Meta-Analysis Ties Gray Matter Loss to Antipsychotic Dose


Antipsychotics are currently the predominant treatment for individuals diagnosed with schizophrenia, but there is an accumulating body of research that links the use of these drugs to structural abnormalities in the brain. A recent meta-analysis suggests that gray matter loss in the brain may depend on the dose and class of the antipsychotic.

New research, published in this month’s issue of Biological Psychiatry, reinforces the link between antipsychotic drug use in patients with schizophrenia and progressive structural brain abnormalities.  Antipsychotic use has been associated, specifically, with a decrease in gray matter in the brain.  Gray matter is mainly located on the brain’s surface and functions, generally, to aid in the processing of information.  The loss of gray matter could represent either cell shrinkage, cell loss, or both.

Past research has found that the dose of antipsychotic is associated with decreased volume of gray matter but has not compared the impact of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs).  The latest study, led by Antonio Vita, set out to do just that.

Vita and his colleagues completed a meta-analysis of longitudinal MRI studies published between 2002 and 2014.  Altogether, their study included the antipsychotic dose and class information as well as gray matter measurements for 1,155 patients and 911 healthy control subjects.   After crunching all of the data, they found that the greater the exposure to antipsychotics, the greater the reduction in gray matter in the brain.

Patients taking FGAs or a combined treatment of both FGAs and SGAs had a significant decrease in brain volume.  For these patients, greater brain volume loss was associated with a higher mean daily dose of antipsychotics.

In patients treated with just SGAs, a significant decrease in volume was not found. Previous studies have also found that SGAs have less of an effect on brain volume, yet even a smaller effect may have significant implications.

The connection between antipsychotic drugs and decreased gray matter may be strengthened by their finding that illness severity, age, and substance abuse were not associated with the reductions in brain volume.

The researchers conclude:

“Although this is a clinically meaningful result, many issues remain to be clarified: for instance, we still do not know whether the effects on the brain of antipsychotics vary as a function of age and stage of illness, or whether they may occur only when a certain threshold of exposure (daily dose or cumulative dose) is reached”



Vita, A., De Peri, L., Deste, G., Barlati, S., & Sacchetti, E. (2015). The effect of antipsychotic treatment on cortical gray matter changes in schizophrenia: does the class matter? A meta-analysis and meta-regression of longitudinal magnetic resonance imaging studies. Biological psychiatry. (Abstract)

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Justin Karter
MIA Research News Editor: Justin M. Karter is the lead research news editor for Mad in America. He completed his doctorate in Counseling Psychology at the University of Massachusetts Boston. He also holds graduate degrees in both Journalism and Community Psychology from Point Park University. He brings a particular interest in examining and decoding cultural narratives of mental health and reimagining the institutions built on these assumptions.


  1. Grey matter = cell bodies. In other words: neurons die. Which in almost all areas of the human brain is practically irreversible (except for hippocampus). Sadly it’s also not unexpected – we know that survival of neurons is tightly linked to their activity. Neurons that don’t receive meaningful inputs commit suicide. When you deprive whole populations of neurons of dopaminergic input for prolonged periods of time it’s not surprising that some of them will die. Btw, it’s “funny what you find when you go to some basic research studies:
    “Adult mice were separated into six groups of n = 5 animals each. Body weight (5 mg/kg) of haloperidol was administered intraperitoneally for 7 days to block dopaminergic D2 receptors and induce degeneration in the motor cortex

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  2. Everyone is magically a “patient” of psychiatry , when there are two different kinds of patients.
    The two are 1) Those that want the drugs, and 2) Those that do not want the drugs.

    First they name you mad, then they make you mad with the drugs and unlawful imprisonment.

    I wonder when/if the confidence trick is going to end.

    Who is going to end it when half the population is the naked emperor?'s_New_Clothes
    “But he isn’t wearing anything at all!”

    “Giving a child a psychiatric drug is poisoning, not treatment.” Szasz

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    • Absolutely, and the neuroleptics / “antipsychotics” are known to cause both the negative and positive symptoms of “schizophrenia.” Via neuroleptic induced deficit syndrome, which is usually misdiagnosed by psychiatrists as the negative symptoms of “schizophrenia.” Resulting in an increase of the drugs, or adding more drugs. And this increase in neuroleptics, and other psychiatric drugs like the benzos and antidepressants, then results in the central symptoms of neuroleptic induced anticholinergic intoxication syndrome, aka anticholinergic toxidrome. Antipsychotics in high doses, or in combination with other psychiatric drug classes, actually cause psychosis via anticholinergic toxidrome.

      Forcing or coercing anyone to take psychiatric drugs is torture and poisoning, not treatment.

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  3. This is one of those situations where the jury is in but the psychiatric field just plain doesn’t want to hear the verdict. There is no doubt that brain cell death is caused by antipsychotics, and if they were anything close to honest scientists, they’d deal with it. This fact has a lot of explanatory value for both cognitive decline and in the increasing relapse rates in long-term users. You’d think that would be of interest, but since it goes against the financial and guild power interests of the profession, they will continue to argue that “we don’t know for sure” until and unless someone forcibly stops them.

    —- Steve

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    • I remember the day that I gave the most influential psychiatrist at the state hospital where I work copies of articles, reports, studies, etc. detailing how the drugs may help in the short term but are detrimental to people’s lives in the long term. I also included a copy of the report just published in New York the week before by the clinical psychologists in England dealing with alternatives to the present treatment.

      I will never forget how he smiled very patronizingly, waved his hand dismissively over the collection of materials and said, “I’ve seen all this before”. He was so smug in dismissing me.

      You are correct. To read the things I gave him would go against the financial and guild power interests of his profession. His young protégé psychiatrist on the unit with him talks with me but always prefaces our conversations by stating for everyone’s benefit in hearing distance about how we agree to disagree about the “treatment”. It is totally frustrating. At least these two will talk with me.

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      • “I will never forget how he smiled very patronizingly, waved his hand dismissively over the collection of materials and said, “I’ve seen all this before”. He was so smug in dismissing me. ”

        What malevolent condescension! The best way to cure this guy and others like him is to make sure that he has no patients. Easier said than done, I know, but that should be the goal.

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  4. I think I must be very lucky- all those years on the toxic anti-psychotic drugs from about 1997 to 2013-2015 and I can still think, read, comprehend, remember, write poetry and other works, draw, create, imagine, intuit, even reason (I do not do numbers and math too well and never really did. My logic may be a little faulty; but it is an intuitive logic; rather than a linear logic.) Yet, despite all those terrible toxic years where I went from “loopy” (my late sister’s words) to being a downright zombie vegetable; I can still think!! Even under those toxic drugs; I wrote poetry as writing poetry is as strong to me as breathing or eating. But, I am separating those poems from my natural state of poetry writing; although they did sometimes help me deal with a toxic situation; but, I was inclined to detail lies about myself due to the treatments and the drugs. Despite all the toxicity from so many, many sources; I am still ME! I do thank the Good Lord for that! And my heart and prayers goes out to those who have become so terribly incapacitated by the toxic drugs; their lives are almost barely livable. I do pray they find help, healing and solace and are freed from their pain. All I can say in regards to the drug makers, prescribers, and most all those in the mental illness criminal conspiracy of these days is; “Vengence is mine; saith the Lord!” Thank you.

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