Grant: Summer Program in Aging

Depression and bipolar disorder are common mental health conditions, but growing evidence suggests they may also be linked to early changes in brain health. Neurodegenerative diseases, such as dementia, affect memory and thinking and are a growing public health concern. Because the hippocampus, a brain region important for memory, is also affected in mood disorders, we are asking whether these conditions might share early brain changes with neurodegenerative diseases. To explore this question, we focused on two brain proteins that can signal different types of changes. Neurofilament light chain (NfL) increases when brain cells are damaged, while p-tau 231 is linked to early processes involved in Alzheimer's-related pathology. We measured these proteins in the brain tissue samples donated by people who had depression, bipolar disorder, or no history of mental illness (controls). The p-tau 231 protein was measured only in the depression and control groups. The brain tissues were donated to the Douglas Brain Bank in Montreal. In our investigation, all individuals with depression and most of those with bipolar disorder had died by suicide. We found that individuals with depression had higher levels of NfL than healthy individuals, suggesting early signs of damage in some brain cells. This increase was not observed in people with bipolar disorder. Levels of p-tau 231 were similar between the depression and control groups, suggesting that this protein may not play a central role in the mechanisms underlying depression. Overall, our findings suggest that depression may involve early damage to brain areas that are important for memory. Understanding these changes may help clarify how mood disorders and neurodegenerative diseases are connected. In the long term, this knowledge could support strategies to monitor and protect brain health in people living with depression, with the goal of reducing their risk of developing dementia.