Linking psychotic-like experiences and brain white matter microstructure in young women

Background: Psychotic-like experiences (PLE) represent a risk factor for later psychotic disorders and may be a general susceptibility marker for mental distress in general. The connectivity and microstructure of key brain white matter pathways, including fronto-temporal trajectories, have been implicated in psychosis and individuals at-risk. The sharp increase in mental health issues during adolescence and early adulthood suggests that neuroimaging markers reflecting neurodevelopmental processes in this period of life may be particularly relevant candidates for mapping the neural underpinnings of mental health problems. While sex differences in the prevalence and clinical characteristics of PLE have been reported, previous neuroimaging studies of PLEs and related clinical traits have primarily included mixed-sex samples and little research has been carried out in females only. Methods: We analyzed cross-sectional diffusion magnetic resonance imaging (dMRI) data and data from a self-report 15-item version of The Community Assessment of Psychic Experiences (CAPE) assessing PLE from 661 females aged 9-44 years. We tested for associations between CAPE subscales and other psychopathology measures assessed through questionnaires. Linked independent component analysis (LICA) was used to decompose the voxel-wise data from 24 dMRI metrics from 5 different diffusion models, resulting in 10 spatially independent components and corresponding subject weights. Next, we examined the association between each component and age, and using Bayesian statistics, we tested for associations between the LICA subject weights and both CAPE total and subscales scores. Results: The analysis revealed that PLE were broadly associated with other domains of psychopathology and psychosocial factors. We found moderate evidence for an association between PLE and a LICA component reflecting a broad and complex pattern of diffusivity in major pathways including the inferior fronto-occipital fasciculus, anterior thalamic radiation, and forceps minor. The strongest effect was found with the persecutory ideations subscale. Conclusion: Our analysis revealed an association between PLE and a multimodal white matter pattern reflecting microstructural characteristics in key commissural, association, and thalamocortical pathways in young females. The findings support that LICA is a valuable tool for fusing and decomposing advanced dMRI metrics to delineate white matter patterns that show sensitivity to neurodevelopmental processes and mental distress.