Depression is linked to extensive alterations in the structure and function of the brain.
- A strong body of research shows that people with depression generally have a smaller hippocampus than similar people without depression. The hippocampus is well known for its importance in memory, as it processes memories for later long-term storage. The hippocampus, however, also connects to many areas of the brain which regulate how we feel and respond to stress. For example, the hippocampus connects to the amygdala (a small almond-shaped part of the brain known to modulate our response to fear) and the prefrontal cortex (the âexecutiveâ brain center known to govern how we think and behave).
2. Depression is a stress-related illness in that stress can precipitate depression, and depression can precipitate stress. To this end, people with depression often have measurably higher levels of stress hormones in their bloodstream, one of which is cortisol. Cortisol, at chronically elevated levels, is deleterious to the structure and function of hippocampal neurons, and is therefore a proposed mechanism for depression associated with hippocampal shrinkage. Interestingly, even in people who have not yet experienced significant stress, a smaller hippocampus increases the risk for acquiring a stress-related psychiatric disease.
Good news: The hippocampus is a relatively unique area in that it can grow new brain cells – this process is called âneurogenesisâ. Notably, numerous studies have shown that antidepressant medication increases the volume of the hippocampus by promoting neurogenesis. It is interesting to note that the growth of new hippocampal neurons takes up to six weeks to complete, and this is about the same time it takes most common antidepressants to take full effect. It is also interesting to note that, in mouse models of depression, drugs that specifically inhibit the process of hippocampal neurogenesis prevent the beneficial effects of antidepressant drugs.
- 2. Information is processed differently and frequently with a negative bias by those who are depressed. That is, depressed people are more likely to notice and respond to the negative things in life rather than the positive things. Some brain imaging research has shown that people with depression seem to have abnormal patterns of brain activation, with some areas overactive and other areas underactive, and this difference has been shown to account for the negative bias. Although this isn’t brain damage per se, it indicates depression is associated with changes in the neural networks which modulate how we think and feel.
Good news: Antidepressants have been shown to change brain activation patterns, and these changes are associated with a normalisation of mood and bias
- Depression is associated with changes to our genes; genes within the brain. Although we are born with a fixed genetic code, our life experience alters the way in which our genes are activated/expressed. Our life experience actually adds certain molecules to our genes (e.g. methylation), which makes it either easier or more difficult for that gene to become active – this field of research is called âepigeneticsâ. Experiments with mice have shown that those mice that were subjected to repeated stressful events showed significant genetic changes, and these changes made them more vulnerable to stress in the future. Recent work has shown that this too happens in humans. Perhaps these changes may have a role to play in the fact that a single episode of depression strongly increases the risk for future episodes.
Good news: Antidepressant medication has been shown to change the way depressed people’s genes are expressed. By reversing the detrimental epigenetic effects of depression, these medications actually return DNA expression to more typical patterns.
Some of these changes may indeed be long-lasting, although the evidence, in my opinion, is unclear. Regardless, it is important and reassuring to understand that treatment is associated with the normalisation of mood, behaviour and many of the brain abnormalities associated with depression.
Addendum: After writing this answer, I have been asked if non-pharmacological treatments such as cognitive behavioural therapy and meditation, etc., can be used to reverse the brain changes associated with depression. The scientific evidence demonstrates that non-pharmacological treatments can indeed induce significant and beneficial changes to both brain and mood. The reason the âgood newsâ within this answer focuses on pharmacological treatments is due to the extensiveness of the pharmacological literature and my familiarity with it.
Regardless of oneâs treatment preference, it is important to note that depression is a very complex illness with a lot of person-to-person variability about cause and treatment. Therefore, if someone is depressed, it is important to seek the advice of a medical doctor so that the appropriate treatment can be provided.
Conclusion
Depression can lead to significant changes in brain structure and function such as hippocampal shrinkage, disrupted neural pathways, and stress-driven biochemical changes but these effects are not necessarily permanent. The brain has an extraordinary ability to heal through neuroplasticity. Evidence-based treatments like antidepressants, Cognitive Behavioural Therapy (CBT), lifestyle improvements, and mindfulness practices can stimulate neurogenesis, rebalance neural activity, and restore healthier patterns of emotional processing. With timely support from a skilled therapist, counsellor, or psychiatrist, most individuals can regain emotional stability and rebuild brain health, highlighting the brainâs remarkable capacity for reversal and recovery.
For young individuals struggling with stress, anxiety, or emotional imbalances linked to social media pressure, comparison, or online harassment, the Psychowellness Center in Dwarka Sector-17 and Janakpuri, New Delhi (011-47039812 / 7827208707), offers targeted youth counselling and emotional wellness programs designed to strengthen resilience and support brain recovery. Their team, including some of the best psychologists near me, uses evidence-based approaches such as CBT, REBT, and Mindfulness-Based Therapy to help young people build clarity, confidence, and healthier thinking patterns. TalktoAngel also provides accessible virtual counselling and strength-based online therapy, supporting youth in cultivating balanced digital habits, emotional well-being, and long-term mental resilience.
Contribution: Dr. R.K. Suri, Clinical Psychologist, and Ms. Sheetal, Counselling Psychologist
References
Bremner, J. D., Narayan, M., Anderson, E. R., Staib, L. H., Miller, H.
L., & Charney, D. S. (2000). Hippocampal volume reduction in major
depression. American Journal of Psychiatry
McKinnon, M. C., Yucel, K., Nazarov, A., & MacQueen, G. M. (2009). A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. Journal of Psychiatry & Neuroscience, 34(1), 41.
Gilbertson, M. W., Shenton, M. E., Ciszewski, A., Kasai, K., Lasko, N. B., Orr, S. P., & Pitman, R. K. (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature Neuroscience, 5(11), 1242-1247.
Boldrini, M., Underwood, M. D., Hen, R., Rosoklija, G. B., Dwork, A. J., Mann, J. J., & Arango, V. (2009). Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology, 34(11), 2376-2389.
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