Progression of neuroanatomical abnormalities after first-episode of psychosis: A 3-year longitudinal sMRI study.

The location, extent and progression of longitudinal morphometric changes after first-episode of psychosis (FEP) remains unclear. We investigated ventricular and cortico-subcortical regions over a 3-year period in FEP patients compared with healthy controls. High resolution 1.5T T1-weighted MR images were obtained at baseline from 28 FEP patients at presentation and 28 controls, and again after 3-years. The longitudinal FreeSurfer pipeline (v.5.3.0) was used for regional volumetric and cortical reconstruction image analyses. Repeated-measures ANCOVA and vertex-wise linear regression analyses compared progressive changes between groups in subcortical structures and cortical thickness respectively. Compared with controls, patients displayed progressively reduced volume of the caudate [F (1,51)=5.86, p=0.02, Hedges' g=0.66], putamen [F (1,51)=6.06, p=0.02, g=0.67], thalamus [F (1,51)=6.99, p=0.01, g=0.72] and increased right lateral ventricular volume [F (1, 51)=4.03, p=0.05], and significantly increased rate of cortical thinning [F (1,52)=5.11, p=0.028)] at a mean difference of 0.84% [95% CI (0.10, 1.59)] in the left lateral orbitofrontal region over the 3-year period. In patients, greater reduction in putamen volume over time was associated with lower cumulative antipsychotic medication dose (r=0.49, p=0.01), and increasing lateral ventricular volume over time was associated with worsening negative symptoms (r=0.41, p=0.04) and poorer global functioning (r= -0.41, p=0.04). This study demonstrates localised progressive structural abnormalities in the cortico-striato-thalamo-cortical circuit after the onset of psychosis, with increasing ventricular volume noted as a neuroanatomical marker of poorer clinical and functional outcome.