Archive for October, 2009

Molecular Neuropathology

Molecular Neuropathology

G Roberts, J Polak, editors

New York: Cambridge University Press; 1995. 190 p

For most practicing pathologists, many aspects of the world of molecular biology remain enigmatic. This is not surprising, as no full-time molecular biologist has a grasp of all developments in this rapidly expanding field. As new techniques are developed and polished, they gradually enter into the realm of clinical practice. We have experienced the growing pains of immunohistochemistry and autoradiography, and now they are beloved adult members of the family, if you will excuse the analogy, acting up only on occasion and usually with good reason. In situ hybridization is still a mischievous, often frustrating toddler, but is gaining trust and increasing utility as techniques become more reliable and practical. Ribonucleic acid- and deoxyribonucleic acid (DNA)-based technologies are the latest on the scene: new-borns full of potential (good and bad). The latter have had tabloid success in the form of DNA fingerprinting in forensic investigations. Their clinical utility is beginning to be realized in the form of probes to DNA sequences and gene products that may be prognostically significant and in the identification of infectious organisms that are present in amounts too small to detect by other means. As with many new technologies, polymerase chain reaction (PCR)-based techniques have strengths and weaknesses that are one and the same. The exponential amplification that makes them useful can likewise make them misleading and therefore harmful in the hands of the careless or unwary.

Molecular Neuropathology provides a thorough review of the techniques that have become valuable parts of neuropathology services and neuroscience laboratories around the world. It also leads the reader into areas of more recent development and smooths this introduction by means of examples. For instance, the chapter on amyloidoses highlights the various ways by which molecular techniques have elucidated pieces of the pathogenetic puzzle. By analogy, readers can well imagine a similar impact on their own areas of interest.

The book is best suited for practicing pathologists, especially neuropathologists and their trainees as well as members of the neuroscience community who use human tissue in their research. It is styled as an introductory text, not intended for reference use, although there are a number of well-chosen aphorisms and “tricks of the trade” from experts in the field. The main intentions of the book are to provide an account of the breadth of molecular neuropathology and to invite readers to explore specific details and experimental applications in their own work. It does a good job of satisfying these goals. The book will help the reader become familiar with techniques in tissue storage and fixation, ribonucleic acid isolation and analysis, PCR technologies, in situ hybridization, immunocytochemistry, autoradiography, and image analysis. The applications demonstrated include human prion diseases, cerebral amyloidoses, intracerebral transplantation, and transgenic animal models.

Overall, the book is clearly written and concise. It is also well conceived, as there is no other text in this style with special reference to molecular aspects of neuropathology. References are, for the most part, representative, and the authors have presented us with up-to-date information on the topics of discussion. One minor criticism is the paucity of references in some chapters from 1993 to 1995 (its year of publication), but this has not had a significant effect on the utility of the book. The reader is guided through accounts of immunohistochemistry and in situ hybridization that are appropriate in depth. The chapters on nucleic acid-based technologies are heavier on technical details, leaving insufficient room to explain theory and logic more simply and completely. This is the only real complaint, but it is a valid one because I believe this to be the component of the book that needs the most explanation. The applications to research on cerebral amyloidoses and prions are good and lend concrete examples to the techniques discussed. Likewise, the chapters addressing intracerebral grafting and transgenics provide other practical insights to the tools of the molecular trade that have made these invaluable opportunities possible.

In summary, it is easy to recommend this very readable, informative, and encouraging book. As an introductory text, it will serve you well. Where technical details are not addressed, appropriate references are given. Finally, it is very reasonably priced.

Akathisia and Restless Legs

Akathisia and Restless Legs

P Sachdev

New York: Cambridge University Press; 1995. 425 p

This book provides the most comprehensive review to date on akathisia, restless legs, and neuroleptic-induced dysphoria. The volume is divided into 4 distinct parts. Part 1 provides a historical review of akathisia and restlessness as well as a concise and excellent review of neuroleptic-induced dysphoria. Part 2 focuses extensively on drug-induced akathisia. The definition, epidemiology, differential diagnosis, and clinical characteristics of both acute and tardive akathisia are well presented. Assessment procedures are discussed, as are the etiology, pathogenesis, and treatment of the disorder. Part 3 reviews the clinical features, pathophysiology, and treatment of restless legs syndrome. Part 4 offers the reader a summary and recommendations for future research followed by appendices of 4 akathisia clinical rating scales.

In part 1, the book offers a detailed introduction to the development of the concept of akathisia, which was 1st reported by Thomas Willis (1621-1675). The term “akathisia” translated from its Greek root, however, means “not to sit” and was 1st used by Lad Haskovec in 1902. Ekbom introduced the term “restless legs syndrome (RLS)” in 1945 and described the most characteristic symptom of this disorder as “creeping or crawling sensations most frequently localized to the lower leg.” By the 1960s, RLS was firmly established as a neurological disorder, albeit of unknown etiology. After antipsychotic drugs became widely available, a number of reports of akathisia appeared in the literature, with descriptions of patients being restless, being unable to sit, or marching like soldiers. In spite of the few interesting papers examining the psychological and psychodynamic meaning of the akathisic reaction, consensus emerged in the early 1960s that akathisia was an extrapyramidal side effect (EPS) of neuroleptic medication.

Acute akathisia (AA) refers to akathisia that develops soon after the introduction of neuroleptic drugs; by contrast, tardive akathisia develops as a delayed side effect of long-term neuroleptic medication.

