Volumetric alterations of the orbitofrontal cortex in autism

doi:10.1016/j.pnpbp.2006.06.007

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 31, Issue 1, 30 January 2007, Pages 41-45

https://doi.org/10.1016/j.pnpbp.2006.06.007 Get rights and content

Abstract

Recent evidence has implicated the orbitofrontal cortex (OFC) in the pathophysiology of social deficits in autism. An MRI-based morphometric study of the OFC was conducted involving 11 children with autism (age range 8.1–12.7 years) and 18 healthy, age-matched controls (age range 8.9–12.8 years). Decreased grey matter volume in the right lateral OFC in the patient group was found, and correlations were observed between social deficits and white, but not grey, matter structures of the OFC. These findings support the role of OFC in autism and warrant further investigations of this structure using structural and functional methodologies.

Introduction

Impairments in social interactions and behaviors are among the essential characteristic features of individuals with autism. A recent hypothesis proposed that abnormalities of the orbitofrontal–amygdala circuit may underlie several of the core features of this severe developmental disorder (Bachevalier and Loveland, 2006). The orbitofrontal cortex (OFC), and more specifically its right lateral subdivision, appears to play an important role in social cognition (O'Doherty et al., 2001, Vollm et al., 2006), with some evidence suggesting its role in the pathophysiology of autism (Bachevalier and Loveland, 2006, Dawson et al., 2002, Salmond et al., 2003). A morphometric MRI investigation reported decreased volume of the total (i.e., grey plus white matter) right lateral OFC in children and adolescents with autism, which contrasted with increased size in adults (Hardan et al., in press). Moreover, a recent fMRI study of healthy adults reported that processing theory of mind tasks, a function believed to be impaired in individuals with autism, was associated with increased activation of the right lateral OFC (Vollm et al., 2006). Finally, the potential relevance of the OFC in autism is highlighted by its role in the reward system (O'Doherty et al., 2001), with evidence suggesting that impairment in assigning and flexibly modifying social reward values may be related to some of the social deficits observed in pervasive developmental disorders (Dawson et al., 2002).

In light of the mounting evidence implicating the OFC in social functioning, this study was conducted in a sample comprised exclusively of children with autism to examine grey and white matter volumes of this structure, and to investigate the relationship between OFC structures and social deficits as measured by the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) (Lord et al., 1989, Lord et al., 1994). We hypothesized that right lateral OFC grey matter would be decreased in children with autism when compared with matched controls, and negative correlations would be observed between OFC grey and white matter structures and social deficits.

Section snippets

Participants

Subjects were 11 boys with autism and 18 healthy male controls between 8 and 12 years of age. The autistic subjects represented all consecutive referrals to a research clinic who were eligible to participate in the study. The diagnosis of autism was established through the administration of the ADI-R and the ADOS, in addition to expert clinical evaluation. Subjects meeting diagnostic criteria for autism but without delayed or abnormal language development were considered to have Asperger's

Results

No differences were observed between the demographic characteristics of patients and controls, except for FSIQ (Table 1). Nine of the children with autism were being prescribed psychotropic medications and most of them were either taking a psychostimulant or a selective serotonin reuptake inhibitor, with only one subject receiving the atypical antipsychotic risperidone. Smaller grey matter volumes were observed in children with autism in the right lateral OFC (Table 2). This finding remained

Discussion

Findings from this study revealed the existence of decreased size of the right lateral OFC in individuals with autism, which appears to be related to abnormalities in grey matter. This finding of morphometric alterations of the OFC is consistent with several (McAlonan et al., 2005, Salmond et al., 2003), but not all (Abell et al., 1999, Boddaert et al., 2004, Carper and Courchesne, 2005, Kwon et al., 2004, Waiter et al., 2004), imaging studies. Differences in the morphometric methodologies

Conclusion

Findings from this investigation support the existence of morphometric abnormalities of the OFC, and in particular grey matter of the right lateral OFC, in children with autism. In addition, preliminary data presented here suggest a role for the OFC in the pathophysiology of social deficits in autism. However, in light of the above limitations, replication of these results is critical before any final statements can be made. Finally, future studies should also examine the age-related

Acknowledgments

This work was supported in part by NIMH grant MH 64027 (AYH) and NICHD grant HD 35469 (NJM). This study was also supported by an NICHD Collaborative Program of Excellence in Autism (CPEA).

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Volumetric alterations of the orbitofrontal cortex in autism

Abstract

Introduction

Section snippets

Participants

Results

Discussion

Conclusion

Acknowledgments

Neurosci Biobehav Rev

Biol Psychiatry

Neuroimage

Biol Psychiatry

Psychiatry Res

Neuroimage

Biol Psychiatry

Comput Med Imaging Graph

Neuroimage

Neuroimage

Biol Psychiatry

The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans

Neuroreport

Effects of age on brain volume and head circumference in autism

Neurology

Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey

J Comp Neurol

Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys

J Comp Neurol

Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study

Neurology