Antibodies Against NMDA Receptors in Schizophrenia

A very exciting and potentially groundbreaking observation in patients with schizophrenia was just published by Johann Steiner and colleagues from the Department of Psychiatry (Chairman: Bernhard Bogerts) of the University of Magdeburg in JAMA Psychiatry (formerly Archives of General Psychiatry – online first on January 23, 2013). They found in 9.9% (n = 15) in a cohort of 121 patients with a schizophrenic disorder antibodies against NMDA (N-methyl-D-aspartate) receptors (Steiner et al., 2013). Such antibodies were found only in 0.4% of the 230 control subjects studied, in none of 38 patients with borderline personality disorder and 2.8% of 70 patients with a depressive disorder. This difference was highly statistically significant even if two patients from the group of those with a diagnosis of schizophrenia were excluded, who later received a diagnosis of anti-NMDA receptor encephalitis. The finding is so exciting because an insufficient function of glutamatergic neurotransmission via the NMDA receptor is believed to be a key pathophysiological component in schizophrenia (see also my lecture on Jan 25th 2013) and because the so-called anti-NMDA receptor encephalitis usually begins with mostly psychiatric symptoms, particularly psychosis.

The anti-NMDA receptor encephalitis was first described in 2007 by the group led by neurologist Josep Dalmau from the University of Pennsylvania in Philadelphia (Dalmau et al., 2007). It begins with nonspecific, flu-like symptoms, which are followed by a variety of psychiatric disorders (anxiety, delirium, psychotic states). Therefore, many of the patients are initially admitted to psychiatric treatment. Later, seizures, movement disorders and autonomic dysfunction will emerge, often leading to coma. Young women are mostly affected, in whom quite often a teratoma (with nerve cells) can be found. The disease then represents a paraneoplastic syndrome, and antibodies against NMDA receptors can be found regularly. Treatment consists of immunosuppressive therapy.

The  findings now published represent an important milestone in the subclassification of schizophrenic disorders, because it may have been possible for the first time to subdivide a subset of patients from the large, heterogeneous group of schizophrenias, and assign them a differentiated pathophysiology, possibly leading to a differential treatment.

If you want to read the original article by Steiner et al., please send me a message using the contact form, I will then send you the PDF.

This post is also available in: German

7 thoughts on “Antibodies Against NMDA Receptors in Schizophrenia

  1. *little correction. I added Pregnonenolone not only to counter-act side effects, because study’s show promising results that it improves negatives and cognitive symptoms in schizophrenics.

  2. Hi,

    I am a 29 year old male diagnosed with schizophrenia, anti-psychotic treatment has no effect on controlling my symptoms, I use benzodiazepines as an anti-psychotic treatment, which work great! Anyway, ever since taking Sarcosine (NMDA inhibitor) I experienced quite some improvement in schizophrenia symptoms (little on positive but quite some improvements on negative and cognitive) but most interesting psychiatric symptoms (which I don’t even know how to call) that are not (directly) linked to schizophrenia improved to the point they disappear as long as I take Sarcosine. (symptoms that make my life a hell)

    So my question would be, might these new findings mean anything for me? Can I go to the doctor and ask him to test me on anti-NMDA antibodies?

    Thank you in advance!

    • First, I like to apologize for not responding earlier. I was quite busy recently and traveling a lot. There are some very promising studies on sarcosine (an inhibitor of the glycine transporter type 1, it facilitates glutamate function via the NMDA receptor, it is not an NMDA inhibitor) in schizophrenia. Several companies are currently developing such drugs. The fact that it works for you does not necessarily mean that you have antibodies against NMDA receptors. Even if you had, there were no treatment applications that are really tested.
      How do you take the sarcosine and in which dose? Where do you get it from?

      Sincerely,

      Gerhard Gründer

      • No problem!

        Yes I know, I’m really excited about Bitopertin, but they keep delaying it (first it was 2013 then 14 then 15 now maybe 2016 when it enters the market). I wanted to enter a trial for Bitopertin but I couldn’t because I was using Sarcosine, to enter the trial I’d had to stop with Sarcosine, and I did, resulting in a very acute psychotic break. After such a high risk I took to be eligible they told me I couldn’t enter the trial because I had too much positive symptoms, that’s just harsh! Even though my doc, whom is the project leader of this Bitopertin trial already knew how much Sarcosine has improved my positive, negatives and cognitive symptoms! When asking why it gets delayed each time he told me because it’s really hard to get into the trial, people have to have very bad negatives symptoms to be eligible.

        Anyway, I take 2-3 grams Sarcosine a day (don’t really measure it, I have a spoon that can only carry 3 grams). My first Sarcosine was from China via Alibaba.com, 1KG for very cheap. Now I get it from an US online supplement store called smartpowders. I also add D-Aspertic-Acid 3 grams (if I’m not mistaken DAA is also activating the NMDA receptors) together with Sarcosine, it’s feels like it gives a boost to Sarcosine, it slightly improves things like showing more emotions, being more social and being able to concentrate and focus better on this combination. I Also added Pregnenolone 50mg (an attempt to counter-act the cognitive side-effects of benzo’s) since a week, so far it seems to help but it’s too soon to come to a conclusion.

        Too bad these findings doesn’t mean anything for me, got excited when reading this article.

        I thank you for reading and taking time to reply to my questions.

        Regards

  3. Could you please send me this article as my brother has schizophrenia and I am a student nurse in Ireland, thank you very interesting

  4. Can you be so kind and send me the article mentioned in your post.

    Congrats by the way!

    Best regards,

    Lukas Pezawas

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