Transient patterns of advanced brain ageing in female adolescents with anorexia nervosa

Anorexia nervosa is a psychiatric disorder characterised by undernutrition, significantly low body weight and large, although possibly transient, reductions in brain structure. Advanced brain ageing tracks accelerated age-related changes in brain morphology that have been linked to psychopathology and adverse clinical outcomes.

The aim of the current case-control study was to characterise cross-sectional and longitudinal patterns of advanced brain age in acute anorexia nervosa and during the recovery process.

Measures of grey- and white-matter-based brain age were obtained from T1-weighted magnetic resonance imaging scans of 129 acutely underweight female anorexia nervosa patients (of which 95 were assessed both at baseline and after approximately 3 months of nutritional therapy), 39 recovered patients and 167 healthy female controls, aged 12-23 years. The difference between chronological age and grey- or white-matter-based brain age was calculated to indicate brain-predicted age difference (BrainAGE_GM and BrainAGE_WM).

Acute anorexia nervosa patients at baseline, but not recovered patients, showed a higher BrainAGE_GM of 1.79 years (95% CI [1.45, 2.13]) compared to healthy controls. However, the difference was largely reduced for BrainAGE_WM. After partial weight restoration, BrainAGE_GM decreased substantially (beta = -1.69; CI [-1.93, -1.46]). BrainAGEs were unrelated to symptom severity or depression, but larger weight gain predicted larger normalisation of BrainAGE_GM in the longitudinal patient sample (beta = -0.65; CI [-0.75, -0.54]).

Our findings suggest that in patients with anorexia nervosa, undernutrition is an important predictor of advanced grey-matter-based brain age, which itself might be transient in nature and largely undetectable after weight recovery.