Objective-To highlight emerging evidence for clinical and biological links between autism/ Pervasive Developmental Disorder (PDD) and schizophrenia, with particular attention to childhood onset schizophrenia (COS).Method-Clinical, demographic and brain developmental data from the NIMH (and other) COS studies, and selected family, imaging and genetic data from studies of autism, PDD and schizophrenia were reviewed.Results-In the two large studies that have examined this systematically, COS is preceded by and comorbid with Pervasive Developmental Disorder in 30%-50% of cases. Epidemiologic and family studies find association between the disorders. Both disorders have evidence of accelerated trajectories of anatomic brain development at ages near disorder onset. A growing number of risk genes and/or rare small chromosomal variants (micro-deletions or duplications) are shared by schizophrenia and autism.Conclusion-Biological risk does not closely follow DSM phenotypes and core neurobiological processes are likely common for subsets of these two heterogeneous clinical groups. Long-term prospective follow up of autistic populations, and greater diagnostic distinction between schizophrenia spectrum and autism spectrum disorders in adult relatives are needed.

Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P ‫؍‬ 0.02, all P values corrected). The greatest differences were in the right hemisphere (P ‫؍‬ 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P ‫؍‬ 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P ‫؍‬ 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P ‫؍‬ 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R ‫؍‬ 0.64, P ‫؍‬ 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth. development ͉ imaging ͉ MRI ͉ white matter

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We explored regional and total volumetric cerebellar differences in probands and their unaffected full siblings relative to typically developing participants. Participants included 94 (51 males) patients diagnosed with childhood onset schizophrenia (COS), 80 related non-psychotic siblings (37 males) and 110 (64 males) typically developing participants scanned longitudinally. The sample mean age was 16.87(SD=4.7; range 6.5 to 29). We performed mixed model regressions to examine group differences in trajectory and volume. The COS group had smaller bilateral anterior lobes and anterior and total vermis volumes than controls. The COS group diverged from controls over time in total, left, right, and bilateral posterior inferior cerebellum. Siblings did not have any fixed volumetric differences relative to controls but differed from controls in developmental trajectories of total and right cerebellum, left inferior posterior, left superior posterior, and superior vermis. Results are consistent with previous COS findings and several reports of decreased cerebellar volume in adult onset schizophrenia. Sibling trajectories may represent a trait marker, although the effect size for volumetric differences in early adulthood may be small.

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