Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis

• Published in: Psychiatry research. Neuroimaging Vol. 234; no. 2; pp. 239 - 251
• Main Authors: Sacco, Roberto, Gabriele, Stefano, Persico, Antonio M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 30.11.2015
• Subjects: Autism Spectrum Disorder - diagnosis; Autism Spectrum Disorder - epidemiology; Autistic disorder; Brain - pathology; Brain volume; Cephalometry; Child, Preschool; Endophenotypes; Female; Head - pathology; Head circumference; Humans; Macrocephaly; Male; Meta-analysis; Prevalence; Psychiatry; Radiology; Structural brain imaging; Brain volume; Autistic disorder; Structural brain imaging; Macrocephaly; Head circumference; Meta-analysis
• ISSN: 0925-4927; 1872-7506
• DOI: 10.1016/j.pscychresns.2015.08.016

Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use. •Prevalence of macrocephaly in ASD was largely higher than in controls.•Excessive Total Brain Volume was associated with ASD although to a lesser extent.•Structural MRI studies underestimate the prevalence of brain overgrowth.•Our meta-analyses also confirms the role of age as a covariate in brain overgrowth.