Akathisia is often used synonymously with neuroleptic-induced restlessness, yet the term was introduced well before neuroleptic drugs became available. In the clinical setting, restlessness can be caused by psychological factors, organic disorders (drug-induced disorders, drug withdrawal reactions, delirium, dementia, head injury, hypoglycemia, and RLS), and nonorganic psychiatric disorders (affective disorders, psychotic disorders, anxiety disorders, and childhood disorders like attention-deficit hyperactivity disorder).

The author distinguishes 2 aspects of restlessness — a motor (objective) component and a mental (subjective) component — and suggests a comprehensive operational definition.

The motor component of restlessness is typically considered to be under voluntary control; there is, however, a compelling need to move, and suppression of movement results in mounting distress. Sachdev reminds us that the functional neuroanatomy and the neurochemical basis of restlessness remain poorly understood. In many cases, restlessness must be treated because of its negative impact on the patient and caregivers. It is important, however, to identify and, if possible, to rectify the various psychological, social, and environmental determinants of restlessness. Drug therapy may be required to reduce motor activity and subjective distress. The choice of a particular drug is guided by the setting and the possible etiology. Neuroleptics are probably the drugs most commonly used for the management of agitation in dementia and delirium. Benzodiazepines are used quite extensively in the treatment of agitation, and a number of studies attest to their efficacy in some patients.

Neuroleptic drugs induce unpleasant subjective effects among healthy controls and in many psychiatric patients. A dysphoric response is often a predictor of neuroleptic non-compliance. The manifestations of neuroleptic-induced dysphoria (NID) are varied and range from complaints like “the drug disagrees with me” and “I feel emotionally unresponsive” to neuroleptic noncompliance, anxiety and dere-alization, school and work avoidance, painful sensory symptoms, and even depression. The question of whether or not NID can also manifest as a cause of or contributor to depression is a controversial issue that remains to be resolved.

NID may result in a poor outcome, but while many NID patients become noncompliant, others benefit from dysphoria by negotiating with their psychiatrists for lower yet effective doses of neuroleptics, resulting in less severe EPS. The neurobiological basis of NID remains poorly understood.

While the importance of akathisia is now well recognized, there is no consensus on its essential characteristics and hence its diagnostic criteria. The essential features of drug-induced akathisia (DIA) are: 1) exposure to neuroleptic drugs; 2) subjective component: feelings of restlessness, constant urge to move the legs, difficulty or inability to maintain a posture for several minutes; 3) objective component: movements while sitting, standing, or lying. The assessment scale Sachdev uses is the Prince Henry Hospital Akathisia Scale, which includes 3 subjective items, 7 objective items, and a global akathisia score. Sachdev also proposes detailed criteria to diagnose akathisia. It is appropriate to consider onset of symptoms after 3 mo of continuous use of the drug without change in dose or type as tardive akathisia. Onset within 6 weeks of stopping or significantly reducing the dosage of a neuroleptic drug should be considered a withdrawal akathisia, and if the diagnosis of akathisia persists beyond 3 mo after drug cessation or reduction, tardive akathisia should be diagnosed. Akathisia that continues for 3 mo or longer is considered to be chronic.

The published rates of AA with conventional neuroleptics vary from 8% to 76%. A conservative estimate of the incidence of akathisia with classical neuroleptics at clinical dosage levels is about 20% to 30%, but this rate is significantly affected by treatment-related and other variables (parenteral administration and drug potency, for example). Akathisia can also be induced by novel or atypical neuroleptic drugs. Current evidence suggests a reduced rate of AA with these novel agents, and further systematic work is necessary. Nonneuroleptic drugs that can also induce AA include serotonin reuptake inhibitors, serotonin antagonists, heterocyclic antidepressants, anticonvulsants, calcium channel antagonists, and lithium carbonate.

There are no accurate estimates available as to the prevalence or incidence of tardive akathisia, and data on the epidemiology of withdrawal akathisia are extremely limited. In children and adolescents, drug-induced movement disorders have been poorly documented, and akathisia has been relatively neglected. In individuals with developmental disabilities on long-term neuroleptic medication, akathisia appears to be common, but the overall data are too few to make comparisons with nondisabled populations. In the geriatric population, reports of akathisia have been few.

The main feature of AA is subjective distress. In its milder form, it is experienced as a vague feeling of apprehension, irritability, dysphoria, impatience, or general unease. While the restlessness of akathisia may be felt in the mind or body or both, the characteristic that distinguishes it from restlessness of other etiology is its reference to the lower limbs. The movements are described as a response to an irresistible urge to move, but the movement alleviates the urge and the distress only temporarily. Akathisia has been associated with psychotic exacerbation, violence, and suicide. Fidgetiness is perhaps the most common motor sign of akathisia and is usually manifest as semipurposive or purposeless movements of legs, feet, and toes. While the emphasis is on leg and postural movements, semipurposeful or purposeless arm and hand movements may occur. Upper limb movements are less prominent and virtually never occur in isolation. Activating maneuvers in the case of akathisia tend to diminish or suppress movements.

Tardive akathisia has not been universally accepted as a distinct syndrome. The phenomenological examination of patients on long-term neuroleptic medication suggests that tardive akathisia is distinct from tardive dyskinesia, with overlap between the 2. “Chronic,” in terms of describing akathisia, refers to the duration of the disorder, irrespective of the nature of onset, whereas “tardive” denotes a delayed onset.

