Meta-analysis reveals a reduced surface area of the amygdala in individuals with attention deficit/hyperactivity disorder.

Despite the reported lack of structural alterations in the amygdala of individuals with attention deficit/hyperactivity disorder (ADHD) in previous meta-analyses, subsequent observational studies produced conflicting results. Through incorporating the updated data from observational studies on structural features of the amygdala in ADHD, the primary goal of this study was to examine the anatomical differences in amygdala between subjects with ADHD and their neurotypical controls. Using the appropriate keyword strings, we searched the PubMed, Embase, and Web of Science databases for English articles from inception to February 2022. Eligibility criteria included observational studies comparing the structure of the amygdala between ADHD subjects and their comparators using magnetic resonance imaging (MRI). Subgroup analyses were conducted focusing on the amygdala side, as well as the use of different scanners and approach to segmentation. The effects of other continuous variables, such as age, intelligence quotient, and male percentage, on amygdala size were also investigated. Of the 5703 participants in 16 eligible studies, 2928 were diagnosed with ADHD. Compared with neurotypical controls, subjects with ADHD had a smaller amygdala surface area (particularly in the left hemisphere) but without a significant difference in volume between the two groups. Subgroup analysis of MRI scanners and different approaches to segmentation showed no statistically significant difference. There was no significant correlation between continuous variables and amygdala size. Our results showed consistent surface morphological alterations of the amygdala, in particular on the left side, in subjects with ADHD. However, the preliminary findings based on the limited data available for analysis warrant future studies for verification.

[1]  Kyung Yol Lee,et al.  Subcortical volumetric alterations as potential predictors of methylphenidate treatment response in youth with attention-deficit/hyperactivity disorder , 2022, Journal of psychiatry & neuroscience : JPN.

[2]  H. Ghim,et al.  Disrupted Association Between Empathy and Brain Structure in Attention-Deficit/Hyperactivity Disorder , 2021, Soa--ch'ongsonyon chongsin uihak = Journal of child & adolescent psychiatry.

[3]  Edmund Sonuga-Barke,et al.  The amygdala in adolescents with attention-deficit/hyperactivity disorder: Structural and functional correlates of delay aversion , 2020, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[4]  Lei Hao,et al.  Attention-deficit/hyperactivity disorder is characterized by a delay in subcortical maturation , 2020, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[5]  C. Francks,et al.  Analysis of structural brain asymmetries in Attention-Deficit/Hyperactivity Disorder in 39 datasets , 2020, bioRxiv.

[6]  Kimihiro Nakamura,et al.  Left Amygdala Regulates the Cerebral Reading Network During Fast Emotion Word Processing , 2020, Frontiers in Psychology.

[7]  J. Arrazola,et al.  Amygdala Abnormalities in Adults With ADHD , 2018, Journal of attention disorders.

[8]  Marko Wilke,et al.  Regional Gray Matter Volume Differences Between Adolescents With ADHD and Typically Developing Controls: Further Evidence for Anterior Cingulate Involvement , 2018, Journal of attention disorders.

[9]  Paul M. Thompson,et al.  Hemispheric brain asymmetry differences in youths with attention-deficit/hyperactivity disorder , 2018, NeuroImage: Clinical.

[10]  Yanpei Wang,et al.  Gender differences in anomalous subcortical morphology for children with ADHD , 2018, Neuroscience Letters.

[11]  B. Franke,et al.  Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder , 2017, Biological Psychiatry.

[12]  A. Philipsen,et al.  Manual morphometry of hippocampus and amygdala in adults with attention-deficit hyperactivity disorder , 2017, Psychiatry Research: Neuroimaging.

[13]  Kristi R. Griffiths,et al.  Regional brain network organization distinguishes the combined and inattentive subtypes of Attention Deficit Hyperactivity Disorder , 2017, NeuroImage: Clinical.

[14]  L. Pessoa A Network Model of the Emotional Brain , 2017, Trends in Cognitive Sciences.

[15]  Xiaoying Tang,et al.  Anomalous subcortical morphology in boys, but not girls, with ADHD compared to typically developing controls and correlates with emotion dysregulation , 2017, Psychiatry Research: Neuroimaging.

[16]  Dhruv Marwha,et al.  Meta-analysis reveals a lack of sexual dimorphism in human amygdala volume , 2017, NeuroImage.

[17]  Salvatore Nigro,et al.  Surface-based morphometry reveals the neuroanatomical basis of the five-factor model of personality , 2017, Social cognitive and affective neuroscience.

[18]  H. Hart,et al.  Structural and Functional Brain Abnormalities in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder: A Comparative Meta-analysis. , 2016, JAMA psychiatry.

[19]  M. Mallar Chakravarty,et al.  Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation , 2016, NeuroImage.

