Shocking Anniversary

Shock therapy--new insights 77 years after the first experiment.

Posted Jan 23, 2011

            Seventy-seven years ago today, on January 23, 1934, a violent seizure was induced in a man in an attempt to cure him of serious mental illness.  The man, suffering from schizophrenia, was hopelessly catatonic.  He had lain in bed still for four years until Hungarian doctor, Ladislaus Meduna, made him the first of several mental patients to become his experimental subjects.  Meduna's strange ideas about mental illness were viewed by his colleagues as aberrant, and he carried out his preliminary research in secret.  The treatment he applied to cure his mental patients seemed barbaric-but it worked.  Today, electroconvulsive therapy (ECT), or "shock treatment," remains the most effective therapy for major depression that cannot be relieved by drugs, yet scientists are still unsure how it works. 

            The story of ECT is even more remarkable than the tale of a cure that remains a mystery.  This date, 77 years ago, marks a radical departure from long-held beliefs about mental illness.  On this date doctors embarked on a new path guided by Meduna's belief that mental illness has a biological basis that is treatable through physical intervention.  Previously psychotherapy was considered the only treatment for disorders of the mind, or patients with serious mental illnesses, such schizophrenia, were condemned to a life without hope because the disorders were understood to be genetic defects, and thus beyond remedy. 

            ECT has been transformative for many; restoring countless men and women to healthy productive lives.  But the way it originated, and was later abused, raise ethical questions about medical research on humans.  That tension persists to this day as doctors struggle to balance between the constraints of medical ethics and the forceful desire to find an effective treatment for desperately ill patients. 

            As a story of scientific discovery, ECT is equally illuminating.  Convulsions are frightening for observer and patient alike, and seizures can be dangerous.  Many patients treated in the early years by ECT suffered fractures from the violent contractions, but today these are prevented by muscle relaxants.  But where did such a radical idea come from:   that causing a "bone-crushing" seizure in a schizophrenic patient could cure him?  I touch on this in my book The Other Brain, but in-depth histories can be found in the books by Shorter and Healy, and by Max Fink, which are referenced below. 

            Ladislaus Meduna was a neuropathologist, not a psychiatrist.  In examining human brain tissue at autopsy or taken by biopsy during brain surgery, he made an interesting observation.  Cells in the brain, called glia, were greatly increased in numbers and they became bloated in brain tissue from people with epilepsy.  On the other hand, brain tissue from patients with schizophrenia had far fewer glia than normal.  Unlike neurons, glia cannot fire electrical impulses, so they were largely ignored by most neuroscientists. 

            Meduna added his observations together with another curious fact.  Dr. Robert Gaupp, psychiatry professor in Tubingen, Germany had already reported in 1926, that while schizophrenia and epilepsy are two very common disorders, few people ever suffer both illnesses.  In 1929, Albin Jablonszky and Julius Nyiro at the state asylum in Budapest reported that on the rare occasions when epileptics did develop schizophrenia, their epilepsy was cured. (The recovery rate from epilepsy was 16 times greater than normal after the first psychotic episode.)

            Meduna, concluded that schizophrenia was the result of an imbalance in glia:  too few glia in schizophrenia, and too many in epilepsy.  He decided to induce a seizure in people with schizophrenia to restore the glial balance.  He had no biological understanding or theory of how glia might affect mental illness, but today we know that glia (the other brain) are in a position to control the balance between mental health and madness.  A type of glia, called astrocytes, wraps around synapses and removes neurotransmitter that is released from neurons in communicating.   All hallucinogenic drugs have their mind-bending effects by disrupting the normal balance of neurotransmitter in brain circuits that are involved in emotion and higher level cognitive function.  All drugs for treating depression and psychotic disorders work by regulating the level of specific neurotransmitters in the brain, such as SSRI medicines used to treat depression and other mental illnesses, but regulating neurotransmitters is precisely what these glial cells do. 

            Meduna induced the seizure by injecting a chemical, camphor, into the catatonic patient's blood stream.  The patient experienced a powerful seizure that wracked his body for a full minute.  Meduna's legs gave out in shock upon witnessing what he had done, and two nurses had to help Meduna back to his apartment to recover.

            Four days later Meduna induced another seizure in the man who for four years had never moved and who had been fed continuously by tube.  By the fifth injection on February 10, the man awoke, dressed himself, requested breakfast, and greeted Dr. Meduna cheerfully by name.  "I hear them talking that you were going to make some crazy experiment?  Did you do it?" he asked (p. 27, Shorter and Healy).

            Eventually chemical injections to induce seizure were replaced by electrical stimulation.  Ugo Cerletti and Lucio Bini in Italy adapted electrodes used to stun pigs at the slaughter house to apply electrical current to the head of mental patients.  Working first with dogs they determined how much voltage could be used and how long it could be applied without killing the animal.  Bini asked Meduna if he thought that convulsions induced by the pig-stunning electrodes would have the same effect as chemically-induced seizures in relieving schizophrenia.  Meduna predicted that they would. 

            On April 11, 1938, electrodes were applied to the temples of Enrico X, as Cerletti, Bini, and several other colleagues witnessed the first convulsions induced by electricity to treat mental illness.   After seven more treatments, Enrico X was discharged "cured" of schizophrenia.

            Although electroshock probably affects many different processes in the brain, and depression and schizophrenia are heterogeneous diseases, the new understanding of glia implicates them in the therapeutic effects of shock therapy.  Glia not only regulate neurotransmitters, they release growth factor proteins and other substances that stimulate growth of neurons, and immature glia can even give birth to new neurons.  A recent discovery is that all antidepressant drugs stimulate the birth of new neurons. 

            The observation Meduna made about the imbalance of glia and his conjectures were correct, but they were a leap of faith into the unknown, spanning 77 years into the future of scientific research before an understanding would emerge of how glia, epilepsy, and schizophrenia could be coupled through glia.   But was it ethical to experiment on mental patients this way? 

            Modern laws and respect for ethics in medical research on humans would strictly bar what Meduna, Cerletti, and the others did.  One wonders, when (if ever) would ECT have been attempted?  Doctors caring for patients with life-threatening incurable illness, such as terminal cancer or serious mental illness, cannot apply experimental treatments to people without sufficient background knowledge, informed consent, and large-scale experimental design including randomized controls before seeking approval to test them on people.  Meduna's experiments were unethical by modern standards, but they transformed thinking about mental illness, they led to a new effective treatment for a life-threatening disorder, and they fundamentally changed thinking about mental illness, which led to development of psychoactive drugs that are the mainstay of modern treatments for depression, schizophrenia, and many other mental illnesses. 

Shock Therapy, A history of Electroconvulsive Treatment in Mental Illness, Edward Shorter and David Healy, Rutgers University Press, 2007.

Electroconvulsive Therapy, a Guide for Professionals and Their Patients, Max Fink, Oxford University Press, 2009.

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