The most popular method of measuring akathisia is with the multiitem rating scales such as the Barnes Akathisia Rating Scale, the Hillside Akathisia Scale, and the Prince Henry Hospital Akathisia Scale. The measurement of akathisia presents a number of difficulties owing to the complex manifestations of the disorder, the lack of a well-accepted definition, and its variability. No instrumental method is totally satisfactory, but a combination of strain-gauge measurements and actigraphy can provide an accurate measurement of the motor component of akathisia.

The etiology of akathisia must be understood in terms of the drugs that are directly causative and in view of a number of background variables that are likely to increase the risk of its development. Its pathogenesis is incompletely understood, and many competing hypotheses exist. tardive akathisia and withdrawal akathisia have not been reported with nonneuroleptic drugs, suggesting that, unlike AA, they may be purely neuroleptic-related syndromes.

Treatments for AA include modification of the offending drug (cessation, dosage reduction, change to another type, reduction in rate of increment); modification of risk factors; and introduction of benzodiazepines, anticholinergic, antiadrenergic (β-antagonists, α2-agonists), or other agents (ristanserin, amantadine, piracetam, tricyclic antidepressants, and sodium valproate). The treatment of tardive akathisia is, in general, unsatisfactory and the main emphasis should be on its prevention.

There is still no consensus on the incidence and prevalence of RLS. Like akathisia, it is characterized by sensory and motor features. The restlessness in RLS is different from the movements seen in DIA. The other main motor feature in RLS is myoclonic jerks. RLS often leads to sleep disruption. The course of idiopathic RLS is variable — starting in childhood, adulthood, or old age, being progressive or staying the same or even getting better. Table 12.5 (p 317-318) contrasts the DIA and RLS disorders clearly. In RLS treatment, clonazepam remains the drug of 1st choice. Although evidence supports the use of 1-dopa, problems with the long-term use of this drug make clonazepam a better initial agent. If 1-dopa is not tolerated, bromocriptine can be used.

In summary, this is a timely, well-written, and well-researched volume. Dr Sachdev is to be congratulated for offering readers the 1st book-length review of akathisia and related syndromes. Undoubtedly, this book will be a welcome reference for psychiatrists and neurologists.

The Natural History of Mania, Depression and Schizophrenia

The Natural History of Mania, Depression and Schizophrenia

G Winokur, MT Tsuang

Washington (DC): American Psychiatric Press; 1996. 372 p

The resident had just presented his formulation of a case. I posited that hysteria might be an important aspect. He seemed genuinely puzzled, even when I told him that terms like “hysteria” and “hypochondriasis” had been available for more than 2 millennia. “But,” he said, “for my boards, I only need to know DSM-IV.”

“Well,” I thought, “if you’re so keen on cookbook psychiatry, why did you not stay with cooking rather than spoiling psychiatry?”

So here is the rub. What are we to do with this charming, scholarly work full of medical science when the psychiatric world has moved as it were, from bookshelves to the Internet? Or is that being too generous? While I acknowledge that the American Psychiatric Association committees have slaved to obtain syndromes made up of a concatenation of symptoms, it might be an overstatement to suggest that these have the same historical significance as the stirrup, the Gothic arch, and the printing press. They might conceivably be compared with gunpowder, however, since it changed the overthrow of castles from sieges lasting several years to crumbling walls in a few days. So the biopsychosocial anamnesis that can take a considerable time to collect might well be thought in the modern era to be replaceable by a convenient American Psychiatric Association cluster analysis.

Nevertheless, the book The Natural History of Mania, Depression and Schizophrenia is based upon the approach recommended by Adolph Meyer at Johns Hopkins at the beginning of this century. What is now called the “biopsychosocial” model is really the same model with a new name and the same methodology by which psychiatric diagnoses and formulations are developed all over the world. Thus psychiatrists in Iowa, London, Sydney, and Bombay have for decades collected the history of the present illness, the family and personal history, and a mental state examination before proposing a formulation for a patient. Examples of these, in copperplate handwriting, lie in the archives of mental hospitals everywhere.

So what is different about Iowa? The answer is professors George Winokur and Ming T Tsuang. Winokur moved to Iowa from Washington University in St Louis a quarter of a century ago. That university, like several in North America and many in Western Europe, did not see psychoanalysis as the Second Coming and fastidiously kept psychiatry on the Meyerian track. In Iowa, Winokur was joined by Tsuang, who eventually became a professor of psychiatry at Harvard. In the best tradition of psychiatric nosology, generously referred to in the preface, they dug like archeologists into their archives and collected a fascinating cache of data hitherto known as the Iowa 500. Case material was available from 1920 and seemed to be comprehensive; thus, “the quality of material in terms of documenting symptomology was quite sufficient for making diagnoses according to modern diagnostic criteria that had been published for research purposes.”

Nevertheless, there is a caveat. Old data have to be updated and massaged as psychiatry goes through another convulsive spasm in terms of the lexicon and nosology. As seen in the Stirling County and Lundby studies, this can be done. So what did they find? A lot. The Iowa 500 was made up of admissions to the Iowa Psychopathic Hospital (later the Iowa Psychiatric Hospital) between 1934 and 1944 and consisted of 100 bipolar disorder, 225 unipolar disorder, and 200 schizophrenia patients (with a few subsequent changes in diagnosis). The study started in 1971 and completed a 27- to 30-y follow-up of a psychiatric population originally “treatment-naive” in modern terms.

