Janowsky Publishes His Theory of Manic Depression

Psychiatrist David S. Janowsky and his coworkers proposed a cholinergic-adrenergic hypothesis of mania and depression that elucidated the illness and facilitated treatment methodologies.

Summary of Event

Hospital beds and mental institutions all over the United States are filled with the victims of serious mental illness. The problem of overcrowding is so severe that many people affected by milder forms of mental illness have been released from these institutions. Many of them wander the streets of the cities, homeless and in severely mentally impaired states. Mental illness;bipolar affective disorder
Cholinergic-adrenergic hypothesis of mania and depression[Cholinergic adrenergic hypothesis]
Bipolar affective disorder
[kw]Janowsky Publishes His Theory of Manic Depression (Sept. 23, 1972)
[kw]Publishes His Theory of Manic Depression, Janowsky (Sept. 23, 1972)
[kw]Theory of Manic Depression, Janowsky Publishes His (Sept. 23, 1972)
[kw]Manic Depression, Janowsky Publishes His Theory of (Sept. 23, 1972)
[kw]Depression, Janowsky Publishes His Theory of Manic (Sept. 23, 1972)
Mental illness;bipolar affective disorder
Cholinergic-adrenergic hypothesis of mania and depression[Cholinergic adrenergic hypothesis]
Bipolar affective disorder
[g]North America;Sept. 23, 1972: Janowsky Publishes His Theory of Manic Depression[00880]
[g]United States;Sept. 23, 1972: Janowsky Publishes His Theory of Manic Depression[00880]
[c]Psychology and psychiatry;Sept. 23, 1972: Janowsky Publishes His Theory of Manic Depression[00880]
[c]Health and medicine;Sept. 23, 1972: Janowsky Publishes His Theory of Manic Depression[00880]
Janowsky, David S.
Davis, John Marcell

Mental illness may be divided into two basic types: organic and functional. Organic mental illness results from an injury or a known disease (for example, diabetes) that alters the structure of the brain, changes its ability to function correctly, or affects some other part of the nervous system. Cure of this type of mental illness depends on surgery and other methods that cure the causative disease.

The causes of functional mental illness—often called “affective disorder”—are subtler and therefore have evaded clear understanding. Functional mental illness is defined as being caused by operational flaws of mental function. One of the most severe types of functional mental illness is bipolar affective disorder, also called manic depression. Those with bipolar affective disorder alternate between an excessively elevated (manic) state and a severely depressed (depressive) state. Consequently, such people have difficulty coping with the world around them. Hypotheses concerning such affective disorders date back to the father of medicine, the Greek physician Hippocrates (c. 460-c. 370 b.c.e.), who coined the term “melancholia” to describe severe depression. Hippocrates suggested that melancholia was caused by the accumulation of “black bile and phlegm, which darkened the spirit and made it become melancholy.” Modern understanding of the phenomenon begins with consideration of the function and dysfunction of the nervous system in which it occurs.

The human nervous system is composed of a central computer—the brain—made up of cells called neurons and a network of nerves that communicate signals to the rest of the body via nerve impulses. Neurons Neurons are separated from one another by tiny spaces called synaptic gaps. The passage of nerve impulses through nerves requires them to cross thousands of these gaps.

The movement of nerve impulses across synaptic gaps is conducted by biochemicals called neurotransmitters. Neurotransmitters One of the principal neurotransmitters is acetylcholine, which acts in “cholinergic” nerves. Cholinergic chemicals Cholinergic chemicals inhibit the transmission of nerve impulses, causing, among other things, the slowing of the heartbeat. Scientists have speculated that the interference of cholinergic chemicals with acetylcholine action is one cause of mental disease. This idea arose, in part, from observations of impaired mental function in people who had been exposed to chemicals that disrupt acetylcholine production and use.

Other neurotransmitters associated with mental disease include catecholamines and indoleamines. Catecholamines Catecholamines control the transmission of nerve impulses by adrenergic portions of the nervous system. Adrenergic chemicals, in contrast to cholinergic chemicals, stimulate the transmission of nerve impulses, causing the heart to speed up. The indoleamines function in neurons related to sleep and sensory perception. They are believed to be associated with symptoms of affective disorders that include sleep and sensory dysfunction.

Theories of depression and mania arose from the catecholamine (or norepinephrine) hypothesis of affective disorders. This hypothesis, published in the American Journal of Psychiatry in 1965, was proposed by Joseph Schildkraut Schildkraut, Joseph and others. The hypothesis focused mostly on the adrenal catecholamine, norepinephrine. It was proposed that the depressive state arose because of suboptimum norepinephrine production or utilization (decreased noradrenergic activity) and that the manic state arose from excess norepinephrine production or utilization (increased noradrenergic activity).

