Researcher: Antidepressants Protect Against Brain Shrinkage, Despite Our Findings

Rob Wipond
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People who have long-term, recurrent depression eventually develop smaller hippocampi in their brains, according to research published in Molecular Psychiatry. And University of Sydney psychiatrist Ian Hickie, a co-author of the study, told The Guardian that there exists “a good bit of evidence” that antidepressants provide a neuroprotective effect against such hippocampal shrinkage. Hickie apparently did not clarify to The Guardian, however, that the particular study he’d just co-authored had actually found the exact opposite — that antidepressants were associated with greater hippocampal shrinkage.

“Using magnetic resonance imaged (MRI) brain scans, and clinical data from 1,728 people with major depression and 7,199 healthy individuals, the study combined 15 datasets from Europe, the USA and Australia,” stated a press release about the study from a large, international team of researchers. Most areas of the brain were not different between the groups, except for generally slightly smaller hippocampi in people who’d had a major depressive disorder (MDD) diagnosis for years. “(P)eople who had a first episode of major depression (34 per cent of study subjects with major depression) did not have a smaller hippocampus than healthy individuals, indicating that the changes are due to the adverse effects of depressive illness on the brain” over long time periods, stated the press release.

“This large study confirms the need to treat first episodes of depression effectively, particularly in teenagers and young adults, to prevent the brain changes that accompany recurrent depression,” co-author Hickie said in the press release.

An article about the study in The Conversation then stated that the study had “proved once and for all that recurrent depression shrinks the hippocampus” and “conclusively” causes “brain damage” that leads “to a loss of emotional and behavioural function.”

Critical commenters prompted the Conversation article author to follow up again with Hickie and then change the article text to indicate that this “brain damage” was readily “reversible.” Meanwhile, in The Guardian article, Hickie clarified that the hippocampus wasn’t so much actually being damaged or losing cells as a result of depression, but temporarily losing “connections between cells”, in the same way that can happen to anyone who might “sit in a room doing nothing” a lot.

The Guardian also reported that, “There was some evidence that the hippocampus was larger in those patients taking antidepressants, Hickie said, indicating these medications could have a protective effect.” The Guardian then quoted Hickey to that effect: “There is a lot of nonsense said about antidepressants that constantly perpetuates the evils of them, but there is a good bit of evidence that they have a protective effect.” However, these statements appeared to exist in direct opposition to the evidence provided in the actual study co-authored by Hickie.

The study in Molecular Psychiatry did not provide detailed data on what percentages of participants were taking psychiatric medications or for how long they may have taken them previously; however, some analysis was included about medication users. “With respect to the moderating effects of medication use, no significant effect of the percentage of patients taking antidepressants was observed, only a trend-wise lower hippocampal volume in MDD patients in samples with a higher percentage of patients taking antidepressants,” the study stated.

The authors cited other studies that have suggested that antidepressants could hypothetically have a neuroprotective effect “by enhancing synaptic plasticity, neurotrophic processes and putatively neurogenesis”. However, the authors then noted that this notion that antidepressants could provide such neuroprotective effects “appears to contradict our current observation” in which they found a “trend effect” of “lower hippocampal volume in antidepressant medication users compared to controls”.

They stated that these differences disappeared when they controlled for depression recurrence, and then concluded that, “(I)ntervention studies with pre- and post-antidepressant treatment comparisons are needed to clarify the impact of antidepressant use on hippocampal volume.”

*

Schmaal, L, D J Veltman, T G M van Erp, P G Samann, T Frodl, N Jahanshad, E Loehrer, et al. “Subcortical Brain Alterations in Major Depressive Disorder: Findings from the ENIGMA Major Depressive Disorder Working Group.” Mol Psychiatry, June 30, 2015. http://dx.doi.org/10.1038/mp.2015.69. (Full text)

Chronic depression shrinks brain’s memories and emotions (The Guardian, June 30, 2015)

Patients with recurrent depression have smaller hippocampi (University of Sydney press release on MedicalXpress, June 29, 2015)

Depression damages parts of the brain, research concludes (The Conversation, June 30, 2015)

22 COMMENTS

  1. The media does not to be a target. Studies have indicated that a very high percentage of people don’t read past the headlines. (It also appears to be true that many doctors only read the abstracts and conclusions in scientific papers). The media is in the entertainment and money-making business, and often doesn’t tell the complete story in nay article. Truth is often found in the details, as is evident here.

