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Dopamine in the Pathophysiology and Treatment of Schizophrenia
Journal of Clinical Neuroscience (2005) 12(4), 508–509
Book reviews
Dopamine in the Pathophysiology and Treatment of Schizophrenia Shitij Kapur, Yves Lecrubier (Eds.), Dopamine in the Pathophysiology and Treatment of Schizophrenia. Martin Dunitz, London and New York, pp. 259. USD $60.00 (approx.) This compendium of 12 chapters explores the role of dopamine transmission in schizophrenia. Put together as a result of the Summer of 2000 Montreal meeting which brought together key people in the field, it spans the historical context of the discovery of chlorpromazine and the myriad of research directions being pursued. The book examines the historical development of how dopamine came to play such a central role in the understanding of the pathogenesis of schizophrenia and how it has re-emerged with different permutations over the past 50 years. The meetings itself was partly a review of the current status of research but also a celebration of the discovery of chlorpromazine only 50 years beforehand. This historical thread runs through the book and emphasises the newness of the field. The various authors are intrigued by the directions research has spread, only to more recently conclude that the original hypothesis regarding the importance of D2 receptors still has a tenacious hold on our understanding of how antipsychotic medications may work. In the opening chapter Carlsson vividly recalls some of the defining moments of the history of dopamine research. Recalling how the synthesis of chlorpromazine led Jean Delay and Pierre Deniker in 1952 to test this new drug on psychotic patients, readers are invited to share in the excitement of these initial discoveries and the start of a complex detective story. Chapters vary from those with little clinical perspective, to those, perhaps the more interesting, that try to integrate psychopharmacology, neuroimaging and the subjective experiences of the patient with schizophrenia. It comes alive and is most readable when the authors place the neuroimaging and biochemistry in the context of what a clinician sees and hears from his patients. For the clinician the going can be heavy in some sections if some of the anatomical pathways and receptor profiles are not familiar. Given the anatomical nature of much of the discussion the book could have been improved by higher quality images of the various neuroanatomical pathways and receptor locations. Nonetheless the key pathways and receptor locations are repeated in several chapters until familiarity is achieved. The principal dopamine pathways – nigrostriatal, mesolimbic and mesocortical are outlined, their possible links to the production of psychosis and how different medications may act are covered in several chapters. The volume includes many tables with no shortage of data and is well referenced. The classical dopamine hypothesis holds that hyperactivity of dopamine transmission results in the positive symptoms of schizophrenia. This initial understanding of an increase in dopamine function in schizophrenia is explored and various alternative hypotheses that flow from this concept, such as dopamine instability, rather than continuous elevation of activity, are critiqued. Despite dopamine’s central role in this book, other neurotransmitters systems such as glutamate and serotonin are canvassed and discussed as to their varying contributions in the pathogenesis of schizophrenia. This is particularly so when discussing how the 508
newer ‘atypical’ antipsychotics may work. It is made clear that despite all the advances, it is uncertain as to how antipsychotic drugs bring about their beneficial effects. Throughout the volume courses a thread of whether the most fruitful research lies within the dopamine system or in the exploration of other neurotransmitters systems. A preoccupation with the role of dopamine receptors has in the opinion of the some of the researchers led to a narrowness of perspective that has inhibited research. The uncertainty of how antipsychotics bring about their therapeutic effects is brought home clearly with two chapters exploring the atypical ‘atypical’ antipsychotic amisulpride. A somewhat paradoxical atypical antipsychotic, amisulpride with its pure dopaminergic blockade is effective in controlling positive and negative symptoms with minimal extrapyramidal side effects. Other atypical medications have a broader receptor profile and have led to notions that these different receptors systems are involved in the production of psychosis. Amisulpride, widely used in the treatment of schizophrenia has a clinical profile similar to other atypical antipsychotics such as quetiapine, risperidone and olanzapine but its receptor profile is almost entirely D2 and thus raises more questions about what are the real mechanisms behind the workings of atypical antipsychotics. Stahl concludes this book by examining the pressing clinical deficits in the pharmacological treatment of schizophrenia. These include that most treatments provide at best partial symptomatic relief; that cognitive deficits that are so debilitating are rarely improved sufficiently and the need for drugs with a quicker onset of action. The volume is very readable and captures the excitement of leading edge research. It promises that there is much to be hoped for in future discoveries for the welfare of patients with schizophrenia. GREGORY DE MOORE Department of Psychiatry, Westmead Hospital University of Sydney NSW 2145 Westmead, Australia doi:10.1016/j.jocn.2004.08.001
Myopathies in clinical practice P.R.J. Barnes, D. Hilton-Jones. Myopathies in clinical practice, Martin Dunitz Publisher – www.dunitz.co.uk, McMillan Distributor – www.palgravemacmillan.com.au, Cost: A$150.00 approx. In just over 150 easy to read pages the authors have encapsulated all that is necessary to know regarding muscle and neuromuscular junction disease for the clinical neurologist. The first third of the book is devoted to the basic principles of neuromuscular clinical assessment and investigations used. The investigations vary from the simple CK measurement, through basic neurophysiology, biochemical studies, basic muscle pathology, and molecular diagnosis, through to some of the more sophisticated imaging techniques. There is a chapter on neuromuscular treatment which includes both specific management of muscle diseases, as well as a discussion of more general aspects, particularly respiratory assessment and care. The text is well supported by clinical
