Abstract
Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.
Highlights
Magnetic resonance imaging (MRI) has been used extensively to document brain changes in psychotic disorders
Baseline differences in total and regional grey matter volume No significant baseline difference in total Grey matter volume (GMV) was detected between patients and healthy control participants (F = 0.297; p = 0.588), nor were any voxel-level regional differences detected following whole-brain family-wise error (FWE)-correction
From baseline to 3 months, GMV in this region remained stable in controls, decreased in the plus intensive psychosocial therapy (PIPT) group, and increased in the medication plus intensive psychosocial therapy (MIPT) group (Fig. 3b)
Summary
Magnetic resonance imaging (MRI) has been used extensively to document brain changes in psychotic disorders. Grey matter volume (GMV) reductions relative to healthy controls are robust, and evident across all illness stages [1,2,3] and in multiple brain regions [2, 4, 5]. Some of these changes appear to worsen with transition to psychosis and ongoing illness [6], which has been taken as evidence of a progressive process associated with illness onset [7], some have opposed this view [8, 9]. One recent placebocontrolled trial in mostly remitted patients with psychotic depression showed that, compared to patients on placebo, those given olanzapine had decreased cortical thickness within both hemispheres [18]
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