Background Dysmyelination could be part of the pathophysiology of schizophrenia spectrum (SCZ) and bipolar disorders (BPD), yet few studies have examined myelination of the cerebral cortex. The ratio of T1- and T2-weighted magnetic resonance images (MRI) correlates with intracortical myelin. We investigated the T1w/T2w-ratio and its age trajectories in patients and healthy controls (CTR) and explored associations with antipsychotic medication use and psychotic symptoms. Methods Patients with SCZ (n=64; mean age = 30.4 years, SD=9.8), BPD (n=91; mean age 31.0 years, SD=10.2), and CTR (n=155; mean age = 31.9 years, SD=9.1) who participated in the TOP study (NORMENT, University of Oslo, Norway) were clinically assessed and scanned using a General Electric 3T MRI system. T1w/T2w-ratio images were computed using an optimized pipeline with intensity normalization and field inhomogeneity correction. Vertex-wise regression models were used to compare groups and examine group x age interactions. In regions showing significant differences, we explored associations with antipsychotic medication use and psychotic symptoms. Results No main effect of diagnosis was found. However, age slopes of the T1w/T2w-ratio differed significantly between SCZ and CTR, predominantly in frontal and temporal lobe regions: Lower T1w/T2w-ratio values with higher age were found in CTR, but not in SCZ. Follow-up analyses revealed a more positive age slope in patients who were using antipsychotics and patients using higher chlorpromazine-equivalent doses. Conclusions While we found no evidence of reduced intracortical myelin in SCZ or BPD relative to CTR, different regional age trajectories in SCZ may suggest a promyelinating effect of antipsychotic medication.

OAA has received a speaker's honorarium from Lundbeck and Sunovion and is a consultant for HealthLytix. IA has received a speaker's honorarium from Lundbeck. The other authors report no conflict of interest.

This work was supported by The Research Council of Norway (grant numbers 223273, 274359) and the South-Eastern Norway Regional Health Authority (grant number 2019-104). The funding sources had no further role in study design, data collection, analysis and interpretation of data, writing the manuscript, or submitting the paper for publication.

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The study complied with the Helsinki Declaration and was approved by the Regional Committee for Medical Research Ethics (REC South-East Norway) and the Norwegian Data Inspectorate. All participants gave informed consent.

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