Schizophrenia as Stress-Induced Dopamine Supersensitivity


Researchers from the University of Toronto departments of Psychiatry and Pharmacology, publishing in Progress in Neuro-Psychopharmacology and Biological Psychiatry, propose that various forms of stress, including prenatal and perinatal events, drug abuse, social isolation, and gene mutations can produce a similar effect on the brain – dopamine supersensitivity – which can in turn result in the signs and symptoms of schizophrenia.

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Seeman, M., Seeman, P.; Is Schizophrenia a Dopamine Supersensitivity Psychotic Reaction? Progress in Neuro-Psychopharmacology and Biological Psychiatry. Online October 12, 2013.

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Kermit Cole
Kermit Cole, MFT, founding editor of Mad in America, works in Santa Fe, New Mexico as a couples and family therapist. Inspired by Open Dialogue, he works as part of a team and consults with couples and families that have members identified as patients. His work in residential treatment — largely with severely traumatized and/or "psychotic" clients — led to an appreciation of the power and beauty of systemic philosophy and practice, as the alternative to the prevailing focus on individual pathology. A former film-maker, he has undergraduate and master's degrees in psychology from Harvard University, as well as an MFT degree from the Council for Relationships in Philadelphia. He is a doctoral candidate with the Taos Institute and the Free University of Brussels. You can reach him at [email protected].


  1. i tend to agree with this – that the aetiology of schizophrenia is a combination of physiological (biologic), psychological/emotional & social/environmental factors. What i would debate is how primary the brain physiology is within it all? at least initially (first psychotic break) – that the primary factors are psychological/emotional/social/environmental – in the majority of cases. How that can be reliably tested i would think is impossible? Although the evidence does suggest that a comprehensive psychological/social approach to healing/recovery, especially at point of first episode – does have the best outcomes.

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  2. I think the excessive focus on dopamine is misguided, but the general idea that psychosis involves extreme reactions to stress and difficulties in living, with additional problems resulting from the reactions to one’s reactions, or counter-reactions, seems sound to me.

    Curious, and sad, that in the otherwise broad list of possible causes of “schizophrenia” these somewhat biologically oriented writers can still not bear to include childhood trauma and abuse in their list of possible causes. Maybe recognizing that would violate their “religious” beliefs?

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  3. I’ve just scanned this article, and will go over it more closely. But the authors focus on dopamine as though it is already established as the physical cause of “schizophrenia.” That would be warranted if dopamine were specifically shown to be the cause, as, as for instance the HIV virus is isolated as the cause of AIDS.

    But that is very far from the case with “schizophrenia.” It is not true that neuroleptics, affecting dopamine, are the “cure” for what is called “schizophrenia.” It is nice that the authors at least focus on environmental influences on the Dopamine system, instead of the usual insistence that genetics is the primary culprit. But the failure to acknowledge that anything but the never-proven dopamine hypothesis could be at work appears to be another example of psychiatry’s “street light” behavior:

    Midnight. Drunk on hands and knees under street lamp.
    –Cop: “What are you doing””
    –Drunk: “Looking for my glasses.”
    –Cop: “Where did you lose them.”
    –Drunk (pointing to the other side of the street): “Over there.”
    –Cop: “Then why are you looking here?”
    –Drunk: “The light’s better here.”

    This article conveniently accepts that dopamine is where they should be looking.

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    • Seeman is saying that all stressors that cause psychosis have this common path for how they work. All those types of life situation stressors cause D2 supersensitivity. This is not dopamine as cause, it’s life situation as cause, and dopamine as mechanism.

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      • One of the bullets at the beginning of the article is, “The schizophrenia reaction is one of dopamine overactivity.” There are somewhere over 100 neurotransmitters (I’ve heard the number estimated as high as 200). Yet psychiatry has focused on only maybe six. It’s interesting that various psychosocial and environmental stressors produce changes in the dopamine system, but it is an incredible over reach to say, “The schizophrenia reaction IS one of dopamine overactivity.”