Acceptance of the catecholamine hypothesis led to the examination of norepinephrine levels in normal and disease states; efforts to use these levels to explain how existing drugs, electric shock, and other known treatments affected mania and depression; attempts to choose new drugs for therapeutic use on the basis of their effects on the norepinephrine levels; and study of other catecholamines and related biogenic amines. These efforts led to the modification of the catecholamine hypothesis. First, dopamine Dopamine (a catecholamine cousin of norepinephrine) was implicated in the function of the central nervous system. Then, it was noticed that several of the major tranquilizers (for example, reserpine) decreased both the dopamine and the norepinephrine levels. Consequently, it was suggested that the catecholamine hypothesis should include dopamine. Furthermore, low central nervous system levels of dopamine became even more intimately associated with depression than low norepinephrine levels. Serotonin Serotonin was also implicated in depression because it, too, was depleted by major tranquilizers like reserpine. Then, it was shown that the action of tricyclic antidepressants was related mostly to serotonin levels. Because of this, an indoleamine (or serotonin) hypothesis of affective disorders was born.

In 1972, David S. Janowsky, John Marcell Davis, and their colleagues at Vanderbilt University’s Psychiatry Department proposed a cholinergic-adrenergic hypothesis of manic depression. The hypothesis focused on the cholinergic neurotransmitter acetylcholine. This hypothesis expanded the conceptual basis of manic depression. Janowsky’s theory, unlike others before it, recognized the importance of interaction between the various systems involved in nervous transmission and proposed that the affective state of any individual represents a balance between the noradrenergic and the cholinergic activity. Janowsky and his colleagues proposed that depression was a disease of “relative cholinergic predominance,” while mania was defined as being a disease of relative “adrenergic predominance.” They also suggested that manic-depressive psychosis was caused by compensatory overreaction of the central autonomic nervous system.


People afflicted with untreated bipolar disorder exhibit severe emotional disturbance and mood swings that make it difficult for them to function in the day-to-day world. Their symptoms may include greatly disordered thought processes, delusions and hallucinations, and feelings of grandeur as well as the opposite, severe depression. The chronic nature of these symptoms, which occur episodically, places such individuals at serious social risk, and victims of severe forms of the disease are often confined to mental institutions.

Janowsky’s explanation of the causes of manic depression helped to spur the discovery of many concepts and treatments now used by psychiatric practitioners to treat the illness. Such methods include drug treatment with tricyclic antidepressants, lithium, and inhibitors as well as innovative cognitive therapies. None of these methods cures the disease, but various combinations often prove effective in helping people with bipolar disorder to live relatively normal lives. Mental illness;bipolar affective disorder
Cholinergic-adrenergic hypothesis of mania and depression[Cholinergic adrenergic hypothesis]
Bipolar affective disorder

Further Reading

  • Cohen, Seth, and David Dunner. “Bipolar Affective Disorder: Review and Update Depression.” In Modern Perspectives in the Psychiatry of the Affective Disorders, edited by John G. Howells. New York: Brunner/Mazel, 1988. Reviews bipolar affective disorder, describes its clinical appearance, and outlines the methods used for its differential diagnosis. Also covers the epidemiology, genetics, and outcome of the disorder and discusses treatment with lithium.
  • Georgotas, Anastasios, and Robert Cancro, eds. Depression and Mania. New York: Elsevier, 1988. Collection of technical articles deals with aspects of mania and depression, including historical issues, epidemiology, diagnosis, disease etiology, medications and other treatments, ways to assess the disease, laboratory tests, and how to differentiate bipolar disorder from related psychoses.
  • Janowsky, David S., Dominick Addario, and S. Craig Risch. Psychopharmacology Case Studies. 2d ed. New York: Guilford Press, 1987. Presents sixty-four case studies and outlines the practical use of psychopharmacologic theory to treat mania, depression, and other mental diseases. Some topics included are treatment of affective disorders, complications of regular medical drug use, side effects of antipsychotic drugs, and antipsychotic drug maintenance.
  • Janowsky, David S., M. Khaled El-Yousef, John M. Davis, and H. Joseph Sekerke. “A Cholinergic-Adrenergic Hypothesis of Mania and Depression.” The Lancet 2 (September, 1972): 632-635. Janowsky’s hypothesis focuses on cholinergic neurotransmission but recognizes the importance of the other systems involved. It proposes that affective state represents a balance between noradrenergic and cholinergic activity. Depression and mania are viewed as diseases of relative cholinergic and adrenergic predominance, respectively.
  • Schildkraut, Joseph J. “The Catecholamine Hypothesis of Affective Disorders: A Review of Supporting Evidence.” American Journal of Psychiatry 2 (November, 1965): 509-522. Describes the clinical basis for the catecholamine (norepinephrine) hypothesis of affective illness. Points out that depression and elation are associated with catecholamine deficiency and excess, respectively, at important brain sites. Cites evidence for the hypothesis, including effects of therapeutic drugs.
  • Sommers, Michael A. Everything You Need to Know About Bipolar Disorder and Manic Depressive Illness. New York: Rosen, 2000. Informative, straightforward text on bipolar disorder intended for adolescent readers. Includes glossary.
  • Stryer, Lubert. Biochemistry. 4th ed. San Francisco: W. H. Freeman, 1996. Chapter 37 of this excellent biochemistry text gives a good summary of the concepts of nerve transmission and neurotransmitters. Topics presented include acetylcholine as a neurotransmitter, acetylcholine-related drugs and poisons, and catecholamines and other neurotransmitters. Includes illustrative diagrams and references.

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