Plasma levels of 3-methoxy-4-hydroxyphenylglycol are associated with microstructural changes within the cerebellum in the early stage of first-episode schizophrenia: a longitudinal VBM study

Abstract

The aims of this study are to determine how the interval changes of the brain structures in the early stage of first-episode schizophrenia relate to the interval changes in the clinical data, including the clinical symptoms of schizophrenia and catecholaminergic measures (plasma homovanillic acid [HVA] and 3-methoxy-4-hydroxyphenylglycol [MHPG]). Regional brain volumes and fractional anisotropy (FA)/mean diffusivity (MD) with diffusion tensor imaging (DTI) were measured at baseline and 6-month follow-up in a 3T magnetic resonance imaging (MRI) system in a cohort of 16 schizophrenic patients, who were in their first episode at the time of baseline MRI. At the time of baseline and follow-up MRI, all 16 patients underwent evaluations that included a psychopathological assessment (Positive and Negative Syndrome Scale [PANSS]) and peripheral catecholaminergic measures (plasma MHPG or HVA). For interval changes between baseline and follow-up MRI data (morphological change, MD, and FA), the correlation/regression analysis was performed as a series of single regression correlations in Statistical Parametric Mapping 5, with the interval changes in PANSS or plasma HVA and MHPG as the covariates of interest. Positive and inverse correlations contrasts were created, and in this preliminary analysis, a family-wise error-corrected threshold of P<0.05 was considered significant. In the correlation/regression analysis, a positive correlation between the FA in the right cerebellar vermis and the MHPG was observed. No significant correlations between the brain volume or MD and any laboratory data (plasma HVA and MHPG) were found. During the 6-month follow-up in the early stage of first-episode schizophrenia, the MHPG changes were correlated with the microstructural FA changes in the cerebellum, which may reflect the functional connections of the noradrenergic system in the cerebellum.

Keywords: 3T MR imaging; apparent diffusion coefficient; fractional anisotropy; homovanillic acid; mean diffusivity; voxel-based morphometry.

Figure 1

Correlation/regression analysis for 16 patients. Notes: (A) Sagittal image; (B) Coronal image; (C) Axial image. Positive correlation of FA with plasma MHPG was seen in the cerebellar vermis. Blue lines indicate the most representative position and the color scale shows the T value. FWE-corrected threshold of P<0.05. Abbreviations: FA, fractional anisotropy; FWE, family-wise error; MHPG, 3-methoxy-4-hydroxyphenylglycol.

Figure 2

Correlation/regression analysis for 16 patients. Notes: (A) Sagittal image; (B) Coronal image; (C) Axial image. Positive correlation of FA with plasma MHPG was seen in the white matter of the cerebellar vermis (red voxels). Green lines show an alignment-invariant tract representation (the “mean FA skeleton”). Uncorrected threshold of P<0.001. Abbreviations: FA, fractional anisotropy; MHPG, 3-methoxy-4-hydroxyphenylglycol.