Pallidum and lateral ventricle volume enlargement in autism spectrum disorder

Studies on structural brain abnormalities in individuals with autism spectrum disorders (ASD) have been of limited size and many findings have not been replicated. In the largest ASD brain morphology study to date, we compared subcortical, total brain (TBV), and intracranial (ICV) volumes between 472 subjects with DSM-IV ASD diagnoses and 538 healthy volunteers (age range: 6-64 years), obtained from high-resolution structural brain scans provided by the Autism Brain Imaging Data Exchange (ABIDE). Compared to healthy volunteers, we found significantly larger pallidum (Cohen's d=0.15) and lateral ventricle volumes (Cohen's d=0.18) in ASD. These enlargements were independent of total brain volume and IQ, passed FDR correction for multiple comparisons, and were observed in overall, male-only, and medication-free subjects. In addition, intracranial, hippocampal, and caudate volumes were enlarged in ASD at a nominal statistical threshold of p<0.05. This study provides the first robust evidence for pallidum enlargement in ASD independent from TBV and encourages further study of the functional role of the pallidum in individuals with autism spectrum disorder.

[1]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[2]  Michele T. Diaz,et al.  Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies , 2012, Journal of magnetic resonance imaging : JMRI.

[3]  M. Chakravarty,et al.  The autism puzzle: Diffuse but not pervasive neuroanatomical abnormalities in children with ASD , 2015, NeuroImage: Clinical.

[4]  E. Courchesne,et al.  When Is the Brain Enlarged in Autism? A Meta-Analysis of All Brain Size Reports , 2005, Biological Psychiatry.

[5]  M. Bellani,et al.  Basal ganglia and restricted and repetitive behaviours in Autism Spectrum Disorders: current status and future perspectives , 2014, Epidemiology and Psychiatric Sciences.

[6]  Takanori Kochiyama,et al.  Increased Putamen Volume in Adults with Autism Spectrum Disorder , 2014, Front. Hum. Neurosci..

[7]  Ruth A. Carper,et al.  Unusual brain growth patterns in early life in patients with autistic disorder , 2001, Neurology.

[8]  M. Seltzer,et al.  Age-Related Differences in Restricted Repetitive Behaviors in Autism Spectrum Disorders , 2009, Journal of autism and developmental disorders.

[9]  Thomas Bourgeron,et al.  Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta-analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and Simulation , 2015, Biological Psychiatry.

[10]  M. Bellani,et al.  Epidemiology and Psychiatric Sciences Basal ganglia and restricted and repetitive behaviours in Autism Spectrum Disorders: current status and future perspectives , 2014 .

[11]  Ir W. De Backer,et al.  Review of neuroimaging studies of child and adolescent psychiatric disorders from the past 10 years. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[12]  Daniel R Weinberger,et al.  Finding the Elusive Psychiatric "Lesion" With 21st-Century Neuroanatomy: A Note of Caution. , 2015, The American journal of psychiatry.

[13]  M. King,et al.  How does environmental enrichment reduce repetitive motor behaviors? Neuronal activation and dendritic morphology in the indirect basal ganglia pathway of a mouse model , 2016, Behavioural Brain Research.

[14]  Geraldine Dawson,et al.  Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder , 2011, Autism research : official journal of the International Society for Autism Research.

[15]  S. Lawrie,et al.  Towards a neuroanatomy of autism: A systematic review and meta-analysis of structural magnetic resonance imaging studies , 2008, European Psychiatry.

[16]  D. Amaral,et al.  Neuroanatomy of autism , 2008, Trends in Neurosciences.

[17]  Daniel P. Kennedy,et al.  The Autism Brain Imaging Data Exchange: Towards Large-Scale Evaluation of the Intrinsic Brain Architecture in Autism , 2013, Molecular Psychiatry.

[18]  David A. Ziegler,et al.  Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. , 2003, Brain : a journal of neurology.

[19]  T. Napier,et al.  The role of the ventral pallidum in psychiatric disorders , 2010, Neuropsychopharmacology.

[20]  B. Thyer,et al.  Social work assessment of adaptive functioning using the vineland adaptive behavior scales: Issues of reliability and validity , 1999 .

[21]  Ruth A. Carper,et al.  Evidence of brain overgrowth in the first year of life in autism. , 2003, JAMA.

[22]  Leif Engqvist,et al.  The mistreatment of covariate interaction terms in linear model analyses of behavioural and evolutionary ecology studies , 2005, Animal Behaviour.

[23]  Sigal Berman,et al.  Anatomical Abnormalities in Autism? , 2016, Cerebral cortex.

[24]  Michael P Milham,et al.  Multicenter mapping of structural network alterations in autism , 2015, Human brain mapping.