Meta-analysis of the time-course of brain volume reduction in schizophrenia: implications for pathogenesis and early treatment

Abstract

Whole brain volume (BV) is significantly reduced in groups of schizophrenic patients, but there is disagreement as to when in relation to onset of illness these losses occur. Given what is known about the normal development and lifetime course of BV, intraventricular volume (IVV), extracerebral volume (ECV), and intracranial volume (ICV) changes, it is possible to allocate (within a narrow range of uncertainty) excessive brain volume loss (EBVL) to either the time before or the time after attainment of maximum brain volume (BVmax). Decreases in patient ICV relative to control ICV reflect early reductions in brain growth, while increases in ECV reflect later BV losses. There is however uncertainty as whether any relative increases in patient IVV occur early, later, or both. IVV differences were first assumed to be of early origin, so that early EBVL was measured by ICV-IVV differences and later EBVL by ECV differences alone. The IVV differences were then assumed to be of later origin, so that early EBVL was measured by ICV differences alone, and later EBVL by ECV+IVV differences. The results taken together delineate the maximum and minimum values for early and later losses. Patient-control volume differences in BV and ICV for 20 published magnetic resonance imaging (MRI) studies of schizophrenic patients (n=982) and controls (n=1049), and differences in ECV for 17 of the same 20 studies, comprising 889 patients and 942 controls, showed a significant patient BV decrease of 34 cc's (t=-4.94, df=19, p<0.0001), ICV decrease of 20.1 cc's (t=-2.64, df=19, p<0.02) and ECV Increase of 14.1 cc's (t=3.65, df=16, p<0.001). In the 17 studies which included ECV and IVV, as well as ICV differences, the patient ICV-IVV decrease was 20.2 cc's (t=-2.56, df=16, p<0.05) and the ECV+IVV increase was 17.1 cc's (t=-4.11, df=16, p<0.001). There is a small but significant whole brain EBVL in schizophrenia patients both before and after BV(max), regardless of when excessive IVV enlargement is assumed to occur.