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Linda J. Lotspeich, MD; Hower Kwon, MD; Cynthia M. Schumann, BS; Susanna L. Fryer, BA; Beth L. Goodlin-Jones, PhD; Michael H. Buonocore, PhD; Cathy R. Lammers, MD; David G. Amaral, PhD; Allan L. Reiss, MD

Arch Gen Psychiatry. 2004;61:291-298.

Background  Autism and Asperger syndrome (ASP) are neurobiological conditions with overlapping behavioral symptoms and of unknown etiologies. Results from previous autism neuroimaging studies have been difficult to replicate, possibly owing to site differences in subject samples, scanning procedures, and image-processing methods. We sought (1) to determine whether low-functioning autism (LFA; IQ<70), high-functioning autism (HFA; IQ70), and ASP constitute distinct biological entities as evidenced by neuroanatomical measures, and (2) to assess for intersite differences.

Methods  Case-control study examining coronally oriented 124-section spoiled gradient echo images acquired on 3 magnetic resonance imaging (MRI) systems, and processed by BrainImage 5.X. Participants were recruited and underwent scanning at 2 academic medicine departments. Participants included 4 age-matched groups of volunteer boys aged 7.8 to 17.9 years (13 patients with LFA, 18 with HFA, 21 with ASP, and 21 control subjects), and 3 volunteer adults for neuroimaging reliability. Main outcome measures included volumetric measures of total, white, and gray matter for cerebral and cerebellar tissues.

Results  Intersite differences were seen for subject age, IQ, and cerebellum measures. Cerebral gray matter volume was enlarged in both HFA and LFA compared with controls (P = .009 and P = .04, respectively). Cerebral gray matter volume in ASP was intermediate between that of HFA and controls, but nonsignificant. Exploratory analyses revealed a negative correlation between cerebral gray matter volume and performance IQ within HFA but not ASP. A positive correlation between cerebral white matter volume and performance IQ was observed within ASP but not HFA.

Conclusions  Lack of replication between previous autism MRI studies could be due to intersite differences in MRI systems and subjects' age and IQ. Cerebral gray tissue findings suggest that ASP is on the mild end of the autism spectrum. However, exploratory assessments of brain-IQ relationships reveal differences between HFA and ASP, indicating that these conditions may be neurodevelopmentally different when patterns of multiple measures are examined. Further investigations of brain-behavior relationships are indicated to confirm these findings.

From the Department of Psychiatry and Behavioral Sciences (Drs Lotspeich, Kwon, and Reiss) and the Stanford Psychiatry Neuroimaging Laboratory (Drs Kwon and Reiss and Ms Fryer), Stanford University School of Medicine, Stanford, Calif; and the Center for Neuroscience and The MIND Institute, Department of Psychiatry (Ms Schumann and Drs Goodlin-Jones, Buonocore, Lammers, and Amaral), and the California National Primate Research Center (Dr Amaral), University of California–Davis.

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