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Psychopharmacology: finding one's way.

The paper recalls the experiences of the author over the past forty-eight years in a field which later became known as psychopharmacology. The author began in physical chemistry and traditional pharmacology. His interest in the nervous system stemmed from X-ray diffraction studies on the structure of living myelin, and led, by way of studies on the distribution of cholinesterases and the effects of atropine, to the study of the effects of drugs on the electrical activity of the brain in the conscious animal. At the clinical level it included studies of the effects of drugs on catatonic schizophrenic stupor. These studies took place before the discovery of chlorpromazine. They led to the creation, in 1951, of the Department of Experimental Psychiatry in Birmingham, England, the first department of its kind in the world. The department included neurochemical, electrophysiological, and animal behavior laboratories and a strong clinical facility (the Uffculme Clinic). The first blind trial of chlorpromazine was carried out in that department in 1953 and 1954. The existence of families of neuroregulatory compounds, having uneven distribution in the brain, and exerting regional chemical field effects in relation to function was postulated on the basis of experimental and clinical findings. The work of colleagues and participants in the various studies is gratefully acknowledged in the text. In 1954 the author served as convening executive secretary of the first International Symposium on Neurochemistry at Oxford, England, the first meeting of its kind. He came to the United States in 1957 and founded, and served as first director of, the new Clinical Neuropharmacology Research Center, now the Center for Neuroscience at St. Elizabeth's Hospital, Washington, DC. He directed this program from 1957 to 1963. Subsequent activities at Johns Hopkins, the World Health Organization, and the International Brain Research Organization (IBRO) are recalled. In 1961 he was elected first president of the American College of Neuropsychopharmacology. In looking back, he notes the sparse and personal nature of the field in the late 1940s and early 1950s, its explosive growth in the wake of the major clinical discoveries, and above all, the emergence of a new science through the interaction of neurochemistry, electrophysiology, studies of animal behavior, and the refinement of the clinical trial. He regards the emergence of concepts of regional chemistry of the brain as particularly significant, and feels that psychopharmacology is ideally positioned to act as an intermediary between classical pharmacology and quantrum biology. The transdisciplinary nature of psychopharmacology provides a template for a comprehensive psychiatry of the future--a discipline which is now positioned to lead.(ABSTRACT TRUNCATED AT 400 WORDS)

England↗

Early discoveries in the penicillin series.

It is now 50 years since the therapeutic potential of penicillin was first demonstrated. This first antibiotic and the series of compounds derived from it have been of immense importance in modern medicine. This article describes the early search for more potent penicillin derivatives, culminating with the discovery of an intermediate of penicillin biosynthesis, 6-beta-amino penicillanic acid (6-APA). A companion article in next month's TIBS will chart the subsequent exploitation of 6-APA and the preparation of a range of clinically important semi-synthetic penicillins.

History, 20th Century↗

Notes on nursing today.

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Attitude of Health Personnel↗

Using source cues and familiarity cues to resist imagination inflation.

To investigate whether people can resist imagination inflation--the imagination-induced increased confidence that fictitious childhood events really happened--we gave them different types of cues. In a three-stage procedure, participants: (1) rated their confidence that a list of childhood events had happened to them, (2) imagined some of these events, and (3) made confidence ratings a second time. Subjects received either no cues about the source of the imagined event, an additional source cue (perspective), an additional familiarity cue (a plausibility questionnaire), or both cues. Only subjects who had both types of cues resisted imagination inflation. These results suggest that additional cues can sometimes safeguard people from becoming more confident that fictitious events were genuine experiences.

Adult↗

The evolution of the helical reservoir pump-oxygenator system at the University of Minnesota.

Open heart surgery was not possible before the early 1950s. The development of controlled cross-circulation at the University of Minnesota in 1953 was a major contributing factor toward operating safely on the interior of the heart. Cross-circulation required connecting a donor's arterial and venous blood vessels to those of a smaller recipient whose heart could then be opened for corrective surgery. At that time no mechanical system was available to serve the role of the donor. The need to replace the donor was recognized. The author describes his experience with the development of the helical reservoir bubble oxygenator, which replaced the donor in cross-circulation supported open heart surgery. Other sidelights of the author's experience during the early days of open heart surgery at the University of Minnesota Department of Surgery are also recounted.

History, 20th Century↗

Neural correlates of temporal-order judgments versus those of spatial-location: deactivation of hippocampus may facilitate spatial performance.

The retrieval of temporal-order versus spatial-location information was investigated using fMRI. The primary finding in the hippocampus proper, seen in region of interest analyses, was an increase in BOLD signal intensity for temporal retrieval, and a decrease in signal intensity for spatial retrieval, relative to baseline. The negative BOLD signal change with spatial memory processing, while unexpected, is consistent with the recent fMRI literature indicating decreased BOLD can be associated with neuronal activation, and it is argued that the deactivation observed here may facilitate spatial performance. Spatial-location judgments also yielded a stronger (positive) response in the right midfrontal gyrus, while temporal-order judgments (autobiographic condition only) showed greater activity in the left superior temporal gyrus, suggesting greater working memory demands and greater semantization for each judgment type, respectively. Finally, all conditions activated the left midfrontal gyrus, although autobiographic memories showed additional activity in the medial frontal gyrus.

Adult↗

Posttraumatic stress disorder and fMRI activation patterns of traumatic memory in patients with borderline personality disorder.

BACKGROUND: Early traumatization and additional posttraumatic stress disorder are frequent in patients with borderline personality disorder (BPD). The purpose of this study was to investigate neural correlates of traumatic memory in BPD with and without posttraumatic stress disorder (PTSD) using functional magnetic resonance imaging (fMRI). METHODS: We studied 12 traumatized female patients BPD, 6 of them with and 6 without PTSD. According to an autobiographical interview key words (cues) were defined for traumatic and for negative but nontraumatic episodes. In a block-designed fMRI task patients recalled these episodes. Contrasts between trauma condition and nontrauma condition were analyzed. RESULTS: Analyses for all subjects revealed activation of orbitofrontal cortex areas in both hemispheres, anterior temporal lobes, and occipital areas. In the subgroup without PTSD, activation of orbitofrontal cortex on both sides and Broca's area predominated. In the subgroup with additional PTSD, we observed right more than left activation of anterior temporal lobes, mesiotemporal areas, amygdala, posterior cingulate gyrus, occipital areas, and cerebellum. CONCLUSIONS: Dependent on absence or presence of additional PTSD different neural networks seem to be involved in the traumatic memory of patients with BPD.

Adult↗