[20]  J. Arrazola,et al.  Correlation between amygdala volume and impulsivity in adults with attention-deficit hyperactivity disorder , 2015, Acta Neuropsychiatrica.

[21]  B. Franke,et al.  Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings. , 2015, JAMA psychiatry.

[22]  P. Peigneux,et al.  Grey matter volumes in treatment naïve vs. chronically treated children with attention deficit/hyperactivity disorder: a combined approach , 2015, European Neuropsychopharmacology.

[23]  K. Tye,et al.  From circuits to behaviour in the amygdala , 2015, Nature.

[24]  M. Banich,et al.  Reduced Amygdala Volume Is Associated with Deficits in Inhibitory Control: A Voxel- and Surface-Based Morphometric Analysis of Comorbid PTSD/Mild TBI , 2014, BioMed research international.

[25]  Ellen Leibenluft,et al.  Emotion dysregulation in attention deficit hyperactivity disorder. , 2014, The American journal of psychiatry.

[26]  B. Franke,et al.  Brain alterations in adult ADHD: Effects of gender, treatment and comorbid depression , 2014, European Neuropsychopharmacology.

[27]  Hisao Nishijo,et al.  Developmental Trajectories of Amygdala and Hippocampus from Infancy to Early Adulthood in Healthy Individuals , 2012, PloS one.

[28]  Katya Rubia,et al.  Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. , 2011, The American journal of psychiatry.

[29]  S. Strakowski,et al.  Progression of amygdala volumetric abnormalities in adolescents after their first manic episode. , 2011, Journal of the American Academy of Child and Adolescent Psychiatry.

[30]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[31]  Richard D Riley,et al.  Interpretation of random effects meta-analyses , 2011, BMJ : British Medical Journal.

[32]  Ruben C. Gur,et al.  Cognitive versus automatic mechanisms of mood induction differentially activate left and right amygdala , 2011, NeuroImage.

[33]  Nikolaos Koutsouleris,et al.  Anterior cingulate cortex gray matter abnormalities in adults with attention deficit hyperactivity disorder: A voxel-based morphometry study , 2011, Psychiatry Research: Neuroimaging.

[34]  Hannah R Rothstein,et al.  A basic introduction to fixed‐effect and random‐effects models for meta‐analysis , 2010, Research synthesis methods.

[35]  R. Barkley,et al.  Social and emotional impairment in children and adolescents with ADHD and the impact on quality of life. , 2010, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[36]  P. Rakic Evolution of the neocortex: Perspective from developmental biology , 2010 .

[37]  L. Hedges,et al.  Introduction to Meta‐Analysis , 2009, International Coaching Psychology Review.

[38]  Nikos Makris,et al.  Subcortical differences among youths with attention-deficit/hyperactivity disorder compared to those with bipolar disorder with and without attention-deficit/hyperactivity disorder. , 2009, Journal of child and adolescent psychopharmacology.

[39]  S. Mostofsky,et al.  Abnormal cerebral cortex structure in children with ADHD , 2009, Human brain mapping.

[40]  A. Philipsen,et al.  Hippocampus and amygdala morphology in adults with attention-deficit hyperactivity disorder. , 2008, Journal of psychiatry & neuroscience : JPN.

[41]  Julian P T Higgins,et al.  Commentary: Heterogeneity in meta-analysis should be expected and appropriately quantified. , 2008, International journal of epidemiology.

[42]  B. Peterson,et al.  Correlates of intellectual ability with morphology of the hippocampus and amygdala in healthy adults , 2008, Brain and Cognition.

[43]  Alan C. Evans,et al.  Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation , 2007, Proceedings of the National Academy of Sciences.

[44]  F Xavier Castellanos,et al.  Brain development and ADHD. , 2006, Clinical psychology review.

[45]  Hongtu Zhu,et al.  Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder. , 2006, Archives of general psychiatry.

[46]  Alan C. Evans,et al.  Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. , 2006, Archives of general psychiatry.

[47]  Clifford R. Jack,et al.  Comparison of different methodological implementations of voxel-based morphometry in neurodegenerative disease , 2005, NeuroImage.

[48]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[49]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology - A proposal for reporting , 2000 .

[50]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[51]  P. Renshaw,et al.  Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls , 1997, Neurology.

[52]  J. Rapoport,et al.  Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. , 1996, Archives of general psychiatry.

[53]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[54]  Jan K. Buitelaar,et al.  Attention-deficit/hyperactivity disorder , 2015, Nature Reviews Disease Primers.

[55]  Neil Roberts,et al.  Measurement of brain volume using MRI : software , techniques , choices and prerequisites , 2009 .

[56]  H. Markowitsch Differential contribution of right and left amygdala to affective information processing. , 1998, Behavioural neurology.

[57]  A. Schleicher,et al.  Gyrification in the cerebral cortex of primates. , 1989, Brain, behavior and evolution.