Journal Article Ahead of print
PubMed: 42841301 DOI: 10.1097/HRP.0000000000000480
Retinal Biomarkers of Cognition in Schizophrenia: A Systematic Review and Meta-Analysis.
Harv Rev Psychiatry
Authors: Sai Spoorthy Mamidipalli, Anu Franco, Janani Duraisamy, Avinash Damodar Segu, Nithin Kondapuram, Sreya Mariyam Salim, Cemal Demirlek, Paulo Lizano, Steven M Silverstein, Sai Krishna Tikka
Affiliations
- From Department of Psychiatry, All India Institute of Medical Sciences (Drs. Mamidipalli and Tikka); Department of Psychiatry, Jubilee Mission Medical College and Research Institute (Dr. Franco); Department of Psychiatry, Karpaga Vinayaka Medical College and Hospital (Dr. Duraisamy); Department of Psychiatry, National Institute of Mental Health and Neurosciences, Karnataka, India (Dr. Segu); Aster Prime Institute of Mental and Neurosciences, Aster Prime Hospital, Telangana, India (Dr. Kondapuram); Powys Teaching Health Board, NHS, Wales, United Kingdom (Dr. Salim); Department of Psychiatry, University of Rochester Medical Center (Drs. Demirlek, Lizano, and Silverstein); Department of Psychiatry, Harvard Medical School (Dr. Lizano).
Abstract
Individuals with schizophrenia consistently show thinning retinal layers, which can potentially serve as neural biomarkers. The association between retinal morphology and core symptom domains like cognitive functioning, however, has not been systematically synthesized. We hypothesize that deficits in retinal structure are associated with cognitive dysfunction in schizophrenia. This systematic review and meta-analysis looks at studies available from inception to June 9, 2026. Outcome measures include correlation coefficients between cognition scores and retinal thickness values (both macular and peripapillary-total and sector-wise) assessed using optical coherence tomography in patients with schizophrenia and related disorders. We assessed risk of bias with the Joanna Briggs Institute critical appraisal tool. Meta-analysis was conducted using the restricted maximum-likelihood method and Fisher's r-to-z transformation. Data from 16 studies (n=1,475 eyes; 847 patients) were included in a series of 88 pooled analyses. Overall cognitive ability correlated with thickness of the macular-retinal nerve fiber layer (mRNFL) (pooled-r=0.180; p=.002; k=7) and the superior-quadrant of the peripapillary RNFL (pRNFL) (pooled-r=0.214; p=.026; k=7). Attention correlated with mRNFL (pooled-r=0.210; p<.001; k=6), macular-inner plexiform layer (mIPL) (pooled-r=0.142; p=.012; k=8), and pRNFL (pooled-r=0.207; p<.001; k=9) thicknesses. Processing speed correlated with foveal thickness (FT) (pooled-r=0.206; p=.008; k=7), mIPL (pooled-r=0.194; p=.001; k=6), and pRNFL (pooled-r=0.211; p<.001; k=5) thicknesses. Executive function correlated with macular thickness (pooled-r=0.099; p=.018; k=10) and mRNFL (pooled-r=0.159; p=.009; k=6). Age, sex, cardiometabolic comorbidities, and smoking moderated these correlations. We provide evidence suggesting that retinal layer thickness is associated with poorer cognitive functioning in schizophrenia, supporting retinal changes as indicators of disease-related neural processes. The small number of available studies limits these conclusions.
MeSH
Biomarkers, Schizophrenia, Tomography, Optical Coherence, Retinaldehyde, Psychotic Disorders, Cognition, Psychiatry