Researchers Fail to Replicate Evidence for “Biotypes” of Depression

A new study casts doubt on whether such biotypes for depression exist.


Two years ago, a study used fMRI technology to come to a startling conclusion—there might be four biological subtypes of depression, called depression biotypes. This would herald a new age of depression research—one where mental health concerns could finally be linked to neurobiology. Now, a new study has attempted to replicate those findings, but their results cast doubt on whether such “biotypes” exist. According to the researchers, no statistically significant differences were found.

“Extending the original methods with additional more rigorous statistical procedures,” the researchers write, “we did not find stable or statistically significant biotypes of depression and anxiety in an independent sample from a different clinical population.”

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The research was led by Richard Dinga at the Department of Psychiatry, University Medical Center, Amsterdam. The researchers attempted to adhere to the exact methodology of the previous study and even contacted the former research team to discuss how to follow their methods precisely.

The 187 participants in this study had a diagnosis of either major depressive disorder or an anxiety disorder or both. They had no other psychiatric diagnosis and were not currently taking any antidepressant medications. Resting-state fMRI brain scans were conducted and then correlated.

Dinga and the other researchers write that the specific type of correlations done by the previous research team could have led to false positives—that is, those statistics were overly likely to lead to positive results. The researchers for the current study used a slightly more conservative method to compensate for this.

The researchers found that although they replicated the correlations of the original paper, none of the findings were statistically significant. These findings were just as likely to be due to chance. Dinga and the others note that the original study did not bother to test the statistical significance of their correlations: “It remains to be confirmed whether the canonical variates identified in their original study were significant.”

Also, Dinga and the others tested whether the clustering of biological data might be due to chance. They found that it very well might have been. According to the researchers, clustering analyses “always yield clusters, regardless of the structure of the data, even if there are no clusters at all.”

The researchers write, though, that the previous study did not analyze this possibility: “In the original study, this was not tested. Therefore, we cannot say if the data in the original study really formed clusters, instead of just random fluctuation of the data.”

Dinga and the others note many problems with clustering based on biology—even if the clusters do exist. For instance, supposed biological subtypes might not be based on mental health symptoms, but instead, be based on other physical traits. “The variability of biological data is more often than not unrelated to any specific psychiatric disorder or symptom class.” It might instead be based on random variations such as “groups of people with similar brain size or body type or common ancestry in the case of genetics.”

Interestingly, in the original study, the researchers admit that there was no way to clinically differentiate the subtypes they found with fMRI data.

“Due to the clinical heterogeneity of many psychiatric disorders and the quest for personalized medicine, there is a tendency towards subtyping and expanding psychiatric nosology,” Dinga and the other researchers write.

“However, the presumption of distinct and homogeneous subtypes might not be clinically useful and might not represent the underlying biology. Many clustering approaches will always produce some clusters and would so even for uniformly distributed data. It is, therefore, crucial to distinguish real biologically or clinically meaningful subtypes from random fluctuation of the data.”



Dinga, R., Schmaal, L., Penninx, B. W. J. H., van Tol, M. J., Veltman, D. J., van Velzen, L. . . . & Marquand, A. F. (2019). Evaluating the evidence for biotypes of depression: Methodological replication and extension of Drysdale et al. (2017). NeuroImage: Clinical. (Link)


  1. “The end of clinical treatment is cure. The process comes to a fruit and all medical measures are stages towards this fulfillment. Consciousness, however, as far as we can read the evidence, comes to no definite goal, no final fruition, but is is a continuous in-going process.
    An analysts who has a notion of cure as a goal of his work is thinking medically. He has not grasped the nature of the complex, the basis of analythical process. There are no antidotes for complexes. The cannot be cured away because complexes are not causes, though they be the determinants of psychic life. A medical model tends to conceive them like a wounds or traumata. or as malignants growths and foreign bodies to be removed in the medical manner.
    But if complexes are energetic centers, the cannot be “cured” without damaging the vitality of the patient.

    Health requires death.

    If lay means unprofessional, then lay means open.



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  2. Wow! Thank you for introducing me to James Hillman.


    That explains a lot about how brutal and dangerous psychiatry is. It also explains why no one is willing to talk to me in any meaningful way.

    That is certainly the way the condemned man is made to feel–as a disease.

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    • “Pathological bias”, chapter IX from Suicide and the soul. The greatest book about psyche ever. Yes, Hillman was great. “Re -Visioning psychology” should be compulsory lecture for people today. They lost their way.

      Manufacture of madness written by Szasz is also a monolith. Psyche is like monolith among angry monkeys.

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      • I think you are being ironic; because I don’t think most people know him.

        You are right. People don’t talk about the truth tellers like Szasz or Hillman at all.

        THE PATIENT IS THE DISEASE is so telliing; because, obviously, it is true for so many unfortunate people.

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        • Yes I am ironic. Wisdom means nothing today. Mental health is not equall to wisdom, psychiatry has nothing in common with wisdom. Because people are not interested in wisdom. They want power and money. That is why empaths or psychological men are losing with them. They are losing because they means more than matter. Generally speaking, this is main reason why psychological man is terrorized. He means more than people who believe in easy things. Because when you are easy or simple it means also you can survive, because you are enough blind to do it. Survival is so plain that only simple people can do it. Psychological man can’t. because he collides with the reality of death. And then he realizes that apollonians and normal are antipsychological idiots and they want to lock you up, because you are destroying their utopia.

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          • That, unfortunately, is what seems to be happening. I definitely do feel like people view me as a threat to their utopia. They won’t talk to me about TRUTH; and they won’t talk about real conspiracies that they themselves invented.

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  3. Depression? There are perhaps dozens of biotypes among the nation’s depressed and different treatments for all of them. Unfortunately many of them don’t require pharmacological treatments, so “researchers” are wasting their time seeking the Magic Antidepressant that will prove to be the Universal Cure for these states of misery.

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  4. Hope is an evil, because it is used to deny WHAT IS REALITY RIGHT NOW.

    The reality is that there are psychiatric scapegoats.

    The reality is that there never will be a finding of the biological cause of “mental illness”.

    Hillman was very smart.

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  5. Hillman was critical about American obsession with the future. He said we should be more focussed with future generations than the future in general.

    And mostly, he said that we should be focussed more on the present. What is happening right now? People are getting shafted by the “justice system” with the help of psychiatry.

    What else is happening? We are ignoring nature. We are not paying attention to the fact that we are polluting the planet and we are using way too many fossil fuels. We are drugging ourselves so that we
    won’t realize that we are destroying the world for future generations.

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  6. Hillman even criticizes the idea of sustainability; because it too much tied to economics.
    If we view everything from an economic point of view, then
    we have lost the ability to even recognize the beauty of the world as it is.

    We need to recognize that the world is profoundly beautiful right now; and that we have to keep it that way–or at least not damage it any more.

    I think Hillman would cheer on the climate change activists.

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  7. Families and communities hire shrinks to scapegoat their family members. And the shrinks hand out phony labels like “depression”.

    I remember the look of disdain on my young shrink. It was unnerving; and it eventually led to distrust and my finally leaving after too many weeks of brain-washing. I wish I realized sooner that the shrink actually hated me and was punishing me as a scapegoat. It has taken decades for that to sink in.

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    James Hillman and Michael Ventura, book title 1992

    I wish I got that book in 1992.

    Another good book title might be:


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  9. New black box warning: Many Psych doctors view their PATIENTS AS THE DISEASE; and so the drugs are punishment. Therefore, do not take these addictive, mind numbing drugs which will cause you to lose interest in life and have many more terrible side effects

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