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.     

History of the Discovery of the Antipsychotic Dopamine D2 Receptor: A Basis for the Dopamine Hypothesis of Schizophrenia

The 1975 publication of Seeman et al. (Proc Nat Acad Sci, USA), reporting the discovery of the antipsychotic receptor in the brain, is a classic example of translational medicine research. In searching for a pathophysiological mechanism of psychosis, the team sought to identify sites that bound the antipsychotic drug haloperidol. Their criterion was that haloperidol bound to the site at one to two nanomoles per liter, corresponding to haloperidol concentrations found in spinal fluid or plasma water in treated patients. They requested de novo synthesis of tritiated haloperidol, and it readily detected specific haloperidol binding sites in brain striatum. With dopamine binding the haloperidol-labeled sites with higher potency than other neurotransmitters, the sites were named antipsychotic/dopamine receptors (now designated dopamine D2 receptors). Most significantly, they found that all antipsychotics bound these sites at concentrations and with a rank order of potencies that were directly related to the mean daily antipsychotic dose taken by patients with schizophrenia. Their findings enabled screening for new antipsychotics, initiated D2 receptor measurements in brain of living patients, and determination of minimum occupancy (65%) of D2 receptors for antipsychotic benefit. The collective work is generally viewed as providing a fundamental basis for the dopamine hypothesis of schizophrenia.     

Neurognostics Question

Abstract

Dopamine is among the most well‐researched neurotransmitters at the present time. For the first half‐century of neurotransmitter research, however, interest in dopamine was minimal, and only a few scattered groups of researchers studied it. It was their research that stimulated current interest, and provided the background for our present understanding of this important substance. By the late 1950s, it was clear to these individuals that dopamine served an important physiological role in mammalian brains, and that its role was most likely that of a central nervous system agonist. Soon after this, dopamine, or more specifically the depletion of dopamine, was clearly implicated in Parkinson's disease. This paper looks at the early history of the physiological roles of this intriguing compound.     

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.     

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.     

Serendipity and the Cerebral Localization of Pleasure

Most accounts of the discovery of “pleasure” circuits in the brain begin with the observation by James Olds and Peter Milner in 1953 that electrical brain stimulation can condition operant responses in rats. Less well-known, pleasurable brain stimulation was previously observed in schizophrenic patients by Robert Heath. However, Heath failed to recognize the significance of this observation, at least in part, because of preconceived notions he held about the etiology of schizophrenia. This episode in the history of neuroscience illustrates the importance of sagacity in serendipitous scientific discoveries. It also shows that “mental preparedness” can be an obstacle to progress.     

Serendipity and the cerebral localization of pleasure

Most accounts of the discovery of "pleasure" circuits in the brain begin with the observation by James Olds and Peter Milner in 1953 that electrical brain stimulation can condition operant responses in rats. Less well-known, pleasurable brain stimulation was previously observed in schizophrenic patients by Robert Heath. However, Heath failed to recognize the significance of this observation, at least in part, because of preconceived notions he held about the etiology of schizophrenia. This episode in the history of neuroscience illustrates the importance of sagacity in serendipitous scientific discoveries. It also shows that "mental preparedness" can be an obstacle to progress.     

The first archaeological example of Freiberg's infraction

Freiberg described a condition in which collapse of the juvenile second metatarsal head gave rise to localized pain and swelling.¹ This eponymous disease is traditionally classed as one of the osteochondroses, a group of disparate lesions that typically manifest as destruction of an immature epiphysis. A medieval second metatarsal is presented, which by osteological and radiological examination is diagnostic of Freiberg's infraction. This is the first reported archaeological example of the condition.     

Women's history in Italy (nineteenth and twentieth centuries)

This essay surveys the development of women's history in Italy since its origins, examining the principal questions that have driven research and debate from the 1960s to the present, the ways in which women's history in other countries (notably the US) has been influential in Italy, the impact of women's history on other branches of historical research in Italy and its place — or rather lack of place ‐ in Italian universities.     

