The first thing the physician noticed about the young woman sitting before him was her sallow complexion. She was 17 years old. He listened carefully, not only to her words but also to the rhythm and emotional tone behind her words. The melody was familiar. Recently he had heard it in the presenting symptoms of 2 other female patients.
The year was 1901 or 1902. The place was the neurological clinic of the Johns Hopkins Dispensary in Baltimore.
A provisional diagnostic impression arose in his mind. Now he knew what steps he needed to follow to verify it. He proceeded with the examination.
Grasping her cool, pale wrist—he had no doubt the girl was anemic—he was not surprised to register an irregular pulse. Vasomotor disturbances were common in patients. He looked carefully at her hands for cyanosis but saw none.
Her pupils responded normally, and her eyes seemed to move smoothly from left to right and back again as she complied with his request to track a moving stimulus. He began to doubt his initial impression. After all, cyanosis of the hands, abnormal pupil reflexes, and eye movement abnormalities were well described in the medical literature for this condition.
He proceeded to the next logical tests. Scratching the surface of her skin—with what, he didn’t say—the physician witnessed her skin swelling and rising in response to his touch. Yes, there it was: dermatographia. Certainty returned.
He noted a certain hesitation or slowness of movement that was similar to that in his other 2 patients, and to many others like them. He suspected that the prodromal phase of the disease often resembled cases of neurasthenia, in which depressive symptoms were prominent. He knew he needed to rule out neurasthenia.
Taking up his percussion hammer, he was gratified to find the hoped-for exaggerations of the knee-jerk and other tendon reflexes. A strong heightening of the reflexes in the absence of signs of brain involvement was consistent with a prodromal phase and inconsistent with neurasthenia. Clear neurological signs of cerebral cortex involvement were said to come later in the course of the disease. But one final test was needed to complete the differential diagnosis.
Hammer in hand, he gently tapped her cheek and noted the abnormal muscle spasm—the final pathognomonic sign. The diagnosis was confirmed: dementia praecox.
The physician was William Rush Dunton Jr (1868-1966), a distant nephew of the man regarded as the first true psychiatrist in the US, Benjamin Rush. When Dunton published an article containing his case summaries of the 3 women with dementia praecox, he made it clear that this was a disease that neurologists and physicians in general practice could easily and reliably diagnose by following his diagnostic procedures.
Dunton had based his examination on the observations reported by German psychiatrist Emil Kraepelin (1856-1926) in the 1899 sixth edition of his textbook Psychiatrie.1(pp109-111) Kraepelin regarded these physical signs to be as relevant to the underlying physiology of dementia praecox as the striking cognitive symptoms of progressive mental deterioration, mental defect, and mental weakness.
“There is a symptom noted by Kraepelin, but not emphasized by him, which I have seen exhibited in a very pronounced manner in a number of cases,” wrote Dunton2 in 1902. “This is the mechanical irritability of the facial nerve which when present and associated with mental aberrations is of diagnostic value.”2 A few years later, in a public admission of medical error that is still as rare today as it was then, Dunton3 retreated from his earlier enthusiasm for his medical discovery: “It must be remembered that the physical signs of dementia praecox are multiform and it is usually a mistake to give undue prominence to any one symptom, which mistake I believed made in my paper.”
In the current psychiatric era, when psychiatrists no longer touch their patients nor rely on pathognomonic physical signs to confirm the diagnosis of most DSM-IV mental disorders, Dunton’s medical evaluation of that young woman would be unthinkable. After all, mental disorders are not truly “diseases,” and if they were, they would only concern the brain and not the peripheral nervous system or vasomotor functioning.
And yet, a century ago, many alienists and neurologists in the US and Britain were convinced by the latest findings of superior German medicine (personified by Kraepelin) that indicated a methodological path that led away from subjective medical error and toward objective diagnostic certainty when confronted with nervous or “insane” patients.
Emil Kraepelin was convinced for the last 30 years of his life that his 2 grand disease concepts—dementia praecox and manic-depressive insanity—were the result of long-term systemic, or “whole body,” disease processes that eventually affected the brain in a final decisive cascade.4(pp121-124) Heredity could not be denied as a factor, but it was only a predisposing one. In the fifth through the ninth editions of Psychiatrie, his famous textbook, Kraepelin consistently speculated that dementia praecox (in particular) was probably the result of a systemic metabolic disease process that might be producing an autointoxication, or “self-poisoning,” of the entire body. In other words, it was not simply a disease of the brain. The peripheral nervous system and its reflexes, the endocrine system, and all other organs of the body were affected as well.