The book itself is made up of 15 chapters, and each contains reams of facts. Each chapter requires careful scrutiny. Perhaps the most salutatory is number 15 entitled “The Contribution of the Iowa 500 to Diagnosis and Classification of the Affective Disorders and Chronic Non-affective Psychosis.” Using symptoms, demographic criteria, and admission criteria, the authors demonstrated that the original diagnoses were stable over time. Thus: “These data strongly suggest an unequivocal separation of the primary affective disorders from the chronic non-affective psychoses according to the factors involved in the medical model.”

The authors worked, albeit inconclusively, on schizoaffective disorder (the border state) and on the types of affective disorder and chronic nonaffective psychoses. They concluded that “the Iowa 500 has presented new ways of investigating clinical entities and family illness… However it is clear that psychiatric illnesses or diseases are often composed of overlapping syndromes and . . . subsequent studies should be planned in a different fashion and less clear cut diagnostic groups should be included as index cases.”

Essentially, what we have here is a wonderful, though somewhat old-fashioned (especially the font), longitudinal study in the best psychopathological fashion. It is descriptive, as psychiatry has remained to this day, but many residents will likely, and regrettably, find it anachronistic. For those of us trained in the Meyerian sense in the best psychiatric institutions of Europe, North America, and Australasia, it validates what we have been doing all of these years. It is not about receptors and cookbooks, but it does provide a warm, fuzzy feeling. All who like a historical perspective to their work should read it.

Serotonin in the Central Nervous System and Periphery

Serotonin in the Central Nervous System and Periphery

A Takada, G Curzon, editors

Amsterdam: Elsevier Science BV; 1995. 260 p

This book is part of the International Congress Series and contains the proceedings of the Symposium on Serotonin in the Central Nervous System and Periphery held in Nagoya, Japan, on April 1 -2, 1995. It is comprised of papers presented at the symposium and contains up-to-date information on the area, written by some of its top researchers, who were selected to participate in the symposium based on their expertise. It has become necessary for clinicians and scientists to focus on the basic science and fundamental actions of the new serotonin-acting drugs in order to understand their functions. This book attempts to provide such information in a timely fashion.

There are 7 sections in the book: Regulatory Mechanisms, Relationship with Feeding, Amines and Stress, Depression and Anxiety, Other Central Aspects, Vascular System, and Lung. The most useful and important section is the first, which covers the regulation of serotonin release, genes, and the pathophysiology of affective disorders. Even with a minimum of prior knowledge of the area, the clinician, by reading this section, can gain an understanding of how serotonergic drugs work. The section on depression and anxiety is a must-read for psychiatrists, though the majority of information refers to animal models. The relationship of serotonin and feeding behavior, pre- and postnatal stress reactions, antipsychotic medications, the psychoprotective effect of estrogen, learning and memory, Alzheimer’s disease, and physical health are also covered in the book.

Although this book suffers stylistically because of the number of different authors, it is, overall, a succinct, well-written, and extremely informative text. It provides recent information in the field of serotonin research and could prove to be a valuable teaching and research reference. We highly recommend this book to clinicians, who could apply it in their use of psychopharmacology, to biological researchers, who will find it a useful reference, and to residents in psychiatry, who may appreciate it as a learning tool.

Human Brain Anatomy in Computerized Images

Human Brain Anatomy in Computerized Images

H Damasio

New York: Oxford University Press; 1995. 303 p

This is a very good textbook which is primarily an atlas of normal human brain anatomy, as seen in T1-weighted magnetic resonance images. As such, it is unique in that it provides exquisite detail of the telencephalon and cerebellum of the human brain. In particular, it identifies and localizes the major gyri and sulci of the cerebral cortex in an accurate and unambiguous fashion. The author is a well-known professor of neurology with special interests in human neuroanatomy and neuroimaging. This textbook will probably have an enthusiastic albeit limited audience and will be especially useful for those involved in clinical neurosciences, including neuroradiologists, neurosurgeons, neurologists, and neuropsychologists. It will undoubtedly be a valuable reference text aiding in the exquisite localization of pathological processes.

An introductory chapter elaborates on the Brainvox 3D technique, which allows reconstruction of the brain in 3 dimensions in such detail that all major sulci and gyri can be identified with the same degree of precision that would be attainable on the autopsy table. Moreover, once identified, these sulci and gyri can be color-traced and the outline of the tracer transferred automatically to the original 2-dimensional images, ensuring their proper location. This allows for accurate sulci and gyri localization on the 2-dimensional images independent of the angle of inclination, which often varies greatly in the axial and coronal planes. The 2nd and 3rd chapters are devoted to 2 different normal brains viewed externally from the lateral and mesial surfaces, the superior and inferior surfaces, and from both the left and right sides. Brain A in chapter 2 is of dolichocephalic configuration, brain B in chapter 3 is brachycephalic in type. A brief descriptive outline precedes both chapters. Chapter 4 is devoted to 24 additional normal brains depicted in the lateral mesial surfaces and from the right and left. The purpose of this chapter is to highlight the marked variation present in areas such as the central sulcus, the superior temporal sulcus, and the calcarine fissure. Chapters 5 and 6 return to the original brains A and B. In these chapters, the brains are depicted in 2 dimensions in 5 different angles of inclination relative to the inferior orbitomeatal line (coronal images being perpendicular to their corresponding axial). Additional parasagittal images are obtained parallel to the hemispheric fissure starting from the left and moving to the right. Chapter 6 also depicts 2-dimensional images, but these are of the dolichocephalic type brain B and include only 2 axial and coronal incidences relative to the infraorbitomeatal line and the corresponding perpendicular coronal counterpart. Finally, chapter 7 includes some focal infarcts that are then localized in both 2- and 3-dimensional images to reinforce the usefulness of the presented gyri and sulci anatomical details.

