Changes in the Developmental Trajectories of Striatum in Autism

BACKGROUND Repetitive and stereotyped behavior has been associated with striatum in various neuropsychiatric disorders. However, striatal involvement has not yet been shown conclusively in autism. Issues include the use of neuroleptic medication and differences in mean age between samples, where conflicting results may reflect differences in developmental stage between samples. The objective was to examine brain development in a homogeneous sample of subjects with high-functioning autism. METHODS Magnetic resonance measures of brain structure of 188 individuals (99 subjects with high-functioning autism and 89 typically developing, matched control subjects) aged between 6 years and 25 years were compared. Measurements included the volume of brain structures, including striatum, as well as voxel-based assessment of gray matter density. RESULTS Developmental trajectories of the caudate nucleus, putamen, and nucleus accumbens differed between subjects with autism and control subjects. Results were not accounted for by overall changes in brain volume or neuroleptic medication. The development of the caudate nucleus differed from typical most, as its volume increased with age in autism, while it decreased for control subjects. Voxel-based analysis showed that changes in striatum localized to the head of the caudate nucleus. Overall, caudate nucleus volume was associated with repetitive behavior in autism. CONCLUSIONS We report changes in striatal development in autism, while caudate volume is associated with repetitive behaviors. This emphasizes the importance of striatum in the etiology of autism, in particular in the development of repetitive behavior that characterizes the disorder.

[1]  W. Honer,et al.  Reduced basal ganglia volumes after switching to olanzapine in chronically treated patients with schizophrenia. , 2004, The American journal of psychiatry.

[2]  M. Keshavan,et al.  Changes in caudate volume with neuroleptic treatment , 1994, The Lancet.

[3]  Marieke Langen,et al.  Caudate Nucleus Is Enlarged in High-Functioning Medication-Naive Subjects with Autism , 2007, Biological Psychiatry.

[4]  M. Reite,et al.  Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms , 2006, BMC psychiatry.

[5]  A. Toga,et al.  Mapping brain maturation , 2006, Trends in Neurosciences.

[6]  S. Kuperman,et al.  Forebrain structure in infantile autism. , 1989, Journal of the American Academy of Child and Adolescent Psychiatry.

[7]  J. Piven,et al.  Evidence for three subtypes of repetitive behavior in autism that differ in familiality and association with other symptoms. , 2008, Journal of child psychology and psychiatry, and allied disciplines.

[8]  R. Kahn,et al.  Effect of clozapine on caudate nucleus volume in relation to symptoms of schizophrenia. , 2001, The American journal of psychiatry.

[9]  R. Kahn,et al.  Automated Separation of Gray and White Matter from MR Images of the Human Brain , 2001, NeuroImage.

[10]  R. S. Kahn,et al.  Automatic Segmentation of the Ventricular System from MR Images of the Human Brain , 2001, NeuroImage.

[11]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[12]  R. McCarley,et al.  MRI anatomy of schizophrenia , 1999, Biological Psychiatry.

[13]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[14]  Erin A Hazlett,et al.  Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders. , 2006, The American journal of psychiatry.

[15]  J. Lieberman,et al.  Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. , 1994, The American journal of psychiatry.

[16]  R. Kahn,et al.  The Effect of Clozapine on Caudate Nucleus Volume in Schizophrenic Patients Previously Treated with Typical Antipsychotics , 2001, Neuropsychopharmacology.

[17]  T. Sigmundsson,et al.  Brain anatomy and sensorimotor gating in Asperger's syndrome. , 2002, Brain : a journal of neurology.

[18]  C. Fennema-Notestine,et al.  Effects of age on tissues and regions of the cerebrum and cerebellum , 2001, Neurobiology of Aging.

[19]  Robert L. Hendren,et al.  Caudate Nucleus Volume and Cognitive Performance: Are They Related in Childhood Psychopathology? , 2006, Biological Psychiatry.

[20]  Pol Coetsier,et al.  Nederlandstalige bewerking van de 'Wechsler Adult Intelligence Scale' , 1970 .

[21]  Beatriz Luna,et al.  Atypical involvement of frontostriatal systems during sensorimotor control in autism , 2007, Psychiatry Research: Neuroimaging.

[22]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[23]  N C Andreasen,et al.  The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. , 1992, Archives of general psychiatry.

[24]  Ralph-Axel Müller,et al.  Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism , 2006, Behavioral and Brain Functions.

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

[26]  H. Kraemer,et al.  How can we learn about developmental processes from cross-sectional studies, or can we? , 2000, The American journal of psychiatry.

[27]  T. Jernigan,et al.  Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study , 2002, Developmental medicine and child neurology.

[28]  Tore Wentzel-Larsen,et al.  Altered interhemispheric connectivity in individuals with Tourette's disorder. , 2004, The American journal of psychiatry.

[29]  J. Giedd,et al.  Brain development in children and adolescents: Insights from anatomical magnetic resonance imaging , 2006, Neuroscience & Biobehavioral Reviews.

[30]  Guy Marchal,et al.  Multimodality image registration by maximization of mutual information , 1997, IEEE Transactions on Medical Imaging.

[31]  Faith M. Gunning-Dixon,et al.  Differential aging of the human striatum: a prospective MR imaging study. , 1998, AJNR. American journal of neuroradiology.

[32]  J. Pierri,et al.  Frontostriatal measurement in treatment-naive children with obsessive-compulsive disorder. , 1997, Archives of general psychiatry.

[33]  A. Couteur,et al.  Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders , 1994, Journal of autism and developmental disorders.

[34]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[35]  Alan C. Evans,et al.  Focal gray matter density changes in schizophrenia. , 2001, Archives of general psychiatry.

[36]  D. Louis Collins,et al.  Automatic 3‐D model‐based neuroanatomical segmentation , 1995 .

[37]  Paul M. Thompson,et al.  Sexual dimorphism of brain developmental trajectories during childhood and adolescence , 2007, NeuroImage.

[38]  S. Haber The primate basal ganglia: parallel and integrative networks , 2003, Journal of Chemical Neuroanatomy.

[39]  Heping Zhang,et al.  Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. , 2003, Archives of general psychiatry.

[40]  Marieke Langen,et al.  Magnetic resonance simulation is effective in reducing anxiety related to magnetic resonance scanning in children. , 2009, Journal of the American Academy of Child and Adolescent Psychiatry.

[41]  E. Smeraldi,et al.  Increased right caudate nucleus size in obsessive-compulsive disorder: Detection with magnetic resonance imaging , 1992, Psychiatry Research: Neuroimaging.

[42]  E J Costello,et al.  Validity of the NIMH Diagnostic Interview Schedule for Children: A comparison between psychiatric and pediatric referrals , 1985, Journal of abnormal child psychology.

[43]  Joseph Piven,et al.  An MRI study of the basal ganglia in autism , 1999, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[44]  M. Mehmet Haznedar,et al.  Striatal Volume on Magnetic Resonance Imaging and Repetitive Behaviors in Autism , 2005, Biological Psychiatry.

[45]  A. Dale,et al.  Effects of age on volumes of cortex, white matter and subcortical structures , 2005, Neurobiology of Aging.

[46]  John L Bradshaw,et al.  Visuospatial processing and the function of prefrontal-parietal networks in autism spectrum disorders: a functional MRI study. , 2006, The American journal of psychiatry.

[47]  Philip D. Harvey,et al.  Dorsal striatal size, shape, and metabolic rate in never-medicated and previously medicated schizophrenics performing a verbal learning task. , 1998, Archives of general psychiatry.