On comparing male and female groups, the bilateral superior frontal region showed high significant hypoperfusion in the female group, greater than the male group, in the mean brain count as shown in Table 5.
Comparison of male and female groups in the ABS showed a significantly lower profile in the female group in the motor milestones of development and language development. In contrast, a significantly higher profile was found in the male group in terms of stereotyped behavior and self-mutilation behavior as shown in Table 6.
A positive relationship between hypoperfusion areas and some representative autistic symptoms in children with childhood autism has been reported in various studies 6. Impairments in communication and social interaction were positively correlated to the left medial prefrontal cortex, whereas an obsessive desire for sameness was correlated positively to the right hippocampus and amygdala. The relationship between brain perfusion SPECT and autistic spectrum disorders (ASD) symptoms has been reported in many studies 6–12. Although frontal lobe hypoperfusion 8 or temporal hypoperfusion 9–11 has been reported in the literature, no consistent results on the relationship between the hypoperfusion area and autistic symptoms have been found in ASD.
In our study, in the male group, the frontal lobe was the most common site for hypoperfusion, followed by the basal ganglia. In the female group, the frontal lobe was the most common site for hypoperfusion, but followed by the cerebellum. On comparing the quantitative SPECT findings using the mean brain count/pixel, the superior frontal lobe was the only region showing significant hypoperfusion in the female group. These findings were in accordance with the findings of a study carried out by Ohnishi et al. 6, in which they found hypoperfusion involving all brain areas, especially the frontal lobe and cerebellum, and yet they did not discuss sex differences in their findings.
However, other SPECT studies carried out on autistic children such as in a study carried out by Sasaki et al.13, in all children who participated in the study, interictal SPECT showed some hypoperfusion areas within the prefrontal cortex, the medial frontal cortex, the anterior cingulated cortex, the medial parietal cortex, or the anterior temporal cortex (right, left, or both). According to many previous studies 6–12, these areas appear to be strongly correlated with the symptoms of autism. The left medial prefrontal cortex is reported to be strongly correlated to the ‘theory of mind’ area 14,15.
SPECT studies have also been carried out previously not only to measure cerebral perfusion among autistic children but also to prove an evidence for a lack of normal hemispheric asymmetry as that done by Chiron et al.29. In their study, brain functional imaging with 133Xe-SPECT was used to measure left/right asymmetry and absolute values of rCBF in 18 children with autism ranging in age from four to 17 years and 10 age-matched controls. All controls, but only 10 children with autism were right-handed. The left-to-right indices, both hemispheric and regional, were positive in controls, indicating higher left than right rCBF values, but were negative in patients with autism. This inversion was statistically significant for total hemispheres, sensorimotor, and language-related cortex, and could be attributed to a significant decrease in the left absolute rCBF values in these regions in patients with autism. The inversion was independent of handedness, sex, and age. These results confirm the existence of left-hemispheric dysfunction in childhood autism, especially in the cortical areas devoted to language and handedness, leading to anomalous hemispheric specialization 29.
Finally, in our study, the ABS showed a significantly lower profile in the female group in terms of the motor milestones of development and language development. In contrast, a significantly higher profile was found in the male group in terms of stereotyped behavior and self-mutilation behavior. A similar study carried out by Lemon et al. 30 examined sex differences in neurobehavioral functioning in boys and girls with ASD. It showed that females with ASD showed a significant increase in stopping time (indicating poorer inhibition). By contrast, no response inhibition impairments were evident among males with ASD. Females with ASD may have a different neurobehavioral profile, and therefore different clinical needs, when compared with males with ASD. Nevertheless, the current findings indicate the possibility of neuropsychological differences in ASD across sexes that would presumably be associated with different clinical presentations and outcomes 30.
The authors thank Prof. Dr Zeinab Bishry, Prof. Dr Mona Abdel Hady, and Ass. Prof. Ahmed El-Missiry.
There are no conflicts of interest.