The images are of good quality and are well labeled by arrows and abbreviations; a complete table of abbreviations of all the relevant sulci, gyri, and midline structures is also included. Additionally, chapters 3 and 5 include color tracing to identify individual gyri, sulci, and lobar subdivisions. This is especially effective in transposing these images from 3 to 2 dimensions.

In summary, I can recommend this textbook as a reference for those departments involved in clinical neuroimaging or as an anatomical atlas for those interested in the detailed topographic anatomy of the brain as related to clinical imaging.

NMR Spectroscopy in Psychiatric Brain Disorders

NMR Spectroscopy in Psychiatric Brain Disorders

HA Nasrallah, JW Pettegrew, editors

Washington (DC): American Psychiatric Press; 1995. 260 p

Every year the American Psychiatric Press publishes several books in the Progress in Psychiatry series based on some of the best symposia presented at the American Psychiatric Association’s annual meeting. The symposia themselves are focused on a particular problem or emerging area of psychiatry and are specifically designed to bring experts together to share their understanding, insights, and directions for future research. The books in this series build on the process begun at the symposia. In publishing the distilled knowledge of leading researchers, the books help “nonexperts” to acquire quickly a sophisticated understanding of areas of psychiatry that are complex or new.

NMR Spectroscopy in Psychiatric Brain Disorders is volume 47 in the Progress in Psychiatry series, and it clearly fulfills the promise of the series to provide “innovative ideas” in a “timely” manner. Nuclear magnetic resonance spectroscopy (NMRS or MRS) is a technique that has been used for many years in basic sciences, but only in the past decade has it been applied to in vivo studies of the human brain. Depending on the technique used, different chemical moieties are “visible” as peaks on a spectrum. For example, N-acetyl-aspartate (a presumed neuronal marker), lactic acid, and glutamate all produce peaks on proton (1H) NMR spectra, while phospholipids and high-energy phosphates such as adenosine triphosphate (ATP) produce peaks that are best resolved using 31P MRS. If it is a “pure” peak, the area under a spectral peak is proportional to the concentration of the particular chemical. What makes MRS particularly enticing to clinician-researchers is that it is a noninvasive approach permitting in vivo biochemical studies without exposing patients to ionizing radiation and that much of the hardware required (for example, magnet, computer) is already available in clinical settings with magnetic resonance imaging.

Each of the 11 chapters of this book is authored by, and represents the work of, 1 of 9 groups currently involved in the application of NMRS to psychiatry. (Two groups have earned 2 chapters.) The 1st 6 chapters examine applications of MRS to the study of psychoses, predominantly schizophrenia. Many of the pilot studies described in these chapters compared concentrations of various metabolites in particular brain regions in different populations. For example, phospho-monoesters (phospholipid precursors) were found to be decreased and phosphodiesters (phospholipid breakdown products) were increased in the prefrontal cortex of 1st-episode, neuroleptic-naive patients. This is the only finding that has been replicated. Other results are conflicting or awaiting replication. Many findings are presented in terms of their consistency with other research in schizophrenia. For example, increased ATP and decreased inorganic phosphate (P1) in the prefrontal cortex is interpreted as being “consistent with” the hypothesis of hypofrontality in schizophrenia (p 65). Preliminary findings in other areas of psychiatry include increased brain lactate levels in patients with panic disorder; transiently increased “lipid” levels (which are believed to be free fatty acids) following electroconvulsive therapy; and whole-brain lithium concentrations that are 40% to 70% of serum levels. In addition to lithium, there are several fluorinated psychotropic medications that are “visible” to MRS and thus amenable to in vivo pharmacokinetic studies (including fluoxetine, haloperidol, fluphenazine, and flurazepam). Precise localization of these drugs in the brain has been limited by technical problems, but it is expected that current constraints will eventually be overcome.

In many respects, this book is like a collection of papers, with each chapter including its own background information on the MRS technique. Unfortunately, this resulted in unnecessary repetition of some basic principles of MRS in nearly every chapter, while other fundamental concepts were not addressed until quite late in the compilation, if at all. As well, more in-depth discussions of technical refinements are scattered throughout the book. This fragmented presentation of technical information was not easily assimilated. An introductory chapter dedicated to providing a comprehensive overview of the technical aspects, including limitations, of MRS would have been preferable. Such an introductory chapter would have been useful as a reference both for subsequent chapters (when concepts are revisited) and for future readings of the literature. Similarly, an early chapter with an overview of the biology of some of the compounds that are visible to MRS (such as phospholipids and high-energy phosphates) would also have been helpful as a reference.

Despite these limitations, the authors have clearly met the goals of the series by amassing an impressive body of knowledge in a new field. They are particularly careful to include as much background biology as necessary to ensure the reader fully understands the rationale for and implications of their studies. Where possible, the authors have indicated how their findings compare with other imaging, postmortem, animal, and in vitro studies. This book certainly provides more than enough background for readers who wish to follow this emerging literature. For those wanting to pursue studies using MRS, it is a point of departure only, providing an overview of all the current (as of 1995) applications of this technique to psychiatry, as well as important references. Because MRS is evolving as an in vivo technique, new researchers in this field will need to be as concerned with technical issues as the current group of authors have been. Let us hope that future developments will prove that MRS has truly opened a new “window” on the brain.