    • I love the rhetoric they used – the same as for “schizophrenia” and “anti-psychotics”: disease causes brain shrinkage, drugs prevent it even though the data shows otherwise.

      Btw, hippocampus constantly kills and adds cells during life (it’s the only known place with robust neurogenesis in the adult human). So even if depression really leads to cell loss, which well may be (due to social deprivation for instance that often goes with feeling down) it can be easily reversed by taking the person out of this state.

  2. Articles like that Guardian one are going to fool more innocent and vulnerable people into to trying these brain damaging drugs thinking they are taking something good for their brain. It’s such an evil practice.

    Here’s a Science Daily article from a few days ago about how brain abnormalities were found in people with schizophrenia.
    http://www.sciencedaily.com/releases/2015/07/150707102051.htm

    Ah yes, at a glance it looks like yet another proof story that people with schizophrenia have brain abnormalities. Yes we all know most schizophrenia patients do have brain abnormalities, but rarely do we see studies actually blame the true cause of these abnormalities. The Science Daily article makes no mention of the study controlling for anti-psychotic drugs, but the study itself very briefly mentions them and pretty much says the anti-psychotic drugs could be the cause for the brain abnormalities.

    http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201563a.html

    • Yes exactly Jobos. As you can see from their qualifications at the end, it seems there’s all kinds of things that can influence volume of brain structures. I would add that these things are not static and interact with each other in ways we just don’t know. It doesn’t seem to stop them from giving the impression to the general public that they “know” something though.

      “Fourth, apart from disease-related biological factors, numerous confounding environmental factors can influence the volume of brain structures, including fetal hypoxia,50 nutritional and hydration status,51, 52, 53 exercise,54 medications,11 smoking,55 cannabis use,41 social isolation56 and the stress associated with severe mental illness.57”

      • One more thing I can’t let go – did you see all the authors? None declared any conflicts of interest. Really? Are we really to believe that not one of the 30+ authors had any relationships to any organizations that might benefit directly from the conclusions of the study?

        Bob’s focus on Cognitive Dissonance is spot on.

  3. The headline on this article is problematic. I cannot share it on Facebook because many people just read the headline and don’t read the full article. For them, the take away would be “Researcher: Antidepressants Protect Against Brain Shrinkage.” They would not get the irony of “despite our findings” because they wouldn’t read the article.

    Since I don’t want to spread this disinformation further I can’t share the article. Please ask your headline writer to consider this in the future!

    Otherwise, thanks for the great work. I really appreciate the news stories you find and summarize for us.

  4. Statistically the difference in hippocampal volumes is almost meaningless. There is over 92% overlap between the depressed group and the control group. If a person from the depressed group was picked at random there is only 56 % chance that he or she will have a smaller hippocampus than a person picked at random from the control group. If the groups were completely equal, the probability would be 50%. So there are 44% of so called “normals” who have smaller volumes than the socalled “depressed”.

    There is a danger with big samples and looking actively for differences. It is like throwing a dart on a wall and then drawing a bullseye around it.
    Anyway, how do we know that a smaller hippocampus is necessarily negative. Are shorter legs nessesaily inferior to longer legs? There is nessesary pruning going on in the brain all the time. Extra cell growth in a region is often looked upon as dangerous and not in any way protective e.g in the prostata.

  5. It is always interesting to look at the tables in these articles. The full text is free as usual with industry friendly results. The cohen’s d which would be zero if there were no difference is extremely close to 0.0 in the confidence interval. This means that just a few cases could render the result statistically non significant. Since this is a meta analysis, the researchers may exclude certain results if the feel the study was not good enough. So these are really weak data indeed.

