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This question originally appeared on Quora. Answer by Lukas Wardrop.

Depression is associated with widespread changes in brain structure and function. Here are a few examples:

1. A strong body of research shows that people with depression often have a smaller hippocampus [1]. The hippocampus is well known to be important in memory as it processes memories for long term storage. The hippocampus, however, also connects to the many areas of the brain which regulate how we feel and respond to stress. For example, the hippocampus connects to the amygdala which controls our experience of fear. 

Depression is regarded as a stress related illness and people with depression often gave higher levels of circulating stress hormones such as cortisol. Cortisol is toxic to the cells within the hippocampus and excess cortisol is a hypothesised mechanism for why people with depression have a smaller hippocampus [2]. Interestingly, even in people who have not yet experienced significant stress, a smaller hippocampus increases the risk for acquiring a stress related psychiatric disease [3].

  • Good news: The hippocampus is a relatively unique area in the brain which can grow new neurons.  Antidepressant medication has been shown to increase the volume of the hippocampus by promoting neurogenesis (i.e. the growth of new brain cells) [4]. It is interesting to note that the growth of new hippocampul neurons takes up to six weeks to complete; and this about the same time it takes for most monoaminergic antidepressants (e.g. SSRI) to take full effect. 

2. People with depression process information differently, often with a negative bias. That is, depressed persons 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 over-active and other areas under-active; and this difference has been shown to account for the negative bias [5]. Although this isn't brain damage it is a brain abnormality and worthy of highlight.

  • Good news: Antidepressants have been shown to change brain activation patterns restoring mood and bias to normal levels [6].

3. 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. Our life experience actually adds certain molecules to our genes which makes it either easier or more difficult for that gene to become active (i.e. epigenetics).  Experiments with mice have shown that those mice who 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  [7]. 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 [8].

  • Good news: Antidepressant medication has been shown to change the way depressed peoples genes are expressed. These drugs actually counteract the negative epigenetic effects of depression restoring genetic expression to more normal patterns [9].

Clearly depression is associated with changes in the brain. Whether these changes are permanent or not is a difficult question to answer. To answer this we would have to examine the brains of people before they became depressed, after they became depressed and after they became well. This, as far as I am aware, has not been done. However what we can say with a high degree of certainty is that people with depression have different brains; both in structure and in function. The good news is that, regardless of this fact, treatment is associated with the normalization of mood, behavior and many of the brain abnormalities associated with depression.

  1. 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
  2. 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: JPN34(1), 41.
  3. 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 neuroscience5(11), 1242-1247.
  4. 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. Neuropsychopharmacology34(11), 2376-2389.
  5. Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., ... & Fox, P. T. (2014). Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. American Journal of Psychiatry.
  6. Delaveau,  P., Jabourian, M., Lemogne, C., Guionnet, S., Bergouignan, L., &  Fossati, P. (2011). Brain effects of antidepressants in major  depression: a meta-analysis of emotional processing studies. Journal of affective disorders130(1), 66-74.
  7. Nestler, E. J. (2014). Epigenetic mechanisms of depression. JAMA psychiatry71(4), 454-456.
  8. Bulloch,  A., Williams,  J., Lavorato, D., & Patten, S. (2014). Recurrence of  major  depressive episodes is strongly dependent on the number of  previous  episodes. Depression and anxiety31(1), 72-76.
  9. Vialou, V., Feng, J., Robison, A. J., & Nestler, E. J. (2013). Epigenetic Mechanisms of Depression and Antidepressants Action. Annual review of pharmacology and toxicology53, 59.

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