Retinal cytoarchitectural changes in schizophrenia and bipolar disorder: a meta-analysis and exploratory study
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INTRODUCTION: Schizophrenia (SZ) and bipolar disorder (BD) are neurodegenerative psychotic disorders hallmarked by reductions in gray and white matter volume. Limitations in neuroimaging have led to the use of OCT to study retinal layer biomarkers and their relation to brain pathology. This thesis includes a meta-analysis of current literature and an exploratory analysis of retinal layer thickness in relation to SZ and BD. METHODS: For the meta-analysis, twelve articles were identified using PubMed, Web of Science, and Cochrane database. Diagnostic groups were proband (SZ and BD combined), SZ only, BD only, and healthy control (HC) eyes. Analyses utilized fixed and random effects models, in addition to assuring that bias was adjusted for and that results were cross-validated. Statistical analyses were performed using the “meta” package in R, with results reported as standard mean differences (SMD). The exploratory analysis included a total of 38 subjects (24 probands and 14 HC). Retinal measures were co-varied for age, sex, race, body mass index (BMI), and best-corrected visual acuity (BCVA). Correlations between retinal and clinical and cortical measures were also performed. Clinical data included illness duration, symptom severity, antipsychotic dosage, and smoking status. Neuroimaging data included gray matter (GM) thickness, gray matter volume, and intracranial volume (ICV). Linear effects and mixed effects models were used to study mean eye and right/left eye measures, respectively. Statistical analysis was done in R. RESULTS: A total of 820 patient eyes (541 SZ and 279 BD) and 904 HC eyes were used for the meta-analysis. Compared to HC eyes, probands, SZ, and BD eyes showed significant thinning the peripapillary retinal nerve fiber layer (RNFL), with atrophy greatest in the nasal, temporal, and superior regions. In addition, all diagnostic groups demonstrated significant reductions in the combined ganglion cell layer and inner plexiform layer (GCL-IPL) compared to HC. No significant differences were found for choroidal and macular measures. No significant relationships were seen from meta-regression analysis for clinical measures. For the exploratory analysis, retinal measures from a total of 24 probands (18 SZ and 6 BD) and 14 HC was studied. Compared to HC, probands showed reductions in overall RNFL in mean eye measures, while increases in the inner and outer RNFL were seen in left eye measures. No significant group differences were seen in the GCL, IPL, and inner nuclear layer (INL). The outer plexiform layer (OPL) showed significant thickening in probands and SZ compared to HC for all eye measures. Probands showed trending reductions in the outer nuclear layer (ONL) in the left eye compared to HC. No significant correlations were found between retinal layers and illness duration, overall PANSS (Positive and Negative Syndrome Scale) score, PANSS negative symptom subscore, and smoking status. PANSS positive symptom subscore showed significant and trending negative correlations to the RNFL and GCL, respectively. Antipsychotic medication dosage displayed a trending negative relationship with the IPL. GM thickness showed a significant and trending negative correlation to the RNFL and ONL, respectively. Furthermore, a trending inverse relationship was observed between GM volume and the OPL. Finally, ICV demonstrated a trending and significant negative relationship with GCL and OPL thickness, respectively. CONCLUSION: The meta-analysis showed that atrophy in RNFL and GCL-IPL measures are widely associated with psychosis. Furthermore, it supports previous findings of gray and white matter reductions in SZ and BD. The exploratory analysis showed psychosis-associated reductions in the RNFL and ONL layers, consistent with previous literature. Contradictory findings, the thickening of the ONL, can be attributed to the conflicting findings, but might also be explained by neuro-inflammatory pathways related to psychotic disorders.
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