Clinical Guide to Alcohol Treatment

Clinical Guide to Alcohol Treatment: The Community Reinforcement Approach

RJ Meyers, JE Smith

New York: Guilford Press; 1995. 215 p

Robert Meyers from the Centre on Alcoholism, Substance Abuse and Addictions (CASAA) and Jane Smith from the Department of Psychology, both from the University of New Mexico, have authored a pragmatic “how-to” instruction book on the Community Reinforcement Approach (CRA) to alcohol treatment. CRA is listed in the US Institute of Medicine’s report on alcohol problems as a contingency management approach designed to provide focused behavioral training to persons with chronic alcohol problems (Institute of Medicine 1990). This approach remains unfamiliar to many clinicians in the field although several grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse have been provided to enrich its research basis.

The 1 st chapter outlines the approach’s empirical pedigree dating back to the work of NH Azrin and his group in 1973. The reinforcers used were access to family, to jobs, and to friends, which were contingent on sobriety. In a series of trials, CRA procedures improved the outcome of traditional 12-step programs, monitored disulfiram compliance, and enhanced an alcohol-free recreational environment as well as the involvement of concerned others. These procedures have also been applied to the management of cocaine and heroin abusers and, more recently, to an alcohol-abusing homeless population.

The book’s main contribution lies in the next 10 chapters. Five chapters provide detailed instruction in the CRA assessment procedure, an intriguing approach to facilitating a client’s acceptance of the need for sobriety through a contractual “time-limited sampling” period, the optimal use of disulfiram, and the planning of a treatment protocol using a quality of life scale and identification of counselling goals. The remaining chapters describe procedures to be used for behavioral skills training as well as coping strategies at work, in one’s social interactions and significant relationships, and in relapse prevention.

The highlights of the book for me were the tables appended at the end of each chapter that could be readily adapted by therapists to their own practice. The book is a good primer for those interested in developing their cognitive-behavioral skills with substance abusers. Some procedures may be more controversial or dated than others. For example, recent studies have provided mixed evidence regarding the usefulness of disulfiram (Institute of Medicine 1990). Will the use of naltrexone replace disulfiram as a preferred pharmacotherapy?

As highlighted by the Director of the Research Division at CASAA, Dr WR Miller, many of the procedures included in the original CRA trials, such as motivational preparation and early relapse prevention strategies, have become important elements in today’s treatment programs and have gained more recognition than their predecessors. Elements of the CRA have been incorporated as part of the cognitive-behavioral intervention to be tested in Project MATCH (1994), the current NIAAA-funded multisite clinical trial of patient-treatment matching.

This book’s content is suitable for a multidisciplinary team dedicated to the field of addiction and for the psychiatric resident or psychiatrist searching for ways to enhance his or her skills with this challenging population. The cost of the book is reasonable.

Medical-Psychiatric Practice

Medical-Psychiatric Practice. Volume 3

A Stoudemire, BS Fogel, editors

Washington (DC): American Psychiatric Press; 1995. 625 p.

Medical-psychiatry (alias consultation-liaison psychiatry, alias psychosomatic medicine) continues to have an identity problem. This is exemplified by its continued search for a name and also by continued uncertainty about its defined area of knowledge. In the United States of America, perhaps more so than in Canada, it is also being affected by economic factors involving health insurance coverage.

In their preface to this the 3rd volume of their series covering the field of medical-psychiatric practice, the editors review the crisis taking place in American psychiatry. They focus on 3 factors: the economics of health care, which discourages referrals to consultants and other specialists; pressure and competition from nonmedical professionals; and the difficulties of recruitment of medical graduates into psychiatry. These difficulties, ironically, are occurring at a time when psychiatric therapies are not only clinically effective but also economically efficient. The editors recommend that the most effective way for psychiatry to counter these pressures is to maintain its close connection to the medical model but to emphasize also its base in the social sciences and humanities. There is no other professional discipline that bridges these spheres of knowledge to an equivalent degree, and the subspecialty of medical-psychiatry is at a leading edge of this development.

The 10 chapters in this volume deal with psychopharmacokinetics and psychopharmacology in medical patients, psychosis in Parkinson’s disease, psychiatric aspects of systemic lupus, HIV infection, bone marrow transplantation, and mild traumatic brain injury. The book also includes chapters on “chemical sensitivity” syndromes and on vulvodynia.

All the chapters are well referenced and have a comparable structure suggesting good editorial control. I particularly appreciated the scholarly and sensitive way that the complex topics of brain trauma and chemical sensitivities were discussed. Chemical sensitivity is a politically explosive area that, whether we like it or not, is assuming increasing importance in the clinical practice of many psychiatrists.

The 3 volumes of this series as a whole can be criticized for the apparent lack of an overall plan. Some topics are dealt with intensively and comprehensively, for example, psychopharmacology, HIV, and the neurological aspects of psychiatry; others are dealt with poorly or not at all, for example, respiratory, gastrointestinal, musculoskeletal, and conversion disorders. This suggests that the editors themselves are not certain which areas should be covered in a compendium of medical psychiatry. These shortcomings make it difficult to recommend this series as the “Bible” of medical-psychiatry. They are likely best used as reference books for residents and psychiatrists requiring updated reviews on particular topics. For this purpose, these volumes can be highly recommended.

