childhood (ages 2-7) and irritability in adolescence (age 12) and tested whether these associations are moderated by parenting behaviors. Results indicate that negative emotion socialization moderated trajectories of irritability - relative to children with low stable irritability, children who exhibited high stable irritability in early childhood and who had parents that exhibited greater negative emotion socialization behaviors had higher irritability in adolescence. Further, negative parental control behavior moderated trajectories of irritability - relative to children with low stable irritability, children who had high decreasing irritability in early childhood and who had parents who exhibited greater negative control behaviors had higher irritability in adolescence. In contrast, positive emotion socialization and control behaviors did not moderate the relations between early childhood irritability and later irritability in adolescence. These results suggest that both irritability in early childhood and negative parenting behaviors may jointly influence irritability in adolescence. The current study underscores the significance of negative parenting behaviors and could inform treatment.
PMCID:9289071
PMID: 35039102
ISSN: 1469-2198
CID: 5364792
Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group
The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.
PMCID:8675407
PMID: 32596977
ISSN: 1097-0193
CID: 5364742
What is next for the neurobiology of temperament, personality and psychopathology?
ISI:000832982500003
ISSN: 2352-1546
CID: 5364892
Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group
The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.
PMCID:8486763
PMID: 34599145
ISSN: 2158-3188
CID: 5039482
Journal of the American Academy of Child & Adolescent Psychiatry. 2021:60(9):1137-1146.DOI: 10.1016/j.jaac.2020.11.021
Amygdala Functional Connectivity and Negative Reactive Temperament at Age 4 Months
OBJECTIVE:Infant amygdala connectivity correlates with maternal reports of infant temperament characterized by novelty-evoked distress and avoidance. However, no studies have examined how human infant amygdala connectivity relates to direct observations of novelty-evoked distress. This study examined the link between amygdala connectivity and infant novelty-evoked distress using direct observation of temperament. METHOD:Novelty-evoked distress was assessed at 4 months of age (N = 90) using a standardized reactivity assessment and parent report. Within 3 weeks of assessment, resting-state functional magnetic resonance imaging was collected in a subset of infants (n = 34). Using a whole-brain voxelwise approach, amygdala connectivity associated with positive and negative affect during the reactivity assessment was examined. Regions where the association of amygdala connectivity with negative affect was higher than with positive affect were then examined. Associations between amygdala connectivity and parent report of temperament were also examined. RESULTS:Greater amygdala-cingulate and amygdala-superior frontal gyrus connectivity was associated with lower positive affect during the reactivity assessment. Further, the association between amygdala-cingulate connectivity was greater for negative affect compared with positive affect. There were no significant associations between latency to approach novelty (as measured by parent report) and amygdala connectivity. Validation analyses conducted using a large independent longitudinal sample (N = 323) demonstrated that negative reactivity was associated with increased child-reported anxiety symptoms in adolescence. CONCLUSION:These results provide novel insight into the developmental pathophysiology of novelty-evoked distress. This is consistent with research linking an altered cognitive control mechanism to temperamental risk for anxiety.
PMID: 33385507
ISSN: 1527-5418
CID: 5364752
Functional Connectivity Relates to Electrophysiological Markers of Attention in Infancy [Meeting Abstract]
ISI:000645683800075
ISSN: 0006-3223
CID: 5364872
Mapping Anxiety and Irritability Trajectories Over Time: Associations With Brain Response During Cognitive Conflict [Meeting Abstract]
ISI:000645683800490
ISSN: 0006-3223
CID: 5364882
Developmental pathways to social anxiety and irritability: The role of the ERN
Early behaviors that differentiate later biomarkers for psychopathology can guide preventive efforts while also facilitating pathophysiological research. We tested whether error-related negativity (ERN) moderates the link between early behavior and later psychopathology in two early childhood phenotypes: behavioral inhibition and irritability. From ages 2 to 7 years, children (n = 291) were assessed longitudinally for behavioral inhibition (BI) and irritability. Behavioral inhibition was assessed via maternal report and behavioral responses to novelty. Childhood irritability was assessed using the Child Behavior Checklist. At age 12, an electroencephalogram (EEG) was recorded while children performed a flanker task to measure ERN, a neural indicator of error monitoring. Clinical assessments of anxiety and irritability were conducted using questionnaires (i.e., Screen for Child Anxiety Related Disorders and Affective Reactivity Index) and clinical interviews. Error monitoring interacted with early BI and early irritability to predict later psychopathology. Among children with high BI, an enhanced ERN predicted greater social anxiety at age 12. In contrast, children with high childhood irritability and blunted ERN predicted greater irritability at age 12. This converges with previous work and provides novel insight into the specificity of pathways associated with psychopathology.
PMID: 31656217
ISSN: 1469-2198
CID: 5364712
Infant behavioral reactivity predicts change in amygdala volume 12 years later
The current study examined the link between temperamental reactivity in infancy and amygdala development in middle childhood. A sample (n = 291) of four-month-old infants was assessed for infant temperament, and two groups were identified: those exhibiting negative reactivity (n = 116) and those exhibiting positive reactivity (n = 106). At 10 and 12 years of age structural imaging was completed on a subset of these participants (n = 75). Results indicate that, between 10 and 12 years of age, left amygdala volume increased more slowly in those with negative compared to positive reactive temperament. These results provide novel evidence linking early temperament to distinct patterns of brain development over middle childhood.
PMCID:7096757
PMID: 32452462
ISSN: 1878-9307
CID: 5364732
ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
PMCID:7083923
PMID: 32198361
ISSN: 2158-3188
CID: 5364722
