The Tulane Electrical Brain Stimulation Program a historical case study in medical ethics

In 1950 physicians at Tulane University School of Medicine began a program of research on the use of electrical brain stimulation that would span three decades and involve approximately 100 patients. Initially, electrical brain stimulation was used to treat of schizophrenia, but later it was applied to a variety of other conditions. Throughout its history the Tulane research was well publicized in both the professional and lay literature, and for almost twenty years, with rare exception, these accounts were laudatory. However, in the early 1970s this work began to draw sharp public criticism. Despite its public and controversial nature, the Tulane electrical brain stimulation program has received relatively little attention from historians. This review recounts the history of the Tulane program with particular emphasis on the ethical propriety of the work. Factors that shaped the historical context in which the Tulane experiments were conducted are discussed.     

Historical development of the dopamine hypothesis of schizophrenia

This review examines the history of discoveries that contributed to development of the dopamine hypothesis of schizophrenia. The origin of the hypothesis is traced to the recognition that neuroleptic drugs interfere with brain dopamine function. This insight was derived from two distinct lines of research. The first line originated from the discovery in 1956 that reserpine depletes brain serotonin. This finding resulted in a sequence of studies that led to the discovery that brain dopamine is involved in neuroleptic-induced extrapyramidal motor disturbances. The second line of research was aimed at determining the mechanism of action of psychomotor stimulants. This research produced evidence that stimulants directly or indirectly activate brain dopamine receptors. Because nonreserpine neuroleptics such as chlorpromazine block stimulant-induced movement, these findings suggested that neuroleptics were dopamine antagonists. Most previous accounts of the development of the dopamine hypothesis of schizophrenia emphasize the first line of research and ignore the second.     

The early history of the neuroscience of attention-deficit/hyperactivity disorder

Research on the neurobiology and pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) has grown exponentially since 1980. A reasonable question is whether this research has improved our understanding and treatment of ADHD. This article describes relevant developments that took place roughly between 1900 and 1970. During this time, the efficacy of stimulant therapy for the disorder was established and the symptoms of ADHD were linked to many possible nervous system disorders including in the brain-stem, reticular formation, diencephalon, basal ganglia, frontal lobes, and cortex. In 1970, the catecholamine hypothesis of ADHD was proposed. It is concluded that early theories about the neurobiologic basis of ADHD anticipated core ideas of modern theory.     

Historical Development of the Dopamine Hypothesis of Schizophrenia

This review examines the history of discoveries that contributed to development of the dopamine hypothesis of schizophrenia. The origin of the hypothesis is traced to the recognition that neuroleptic drugs interfere with brain dopamine function. This insight was derived from two distinct lines of research. The first line originated from the discovery in 1956 that reserpine depletes brain serotonin. This finding resulted in a sequence of studies that led to the discovery that brain dopamine is involved in neuroleptic-induced extrapyramidal motor disturbances. The second line of research was aimed at determining the mechanism of action of psychomotor stimulants. This research produced evidence that stimulants directly or indirectly activate brain dopamine receptors. Because nonreserpine neuroleptics such as chlorpromazine block stimulant-induced movement, these findings suggested that neuroleptics were dopamine antagonists. Most previous accounts of the development of the dopamine hypothesis of schizophrenia emphasize the first line of research and ignore the second.     

The Myth of Reserpine-Induced Depression: Role in the Historical Development of the Monoamine Hypothesis

For five decades it has been generally accepted that reserpine, an antihypertensive and antipsychotic drug, causes depression. The discovery that reserpine depletes brain monoamines was an important factor in the development of the monoamine hypothesis of depression, and it continues to be widely cited in support of this hypothesis. The present paper argues that, contrary to prevailing belief, reserpine is not depressogenic. The reason for perpetuation of this myth is reluctance to discard the monoamine hypothesis. This hypothesis ushered the modern biochemical paradigm into psychiatry and is still of great importance. It serves as a heuristic to guide research, it enhances psychiatry’s prestige, and it helps to validate and promote drug therapy for depression and other mental disorders.     

Continuity and discontinuity in the historical development of modern psychopharmacology

In the middle of the twentieth century psychiatry underwent a transition that is often referred to as the "psychopharmacology revolution." Implicit in the term revolution is the idea that a paradigm shift occurred. Specifically, it has been argued that psychiatry abandoned the psychoanalytic paradigm in favor of a qualitatively distinct conceptual system based on brain chemistry. The validity of this view requires that psychoanalysis had the status of a paradigm. This paper presents evidence that psychoanalysis did not constitute a paradigm and that the advent of psychopharmacology was not, technically, a scientific revolution. Instead, the rise of modern psychopharmacology was the culmination of a linear growth of biological knowledge that began to develop in the nineteenth century.     

The search for an endogenous schizogen: the strange case of taraxein

In 1956, Dr. Robert Galbraith Heath, Chair of Psychiatry and Neurology at Tulane University School of Medicine in New Orleans, announced that he and colleagues had discovered a protein they called taraxein in the blood of schizophrenic patients that caused symptoms of schizophrenia when injected into healthy volunteers. Heath's claim received wide public and professional attention. Researchers quickly tried to confirm the discovery. These efforts, which were rigorous and in some cases conducted in consultation with the Tulane researchers, failed. Nevertheless, for the next four decades Heath continued to defend his claim. This article recounts the scientific developments that led up to Heath's putative discovery and it explores the scientific findings for and against the taraxein theory of schizophrenia.     

Continuity and Discontinuity in the Historical Development of Modern Psychopharmacology

In the middle of the twentieth century psychiatry underwent a transition that is often referred to as the “psychopharmacology revolution.” Implicit in the term revolution is the idea that a paradigm shift occurred. Specifically, it has been argued that psychiatry abandoned the psychoanalytic paradigm in favor of a qualitatively distinct conceptual system based on brain chemistry. The validity of this view requires that psychoanalysis had the status of a paradigm. This paper presents evidence that psychoanalysis did not constitute a paradigm and that the advent of psychopharmacology was not, technically, a scientific revolution. Instead, the rise of modern psychopharmacology was the culmination of a linear growth of biological knowledge that began to develop in the nineteenth century.     

The Early History of the Neuroscience of Attention-Deficit/Hyperactivity Disorder

Research on the neurobiology and pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) has grown exponentially since 1980. A reasonable question is whether this research has improved our understanding and treatment of ADHD. This article describes relevant developments that took place roughly between 1900 and 1970. During this time, the efficacy of stimulant therapy for the disorder was established and the symptoms of ADHD were linked to many possible nervous system disorders including in the brain-stem, reticular formation, diencephalon, basal ganglia, frontal lobes, and cortex. In 1970, the catecholamine hypothesis of ADHD was proposed. It is concluded that early theories about the neurobiologic basis of ADHD anticipated core ideas of modern theory.     

The myth of reserpine-induced depression: role in the historical development of the monoamine hypothesis

For five decades it has been generally accepted that reserpine, an antihypertensive and antipsychotic drug, causes depression. The discovery that reserpine depletes brain monoamines was an important factor in the development of the monoamine hypothesis of depression, and it continues to be widely cited in support of this hypothesis. The present paper argues that, contrary to prevailing belief, reserpine is not depressogenic. The reason for perpetuation of this myth is reluctance to discard the monoamine hypothesis. This hypothesis ushered the modern biochemical paradigm into psychiatry and is still of great importance. It serves as a heuristic to guide research, it enhances psychiatry's prestige, and it helps to validate and promote drug therapy for depression and other mental disorders.