Abnormal white matter integrity in antipsychotic-naïve first-episode psychosis patients assessed by a DTI principal component analysis

Abstract

Introduction Diffusion tensor imaging (DTI) studies in patients with schizophrenia have shown abnormalities in the microstructure of white matter tracts. Specifically, reduced fractional anisotropy (FA) has been described across multiple white matter tracts, in studies that have mainly included patients treated with antipsychotic medications. Objective To compare FA in antipsychotic-naïve patients experiencing a first episode of psychosis (FEP) to FA in healthy controls to demonstrate that the variance of FA can be grouped, in a coincidental manner, in four predetermined factors in accordance with a theoretical partition of the white matter tracts, using a principal components analysis (PCA). Methods Thirty-five antipsychotic-naïve FEP patients and 35 age- and gender-matched healthy controls underwent DTI at 3T. Analysis was performed using a tract-based spatial statistics (TBSS) method and exploratory PCA. Results DTI analysis showed extensive FA reduction in white matter tracts in FEP patients compared with the control group. The PCA grouped the white matter tracts into four factors explaining 66% of the total variance. Comparison of the FA values within each factor highlighted the differences between FEP patients and controls. Discussion Our study confirms extensive white matter tracts anomalies in patients with schizophrenia, more specifically, in drug-naïve FEP patients. The results also indicate that a small number of white matter tracts share common FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a growing body of literature emphasizing the need for treatments targeting white matter function and structure in FEP patients.

A combined diffusion tensor imaging and magnetic resonance spectroscopy study of patients with schizophrenia

“…Our finding is consistent with studies showing reduced FA (Alvarado-Alanis et al, 2015; Cheung et al, 2008) or elevated RD (Lee et al, 2013) in the midbrain of first-episode patients. This is important because the substantia nigra and ventral tegmental area are the primary sites of dopamine synthesis, and patients have elevated dopamine release in the striatum (Abi-Dargham et al, 1998; Laruelle et al, 1996), one of the targets of midbrain dopaminergic neurons.…”

“…DTI measurements could potentially be influenced by antipsychotic medication (Minami et al, 2003). However, we note that DTI abnormalities have been observed in medication-naïve patients (Alvarado-Alanis et al, 2015; Cheung et al, 2008; Cheung et al, 2011; Gasparotti et al, 2009; Mandl et al, 2013). Second, although our goal was to explore the relationship between the neuronal biochemistry of two cortical regions and the white matter tract connecting them, the MRS voxels included both gray and white matter, which both contribute to the NAA and Glx signals and have different concentrations (Sailasuta et al, 2008; Wang and Li, 1998).…”

“…White matter abnormalities identified by TBSS have been remarkably consistent across illness stage and medication status. FA reductions and RD elevations have been observed in medication-naïve first-episode patients (Alvarado-Alanis et al, 2015), medicated first-episode patients (Lee et al, 2013), and medicated patients with chronic schizophrenia (Asami et al, 2014; Holleran et al, 2014). These studies, along with our findings, suggest FA differences could be primarily driven by disruption of myelin integrity (Song et al, 2003; Song et al, 2002).…”

Brain in flames – animal models of psychosis: utility and limitations

“… 136 White matter pathology in schizophrenic patients and in PolyI:C mice has also been shown in vivo using diffusion tensor imaging, which is a particular kind of magnetic resonance imaging often used to analyze white matter structural integrity. 137 Using this method, Alvarado-Alanis et al 138 and Li et al 139 found white matter abnormalities in frontostriatal–limbic tracts in the adult PolyI:C mice, reflecting the human abnormalities especially in treatment-naive first-episode patients.…”

Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia

“…This dysconnection hypothesis suggests that schizophrenia may be understood in terms of cognition and pathophysiology as aberrant brain integration (Friston, 1998). It has been suggested that abnormalities in white matter microstructure may produce the anatomical substrate for the dysconnectivity hypothesis (Alvarado-Alanis et al, 2015;Weinberger, 1987). White matter deficits are the most consistent neuroimaging findings in this disorder and it has been reported that white matter integrity may be predictive of conversion to schizophrenia and functional outcome (reviewed in Karlsgodt et al, 2012).…”