        This reinforces the distorted brain science behind the medical model’s narrative that dopamine is at the heart of “schizophrenia” – based solely on the way neuroleptics suppress all kinds of brain activity, making people indifferent to their “psychotic” symptoms (and to much of their lives).

        Giving aid and comfort to psychiatry’s flawed model is the opposite of what we need: honest, non-blinkered research that doesn’t play to the prejudices of the huge economic powers that control and distorted the field.

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        • It’s not aid and comfort to the disease model. It’s a very subtle, politic, effective way to tear down the disease model.

          As far as focusing on dopamine – it’s because that mechanism is the ONLY mechanism common to every single one of the life aituations that cause a separation from reality (in animal models).

          Here is a metaphor that might explain the difference between mechanism and cause. There are many many life situations that cause bleeding (fights, self-harm, menstrual cycles, the brain clot I gotta watch out for, dog bite, etc.) However, each of the enzymes in the clotting cascade works by one specific mechanism.

          There are life situations that cause psychosis. Seeman is saying that the D2 supersensitivity is like the clotting cascade. It’s a protective mechanism to keep the brain from further harm. He is on our side, folks, but he has to speak the research disease model language to get published.

          This is again why it’s important to distinguish between saying “medical model” and disease model. Everything is biochemisty. But not all emotional distress is a disease.

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  4. If its true that dopamine supersensitivity is the cause of ‘schizophrenia’, why are we giving individuals a class of medication that causes patients to develop more dopamine receptor sites which has been argued, makes individuals more sensitive to psychosis? Even if one believed that dopamine dysregulation was the causeof psychotic disorders, until the dopamine mechanism is more fully understood, why would doctors be prescribing potentially harmful medication, which could permanently dismantle the dopamine system?

    Why won’t they instead, try and understand why more people recover from psychosis if they reject labels and medication early on? We should be looking at placebo’s, why do they work? How are placebo’s related to stress? What is the role of suggestion for people in extreme states? We should evaluate a condition called tardive psychosis and consider that this condition may often not represent the normal trajectory of a disease, but instead, be the outcome of long term neuroleptic use and evaluating why the window of opportunity to wean safely off neuroleptic medication and enjoy a full recovery appears to decline the longer one is forced to remain on medication. Doctors are harming people in great numbers.

    My step daughter just collapsed at work and was rushed to the ER with seizures caused by seratonin syndrome; She may now be permanently disabled from decades of poorly regulated, monitored cocktails of legally prescribed SSRI’s, Benzo’s for anxiety, and neuroleptics for sleep. How many people must be crippled or killed by these cocktails before doctors will stop conducting business as usual? Doctors with common sense, must not be afraid to speak up among their peers or resist their patients who get ridiculous ideas from watching TV. They must put their tenures and IRA’s at risk and do the right thing even if it means risk getting fired. Why are people’s lives less important than the tenure of a medical doctor?

    Too many people are dying. And for god’s sake, when are doctors going to revolt against these constant television commercials? Why are doctors so silent while people are dying?

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    • Madmom – I am sorry about your step daughter; I wish her and your whole family the best. Your post makes excellent points. Why, indeed would psychiatrists seek to remedy what they see as dopamine disregulation by lobbing bombs like Haldol and Zyprexa into the dopamine systems of people who are already struggling?

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    • Dr. Seeman and his wife gave me permission to post this:

      On Wed, Oct 16, 2013 at 12:25 PM, Philip Seeman wrote:

      Dear Corinna,

      Mary and I are concerned about your brain injury now causing you to stay in bed and spend much time on the phone rather than being up and around.

      Thank you for sending me the conversation going on in MadinAmerica, very interesting.

      Your explanations in the conversation, Corinna, are excellent and clear, so there is not much that I can add at this time.

