Lonning, V. | Search bioRxiv

bioRxiv2019

Impact of second-generation antipsychotics on white matter microstructure in adolescent-onset psychosis.

White matter abnormalities are well-established in adult patients with psychosis. Yet less is known about changes in early onset psychosis (EOP) during adolescence, especially whether antipsychotic medication might impact white matter microstructure in this sensitive phase. Here, we utilized Magnetic Resonance Imaging (MRI) in unmedicated and medicated adolescent EOP patients in comparison to healthy controls to examine the impact of antipsychotic medication status on indices of white matter microstructure. Twenty-two EOP patients (11 unmedicated) and 33 healthy controls, aged between 12-18 years, underwent 3T diffusion-weighted MRI. Using Tract-based Spatial Statistics, we calculate case-control differences in scalar diffusion measures, i.e. fractional anisotropy (FA), axial diffusion (AD) and radial diffusion (RD), and investigated their association with antipsychotic medication. We found significantly lower mean FA and AD in largely overlapping areas, particularly in left anterior corona radiata (ACR), in EOP patients relative to healthy controls. Mean FA in the left ACR was significantly associated with antipsychotic medication status (t = 2.991, p = 0.008, R2 = 0.298), showing higher FA values in medicated compared to unmedicated EOP patients. The present study is the first to link antipsychotic medication status to altered regional FA in the left ACR, a region being discussed to contribute to the etiology of psychosis. Yet, further work with larger samples is needed to draw firm conclusions about putatively enhancing effects of antipsychotic medication on white matter microstructure early in the disease process.

neuroscience↗

bioRxiv2019

Microstructural white matter changes and links with subcortical structures in chronic schizophrenia: A free-water imaging approach.

Schizophrenia is a severe mental disorder with often a chronic course. Neuroimaging studies report brain abnormalities in both white and gray matter structures. However, the relationship between microstructural white matter differences and volumetric subcortical structures is not known.\n\nWe investigated 30 long-term treated patients with schizophrenia (mean age 51.1{+/-}7.9 years, illness duration 27.6{+/-}8.0 years) and 42 healthy controls (mean age 54.1{+/-}9.1 years) using 3 T diffusion and structural magnetic resonance imaging. The free-water imaging method was used to model the diffusion signal, and subcortical volumes were obtained from FreeSurfer. We applied multiple linear regression to investigate associations between (i) patient status and regional white matter microstructure, (ii) medication dose or clinical symptoms on white matter microstructure in patients, and (iii) for interactions between subcortical volumes and diagnosis for microstructural white matter regions showing significant patient-control differences.\n\nThe patients had significantly decreased free-water corrected fractional anisotropy (FAt), explained by decreased axial diffusivity and increased radial diffusivity (RDt) bilaterally in the anterior corona radiata (ACR) and the left anterior limb of the internal capsule (ALIC) compared to controls. In the fornix, the patients had significantly increased RDt. In patients, positive symptoms were associated with localized increased free-water and negative symptoms with localized decreased FAt and increased RDt. There were significant interactions between patient status and several subcortical structures on white matter microstructure and the free-water compartment for left ACR and fornix, and limited to the free-water compartment for right ACR and left ALIC. The Cohens d effect sizes were medium to large (0.61 to 1.20, absolute values).\n\nThe results suggest a specific pattern of frontal white matter axonal degeneration and demyelination and fornix demyelination that is attenuated in the presence of larger structures of the limbic system in patients with chronic schizophrenia. Findings warrants replication in larger samples.

neuroscience↗