4. Nihira K, Foster R, Shellhaas M, Leland H Adaptive Behavior Scale. 1974 Washington American Association on Mental Deficiency
5. Farag S, Ramzy N Arabic translation of the Adaptive Behavior Scale (committee of American Associate of Mental Retardation). 19954th ed. El Anglo Egyptian Library
6. Ohnishi T, Matsuda H, Hashimoto T, Kunihiro T, Nishikawa M, Uema T, Sasaki M. Abnormal regional cerebral blood flow in childhood autism
. Brain. 2000;123:1838–1844
7. Hashimoto T, Sasaki M, Fukumizu M, Hanaoka S, Sugai K, Matsuda H. Single-photon emission computed tomography of the brain in autism
: effect of the developmental level. Pediatr Neurol. 2000;23:416–420
8. Zilbovicius M, Garreau B, Samson Y, Remy P, Barthelemy C, Syrota A, Lelord G. Delayed maturation of the frontal cortex in childhood autism
. Am J Psychiatry. 1995;152:248–252
9. Mountz JM, Tolbert LC, Lill DW, Katholi CR, Liu HG. Functional deficits in autistic disorder: characterization by technetium-99m-HMPAO and SPECT. J Nucl Med. 1995;36:1156–1162
10. Ito H, Mori K, Hashimoto T, Miyazaki M, Hori A, Kagami S, Kuroda Y. Findings of brain 99m
Tc-ECD SPECT in high-functioning autism
– 3-dimensional stereotactic ROI template analysis of brain SPECT. J Med Invest. 2005;52:49–56
11. Kaya M, Karasaliholu S, Üstün F, Gültekin A, Çermik TF, Fazlolu Y, et al. The relationship between 99m
Tc-HMPAO brain SPECT and the scores of real life rating scale in autistic children. Brain Dev. 2002;24:77–81
12. Burroni L, Orsi A, Monti L, Hayek Y, Rocchi R, Vattimo AG. Regional cerebral blood flow in childhood autism
: a SPET study with SPM evaluation. Nucl Med Commun. 2008;29:150–156
13. Sasaki M, Nakagawa E, Sugai K, Shimizu Y, Hattori A, Nonoda Y, Sato N. Brain perfusion SPECT and EEG findings in children with autism
spectrum disorders and medically intractable epilepsy. Brain Dev. 2010;32:776–782
14. Happé F, Ehlers S, Fletcher P, Frith U, Johansson M, Gillberg C, et al. Theory of mind’ in the brain. Evidence from a PET scan study of Asperger syndrome. Neuroreport. 1997;8:197–201
15. Ernst M, Zametkin AJ, Matochik JA, Pascualvaca D, Cohen RM. Low medial prefrontal dopaminergic activity in autistic children (4). Lancet. 1997;350:638
16. Gupta SK, Ratnam BV. Cerebral perfusion abnormalities in children with autism
and mental retardation: a segmental quantitative SPECT study. Indian Pediatr. 2009;46:161–164
17. Tepest R, Jacobi E, Gawronski A, Krug B, Möller-Hartmann W, Lehnhardt FG, Vogeley K. Corpus callosum size in adults with high-functioning autism
and the relevance of gender. Psychiatry Res. 2010;183:38–43
18. Tomasi D, Volkow ND. Gender differences in brain functional connectivity density. Hum Brain Mapp. 2012;33:849–860
19. Traverthen C, Aitken K, Papoudi D, Robart JTraverthen C, Aitken K, Papoudi D, Robart J. Children with autism
. Diagnosis and interventions to meet their needs. Brain development and autism
. 19992nd ed. Philadelphia Jessica Kingsley Publishers:62–77
20. Wing L. Sex
ratios in early childhood autism
and related conditions. Psychiatry Res. 1981;5:129–137
21. Lord C, Schopler E, Revicki D. Sex
differences in autism
. J Autism
Dev Disord. 1982;12:317–330
22. Gillberg C. Subgroups in autism
: are there behavioural phenotypes typical of underlying medical conditions? J Intellect Disabil Res. 1992;36:201–214
23. Pilowsky T, Yirmiya N, Shulman C, Dover R. The autism
diagnostic interview-revised and the childhood autism
rating scale: differences between diagnostic systems and comparison between genders. J Autism
Dev Disord. 1998;28:143–151
24. Gillberg C, Coleman M Introduction, the biology of the autistic syndromes. 2000 Cambridge University Press:1–3
25. Makkonen I, Riikonen R, Kokki H, Airaksinen MM, Kuikka JT. Serotonin and dopamine transporter binding in children with autism
determined by SPECT. Dev Med Child Neurol. 2008;50:593–597
26. Barthel H, Wiener M, Dannenberg C, Bettin S, Sattler B, Knapp WH. Age-specific cerebral perfusion in 4- to 15-year-old children: a high-resolution brain SPET study using 99m
Tc-ECD. Eur J Nucl Med. 1997;24:1245–1252
27. Van Dyck CH, Malison RT, Staley JK, Jacobsen LK, Seibyl JP, Laruelle M, et al. Central serotonin transporter availability measured with [123
I]β-CIT SPECT in relation to serotonin transporter genotype. Am J Psychiatry. 2004;161:525–531
28. Kuikka JT, Tammela L, Bergström KA, Karhunen L, Uusitupa M, Tiihonen J. Effects of ageing on serotonin transporters in healthy females. Eur J Nucl Med. 2001;28:911–913
29. Chiron C, Leboyer M, Leon F, Jambaque I, Nuttin C, Syrota A. SPECT of the brain in childhood autism
: evidence for a lack of normal hemispheric asymmetry. Dev Med Child Neurol. 1995;37:849–860
30. Lemon JM, Gargaro B, Enticott PG, Rinehart NJ. Brief report: executive functioning in autism
spectrum disorders: a gender comparison of response inhibition. J Autism
Dev Disord. 2011;41:352–356