Asian Journal of Psychiatry 27 (2017) 127–128
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Letter to the Editor Cortical surface area hyperexpansion in infants: A promising biomarker for autism spectrum disorder
Sir, Brain images of high risk infants have revealed expansion of cortical surface to be highly associated with later diagnosis of autism spectrum disorders. Children diagnosed with autism at 24 months of age show cortical surface overgrowth at six months and increased brain volume in MRI scans at one year of age (Hazlett et al., 2017). These MRI images can be understood as early predictors of social and communication deﬁcits which appear much later and hence are potential biomarkers for autism. Identiﬁcation of at risk infants before two years of age can increase the effectiveness of early interventions as this is the period when rate of brain growth is at its highest. Autism is an extremely heterogeneous disorder in terms of symptom proﬁle, severity of presentation as well as temporal sequence of symptom appearance. While social communication deﬁcits appear at around two years of age, repetitive behaviors appear later at three to four year of age. Symptomatic stability is established only at around three years of age (Guthrie et al., 2013). Much less is known about early symptoms of autism, with some insights now being made into behavioral signs. Mullen’s Scale for Early Learning and Autism Observation Scales for Infants have been found useful for psychological and developmental assessment of infants (Akshoomoff, 2006; Bryson et al., 2008). These scales have been used in high familial risk infants who are 20 times more likely than general population to develop autism (Chawarska et al., 2013). High risk infants can be differentiated from typically developing infants even at ﬁrst year of age on the basis of socio-behavioral difﬁculties, difﬁculties in visual tracking, sensory issues, temperamental problems and delay in receptive and expressive language. Abnormalities in eye contact, social imitation, interest and responsiveness can also be observed before one year of age. Temperamental difﬁculties are apparent at as early as six months of age when these high risk infants appear more passive and aloof or show extreme reactive irritability (Zwaigenbaum et al., 2005). While behavioral manifestations of autism become apparent after one year of age, biological substrates appear before birth in the form of neurodevelopmental abnormalities. Brain overgrowth is seen at 2–4 years of age when MRI scans show generalized cortical enlargements speciﬁcally in frontal and temporal regions. Cortical enlargement is currently understood to be the result of cortical surface hyperextension rather than increased cortical thickness which has a different embryonic origin. Cortical surface overgrowth is due to proliferation of radial unit neuronal
http://dx.doi.org/10.1016/j.ajp.2017.02.025 1876-2018/© 2017 Elsevier B.V. All rights reserved.
progenitor cells which causes increase in ontologic columns (Pontious et al., 2008). The involvement of neural circuits in frontal and temporal lobes as well as in amygdale and hippocampus are currently understood as the underlying mechanism for sociocommunicative-emotional deﬁcits. Repetitive and stereotyped behaviors are known to be associated with abnormalities in fronto-striatal circuit (Ecker et al., 2015). At a structural level, cortical gyriﬁcation abnormalities like polymicrogyria, schizencephaly and macrogyria have been reported whereas at functional level, decreased activation in inferior frontal lobes during sociocommunication and emotional tasks, and hyper activation in temporal parietal cortex in response to irritant stimuli have been documented in fMRI scans. Cortical overgrowth and anomalies in neural connection have been reported in syndromic autism (Fragile X syndrome, 15qdup and 22qdel) as well as idiopathic autism. 16p11del (CNV) copy number variants is associated with increased brain size, increased brain volume and has dose response relationship with cortical surface area. Mutation of CHD8 is another genetic risk factor which is associated with macrocephaly in the frontal lobes. Cortical hyperexpansion due to increased proliferation of neural progenitor cells is similar to those observed in syndromic autism. Hence, understanding the underlying mechanism of cortical hyperexpansion may provide insights about the connection between structural changes in the brain and behavioral manifestations of autism (Hazlett et al., 2017). More reliability studies are needed to establish whether cortical surface hyperexpansion can be considered a biomarker for autism. The availability of a biomarker would mean early identiﬁcation of at risk infants and would widen the window of opportunity for early intervention. In addition, it can shift prevailing behavioral diagnostic approach towards a more robust biological one paving the way towards establishing therapeutic targets of autism. References Akshoomoff, N., 2006. Use of the Mullen Scales of Early Learning for the assessment of young children with autism spectrum disorders. Child Neuropsychol. 12 (4–5), 269–277. Bryson, S.E., Zwaigenbaum, L., McDermott, C., Rombough, V., Brian, J., 2008. The Autism Observation Scale for Infants: scale development and reliability data? J. Autism Dev. Disord. 38 (4), 731–738. Chawarska, K., Macari, S., Shic, F., 2013. Decreased spontaneous attention to social scenes in 6-month-old infants later diagnosed with autism spectrum disorders. Biol. Psychiatry 74, 195–203. Ecker, C., Bookheimer, S.Y., Murphy, D.G., 2015. Neuroimaging in autism spectrum disorder:brain structure and function across the lifespan. Lancet Neurol. 14 (11), 1121–1134. Guthrie, W., Swineford, L.B., Nottke, C., Wetherby, A.M., 2013. Early diagnosis of autism spectrum disorder: stability and change in clinical diagnosis and symptom presentation. J. Child Psychol. Psychiatry 54 (5), 582–590. Hazlett, H.C., Gu, H., Munsell, B.C., The IBIS Network, et al., 2017. Early brain development in infants at high risk for autism spectrum disorder. Nature 542 (7641), 348–351.
Letter to the Editor / Asian Journal of PsychiatryAJP 27 (2017) 127–128
Pontious, A., Kowalczyk, T., Englund, C., et al., 2008. Role of intermediate progenitor cells in cerebral cortex development. Dev. Neurosci. 30, 24–32. Zwaigenbaum, L., Bryson, S., Rogers, T., et al., 2005. Behavioral manifestations of autism in the ﬁrst year of life. Int. J. Dev. Neurosci. 23, 143–152.
Suravi Patra Department of Psychiatry, AIIMS, Bhubaneswar, Odisha, 751019, IndiaE-mail address: [email protected]
Received 24 February 2017 Available online xxx