Irritability is a transdiagnostic symptom that often leads to a child’s referral to mental health services and is associated with neuro-structural abnormalities. Disruptions in neural circuits are caused by differences in sensory processing, brain regions associated with memory, or increased involvement of self-referential neural circuits. In predicting mental health problems, irritability symptoms and especially brain structure are considered, and differences in gray matter volume, cortical thickness, and surface area are among the important factors.
Pagliaccio et al. aimed to investigate the correlation between irritability and gray matter volume, cortical thickness, and surface area in various brain regions of irritability in children aged 9-10 years, focusing on identifying structural differences that may be specific to irritability symptoms. By contributing to the understanding of the neurobiological mechanisms underlying various mental health disorders, it was wanted to emphasize the complexity of the relationship between brain structure and irritability symptoms. In the study, data from 11,868 children from the Adolescent Brain Cognitive Development (ABCD) Study were used to examine their relationships at the age of 9-10 years and then at 3 years. In addition, using confirmatory factor analysis, a latent irritability variable was derived and associated with gray matter volume, cortical thickness, and surface area, which both control anxiety symptoms, depressive symptoms, or total mental health symptoms and do not control it.
In the study, complex factors such as age, gender, race/ethnicity, scanner model, parent’s highest education level, medication use, and total intracranial volume were controlled. After excluding the cases whose data were incomplete or failed to pass the quality assurance measures, the final sample size included in the analyses was determined as N = 10,647. Structural equation modeling was used to correlate 10,647 participants from the ABCD Study and a latent irritability factor with gray matter volume, cortical thickness and surface area in various brain regions. In addition; the Diagnostic and Statistical Manual of Mental Disorders (DSM) focused Child Behavior Checklist (CBCL) subscales were used to examine anxiety and depressive symptoms as separate variables: Anxiety problems and affective problems. In addition, by collecting all the CBCL elements, the CBCL total score was created, and structural equation modeling of the analyses was used. The relationships between irritability, gray matter volume, cortical thickness and surface area were studied in 68 cortical regions (34 regions in each hemisphere) derived from a surface-based atlas procedure. For the gray matter volume, 19 subcortical regions derived by an automatic labeling procedure were tested. The DSM discovery rate in version R was used to control multiple tests between regions. Anxious, depressive, or total psychopathology symptoms were included as an additional variable to determine the specificity of the findings. In addition, it was also tested whether the brain structure predicted future irritability symptoms collected during the 3-year follow-up session at the beginning.
In studies, they found that irritability was initially associated mainly with smaller volumes in the temporal and parietal regions, reflecting emotional processing, social cognition, distraction, and movement/perception. Longitudinal analyses found that the initial gray matter volume did not predict irritability symptoms at 3-year follow-up and had no significant association with cortical thickness or surface area. In particular, no significant differences were found in the frontal regions associated with emotional regulation (anterior cingulate and prefrontal cortices) in specific diagnostic groups. In addition; smaller volumes have been found in the supramarginal gyrus, a region involved in interoception, or perceiving the internal state of the body, and which may be related to the redirection of attention. It also showed that irritability is associated with the posterior cingulate gyrus, a central center related to internally directed processes in the default mode network and regulating its focus. In addition, it has been determined that irritability is a transdiagnostic trait and is a basic trait in various mental health conditions.
As a result, the study expands on previous studies by examining the neuro-structural correlations of irritability in young people using a large, well-defined sample, creating a hidden measure of irritability, and using a longitudinal design to predict future symptoms. These findings underscore the importance of brain regions associated with emotional processing, social cognition, distraction, and movement/perception in understanding the symptoms of irritability in children. Taken all together, the results of this study provide a deeper understanding of the neuro-structural substrates that may be associated with multiple disorders involving irritability as a basic symptom, thereby increasing our understanding of the neurobiological mechanisms underlying various mental health conditions.
Author: Sudenur Dinç
Editor: Elif Duymaz
Reference: Archer, C., Hee Jung Jeong, Reimann, G.E., E. Leighton Durham, Moore, T.M., Wang, S., Ashar, D.A. and Kaczkurkin, A.N. (2024). Concurrent and longitudinal neurostructural correlates of irritability in children. Neuropsychopharmacology. doi:https://doi.org/10.1038/s41386-024-01966-4
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