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Brain anatomy of autism spectrum disorders I. Focus on corpus callosum

Published online by Cambridge University Press:  26 March 2013

M. Bellani*
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Section of Clinical Psychology, Inter-University Center for Behavioural Neurosciences (ICBN), University of Verona, Verona, Italy
S. Calderoni
Affiliation:
IRCCS Stella Maris Foundation, Pisa, Italy
F. Muratori
Affiliation:
IRCCS Stella Maris Foundation, Pisa, Italy Department of Child Neurology and Psychiatry, University of Pisa, Pisa, Italy
P. Brambilla
Affiliation:
Department of Experimental Clinical Medicine, Inter-University Center for Behavioural Neurosciences (ICBN), University of Udine, Udine, Italy Department of Psychiatry and Behavioral Sciences, University of Texas Medical School at Houston, TX, USA
*
*Address for correspondence: Dr. M. Bellani, Department of Public Health and Community Medicine, Section of Psychiatry and Section of Clinical Psychology, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy. (Email: marcella.bellani@univr.it)
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Abstract

This brief review aims to examine the structural magnetic resonance imaging (sMRI) studies on corpus callosum in autism spectrum disorders (ASD) and discuss the clinical and demographic factors involved in the interpretation of results.

Type
Neurobiology of Psychosis
Copyright
Copyright © Cambridge University Press 2013 

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental pathologies whose diagnosis is based on the behavioural symptoms (Muratori et al. Reference Muratori, Narzisi, Tancredi, Cosenza, Calugi, Saviozzi, Santocchi and Calderoni2011) and whose intervention strategies aimed at improving socio-communicative skills as well as daily life abilities (Bellani et al. Reference Bellani, Fornasari, Chittaro and Brambilla2011). The neuroanatomical correlates of ASD are not fully elucidated. However, consistent findings based on structural magnetic resonance imaging (sMRI) data reported widespread cerebral abnormalities that include differences between ASD patients and controls in total brain volume, fronto-parieto-temporal and cerebellar regions. Moreover, a replicated altered corpus callosum (CC) size has been reported in the first sMRI analyses (for a review, see Brambilla et al. Reference Brambilla, Hardan, di Nemi, Perez, Soares and Barale2003). In particular, the altered CC has been considered as an anatomical substrate of processing and integration deficits peculiar to ASD, supporting the hypothesis of abnormal cortical connectivity in autism (Just et al. Reference Just, Cherkassky, Keller, Kana and Minshew2007). The CC is the largest commissural white matter (WM) tract in the human brain, and is conventionally divided into anterior CC, which comprises the rostrum, genu, rostral body, anterior mid-body and posterior CC, which includes the posterior mid-body, isthmus and splenium (Witelson, Reference Witelson1989). This primary WM structure connects homologous and heterotopic cortical areas of the two cerebral hemispheres and it is thought to be involved in motor and sensory integration as well as in higher cognitive function, including abstract reasoning, problem solving, ability to generalize, planning, social skills, attention, arousal, language comprehension and expression of syntax and pragmatics, emotion, memory (Paul et al. Reference Paul, Brown, Adolphs, Tyszka, Richards, Mukherjee and Sherr2007). Recent investigations have employed a three-dimensional volumetric measurement of CC in ASD and frequently reported a reduction in the overall structure (Hardan et al. Reference Hardan, Pabalan, Gupta, Bansal, Melhem and Fedorov2009; McAlonan et al. Reference McAlonan, Cheung, Cheung, Wong, Suckling and Chua2009; Duan et al. Reference Duan, He, Yin, Gu, Karsch and Miles2010; Anderson et al. Reference Anderson, Druzgal, Froehlich, DuBray, Lange, Alexander, Abildskov, Nielsen, Cariello, Cooperrider, Bigler and Lainhart2011; Frazier et al. Reference Frazier, Keshavan, Minshew and Hardan2012), or in one or more components of this axonal pathway, including the anterior (Alexander et al. Reference Alexander, Lee, Lazar, Boudos, DuBray, Oakes, Miller, Lu, Jeong, McMahon, Bigler and Lainhart2007; Keary et al. Reference Keary, Minshew, Bansal, Goradia, Fedorov, Keshavan and Hardan2009; Thomas et al. Reference Thomas, Humphreys, Jung, Minshew and Behrmann2011), the posterior sub-regions (Waiter et al. Reference Waiter, Williams, Murray, Gilchrist, Perrett and Whiten2005) or some of the anterior and posterior regions contemporaneously (Vidal et al. Reference Vidal, Nicolson, DeVito, Hayashi, Geaga, Drost, Williamson, Rajakumar, Sui, Dutton, Toga and Thompson2006). The reductions in the CC volume is present over a wide age-range, since it is reported in ASD studies involving children (Vidal et al. Reference Vidal, Nicolson, DeVito, Hayashi, Geaga, Drost, Williamson, Rajakumar, Sui, Dutton, Toga and Thompson2006; Hardan et al. Reference Hardan, Pabalan, Gupta, Bansal, Melhem and Fedorov2009; McAlonan et al. Reference McAlonan, Cheung, Cheung, Wong, Suckling and Chua2009; Frazier et al. Reference Frazier, Keshavan, Minshew and Hardan2012), adolescents (Waiter et al. Reference Waiter, Williams, Murray, Gilchrist, Perrett and Whiten2004, Reference Waiter, Williams, Murray, Gilchrist, Perrett and Whiten2005; Alexander et al. Reference Alexander, Lee, Lazar, Boudos, DuBray, Oakes, Miller, Lu, Jeong, McMahon, Bigler and Lainhart2007) and adults (Keary et al. Reference Keary, Minshew, Bansal, Goradia, Fedorov, Keshavan and Hardan2009; Ecker et al. Reference Ecker, Rocha-Rego, Johnston, Mourao-Miranda, Marquand, Daly, Brammer, Murphy and Murphy2010; Anderson et al. Reference Anderson, Druzgal, Froehlich, DuBray, Lange, Alexander, Abildskov, Nielsen, Cariello, Cooperrider, Bigler and Lainhart2011; Thomas et al. Reference Thomas, Humphreys, Jung, Minshew and Behrmann2011). On the other hand, the sparse literature on CC volume in low-functioning ASD (Riva et al. Reference Riva, Bulgheroni, Aquino, Di Salle, Savoiardo and Erbetta2011) prevents us from drawing inferences about the influence of IQ on CC volume and calls for further investigation. Only a relatively few studies did not reveal significant CC volume differences between ASD patients and typically developing controls; in particular, this finding has been reported more often in voxel-based morphometry (Waiter et al. Reference Waiter, Williams, Murray, Gilchrist, Perrett and Whiten2004; Bonilha et al. Reference Bonilha, Cendes, Rorden, Eckert, Dalgalarrondo, Li and Steiner2008; Ke et al. Reference Ke, Hong, Tang, Zou, Li, Hang, Zhou, Ruan, Lu, Tao and Liu2008; Ecker et al. Reference Ecker, Rocha-Rego, Johnston, Mourao-Miranda, Marquand, Daly, Brammer, Murphy and Murphy2010; Toal et al. Reference Toal, Daly, Page, Deeley, Hallahan, Bloemen, Cutter, Brammer, Curran, Robertson, Murphy, Murphy and Murphy2010; Cheng et al. Reference Cheng, Chou, Fan and Lin2011; Mengotti et al. Reference Mengotti, D'Agostini, Terlevic, De Colle, Biasizzo, Londero, Ferro, Rambaldelli, Balestrieri, Zanini, Fabbro, Molteni and Brambilla2011; Calderoni et al. Reference Calderoni, Retico, Biagi, Tancredi, Muratori and Tosetti2012) than in region of interest-based (Hong et al. Reference Hong, Ke, Tang, Hang, Chu, Huang, Ruan, Lu, Tao and Liu2011) analyses. Notably, to our knowledge, there have been no published studies reporting volumetric increase of CC (Table 1). Anyway, till date, few papers have examined the relationship between demographic/clinical data and CC volume in ASD patients. Interestingly, positive correlations of age with total CC volume were observed in ASD subjects when a longitudinal design was performed (Frazier et al. Reference Frazier, Keshavan, Minshew and Hardan2012), whereas a cross-sectional approach failed to detect such relationship (Alexander et al. Reference Alexander, Lee, Lazar, Boudos, DuBray, Oakes, Miller, Lu, Jeong, McMahon, Bigler and Lainhart2007). In addition, volume reduction in the CC has been found to correlate with core ASD features such social deficits, repetitive behaviours and sensory abnormalities (Frazier et al. Reference Frazier, Keshavan, Minshew and Hardan2012), as well as executive function and complex motor tasks deficits (Keary et al. Reference Keary, Minshew, Bansal, Goradia, Fedorov, Keshavan and Hardan2009).

