The ‘amygdala theory of autism’ revisited: Linking structure to behavior

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Abstract

The ‘amygdala theory of autism’ suggests a crucial role for the amygdala in the neurobiological basis of autism spectrum disorders. However, to date evidence is lacking of a direct relationship between amygdala measures and behavioral manifestations of autism in affected individuals. In 17 adult individuals with Asperger syndrome (AS) and 17 well-matched controls we therefore assessed associations between MRI-derived amygdala volume and behavioral variables of emotion recognition and social cognition, as well as with core AS symptomatology. Results revealed that individuals with AS exhibited impairments in emotion recognition and social cognition compared to controls and also showed atypical relationships between amygdala volumes and overall head size. We found positive associations between emotional and social understanding and amygdala volume in the control group, but not in the AS group. In the AS group however, amygdala size was negatively related to diagnostic parameters, with smaller amygdala volumes involving higher levels of restricted-repetitive behavior domains. Our data seem to indicate that in AS the amygdala is not crucially involved in social and emotional understanding. It may, however, be a mediator for narrow interest patterns and the imposition of routines and rituals. Our data, in conjunction with current literature, seem to argue for a modification of the ‘amygdala theory of autism’.

Introduction

Asperger syndrome (AS) is a neurodevelopmental disorder on the autism spectrum, which involves impairments in reciprocal social interactions and restricted-repetitive patterns of behavior in the absence of intellectual dysfunction (American Psychiatric Association, 1994). Although the etiology of AS and autism remains to be established, it is well accepted that these conditions strongly impact the central nervous system (Brambilla et al., 2003). Of the several structures that have been suggested to play a part in the neurobiological basis of autistic symptomatology, evidence for involvement of the amygdala is particularly compelling (Pelphrey, Adolphs, & Morris, 2004). This has led to the postulation of the ‘amygdala theory of autism’ (Baron-Cohen et al., 2000). Most of the support for the ‘amygdala theory of autism’ comes from studies in non-autistic populations implicating the amygdala in social and emotional behaviors, while little evidence has emerged from studies involving affected individuals.

A crucial role of the amygdala in social behavior and cognition, as well as emotional functioning has been established by studies of non-human primates (Brothers, Ring, & Kling, 1990; Emery et al., 2001; Thompson & Towfighi, 1976), humans with selective amygdala lesions (Adolphs et al., 1999; Adolphs, Baron-Cohen, & Tranel, 2002; Heberlein & Adolphs 2004), and PET and fMRI activation studies of neurotypical individuals (Baas, Aleman, & Kahn, 2004; Kawashima et al., 1999; Phan et al., 2005; Singer, Kiebel, Winston, Dolan, & Frith, 2004; Winston, Strange, O’Doherty, & Dolan, 2002). It is these findings, along with the impairments of autistic individuals to process emotional and social information (Frith, 2004; Kleinman, Marciano, & Ault, 2001; Macdonald et al., 1989), that has led researchers to postulate an involvement of the amygdala in autism.

Other, albeit also indirect support for the ‘amygdala theory of autism’ comes from both neuropathological and structural brain imaging studies that reported abnormalities in the amygdala of affected individuals (for review see, Brambilla et al., 2003; Palmen, van Engeland, Hof, & Schmitz, 2004). However, most neuropathological findings were not specific (e.g., also applied to the hippocampus) (Kemper & Bauman, 1993) and volumetric in vivo studies have been largely inconsistent, reporting no change (Haznedar et al., 2000), increases (Howard et al., 2000), or decreases (Aylward et al., 1999) in amygdala volume. More importantly, studies assessing the amygdala in vivo have failed to report concomitant autism related behavioral and cognitive impairments. Data on such associations would be especially helpful and provide information on whether amygdala structural findings are relevant to autism; that is whether they are a true pathophysiological mediator, or whether they only represent an epiphenomenon. The single structural brain imaging study in individuals with autism that measured both amygdala volumes and behavioral parameters that are considered suggestive of amygdala damage (impaired emotion recognition), did not report associations between the two (Howard et al., 2000).

More direct evidence for the ‘amygdala theory of autism’ can be derived from a few functional imaging studies involving autistic individuals. Compared to control subjects, autistic individuals showed less amygdala activation when inferring mental states from eyes (Baron-Cohen et al., 1999), viewing faces of emotional expressions (Critchley et al., 2000), or in response to changing task demands in an emotion recognition task (Wang, Dapretto, Hariri, Sigman, & Bookheimer, 2004). However, it should be noted that the first two studies do not report relationships between task accuracy and amygdala activation, and the latter study found no such association.

Interestingly, to date no studies have tried to link the amygdala to core diagnostic features of autism spectrum disorders as defined by the diagnostic criteria in DSM-IV (American Psychiatric Association, 1994) and ICD-10 (World Health Organization, 1992). Although problems in social cognition and emotion recognition could be interpreted as indicative of impairments in social interaction, which in turn represents diagnostic cluster A in the DSM-IV and ICD-10, they are currently not an integral part of the diagnostic criteria. Hence, it can be argued that for the ‘amygdala theory of autism’ to be validated, a link between core diagnostic criteria of autism spectrum disorders and the amygdala needs to be established.

