Central Obesity-related Brain Alterations Predict Cognitive Impairments in First Episode of Psychosis.
Authors
Affiliations (5)
Affiliations (5)
- National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic.
- 3rd Faculty of Medicine, Charles University, Ruská 2411, 100 00 Prague, Czech Republic.
- Department of Psychiatry, Dalhousie University, 5909 Veteran's Memorial Lane, Halifax, NS B3H 2E2, Canada.
- Structural Brain Mapping Group, Department of Neurology, Jena University Hospital, Erlanger Alle 101, D-07747 Jena, Germany.
- Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Abstract
Cognitive impairment is a key contributor to disability and poor outcomes in schizophrenia, yet it is not adequately addressed by currently available treatments. Thus, it is important to search for preventable or treatable risk factors for cognitive impairment. Here, we hypothesized that obesity-related neurostructural alterations will be associated with worse cognitive outcomes in people with first episode of psychosis (FEP). This observational study presents cross-sectional data from the Early-Stage Schizophrenia Outcome project. We acquired T1-weighted 3D MRI scans in 440 participants with FEP at the time of the first hospitalization and in 257 controls. Metabolic assessments included body mass index (BMI), waist-to-hip ratio (WHR), serum concentrations of triglycerides, cholesterol, glucose, insulin, and hs-CRP. We chose machine learning-derived brain age gap estimate (BrainAGE) as our measure of neurostructural changes and assessed attention, working memory and verbal learning using Digit Span and the Auditory Verbal Learning Test. Among obesity/metabolic markers, only WHR significantly predicted both, higher BrainAGE (t(281)=2.53, p=0.012) and worse verbal learning (t(290) = -2.51, P = .026). The association between FEP and verbal learning was partially mediated by BrainAGE (average causal mediated effects, ACME = -0.04 [-0.10, -0.01], P = .022) and the higher BrainAGE in FEP was partially mediated by higher WHR (ACME = 0.08 [0.02, 0.15], P = .006). Central obesity-related brain alterations were linked with worse cognitive performance already early in the course of psychosis. These structure-function links suggest that preventing or treating central obesity could target brain and cognitive impairments in FEP.