Longitudinal loss of gray matter volume in patients with first-episode schizophrenia: DARTEL automated analysis and ROI validation

Abstract

Region of Interest (ROI) longitudinal studies have detected progressive gray matter (GM) volume reductions in patients with first-episode schizophrenia (FESZ). However, there are only a few longitudinal voxel-based morphometry (VBM) studies, and these have been limited in ability to detect relationships between volume loss and symptoms, perhaps because of methodologic issues. Nor have previous studies compared and validated VBM results with manual Region of Interest (ROI) analysis. In the present VBM study, high-dimensional warping and individualized baseline-rescan templates were used to evaluate longitudinal volume changes within subjects and compared with longitudinal manual ROI analysis on the same subjects. VBM evaluated thirty-three FESZ and thirty-six matched healthy control subjects (HC) at baseline (cross-sectionally) and longitudinally evaluated 21 FESZ and 23 HC after an average of 1.5 years from baseline scans. Correlation analyses detected the relationship between changes in regional GM volumes in FESZ and clinical symptoms derived from the Brief Psychiatric Rating Scale, as well as cognitive function as assessed by the Mini-Mental State Examination. At baseline, patients with FESZ had significantly smaller GM volume compared to HC in some regions including the left superior temporal gyrus (STG). On rescan after 1.5 years, patients showed significant GM volume reductions compared with HC in the left STG including Heschl's gyrus, and in widespread brain neocortical regions of frontal, parietal, and limbic regions including the cingulate gyrus. FESZ showed an association of positive symptoms and volume loss in temporal (especially STG) and frontal regions, and negative symptoms and volume loss in STG and frontal regions. Worse cognitive function was linked to widespread volume reduction, in frontal, temporal and parietal regions. The validation VBM analyses showed results similar to our previous ROI findings for STG and Cingulate Gyrus. We conclude FESZ show widespread, progressive GM volume reductions in many brain regions. Importantly, these reductions are directly associated with a worse clinical course. Congruence with ROI analyses suggests the promise of this longitudinal VBM methodology.

Association of IQ Changes and Progressive Brain Changes in Patients With Schizophrenia

“…In addition, our findings of progressive loss in cortical and cerebral GM volume, cortical thinning, and increases in V3 volume are consistent with previous findings. 1,[3][4][5][6] Unlike previous studies, [3][4][5] we did not find significant volume or thickness loss in frontal regions. Possible reasons for the discrepancy include a longer duration of the illness or more severe symptoms in the patient samples included in those studies.…”

“…6,7 These brain changes appear to be clinically relevant because they are linked to outcome, 4,5,8 although confounding effects of antipsychotic medications cannot be ruled out. [9][10][11][12] Schizophrenia is characterized by global cognitive impairments 13 and deficits in specific domains, such as verbal, memory, and executive functioning.…”

Long-Term Effects of Prenatal Hypoxia on Schizophrenia-Like Phenotype in Heterozygous Reeler Mice

“…Therefore, hypoxia can cause changes to the VEGF signaling pathway during early development leading to changes in blood flow and brain volume as seen in individuals with schizophrenia [16,17]. In this regard, studies have shown that rodents exposed to hypoxia incur anatomical changes relevant to schizophrenia in adult offspring [18][19][20][21].…”

Dissociation of anatomical and functional alterations of the default-mode network in first-episode, drug-naive schizophrenia

“…The dissociation of anatomical and functional alterations might result from the different analysis methods, which measure different aspects of gray matter in schizophrenia. In the present study, VBM measures GMV changes which are stable and long-standing (Chan et al, 2011;Asami et al, 2012). On the contrary, functional alterations measured by fALFF may represent physiological changes in acute stage of disease .…”