The History of the Psychopharmacology of Schizophrenia

Lehmann, H. E.; Ban, Thomas A.

doi:10.1177/070674379704200205

Cited by 86 publications

(55 citation statements)

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“…[20][21][22][23] Following the introduction of chlorpromazine and the first neuroleptics, EPS were thought to be a prerequisite for antipsychotic efficacy. 2,24 Clozapine and other SGAs violated this principle by having antipsychotic efficacy with little or no EPS, 3 hence the term 'atypical' antipsychotic. Subsequently, SGAs were observed to have an increased risk of metabolic side effects.…”

Section: The Relationship Between the Comparative Effectiveness And Mmentioning

confidence: 99%

“…1 Antipsychotic drugs have been the primary treatment for approximately half of a century, beginning with the discovery and introduction of chlorpromazine. 2 However, despite the extensive use and study of these agents, questions remain regarding their exact mechanism of action. 3 Much of the study to date has focused on the receptor profiles of these medications.…”

Section: Introductionmentioning

confidence: 99%

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Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway

2008

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The exact therapeutic mechanism of action of antipsychotic drugs remains unclear. Recent evidence has shown that second-generation antipsychotic drugs (SGAs) are differentially associated with metabolic side effects compared to first-generation antipsychotic drugs (FGAs). Their proclivity to cause metabolic disturbances correlates, to some degree, with their comparative efficacy. This is particularly the case for clozapine and olanzapine. In addition, the insulin signaling pathway is vital for normal brain development and function. Abnormalities of this pathway have been found in persons with schizophrenia and antipsychotic drugs may ameliorate some of these alterations. This prompted us to hypothesize that the therapeutic antipsychotic and adverse metabolic effects of antipsychotic drugs might be related to a common pharmacologic mechanism. This article reviews insulin metabolism in the brain and related abnormalities associated with schizophrenia with the goals of gaining insight into antipsychotic drug effects and possibly also into the pathophysiology of schizophrenia. Finally, we speculate about one potential mechanism of action (that is, functional selectivity) that would be consistent with the data reviewed herein and make suggestions for the future investigation that is required before a therapeutic agent based on these data can be realized.

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Section: The Relationship Between the Comparative Effectiveness And Mmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway

2008

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“…Mn has a role in thyroxine synthesis and thyroxine effects G6PD enzyme synthesis in a similar way. There is also a relationship between Mn and dopamine and it has been reported that antipsychotic drugs chelate body Mn (16,36).…”

Section: Discussionmentioning

confidence: 99%

Şizofreni hastalarında kanda glukoz-6-fosfat dehidrogenaz aktivitesi ve element düzeyleri / Elements levels and glucose-6-phosphate dehydrogenase activity in blood of patients with schizophrenia

