Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

Abstract

Background: Disrupted white matter (WM) microstructure has been commonly identified in youth at clinical high risk (CHR) for psychosis. Several lines of evidence suggest that fatty acids, especially unsaturated fatty acids (UFAs), might play a crucial role in the WM pathology of early onset psychosis. However, evidence linking UFA and WM microstructure in CHR is quite sparse.

Aims: We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls (HC).

Methods: Plasma fatty acids were assessed and diffusion tensor imaging (DTI) data were performed with tract-based spatial statistics (TBSS) analysis for 66 individuals at CHR for psychosis and 70 HC.

Results: Both the global and regional diffusion measures showed significant between-group differences, with decreased fractional anisotropy (FA) but increased mean diffusivity (MD) and radial diffusivity (RD) found in the CHR group compared with the HC group. On top of that, we found that in the HC group, plasma arachidic acid showed obvious trend-level associations with higher global FA, lower global MD and lower global RD, which regionally spread over the corpus callosum, right anterior and superior corona radiata, bilateral anterior and posterior limb of the internal capsule, and bilateral superior longitudinal fasciculus. However, there were no associations between global WM measures and any UFA in the CHR group. Conversely, we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.

Conclusions: Compared with the HC group, CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA, with a neuroprotective effect found in the HC group but not in the CHR group. Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group, highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.

Keywords: schizophrenia.

Figure 1

Flowchart of sample selection. CHR, clinical high risk; HC, healthy controls; MRI, magnetic resonance imaging; SIPS, Structured Interview for Prodromal Syndromes; SOPS, Scale of Prodromal Symptoms.

Figure 2

Group comparison for regional and global fractional anisotropy (FA), radial diffusivity (RD) and mean diffusivity (MD) in clinical high risk (CHR) group and healthy control (HC) group. (A) Tract-based spatial statistics analysis (TBSS) showed widespread significant between-group difference in regional microstructural diffusion magnetic resonance imaging (dMRI) measures, with significantly lower FA but higher MD and RD values found in the CHR group, compared with the HC group. Significant lower FA values (red), higher MD (pink) and higher RD (blue) are drawn on top of the white matter skeleton (green). Images are shown at a permutation-based threshold of p<0.05 (family-wise error corrected). The colour bars represent the 1-p value (0.95–1). (B) Two independent samples t-tests of global FA (gFA), global MD (gMD) and global RD (gRD) between CHR and HC group. CHR showed significant decreased gFA, increased gMD and gRD compared with HC group. ACR, anterior corona radiata; ALIC, anterior limb of internal capsule; BCC, body of the corpus callosum; CP, cerebral peduncle; GCC, genu of the corpus callosum; PCR, posterior corona radiata; PLIC, posterior limb of internal capsule; SCC, splenium of the corpus callosum; SCR, superior corona radiata; SLF, superior longitudinal fasciculus. ***p<0.001.

Figure 3

Association between plasma arachidic acid level and regional/global fractional anisotropy (FA), radial diffusivity (RD) and mean diffusivity (MD) in clinical high risk (CHR) group and healthy control (HC) group. (A) In the HC group, arachidic acid level showed obvious trend-level associations with all the global diffusion magnetic resonance imaging (dMRI) measures, with a positive association related to global FA (gFA), but a negative association with global MD (gMD) and global RD (gRD). (B) Association coefficients between arachidic acid level and regional FA, MD and RD values. ACR, anterior corona radiata; ALIC, anterior limb of internal capsule; BCC, body of the corpus callosum; CGC, cingulum; CP, cerebral peduncle; EC, external capsule; FX, fornix; FX/ST, fornix stria terminalis; GCC, genu of the corpus callosum; ICP, inferior cerebellar peduncle; MCP, middle cerebellar peduncle; ML, medial lemniscus; PCR, posterior corona radiata; PCT, pontine crossing tract; PLIC, posterior limb of internal capsule; PTR, posterior thalamic radiation; RLIC, retrolenticular part of internal capsule; SCC, splenium of the corpus callosum; SCP, superior cerebellar peduncle; SCR, superior corona radiata; SFOF, superior fronto-occipital fasciculus; SLF, superior longitudinal fasciculus; SS, sagittal stratum. *p<0.05.

Figure 4

Association between clinical characteristics and global diffusion magnetic resonance imaging (dMRI) measures. (A) Global mean diffusivity (gMD) showed significant negative association with Global Assessment of Functioning Scale (GAF) current scores, but positive association with GAF scores drop in 12 months, and Scale of Prodromal Symptoms (SOPS) negative scores. (B) Global radial diffusivity (gRD) showed significant negative association with GAF current scores and positive association with GAF score drop in the past 12 months, and also showed a marginally positive association with SOPS negative scores.