Resistencia a la insulina y desregulación de la leptina: impacto en la estructura cerebral in vivo y la función...

Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are associated with persistent cognitive deficits, yet the biological mechanisms underlying these impairments remain unclear. Metabolic dysfunction, particularly insulin resistance (IR), may contribute to brain structural alterations and cognitive decline. However, diagnosis-specific metabolic effects on gray matter volumes (GMV) and cognition were not fully explored. Partial Least Squares Path Modeling was applied to examine associations among metabolic biomarkers, GMV, and cognitive performance in mood disorders, stratifying by diagnosis.

81 BD (F=55, M=26) and 78 MDD (F=45, M=33) inpatients underwent neuropsychological evaluation with the Brief Assessment of Cognition in Schizophrenia. T1-weighted MRI images were processed to extract GMV. Blood samples were collected to assess metabolic markers.

In the whole sample, the metabolism latent construct negatively predicted both GMV and cognition, with the GMV factor positively affecting cognition. A significant diagnostic difference emerged for the metabolism-to-cognition path (p = 0.0196). Stratified analyses showed that in BD, metabolism was significantly associated with both reduced GMV and poorer cognition, whereas in MDD no significant structural paths were identified. IR markers and leptin were the strongest positive contributors to the metabolism factor in both the full sample and BD group. Brain regions most affected encompassed areas central to cognitive and emotional regulation, characterized by a high density of insulin and leptin receptors.

These findings highlight the role of IR and leptin in shaping cognition in mood disorders and underscore the potential of insulin-related pathways as therapeutic targets, especially in BD with metabolic comorbidities.