Kaya¹,

Akdağ²,

Fadıllıoğlu³

et al. 2012

Dusunen Adam

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Researches ABSTRACTElements levels and glucose-6-phosphate dehydrogenase activity in blood of patients with schizophreniaObjectives: Glucose-6-phosphate dehydrogenase (G6PD) is the rate limiting enzyme of the hexose monophosphate cascade which plays role in the synthesis of nucleotide, reduced glutathion, fatty acid and cholesterol precursors. At the same time, it is an important enzyme for neuronal development during and after fetal life and for neurotransmitters. Serum elements are necessary for neuronal development and synthesis and activity of enzymes and hormones. The aim of this study was to compare serum levels of some elements and G6PD enzyme activity in schizophrenic patients with those in healthy individuals. Methods: This study involved blood serum analysis of 32 schizophrenia patients and 32 age-and sexmatched healthy controls. Copper, zinc, iron, magnesium levels were determined with a double lighted, deuterium sourced, background proof reading fire atomic spectrophotometer and in order to determine aluminum and manganese levels, a graphite tube atomizer spectroscope was used. G6PD enzyme activity was analyzed by the Glock and Mclean Method. Results: This analysis revealed higher levels of G6PD activity, copper, iron, magnesium and aluminum in schizophrenia patients compared to controls, whereas zinc and manganese levels showed a decreasing trend on the contrary. Discussion: The higher levels of G6PD activity in schizophrenic patients is not consistent with the literature in general. It is considered that results on G6PD and element levels may be explained as the effects of specific hormones, antipsychotic medications, or by schizophrenia itself. Conclusion: The elements we investigated and G6PD are important for the antioxidant system. Thus changing levels of elements in patients with schizophrenia may lead to disturbed functions of antioxidant enzymes and G6PD. Further researches on this subject conducted with larger and drug naïve patient groups are needed. Key words: Schizophrenia, glucose-6-phosphate dehydrogenase, serum element level ÖZET Şizofreni hastalarında kanda glukoz-6-fosfat dehidrogenaz aktivitesi ve element düzeyleriAmaç: Glukoz-6-fosfat dehidrogenaz (G6PD); nukleotid, indirgenmiş glutatyon, yağ asidi ve kolesterol öncüllerinin sentezlerinde rol alan heksoz monofosfat kaskadının hız kısıtlayıcı enzimidir. Aynı zamanda, fetal dönem sırasında ve sonrasında nöral gelişim ve nörotransmitterler için önemli bir enzimdir. Serumda bulunan elementler nöral gelişim, enzim ve hormonların sentez ve aktiviteleri için gereklidirler. Bu çalışmanın amacı, şizofreni hastaları ve sağlıklı kontrollerin bazı serum element düzeylerini ve G6PD enzim aktivitelerini karşılaştırmaktır. Yöntem: Çalışmaya, 32 şizofreni hastası ile yaş ve cinsiyet açısından eşleştirilmiş 32 sağlıklı kontrol dahil edilmiştir. Bakır, çinko, demir ve magnezyum düzeyleri çifte ışıklandırılmış, döteryum kaynaklı, zemin düzeltmesi yapabilen alevli atomik spektrofotometre ile belirlenmiş; alüminyum ve manganez düzeylerini belirlemek i...

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“…These assumed remedies were not based on sound pathological data, but nevertheless reflected the predominant somatic perception of schizophrenia at this time. Because the etiological nature of the disorder was entirely unknown, extant treatments, including insulin coma therapy (Sakel, 1937;Jones, 2000) and metrazol therapy (Lehmann & Ban, 1997), were administered on a trial and error basis; they were largely unsuccessful and ultimately abandoned (Lehmann & Ban, 1997). Although the somatic perception of schizophrenia dominated psychiatric thinking during this time, psychoanalytic theory also had a significant impact on the thinking and, in certain places, on the treatment of such patients.…”

Section: Schizophrenia Circa 1930mentioning

confidence: 98%

David Shakow and schizophrenia research at Worcester State Hospital: The roots of the scientist‐practitioner model

Cautin

2008

J History Behavioral Science

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As Chief Psychologist and Director of Psychological Research at Worcester State Hospital (WSH), David Shakow (1901-1981) made substantial contributions to the scientific study of schizophrenia and by extension to the study of psychopathology in general. His methodological innovations--particularly on issues of diagnosis and conditions of testing-set a new standard for experimental rigor in the field. Shakow helped to establish many of what are considered basic facts about schizophrenia. His empirical work at WSH-specifically on the crossover effect--provided the scientific foundation for his theory of schizophrenic cognition, known as segmental set. Moreover, Shakow's schizophrenia work informed his developing ideas on the synergy between clinical practice and research.

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The History of the Psychopharmacology of Schizophrenia

Abstract: Close collaboration between basic neuroscience and careful and informed clinical practice are likely to lead to continued progress.

Cited by 86 publications

References 64 publications

Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway

Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway

Şizofreni hastalarında kanda glukoz-6-fosfat dehidrogenaz aktivitesi ve element düzeyleri / Elements levels and glucose-6-phosphate dehydrogenase activity in blood of patients with schizophrenia

David Shakow and schizophrenia research at Worcester State Hospital: The roots of the scientist‐practitioner model

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