New scientific review warns that chronic stress and anxiety can harm the brain and raise the risk of depression and dementia.
Researchers from the Rotman Research Institute at Baycrest Health Sciences reviewed existing animal and human studies to identify how chronic anxiety, prolonged stress and persistent fear affect brain structure and function. The authors found extensive overlap in the neurocircuitry involved in stress, fear and anxiety, offering a biological explanation for why chronic stress is linked to later neuropsychiatric disorders such as major depression and Alzheimer’s disease. The review was published online in the journal Current Opinion in Psychiatry.
Anxiety, fear and stress are normal, adaptive responses when they occur briefly—for example, before an exam or a job interview. But when these emotional states become frequent or persistent, they can interfere with daily life, affecting work, school, family and social relationships. Chronic stress represents a pathological state: prolonged activation of the body’s acute stress response alters immune, metabolic and cardiovascular systems, and can lead to structural brain changes such as hippocampal atrophy. The hippocampus is essential for long-term memory and spatial navigation, so damage here has clear implications for cognition.
“Pathological anxiety and chronic stress are associated with structural degeneration and impaired functioning of the hippocampus and the prefrontal cortex (PFC), which may account for the increased risk of developing neuropsychiatric disorders, including depression and dementia,” said Dr. Linda Mah, clinician scientist at the Rotman Research Institute and lead author of the review.
The review synthesizes evidence from animal models of stress and fear conditioning as well as human neuroimaging studies in both healthy individuals and clinical populations. The authors focused on the key nodes of fear and anxiety neurocircuitry—the amygdala, medial prefrontal cortex and hippocampus—and how these regions respond to chronic stress.
Across studies, a consistent pattern emerges: chronic stress and anxiety are linked to an overactive amygdala (the brain’s emotional alarm system) alongside reduced activity in the medial prefrontal cortex (the cognitive control region responsible for regulating emotional responses). This imbalance—heightened “bottom-up” emotional signaling from the amygdala combined with weakened “top-down” regulation by the PFC—helps explain why persistent anxiety can lead to sustained emotional reactivity and impaired regulation. Similar patterns of dysfunction also implicate the hippocampus, where structural degeneration undermines memory and cognitive resilience.
The review notes that this amygdala–PFC–hippocampus interaction is well established in the literature and was highlighted in earlier landmark work on depression and brain circuitry. Importantly, Dr. Mah emphasizes that stress-related brain changes may not be entirely irreversible. Evidence shows that antidepressant medications and physical activity can promote hippocampal neurogenesis (the birth of new neurons) and improve neural health.
Dr. Mah and colleagues call for further research to test whether targeted interventions can both reduce chronic stress and prevent or reverse stress-related brain alterations. Promising approaches include exercise, mindfulness training, and cognitive behavioral therapy (CBT). These nonpharmacological strategies—along with pharmacological treatments when appropriate—may restore PFC and hippocampal function, reduce amygdala hyper-reactivity, and thereby lower the risk of developing depression or dementia following prolonged stress or anxiety.
The review builds on earlier work by Dr. Mah and collaborators that found anxiety can accelerate progression to Alzheimer’s disease in people with mild cognitive impairment. Taken together, these findings underscore the importance of early identification and treatment of pathological anxiety and chronic stress as part of strategies to protect brain health and reduce long-term risk of neuropsychiatric and neurodegenerative disease.
Dr. Alexandra Fiocco of the Institute for Stress and Wellbeing Research contributed to the review. Funding support included the Ministry of Health and Long-Term Care AFP Innovation Fund.
Abstract (summary)
Can anxiety damage the brain?
Purpose of review: Chronic stress and anxiety worsen mood disorders such as depression and may increase dementia risk. This review examines whether anxiety causes brain damage and explores mechanisms linking stress to affective and cognitive decline.
Recent findings: Anxiety disorders show exaggerated bottom-up threat signaling from the amygdala, with impaired regulatory control from the PFC and hippocampus. Chronic stress produces similar changes: increased amygdala activity and structural degeneration in the PFC and hippocampus, which undermines top-down regulation. Both pharmacological treatments (for example, antidepressants) and nonpharmacological interventions (CBT, exercise, mindfulness) show potential to reverse some stress-induced brain changes.
Summary: Pathological anxiety and prolonged stress contribute to structural degeneration and functional impairment in the hippocampus and prefrontal cortex, which may increase risk for depression and dementia. Longitudinal clinical studies are needed to determine whether interventions that reduce stress and restore brain function can lower long-term neuropsychiatric risk.
Reference: Mah, Linda; Szabuniewicz, Claudia; Fiocco, Alexandra J. “Can anxiety damage the brain?” Current Opinion in Psychiatry. Published online January 2016. doi:10.1097/YCO.0000000000000223