In Kraepelin’s view, the true origin of dementia praecox was not to be found in the cells of the CNS, nor (entirely) in the shadowy ancestral chambers of the germplasm, but active and alive elsewhere, perhaps everywhere, in the present body. Furthermore, if dementia praecox were directly caused by proximal rather than distal biological processes, it was a potentially preventable and treatable disease. He tried various experimental treatments, such as the injection of extracts from various glands (to alter metabolic functioning) and injections of sodium nucleate (to provoke an immune response), and failed. But he never doubted his core intuition about the physiological source of the melodies of madness.
He also never doubted how modern science would one day detect the distinct molecular phenotypes of madness: they would be found in the blood. “The careful study of the processes of metabolism and blood chemistry will provide us with important clues to the characterization and delineation of natural disease groups,” Kraepelin wrote in a 1919 article.5
One year before he died, Kraepelin was visited at his clinic in Munich in November 1925 by Alan Gregg of the Rockefeller Foundation. “I questioned K offhand on any shift that may have taken place in his interests in psychiatry in the last 10 years, and he replied that the development of serology had greatly changed his attitude,” reported Gregg.6 “He stated that it had been very difficult for him to write the last edition of his book, in view of the great progress made in that field. He mentioned nothing besides serology; he is openly intolerant of Freud and Jung.”4(p272)
Whole body madness? Evidence of insanity in the blood? Not anymore. Neither Dunton nor Kraepelin would recognize the scientific narratives of today, although they would understand and appreciate them.
Our present master narratives often only tell tales of genes, neurotransmitters, receptors and a brain that is oddly spoken of as if it were disconnected from the physiological tides that surge through the other organs and structures of the body. For more than 3 decades, these have been the familiar characters of the stories in psychiatric journals. The repetition of these stories comforts us.
Alternative narratives that offer stories of mental disorders as systemic, or “whole body,” metabolic or immunological disease processes now seem to provoke a queasy cognitive dissonance in psychiatrists. They are “incommensurable” with our familiar paradigm in the sense that Thomas Kuhn6 employed this term.
But these stories do exist.7,8 And one day they may frame the new master narratives of mental disorder, leaving behind our comforting anchor of the genome for the transcriptome, the proteome, and the metabolome. The new percussion hammers might turn out to be machines that recognize molecules in the blood and cerebrospinal fluid.9 New sciences that focus on identifying such biomarkers are being born in this century, and many researchers will make premature and erroneous claims about the validity of their biomarkers for specific mental disorders. Many will most assuredly suffer Dunton’s fate. But perhaps some won’t.
Whole body madness? A blood test for mental disorders?10 Perhaps the past is prologue.
1. Kraepelin E. Psychiatry: A Textbook for Students and Physicians. Ayed S, trans. Canton, MA: Science History Publications; 1990. Clinical Psychiatry; vol 2.
2. Dunton WR. Some points in the diagnosis of dementia praecox. Am J Psychiatry. 1902;59:53-61.
3. Dunton WR. Note on the mechanical irritability of the facial nerve in dementia praecox. Am J Psychiatry. 1905;62:154-155.
4. Noll R. American Madness: The Rise and Fall of Dementia Praecox. Cambridge, MA: Harvard University Press; 2011.
5. Kendler KS, Jablensky A. Kraepelin’s concept of psychiatric illness. Psychol Med. 2010 Sep 1; [Epub ahead of print].
6. Kuhn TS. The Structure of Scientific Revolutions. Chicago: University of Chicago Press; 1962.
7. Müller N, Schwarz MJ. Immune system and schizophrenia. Curr Immunol Rev. 2010;6:213-220.
8. Guest PC, Martins-de-Souza D, Vanattou-Saifoudine N, et al. Abnormalities in metabolism and hypothalamic-pituitary-adrenal axis function in schizophrenia. Int Rev Neurobiol. 2011;101:145-168.
9. Martins-de-Souza D, Guest PC, Rahmoune H, Bahn S. Proteomic approaches to unravel the complexity of schizophrenia. Expert Rev Proteomics. 2012;9:97-108.
10. Schwarz E, Guest PC, Rahmoune H, et al. Identification of a biological signature for schizophrenia in serum. Mol Psychiatry. 2012;17:494-502.