Edad Cerebral en el Trastorno Bipolar: Impacto de la Selección del Modelo y Factores Clínicos

Bipolar disorder (BD) has been associated with accelerated aging, but studies investigating Brain Age have yielded mixed results. This may reflect differences in methodology and model sensitivity.

We compared three publicly available Brain Age models (ENIGMA, PyBrainAge, Pyment) using T1-weighted MRI scans from 352 individuals with BD Type I and 327 controls across four sites. Predicted age difference (PAD) was calculated as Brain Age minus chronological age. We examined group differences, medication effects, and age-related patterns using linear mixed-effects models controlling for chronological age, sex, and scanner.

PAD was higher in BD than controls across all models (PyBrainAge: +3.03 years; ENIGMA: +2.78 years; Pyment: +1.43 years; Cohen's d=0.26-0.36; all p<.001) with group differences more pronounced in participants ≥40 years. In region-based models, thalamic and ventricular volumes contributed most consistently to elevated PAD in BD. Across all models, lithium-treated BD participants showed no significant PAD elevation compared to controls (all p>.5), while non-lithium-treated participants exhibited significant elevation (+1.47-3.24 years all: p<.01). Within BD participants, mixed modeling of current any medication status, lithium treatment, and illness duration/severity measures showed current any medication status to be associated with increased PAD (+2.03-4.48 years; all: p<.05) whereas lithium use was associated with a 1.87-3.67-year reduction in PAD (all p<.05) and no associations were found with duration/severity metrics.

Our findings support the presence of elevated Brain Age in BD, lithium's suggested neuroprotective profile, and highlight the influence of the Brain Age model, MRI scanner, and other confounders on predictions.