The cost of this book was not available in the book reviewed.

Handbook of Culture and Mental Illness: An International Perspective

Handbook of Culture and Mental Illness: An International Perspective

I Al-Issa, editor

Madison (CT): International Universities Press; 1995. 391 p

With the hectic pace of travel, migration, and social change of the modern world, psychiatrists, mental health professionals, and trainees can expect to see people from all continents and many cultures. Moreover, they are required to be knowledgeable about and sensitive to the different backgrounds of these people and to be able to make a diagnosis, understand the psychopathology, and conduct a treatment relevant to these cultures. This is a tall order. How can any single professional become acquainted with, let alone gain expertise about the predominant cultures in each continent? These are precisely the goals that the body of knowledge and practice called cultural psychiatry or transcultural or cross-cultural psychiatry has been pursuing over the past few decades. The burning question, then, is how far can Dr Al-Issa’s book advance the practitioners, teachers, or trainees in this field in their endeavors to understand and treat effectively people from all continents and main cultural groups with full awareness and systematic use of their background and experiences? The brief answer is that indeed this book advances the body of knowledge very significantly in this direction.

The volume has a simple and bold structure. Its main parts are dedicated to Africa, Asia, Australia, the South Pacific, Central and South America, and Eastern and Western Europe; within each part about 5 specific countries or cultures are presented in terms of historical background, epidemiology of illness, cultural context, psychopathology, and treatment practices. Ethnic groups and minorities, including immigrants and aboriginals, are dealt with in a special chapter at the end. The introductory chapter by Dr Al-Issa offers an international perspective on the main psychiatric syndromes, including somatization and alcohol abuse, and on ethnic and immigrant minorities. Dr Al-Issa shows both a command of the broad field of epidemiology, including the most recent studies of the World Health Organization and associate groups, and a critical focus on controversial issues, for example, somatization in Third World versus industrial societies, multiculturalism as potential neoracism, or the suggested incapacity of some “non-Indo-European languages to differentiate between some emotions” (p 21). It closes with about 150 well-selected references that would be extremely helpful to any trainee or researcher.

The chapters that follow are innovative and mark a new era in cultural psychiatry. All of the leading books on cultural psychiatry of the past 4 decades were wholly or partially written or edited by Western-trained and -rooted professionals such as Ari Kiev, Transcultural Psychiatry (1972); HBM Murphy, Comparative Psychiatry (1982); or even I Al-Issa’s previous book, Culture and Psychopathology (1982). By contrast, all 24 chapters of this volume are written singly or in coauthorship by professionals who, by all indications, practice or have roots in the culture on which they are reporting. Clearly, they are also highly trained in Western medicine and psychiatry and maintain ongoing contacts with Western ideas and practices. One or 2 exceptions might be the report on the Inuit in Greenland and possibly the Maoris from New Zealand. This knowledge of both worlds is manifest in the twin advantages of sophisticated Western epidemiological knowledge and intimate understanding of cultural dynamics, psychopathology, and native treatment modalities. In this respect, this volume is also politically correct: nobody could accuse the authors of “stealing a people’s voice,” since they are themselves of those peoples.

Africa is represented by Egypt, Nigeria, Tanzania, South Africa, and French West Africa. All are most interesting and well-documented chapters. Especially rich is the chapter on West Africa. To the pioneer work of Henri Collomb in Dakar and the psychoanalytical work of E and M-C Ortigues on the African oedipus is added a review of the work of Andras Zempleni on the transformation of persecutory ideas and agents into modes of control of individual anger and the development of inner self as a psychological space. Self psychologists would find these ideas of special interest.

The chapter on India is also exceptional. VR Varma, based on his own work in the Indian continent, addresses 2 frontline issues in the development of or controversy about cultural psychiatry: cultural formulation and basic or ethnic “modal” personality. The issues, of course, are not resolved but are considerably elucidated.

The chapter on Jamaica, or rather Jamaicans at home and abroad, deals with the perennial theme of culture and personality and attempts to explain the high rates of schizophrenia diagnosed in Western mental hospitals. It is a matter of some curiosity that this phenomenon has been well researched in Great Britain, but not in Canada, where, since the 1970s, some 100 000 West Indians have arrived. The chapter on immigrants and minorities in Great Britain shows excellent documentation on the Irish, Jewish, and West Indians, but a similar vacuum is left in the book with respect to minorities in Canada.

Mexico, Uruguay, and the Iberian Peninsula (primarily focused on Spain) are dealt with in terms of epidemiology and, rather weakly, cultural dynamics. Important in Spain are the high rates of alcoholism, migrant adaptation, and the burden on families of the “new chronic” mentally ill population after the poorly coordinated mental health reform of 1986.

The critical, often refreshing approach of the book is shown once more in the chapter on Germany where, applying to this industrial society the same standards as one would use on any Third World country, we discover that about half to one-third of the clergy believes in demonic possession and exorcism. Of course, the sad legacy of Nazism is briefly examined, revealing that much denial and avoidance apparently still persists among the medical profession.

The chapter on Hungary is a masterpiece on the epidemiology and dynamics of suicide, topics on which the authors, Buda and Furedi, are experts. The chapter on multicultural Australia, which reviews adequately the work of Krupinski and colleagues, should be of great interest to Canadians as we share the same British traditions and institutions, a recent multicultural immigrant community, and a native population.

