Longitudinal Brain Volume Growth Curves in Autism Spectrum Disorder Ages 3 to 25 Years

Background:  Autism spectrum disorder (ASD) is a brain-based, individually heterochronous and heterogeneous developmental disorder, and a lifelong problem.  Although brain growth in young children with ASD has been investigated, very little is known about how the brains of these individuals grow and mature as they pass from childhood through adolescence into adulthood.

Objectives: To identify longitudinal brain growth differences between individuals with ASD and healthy age-matched individuals during key developmental epochs, and to further investigate individual heterogeneity.

Methods: Participants included 67 males with ASD aged 3.9-24.4 years and 36 healthy males aged 6.4-25.0 years, each contributing 1-3 MRI scans at 3T over 8 years (272 scans).  Repeated volumes of the entire brain, whole-brain gray matter (GM), whole-brain white matter (WM), lobar GM, lobar WM, subcortical GM, lateral ventricles, brainstem and cerebellum were examined by mixed-effects growth curve analysis.

Results:  All comparisons are to healthy controls and on average. Reported growth and curvature percentages represent linear and quadratic growth curve changes.  Total brain volume.  The brains of individuals with ASD had ~14.0% less volume (p=0.043) yet grew ~1.9% more rapidly at ~3.1% per year (p=0.038), and greater inverted-U shaped decreases during young adulthood (curvature -0.11% versus -0.04, p=0.028).  All subsequent differences reported here have been adjusted for total brain volume.  Brainstem.  Subjects with ASD had equal brainstem volume that increased at ~3.0% per year (p<0.0005), and greater inverted-U shaped decreases during young adulthood (curvature -0.08% versus -0.06, p=0.019).  Frontal GM.  Subjects with ASD had ~9.8% less frontal GM volume (p=0.005) that increased ~0.1% per year, compared to a decline of 1.2% per year (p=0.003).  Parietal lobe.  Subjects with ASD had ~7.0% more parietal lobe volume (p=0.033) that declined ~0.9% more rapidly at ~1.2% per year, with U-shaped increases during young adulthood (curvature ~0.02%, p=0.048).  Occipital lobe.  Subjects with ASD had ~13.4% more occipital lobe volume (p=0.009) that declined at  ~1.2% per year (p=0.017).  Occipital GM and occipital WM volumes increased equally until young adulthood, during which there were GM increases and WM decreases (curvatures 0.06 and -0.04, p=0.001, 0.033). Temporal lobe, subcortical GM, lateral ventricle and cerebellum volumes were unaffected.  No differences in total or regional hemispheric asymmetries were found. After average growth curves were extracted, subjects with ASD showed more individual volumetric variability than seen in healthy brain development.

Conclusions: In this investigation, the brains of individuals with ASD grew, and matured, in very different ways compared to the brains of healthy individuals.  On average, the ASD sample had less frontal GM volume, which did not decline as in the control sample, and more parietal and occipital volumes that declined more rapidly. During young adulthood, further volumetric decreases in total brain and brainstem volumes, and further increases in parietal lobe volume, were seen in those with ASD.  This study also found greater developmental heterogeneity in the brains of individuals with ASD beyond that captured by these average group trends.  The relation of these new findings to the core cognitive and behavioral deficits in ASD is not yet known.