  6. Here is a very interesting sentence: “With respect to the moderating effects of medication use, no significant effect of the percentage of patients taking antidepressants was observed, only a trend-wise lower hippocampal volume in MDD patients in samples with a higher percentage of patients taking antidepressants.” this means that the patients who we’re taking antidepressants actually had most shrinkage. So much for starting treatment with medication early…

  7. After reading “Influence”, I know to google Hickie + conflict of interest in these situations

    http://www.abc.net.au/news/2012-02-13/psychiatrist-accused-of-conflict-of-interest/3826698

    There always seems to me to be a giant implicit hole in these arguments. Even if the reported results are correct that does not imply that you should use antidepressant drugs. To use those drugs, you must show that they are *superior* to exercise, diet, meditation, therapy, EMDR,…whatever safe treatments exist, *and* that the benefit outweighs the harm.

  8. Sometimes you have to wonder if clowns from the Onion are behind these reports. What a waste of time and money…

    And here I am wasting time commenting on it 🙂 But I want to make my usual attack against the fake “science” behind this study.

    Major Depression is not a valid diagnosis. Just look at the reliability rating for MDD in the DSM (0.32 in DSM V, close to the pure chance level of 0.20). It’s almost random chance whether someone gets diagnosed with “it” or not. Many of the “controls” in this study could have “had major depression.”

    The only reason BS like this study gets published is drug company money. If not for the need to sell zombifying pills, people would wake up to the fact that severe emotional distress (“major depression”) cannot be reduced to an illness nor studied via this distorted reductionistic methodology. We would start asking people what happened to them and what is causing their distress, instead of believing the lie that there’s some isolated in-brain illness called major depression that is magically shrinking people’s brains (of course, their brains are changing due to distress in their real lives, it just has nothing to do with an illness called “major depression”).

    This article should really be in a joke section of the news, because this is not real research.

    • “We would start asking people what happened to them and what is causing their distress.”

      I totally agree, but it is not always or solely emotional distress that causes/triggers/explains mental problems. The low-fat diet craze and obsession with low cholesterol levels has led to increased levels of depression. The wrecking of beneficial gut flora (thanks to the overuse of antibiotics, poor diets and heightened sanitary practices) has produced more anxiety and other ills. Ditto for poor nutrition; progressively decreased nutrient content of our foods; pesticides and other environmental hazards and the irresponsible growth of modern technology. I am not discounting or minimizing factors such as trauma, social isolation or lack of social integration; far from it. But when we ask: “what happened to you to overwhelm you,” we should not take anything off the table, including real physical causes that diminish one’s resilience. Interestingly, mainstream allopathic (pill-pushing) medicine has done more than its share to push people over the line. Mainstream psychiatry is just the worst of an increasingly bad lot.

      • I generally agree with this. But I didn’t mean that only emotional distress explains mental problems. Saying that (only) emotional distress causes mental problems is kind of nonsensical actually. Emotional distress is in some sense mental problems so it doesn’t cause itself. And emotional distress is caused by innumerable possible factors / stresses. These can include relationship stress, problems with work, financial insecurity, poor diet as you said, lack of exercise, etc.

  9. Ian Hickie is pretty much the go-to guy to talk about “mental health” on the TV here in Australia.

    Not surprised he usually appears on the ABC and i’m not surprised this story is on the Guardian.

    It’s usually just all bullshit. It’s getting more obvious every day that even the state run broadcaster here is always pushing an agenda that the people probably don’t want.

  10. We have examined this study in detail, and published a commentary in the same Journal (Molecular Psychiatry) that comes to a very different conclusion than the authors.

    In sum, we simulated hippocampal volume data based on the sample and effect sizes reported by the authors. We find that the hippocampal volume differences are so small that knowing a person’s hippocampus size does not predict group membership much above chance (the discrimination accuracy is ~52.6%). While the volume is smaller in depressed patients than healthy participants, it certainly does not “robustly discriminate”. We also discuss why hippocampal volume may not be related to depression at all (for reasons such as lack of disease specificity and confounds), and even if it would be related, why it may not be reasonable to consider it a biomarker.

    You can find the commentary here:
    http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2015199a.html

    If you do not have access to the Journal, we have also uploaded a openly accessible version of the manuscript here:
    https://figshare.com/articles/Fried_amp_Kievit/1549680/5

    Eiko Fried