Population,light, and the size distribution of cities

We provide new insights on the city size distribution of countries around the world. Using more than 10,000 cities delineated via geospatial data and a globally consistent city identification scheme, we investigate distributional shapes in all countries. In terms of population, we find that Zipf's law holds for many, but not all, countries. Contrasting the distribution of population with the distribution of economic activity, measured by nighttime lights, across cities we shed light on the globally variant magnitude of agglomeration economies. Deviations from Zipf's law are to a large extent driven by an undue concentration in the largest cities. They benefit from agglomeration effects which seem to work through area rather than through density. Examining the cross‐country heterogeneity in the city size distribution, our model selection approach suggests that historical factors play an important role, in line with the time of development hypothesis.     

From DOPA to Parkinson's disease: the early history of dopamine research

Dopamine is among the most well-researched neurotransmitters at the present time. For the first half-century of neurotransmitter research, however, interest in dopamine was minimal, and only a few scattered groups of researchers studied it. It was their research that stimulated current interest, and provided the background for our present understanding of this important substance. By the late 1950s, it was clear to these individuals that dopamine served an important physiological role in mammalian brains, and that its role was most likely that of a central nervous system agonist. Soon after this, dopamine, or more specifically the depletion of dopamine, was clearly implicated in Parkinson's disease. This paper looks at the early history of the physiological roles of this intriguing compound.     

Democracy and the rights of women in the thinking of Giuseppe Mazzini

Addressing Italian workers in his Doveri dell’uomo of 1860, Mazzini unequivocally laid out his thoughts on women's rights. The thinker from Genoa, all the more after his encounters with other political philosophers from different national environments such as Britain and France, saw the principle of equality between men and women as fundamental to his project of constructing first the nation, and second a democratic republic. In his ideas regarding emancipation Mazzini, who spent a good 40 years of his life in exile, was one of a small group of European thinkers who in challenging the established customs and prevailing laws not only hoped for the end of women's social and judicial subordination, but also held that changes to the position of women were essential to the realisation of their political projects. Thanks to this respected group of intellectuals, the issue of female emancipation found a place in the nineteenth-century European debate regarding democracy and the formation of national states. The closeness of the positions of these thinkers, and their commitment in practice as well as theory, mean that it can legitimately be argued that in the course of the nineteenth century a current of feminist thinking took shape. This was born of the encounters between and reflections of various intellectuals who met first in France and then in England, and who came to see women's rights not just as a discrete issue for resolution but as fundamental to their projects for the regeneration of nations, or, as in the Italian case, for the construction and rebirth of a nation.     

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.     

The serotonin hypothesis of schizophrenia: a historical case study on the heuristic value of theory in clinical neuroscience

Clinical examination of the reliability and coherence of the evidence concerning modern neurochemical theories of mental disorders has led some scholars to conclude that support for many of these theories is weak. Nevertheless, these theories continue to be widely promoted. One explanation that has been offered for continued adherence to questionable theory is that it stimulates and gives direction to research. The heuristic value of theory is examined in the present paper by tracing the discoveries that followed from an old theory of schizophrenia, which is--by current consensus--false. It is shown that the original serotonin hypothesis of schizophrenia did, in fact, lead to significant advances in neuropharmacology, neurology and psychiatry.     

Ivane Beritashvili: founder of physiology and neuroscience in Georgia

This paper is dedicated to one of the outstanding scientists of the twentieth century--Ivane Beritashvili. He was a Georgian physiologist who graduated from St. Petersburg University and worked under the supervision of N. Wedensky. He founded the Department of Physiology and the Institute of Physiology at the University of Tbilisi, Georgia. Among his numerous contributions was the discovery of the rhythmical course of reciprocal inhibition in spinal reflexes, the first demonstration of the excitatory and inhibitory reactions in the brain stem neuropil. But Beritashvili's most significant contribution was the discovery of the mediation of animal psychoneural behavior by image-driven memory.     