The chapters on Egypt include references to the seminal contributions of Ahmed Okasha to the epidemiology and dynamic understanding of suicide, somatization, and the rituals of Zar. Including a chapter on Turkey, the book provides a good report on Islamic societies, never adequately treated in this type of volume until now. The chapter on Israel deals extensively with the issue of religion, intragroup variations, and posttraumatic stress disorder, referring to the comprehensive work of Dasberg on holocaust survivors and more recent civilian and military populations exposed to the trauma of war and armed conflict. South Korea, Singapore, and Bali (Indonesia) are Asiatic countries with epidemiological information limited to key issues: suicide, substance abuse, and culture-bound syndromes such as epidemic koro and hysteria, somatization, and illness behavior in various groups. In South Korea, a traditional country in the process of rapid modernization, the majority of people tend to use both traditional and modern therapies and remedies.

There are necessarily deficits or limitations to be found in a book of such ambitious scope. Russia or any country of the former Soviet Union, China, the United States of America, and Canada are not included. On various issues, however, the references to North America and China are plentiful, and one gets some idea of sociocultural variations in these regions. Dissociation is not listed in the subject index, although frequent references exist throughout the text when it deals with possession states and hysterical psychosis. Posttraumatic stress disorder, a major issue in refugee populations at present, has only a few references. There is not a single reference on psychopharmacology or biological studies among the various ethnic groups.

I would recommend this book to practitioners and trainees in psychiatry, psychology, and social work because the advances reported in the dynamic understanding of cultural groups will be helpful in clinical practice.

Basic Neurochemistry: Molecular, Cellular and Medical Aspects

Basic Neurochemistry: Molecular, Cellular and Medical Aspects

GJ Siegel, editor

New York: Raven Press; 1994. 1080 p

This multiauthor volume (80 contributors) is a 5th edition of the book published under the auspices of the American Society for Neurochemistry. The 4th edition was published in 1989 under the same editorship. The book is divided into 6 parts: neuronal membranes, synaptic function, molecular neurobiology, cellular neurochemistry, medical neurochemistry, and behavioral neurochemistry. Each part contains several (from 3 to 14) chapters; there are 50 chapters in total. Each chapter is further divided into sections and has a separate bibliography.

Rapid advances in the field of neurosciences and a virtual explosion of information in areas of molecular biology and genetics during the last several years have presented the editors with the enormous challenge of conveying the material in a comprehensive yet readable manner within a single volume. It appears that they have successfully met this challenge. They have expanded the book by only about 100 pages in adding new chapters on the molecular basis of olfaction and taste, neurotransmitter and growth factor receptor families and 2nd-messenger signaling systems, amino acid and purinergic neurotransmission, neurotransmitter uptake system, and molecular targets of drugs of abuse. Many other chapters have been revised or rewritten to include new information on amine transmitters, eicosanoids and neuronal function, developmental neurobiology, gene expression, aging, cytoskeletal development and plasticity, and cognitive functions. An important new feature of this edition is the introduction of color plates for figures and tables and color subheading summarizing key concepts. The cartoons illustrating important concepts and mechanisms are instructive, and some of them use witty symbols (turtles) to indicate various pathways. They are easy to follow and to read. It is, though, a pity that 2 chapters in the behavioral neurochemistry section do not have any illustrations. All of these features make this volume virtually a new book, more readable and appealing than the last edition.

The 2 parts of the book with most extensive coverage of the subject are synaptic function and medical neurochemistry. I found the part on synaptic function well balanced and coordinated with excellent chapters on neuronal proteins and role of protein phosphorylation in regulation of neuronal function. The receptor classification is up to date (that is, to the book’s publication date). The readers will notice that some classifications have changed and new receptors have been identified since the book has appeared. An example at hand is the 5-HT1c receptor that is now classified as a member of the 5-HT2 receptor family (5-HT2C receptor). In addition, 5-HT2A and 5-HT2B receptors have been identified as distinct receptors. The part on medical neurochemistry includes chapters dealing with bio- and neurochemistry of some muscular disorders, vitamin and nutritional deficiencies, neuropathies, myelin diseases, metabolic disorders, drug abuse, ischemia, epilepsy, basal ganglia disorders, and Alzheimer’s disease. A chapter on brain imaging emphasizes the important role of positron emission tomography in studying brain function. Perhaps other techniques (magnetic resonance imaging [MRI], single photon emission computed tomography [SPECT]) could also have been described, at least briefly.

The behavioral neurochemistry part contains chapters on biological aspects of psychotic disorders, hypotheses of mood and anxiety disorders, as well as chapters on learning and memory. It was slightly disappointing to this reviewer that psychiatric disorders received much less prominent treatment than some neurologic disorders (for example, epilepsy). The chapter on mood disorders is actually confined to biochemical hypotheses without presenting some at least illustrative biochemical and clinical data. In this chapter, all hypotheses are given equal importance, although evidence would indicate otherwise (for example, importance of the serotonergic versus the cholinergic system). One of the important hypotheses of depression and mode of action of antidepressants involving adaptive changes of presynaptic 5-HT1A receptor is not even mentioned, though it is often quoted in other textbooks.

Considering that the volume has so many contributors, the chapters are, on the whole, well balanced, and the style of introducing concepts, supporting evidence, illustrations, and conclusions is remarkably uniform. Credit for this goes undoubtedly to the editors. The quality of print and reproductions is high. This is a book that should be a part of the personal library of any worker in the various fields of neuroscience, clinical medicine, and psychiatry who look not only for factual information but also for a feast of ideas.