      “madmom” does ask a very important question that I would like to answer, and you may wish to modify my reply in the language of survivors:

      This is a very important question. Namely, “If it’s true that dopamine supersensitivity is the cause of ‘schizophrenia’, why are we giving individuals a class of medication that causes patients to develop more dopamine receptor sites which has been argued, makes individuals more sensitive to psychosis?”

      In reply, and in short, the answer is that the antipsychotic medication is given to get over the acute signs and symptoms in a service-user who may be actively hallucinating or delusional, and may be a danger to herself/himself or others. [If they are not able to access programs like Soteria or Open Dialogue that could handle the initial separation from reality. My edit -CW] The “acute” time period may be weeks or months in order for the overactive dopamine system to settle down, after which the antipsychotic medication can be gradually reduced to as low as possible (unless there is further stress). Because antipsychotic medication can itself add somewhat to the dopamine supersensitivity of the service-user individual, this is why it’s best to gradually taper and reduce the medication, in order to prevent a rebound worsening of any psychotic features.

      Best wishes, Corinna,


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  5. “Why won’t they instead, try and understand why more people recover from psychosis if they reject labels and medication early on?”

    Was it really any different 400 years ago? Was it any different when any more humane & caring approach have been tried? From the Quakers & moral treatment to Soteria & Diabasis in the 60’s – to Open Dialogue today? It’s always the minority that speak out – & the masses/establishment/system largely ignores & denies them.

    If anything the trajectory is following more pathology, more drugs, & less care, less humane treatment.

    Yes, ‘we’ have Whitaker, we have others, but in the Grand Scheme of the reality of how things are & where things are headed, what is really changing? What is going to change?

    i’m sorry to sound negative, & i really hope that i’m wrong, but i don’t see that things are suddenly going to change to comprehensive & effective systems of understanding & care that are fit for purpose?

    i’ve been posting all ‘this’ material, about genuine healing & recovery for close to 10 years on-line – mainly on mental health forums – & the majority are not interested – they will & do attack, deny, ridicule, invalidate & trash all of it – over ‘labels & drugs’, especially when push comes to shove.

    i don’t see how it’s all going to change or how it’s all going to change? But as i said – i hope i’m wrong…….

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  6. I understand the cascade that you describe. But it isn’t possible to say that D2 super sensitivity is like the clotting cascade, because we simply don’t have much of an idea about most of what goes on in the brain, and therefore can’t rule out what else is happening with the brain’s other 100+ transmitters, much less what some of those transmitters and other chemicals do elsewhere in the body (see Candace Pert’s “Molecules of Emotion”).

    Also, I don’t completely agree that, “everything is biochemistry.” It’s true that without biochemistry, there wouldn’t be humans or “schizophrenia” – but I am drawn to the analogy of movies and film. There wouldn’t be movies without celluloid, projectors and various chemicals, but it’s not very productive to critique the plot, the dialogue, the acting, music and sets in terms of celluloid. Those things involve relationships of things or concepts to each other that are more directly involved with the success or failure of a movie than are the components of the celluloid.

    I get your distinction between “medical model” and “disease model,” but cultural, political and professional conditions make it impossible for the public and doctors to keep the two models distinct. The pull of doctors to turn problematic human phenomena into “diseases” seems irresistible, and until there is far more consensus about the non-disease model, doctors and the rest of us will constantly find our thinking dragged back to “disease model” when “medical model” is used. I think we need a radical re-working of how we talk about the whole area – ditching “disorder,” “diagnosis,” “mental illness,” and at least putting quotation marks around “schizophrenia,” “depression,” etc. Kind of like the way Open Dialogue works without using diagnostic labels.

    I’m glad to hear that Seeman is not an apologist for bio-psychiatry. And I understand that he has to put things in terms that will pass peer review. But I’m not sure he had to be absolute in saying “schizophrenia” is caused by the dopamine system. He could have been closer to the truth without running afoul of the establishment if he had said D2 is “implicated” in the process – scientific writing is full of that kind of language. But maybe the politics wouldn’t even allow that.