Maritime Archaeology and the Early Atlantic Trade: research at Elmina,Ghana

This article details recent maritime archaeological research off the town of Elmina in coastal Ghana. Founded in 1482, Elmina Castle was the first and largest European outpost in sub‐Saharan West Africa, and remained a centre of maritime trade for almost four centuries. Survey and diver investigations led to the discovery of several sites, including a shipwreck dating to the mid 17th century, which is characterized by a mass of trade goods, cannon and buried hull remains. A second Dutch vessel dating to c.1700 was documented after its discovery during dredging operations in the Benya Lagoon adjacent to Elmina. These sites present an opportunity to study ships and cargoes involved in the West African trade.     

Study of stafne's defects in Late Neolithic,Late Roman,Medieval and Modern skeletal samples from Portugal

Lingual mandibular cortical defects (Stafne's defects) are relatively uncommon in recent as well as past populations, but while this condition is often discussed in clinical reports, they are rarely the subject of anthropological research. In this paper, the prevalence of Stafne's bone defects in skeletal samples from Late Neolithic, Late Roman, Medieval and Modern Portugal is investigated (N = 704 complete mandibles and 111 incomplete mandibles). The aims of this paper are threefold: (1) to present and analyse for the first time in Portuguese osteological record prevalence data on Stafne's bone defect, (2) to analyse variations in defect prevalence between skeletal samples from a wide temporal array and (3) to verify if more tenuous lesions in which resorption of the lingual cortex was not yet extensive had the classic radiographic appearance described by Stafne in order to validate the hypothesis that lesions are present clinically in many more cases than published figures indicate. In all cases, differential diagnosis against other conditions that mimic Stafne's defects, namely odontogenic lesions, cysts and neoplasms, was done. In all samples, the evidence of Stafne's defect occurred in 12 individuals (1.7%), and males (2.84%) were more frequently affected than females (0.61%). When incomplete mandibles were considered, only one left fragment (0.90%) exhibited Stafne's defect. Accurate identification of all examples of Stafne's bone defects in antiquity is thought to represent an important contribution to elucidate which factors may be responsible for this trait's cultural, ecological, temporal and geographical patterning. Copyright © 2010 John Wiley & Sons, Ltd.     

Memories of John Eccles

This article contains an account of the career of John Eccles that can be divided into two parts. The first extends from 1925, when he won a Rhodes scholarship to Magdalen College Oxford, to 1975, when he took voluntary retirement from the State University of New York at Buffalo. During this period, he set up six different laboratories in which he carried out research on synaptic mechanisms that provide the basis of neuroscience. The second period is the 20 years between his retirement and death in Switzerland, which he spent on the problem of the relationship between mind and brain.     

Ivane Beritashvili: Founder of Physiology and Neuroscience in Georgia

This paper is dedicated to one of the outstanding scientists of the twentieth century—Ivane Beritashvili. He was a Georgian physiologist who graduated from St. Petersburg University and worked under the supervision of N. Wedensky. He founded the Department of Physiology and the Institute of Physiology at the University of Tbilisi, Georgia. Among his numerous contributions was the discovery of the rhythmical course of reciprocal inhibition in spinal reflexes, the first demonstration of the excitatory and inhibitory reactions in the brain stem neuropil. But Beritashvili's most significant contribution was the discovery of the mediation of animal psychoneural behavior by image-driven memory.     

A Concert Hall for Stringed Musical Instruments Under the Splenium of the Corpus Callosum

This article contains an account of the career of John Eccles that can be divided into two parts. The first extends from 1925, when he won a Rhodes scholarship to Magdalen College Oxford, to 1975, when he took voluntary retirement from the State University of New York at Buffalo. During this period, he set up six different laboratories in which he carried out research on synaptic mechanisms that provide the basis of neuroscience. The second period is the 20 years between his retirement and death in Switzerland, which he spent on the problem of the relationship between mind and brain.