In sum, although the last decade has generated a host of evidence supportive of the ‘amygdala theory of autism’, relatively little of this evidence comes from studies directly relating the structure to behavior relevant to autism. To date, relationships between amygdala structure and behavioral variables of emotion recognition and social cognition have not been assessed in affected individuals. In addition, the relationship between amygdala structure and the core symptoms of autism and AS is poorly understood. Thus, in the current study we sought to assess relationships between amygdala volume and emotional and social cognition, as well as amygdala volume and diagnostic parameters of AS.

Section snippets

Participants

Seventeen adults with Asperger syndrome (14 men and 3 women, mean age = 41.4) participated in the study. Individuals with AS were recruited through local support groups or were referred by specialized clinicians. Every subject underwent a videotaped semi-structured diagnostic interview and diagnoses of AS were made according to DSM-IV AS criteria (American Psychiatric Association, 1994). Diagnostic discrepancies were resolved by consensus of one psychiatrist and two psychologists. In addition,

Background variables

As expected because of group matching, comparisons between groups for age, gender, education, and IQ were non-significant. Descriptive statistics of the two groups are shown in Table 1.

Measures of emotion recognition and social cognition

Individuals with AS scored significantly lower than the control group in the emotion recognition task. In addition, the difference in correct mental state inferences for the MASC was highly significant, indicating greater difficulties in the group with AS. The same difficulties were reflected in lower scores on

Discussion

The main goal of the current study was to determine relationships between amygdala volume and emotional and social cognition, as well as amygdala volume and diagnostic parameters in individuals with Asperger syndrome. To this end, we administered a test of basic emotion recognition and the Movie for the Assessment of Social Cognition (MASC). Furthermore, we assessed amygdala volumes by means of manual anatomical tracings.

Conclusion

The data presented in this paper lends further support to a role of the amygdala in autism spectrum disorders. We corroborated findings of impaired emotion recognition and social cognition as well as differing associations between amygdala volume and overall head size in AS. In addition, we extended the current literature by reporting for the first time associations between amygdala size and emotional/social reasoning in neurotypical individuals and between amygdala size and symptom severity in

Acknowledgements

The study was funded by a grant from the National Alliance for Autism Research (NAAR) to Antonio Convit and support from the NYU General Clinical Research Center (NCRR M01 RR00096). Isabel Dziobek was in part supported by the Cusanuswerk.

References (65)

  • P.A. Cannistraro et al.

    Amygdala responses to human faces in obsessive-compulsive disorder

    Biological Psychiatry

    (2004)
  • A. Convit et al.

    MRI volume of the amygdala: A reliable method allowing separation from the hippocampal formation

    Psychiatry Research Neuroimaging

    (1999)
  • A. Convit et al.

    Volumetric analysis of pre-frontal regions: findings in aging and schizophrenia

    Psychiatry Research: Neuroimaging

    (2001)
  • T.L. Kemper et al.

    The contribution of neuropathologic studies to the understanding of autism

    Neurologic Clinics

    (1993)
  • D. Mataix-Cols et al.

    Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers

    Biological Psychiatry

    (2003)
  • J.W. Mink

    Basal ganglia dysfunction in Tourette's syndrome: A new hypothesis

    Pediatric Neurology

    (2001)
  • K.L. Phan et al.

    Neural substrates for voluntary suppression of negative affect: A functional magnetic resonance imaging study

    Biological Psychiatry

    (2005)
  • S.L. Rauch et al.

    Neurobiological models of obsessive-compulsive disorder

    Psychosomatics

    (1993)
  • L.L. Sears et al.

    An MRI study of the basal ganglia in autism

    Progress in Neuro-psychopharmacology and Biological Psychiatry

    (1999)
  • T. Singer et al.

    Brain responses to the acquired moral status of faces

    Neuron

    (2004)
  • C.I. Thompson et al.

    Social behavior of juvenile rhesus monkeys after amygdalectomy in infancy

    Physiology and Behavior

    (1976)
  • C. Van Petten

    Relationship between hippocampal volume and memory ability in healthy individuals across the lifespan: Review and meta-analysis

    Neuropsychologia

    (2004)
  • A.T. Wang et al.

    Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder

    Journal of the American Academy of Child and Adolescent Psychiatry

    (2004)
  • F. Abell et al.

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

    NeuroReport

    (1999)
  • R. Adolphs

    Is the human amygdala specialized for processing social information?

    Annals of the New York Academy of Sciences

    (2003)
  • R. Adolphs et al.

    Impaired recognition of social emotions following amygdala damage

    Journal of Cognitive Neuroscience

    (2002)
  • American Psychiatric Association

    Diagnostic and statistical manual of mental disorders

    (1994)
  • A.K. Anderson et al.

    Lesions of the human amygdala impair enhanced perception of emotionally salient events

    Nature

    (2001)
  • E.H. Aylward et al.

    MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults

    Neurology

    (1999)
  • S. Baron-Cohen et al.

    Social intelligence in the normal and autistic brain: An fMRI study

    The European Journal of Neuroscience

    (1999)
  • M.D. Bauman et al.

    The development of social behavior following neonatal amygdala lesions in rhesus monkeys

    Journal of Cognitive Neuroscience

    (2004)
  • A. Bertolino et al.

    Altered development of prefrontal neurons in rhesus monkeys with neonatal mesial temporo-limbic lesions: A proton magnetic resonance spectroscopic imaging study

    Cerebral Cortex

    (1997)
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