Brain ageing and neurodegeneration in bipolar disorder

Background: Bipolar disorder (BD) is a psychiatric condition characterized by alternating episodes of mania and depression frequently associated with cognitive impairments. BD is associated with brain alterations in fronto-temporal and limbic networks. Recent conceptualizations view BD as a neurodegenerative disorder characterized by progressive deterioration of grey and white matter (GM, WM) volumes and accelerated brain ageing. Therefore, we conducted a review gathering neuroimaging evidence about neurodegenerative processes in BD. Methods: A literature search was conducted on the PubMed, Scopus and Web of Science databases in September 2021. After title and abstract screening of the retrieved records, 19 studies that met our inclusion criteria were included in the review. Results: The available evidence suggests the presence of a progressive reduction of GM volumes at the whole-brain level and in the amygdala, prefrontal regions and the anterior cingulate cortex. Conversely, WM lesions and alterations seem to emerge only in the early phases of the condition masking the effects of normal ageing. Lastly, machine learning models indicate that the gap between predicted and chronological brain age differs considerably between healthy controls and BD patients, as the latter are characterized by larger gaps. Limitations: The included studies had cross-sectional study design, small sample sizes and heterogeneous methodology, and lack of control for pharmacological treatment. Conclusions: BD seems to be associated with generalized age-related structural GM volumes reductions and functional brain alterations thus suggesting the presence of neurodegenerative processes. Future systematic reviews and meta-analyses should be conducted to quantify the magnitude of brain ageing-related effects in BD.