WITHDRAWN: Structural impairment in superficial and deep white matter and its association with clinical symptoms in schizophrenia: A harmonized, multisite diffusion MRI study

Abstract

While the disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, superficial white matter (SWM) has drawn less attention in schizophrenia research than deep white matter (DWM). Using the structural equation model (SEM), we aimed to investigate the structural abnormalities of SWM and DWM in schizophrenia and their association with clinical symptoms. We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 schizophrenia patients. After harmonizing the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fiber clustering of the tractography data, resulting in 8 SWM and 33 DWM tracts. In the patient group, we adopted an SEM for the association with clinical symptoms, using the fractional anisotropy (FA) deviation and the Positive and Negative Syndrome Scale scores. Among the 18 tracts with a lower FA in the patient group, the following structures were included in the SEM: the cingulum bundle, genu, rostral body, and isthmus of the corpus callosum; and striato-frontal, superficial frontal, and superficial temporal tracts. The latent variable white matter impairment , consisting of the FA deviations of the seven white matter tracts, was negatively correlated with the latent variable clinical symptom severity (B=-0.23, p=0.047). The negative symptoms (B=1.12) contributed more to the latent variable clinical symptom severity than did the positive symptoms (B=0.74). The SWM and DWM tract structural abnormalities were identified in schizophrenia patients. The association with clinical symptoms was more prominent in the negative symptoms. • The harmonized diffusion MRI data was analyzed using the whole-brain tractography and fiber clustering. • The patients with schizophrenia had a significantly lower FA in 14 DWM and 4 SWM tracts. • The association of white matter impairments with clinical symptoms was more prominent in the negative symptoms.