    Finally, I want to thank you for your many contributions to this site. What you say is interesting and helpful.

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    • Well, it actually is pretty absolute. D2 was connected to every single animal model of psychosis. They did a lot of work to rule out a whole lot of other neurotransmitters. The article was a huge splash in the research world, 212 citations in PNAS, one of the most prestigious journals.

      As far as how this is useful to advocates who want to show emotional distress is temporary? I tried to do a blog about this once but think I need to do a better job about it.

      There’s always going to be mechanistic basic sciency type researchers. The trick is not to give them 98% of all mental health research dollars, something Seeman mentions in several articles, explaining that the search for a gene is a bust. I guess that’s where advocates come in, redirecting the billions of research money being wasted on stuff that doesn’t help us.

      And I’ve got to bow out now because I gave myself another re-concussion stepping down into the driveway to go to the dentist two hours ago. So this is my last pitch of something electronic as I’m sliding back down into that pain and dark and confusion land. I’ll probably be AWOL the next couple of days, sorry.

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    • Thomas Insel, Director of NIMH, has stated that their brain research (disease or otherwise) will no longer employ the DSM categories — “schizophrenia” is scientifically null and void. Why wouldn’t Dr. Seeman, or other psychiatrists, know this and act on it…you know, be up to date with the leading thought in their professional field?

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    • Another fantastic comparison of celluloid vs. content of a movie. I’m going to have to have to remember these comparisons to trot out later.

      And about the “mental illness” and “disease” language, I quite agree – as long as we are using it, we’re going to be pulled into that mode of thinking where it’s easy to get stuck.

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  7. Corinna – I’m sorry to hear you’ve hit a bad spot, and hope you’re though it asap.

    I remain very skeptical that the article’s characterization of the D2 system’s role in psychosis is as 1-to-1 as it presents. Animal models are important, but don’t say it all about humans; Seeman may have ruled out some transmitters, but I doubt he controlled for all 100+ neurotransmitters; the fact that D2 is common to all psychotic reactions doesn’t mean other systems aren’t critical to psychotic reactions; there have to be many blanks to fill in re how particular traumatic experiences translate to D2 sensitivity; ditto blanks re the internal process by which we recover from psychosis; what is the relationship between D2 and the meaning that is inherent in “psychotic” experiences?

    I think our minds/brains have inherent drives to recover from trauma and “mental illness,” and in some sense our “mental illness symptoms” are purposive attempts by our minds to work through whatever has hurt us. I don’t think anyone has approached understanding this process anatomically.

    I’m putting too great a burden on the article – it shouldn’t be dismissed because it doesn’t answer every question. But I’m still stuck on the unqualified bulleted claim. You obviously know a lot about brain science and the body of research – maybe it would help many of us if you wrote something to translate the technical research into lay terms?

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  8. I don’t want to give Corinna and Dr. Seeman a hard time. His article has positive implications for the view that trauma of various kinds begins the cascade that produces “psychosis.” Dr. Seeman’s post is a lot more to my liking than you would get from most of psychiatry. And Corinna correctly points out that progressive psychiatrists have to be careful of what they say – straying too far from orthodoxy all at once can damage credibility within the profession.

    But Dr. Seeman’s scenario for a first episode “schizophrenia” sufferer is pretty medical/disease model: it is Corinna who edits into his writing the provision about non-or-limited drug programs like Open Dialogue or Soteria, and there is no acknowledgement of the WHO studies showing better results with little or no drug treatment. Dr. Seeman advocates initial drugging and gradual tapering to a low dose (apparently not anticipating complete withdrawal); and he qualifies that taper with the exception of periods of stress. I appreciate the desire to taper to low dose, but it is worth noting the ways Dr. Seeman’s model overlaps with mainstream psychiatry.

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