Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia

Neurodevelopmental models for the pathology of schizophrenia propose both p olygenetic and environmental risks, as well as early (pre/perinatal) and la te (usually adolescent) developmental brain abnormalities. With the use of brain mapping algorithms, we detected striking anatomical profiles of accel erated gray matter loss in very early-onset schizophrenia; surprisingly, de ficits moved in a dynamic pattern, enveloping increasing amounts of cortex throughout adolescence. Early-onset patients were rescanned prospectively w ith MRI, at 2-year intervals at three time points, to uncover the dynamics and timing of disease progression during adolescence. The earliest deficits were found in parietal brain regions, supporting visuospatial and associat ive thinking, where adult deficits are known to be mediated by environmenta l (nongenetic) factors. Over 5 years, these deficits progressed anteriorly into temporal lobes, engulfing sensorimotor and dorsolateral prefrontal cor tices, and frontal eye fields. These emerging patterns correlated with psyc hotic symptom severity and mirrored the neuromotor, auditory, visual search , and frontal executive impairments in the disease. In temporal regions, gr ay matter loss was completely absent early in the disease but became pervas ive later. Only the latest changes included dorsolateral prefrontal cortex and superior temporal gyri, deficit regions found consistently in adult stu dies. These emerging dynamic patterns were (i) controlled for medication an d IQ effects, (it) replicated in independent groups of males and females, a nd (fit) charted in individuals and groups. The resulting mapping strategy reveals a shifting pattern of tissue loss in schizophrenia. Aspects of the anatomy and dynamics of disease are uncovered, in a changing profile that i mplicates genetic and nongenetic patterns of deficits.