Longitudinal Allometry of Sulcal Morphology in Health and Schizophrenia

Scaling between subcomponents of folding and total brain volume (TBV) in healthy individuals (HIs) is allometric. It is unclear whether this is true in schizophrenia (SZ) or first-episode psychosis (FEP). This study confirmed normative allometric scaling norms in HIs using discovery and replication samples. Cross-sectional and longitudinal diagnostic differences in folding subcomponents were then assessed using an allometric framework. Structural imaging from a longitudinal (Sample 1: HI and SZ, nHI Baseline = 298, nSZ Baseline = 169, nHI Follow-up = 293, nSZ Follow-up = 168, totaling 1087 images, all individuals > 2 images, age 16-69 years) and a cross-sectional sample (Sample 2: nHI = 61 and nFEP = 89, age 10-30 years), all human males and females, is leveraged to calculate global folding and its nested subcomponents: sulcation index (SI, total sulcal/cortical hull area) and determinants of sulcal area: sulcal length and sulcal depth. Scaling of SI, sulcal area, and sulcal length with TBV in SZ and FEP was allometric and did not differ from HIs. Longitudinal age trajectories demonstrated steeper loss of SI and sulcal area through adulthood in SZ. Longitudinal allometric analysis revealed that both annual change in SI and sulcal area was significantly stronger related to change in TBV in SZ compared with HIs. Our results detail the first evidence of the disproportionate contribution of changes in SI and sulcal area to TBV changes in SZ. Longitudinal allometric analysis of sulcal morphology provides deeper insight into lifespan trajectories of cortical folding in SZ.