Book reviews
Dopamine in the Pathophysiology and Treatment of Schizophrenia Shitij Kapur, Yves Lecrubier (Eds.), Dopamine in the Pathophysiology and Treatment of Schizophrenia. Martin Dunitz, London and New York, pp. 259. USD $60.00 (approx.) This compendium of 12 chapters explores the role of dopamine transmission in schizophrenia. Put together as a result of the Summer of 2000 Montreal meeting which brought together key people in the field, it spans the historical context of the discovery of chlorpromazine and the myriad of research directions being pursued. The book examines the historical development of how dopamine came to play such a central role in the understanding of the pathogenesis of schizophrenia and how it has re-emerged with different permutations over the past 50 years. The meetings itself was partly a review of the current status of research but also a celebration of the discovery of chlorpromazine only 50 years beforehand. This historical thread runs through the book and emphasises the newness of the field. The various authors are intrigued by the directions research has spread, only to more recently conclude that the original hypothesis regarding the importance of D2 receptors still has a tenacious hold on our understanding of how antipsychotic medications may work. In the opening chapter Carlsson vividly recalls some of the defining moments of the history of dopamine research. Recalling how the synthesis of chlorpromazine led Jean Delay and Pierre Deniker in 1952 to test this new drug on psychotic patients, readers are invited to share in the excitement of these initial discoveries and the start of a complex detective story. Chapters vary from those with little clinical perspective, to those, perhaps the more interesting, that try to integrate psychopharmacology, neuroimaging and the subjective experiences of the patient with schizophrenia. It comes alive and is most readable when the authors place the neuroimaging and biochemistry in the context of what a clinician sees and hears from his patients. For the clinician the going can be heavy in some sections if some of the anatomical pathways and receptor profiles are not familiar. Given the anatomical nature of much of the discussion the book could have been improved by higher quality images of the various neuroanatomical pathways and receptor locations. Nonetheless the key pathways and receptor locations are repeated in several chapters until familiarity is achieved. The principal dopamine pathways – nigrostriatal, mesolimbic and mesocortical are outlined, their possible links to the production of psychosis and how different medications may act are covered in several chapters. The volume includes many tables with no shortage of data and is well referenced. The classical dopamine hypothesis holds that hyperactivity of dopamine transmission results in the positive symptoms of schizophrenia. This initial understanding of an increase in dopamine function in schizophrenia is explored and various alternative hypotheses that flow from this concept, such as dopamine instability, rather than continuous elevation of activity, are critiqued. Despite dopamine’s central role in this book, other neurotransmitters systems such as glutamate and serotonin are canvassed and discussed as to their varying contributions in the pathogenesis of schizophrenia. This is particularly so when discussing how the 508
newer ‘atypical’ antipsychotics may work. It is made clear that despite all the advances, it is uncertain as to how antipsychotic drugs bring about their beneficial effects. Throughout the volume courses a thread of whether the most fruitful research lies within the dopamine system or in the exploration of other neurotransmitters systems. A preoccupation with the role of dopamine receptors has in the opinion of the some of the researchers led to a narrowness of perspective that has inhibited research. The uncertainty of how antipsychotics bring about their therapeutic effects is brought home clearly with two chapters exploring the atypical ‘atypical’ antipsychotic amisulpride. A somewhat paradoxical atypical antipsychotic, amisulpride with its pure dopaminergic blockade is effective in controlling positive and negative symptoms with minimal extrapyramidal side effects. Other atypical medications have a broader receptor profile and have led to notions that these different receptors systems are involved in the production of psychosis. Amisulpride, widely used in the treatment of schizophrenia has a clinical profile similar to other atypical antipsychotics such as quetiapine, risperidone and olanzapine but its receptor profile is almost entirely D2 and thus raises more questions about what are the real mechanisms behind the workings of atypical antipsychotics. Stahl concludes this book by examining the pressing clinical deficits in the pharmacological treatment of schizophrenia. These include that most treatments provide at best partial symptomatic relief; that cognitive deficits that are so debilitating are rarely improved sufficiently and the need for drugs with a quicker onset of action. The volume is very readable and captures the excitement of leading edge research. It promises that there is much to be hoped for in future discoveries for the welfare of patients with schizophrenia. GREGORY DE MOORE Department of Psychiatry, Westmead Hospital University of Sydney NSW 2145 Westmead, Australia doi:10.1016/j.jocn.2004.08.001
Myopathies in clinical practice P.R.J. Barnes, D. Hilton-Jones. Myopathies in clinical practice, Martin Dunitz Publisher – www.dunitz.co.uk, McMillan Distributor – www.palgravemacmillan.com.au, Cost: A$150.00 approx. In just over 150 easy to read pages the authors have encapsulated all that is necessary to know regarding muscle and neuromuscular junction disease for the clinical neurologist. The first third of the book is devoted to the basic principles of neuromuscular clinical assessment and investigations used. The investigations vary from the simple CK measurement, through basic neurophysiology, biochemical studies, basic muscle pathology, and molecular diagnosis, through to some of the more sophisticated imaging techniques. There is a chapter on neuromuscular treatment which includes both specific management of muscle diseases, as well as a discussion of more general aspects, particularly respiratory assessment and care. The text is well supported by clinical