Table 1. Studies investigating CC volumetry in patients with ASD compared with typically developing control subjects

AD, autistic disorder; ASD, autism spectrum disorders; ASP, Asperger's syndrome; DD, developmental delay; DLD, developmental language disorder; CC, corpus callosum; DTI, diffusion tensor imaging; HFA, high-functioning autism; LFA, low-functioning autism; no DD, without developmental delay; n.r., not reported; PIQ, performance IQ; ROI, region of interest; TD, typically developing control subjects; VBM, voxel-based morphometry.

*Follow-up study.

In sum, although there is more evidence to support the notion that the CC volume, especially its anterior sectors, is decreased in ASD, there are some suggestions that no differences relative to controls occurs. Specifically, the CC volume reduction may be related to altered patterns of connectivity between brain areas, and in turn it might be responsible for some of the cardinal behavioural impairments of ASD. However, a number of crucial questions remain unanswered: volumetric alterations of the CC are specific to ASD or are a more general marker of abnormal brain development shared with other neuropsychiatric disorders? What is the relationship between alterations of the CC volume and demographic and clinical variables such as age, gender, handedness, intellective functioning, severity of symptoms, psychiatric comorbidity, psychotropic medications? What is the contribution of different CC subdivisions to overall CC volume alterations? Do the CC volume alterations persist into adulthood? What are the underlying neuropathological changes (e.g. reduction in number and/or size of axons, impaired myelination, excessive synaptic pruning) responsible for decreased CC volume? Future dedicated studies should aim to address these issues more specifically.

Acknowledgements

None.

Financial Support

S. C. was partly supported by the Italian Ministry of Health and by Tuscany Region with the grant ‘GR-2010-2317873’. F. M. and S. C. were partly supported by the European Union (The MICHELANGELO Project). The other authors received no specific grant from any funding agency, commercial or not-for-profit sectors.

Conflict of Interest

None.

Ethical Standards

The authors declare that no human or animal experimentation was conducted for this work.

Footnotes

This Section of Epidemiology and Psychiatric Sciences regularly appears in each issue of the Journal to describe relevant studies investigating the relationship between neurobiology and psychosocial psychiatry in major psychoses. The aim of these Editorials is to provide a better understanding of the neural basis of psychopathology and clinical features of these disorders, in order to raise new perspectives in every-day clinical practice.

Paolo Brambilla, Section Editor and Michele Tansella, Editor EPS

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Table 1. Studies investigating CC volumetry in patients with ASD compared with typically developing control subjects