The effect of weight loss on brain age in schizophrenia spectrum disorders

Individuals with schizophrenia spectrum disorders (SSDs) suffer from metabolic conditions including type 2 diabetes (T2D) and obesity. Moreover, they are at a high risk for cardiovascular disease and this could lead to a shortened life expectancy. Obesity is one of common comorbid conditions in SSDs, which has adverse effects on brain health. However, it is still unknown how metabolic disorders affect brain anatomy in SSDs, and the impacts of weight loss from pharmacological interventions are yet to be studied. This study includes a total of 48 patients with SSDs from three different clinical trials focusing on weight loss interventions. We acquired metabolic parameters, brain anatomical MRI, body mass index (BMI), cognition, and psychopathology scores at baseline and endpoint. We used a convolutional neural network-based classifier to calculate each patient's brain-age gap estimate (brainAGE) based on high-quality brain structural T1 images. We examined the relationship between the reduction in BMI and brainAGE between two timepoints. There was a significant reduction in BMI (p < 0.001) between two timepoints. Additionally, the analysis revealed that none of the cognitive, or psychopathology measures demonstrated significant differences between the timepoints (p > 0.05). The results of the multiple regression analysis showed a positive association between the reduction in BMI and brainAGE (F(2,44) = 3.69, p = 0.03). Furthermore, there were no noteworthy associations observed between brainAGE and the aforementioned parameters (p > 0.05). This study revealed a positive correlation between brainAGE and significant weight loss in SSDs with comorbid obesity.