Liberman and Corrigan stated in a 1992 editorial in the Journal of Neuropsychiatry and Clinical Neuroscience, “The question is no longer whether schizophrenia is a brain disease but rather what type of disease underlies its characteristics, symptoms, signs, and associated disabilities” (p. 119). It has been 13 years since Liberman and Corrigan wrote this editorial, and there has been a steady increase in the interest in schizophrenia among neuropsychologists as judged by the quality and quantity of papers presented at professional meetings and published in neuropsychology journals. In the April 2005 issue of The American Psychologist, Heinrichs asserted that effect sizes derived from neuropsychological tests of memory, attention, language, and reasoning are twice as large as those obtained from neuroimaging studies on individuals with schizophrenia. He concludes that “schizophrenia is a complex biobehavioral disorder that manifests itself primarily in cognition.” (p. 229). However, large effect sizes on neuropsychological tests are considerably “downstream” from the genesis of the disorder, which is widely believed to be neurodevelopmental in nature, rather than neurodegenerative. What is the neuropathological mechanism that underlies this complex cognitive disorder? This book, Neurodevelopment in Schizophrenia, is an edited volume that brings together basic and clinical neuroscientists who are trying to answer this question—what is the disease mechanism underlying schizophrenia that derails normal neurodevelopment?

The book is organized into four sections: Basic Concepts, Etiological Factors, Pathophysiology, and Clinical Implications. In Part I, Basic Concepts, normal brain development, including genetics, structure, cognition, and neuronal plasticity are reviewed. Chapter 1 provides a very detailed overview of genes and brain development. There are two neuroimaging chapters in Part I. Chapter 2 is a very brief (7 pages) overview written by Giedd et al. from the NIMH Child Psychiatry Branch project on neuroimaging healthy children and adolescents. Chapter 3 by Luna and Sweeney on functional magnetic resonance imaging and cognitive development in ADHD, dyslexic, and high-risk children of schizophrenic parents was well explained and easy to follow. Chapters 4 and 5 discuss cognitive development in adolescence, and brain plasticity and long-term function after early cerebral insult. These chapters include a discussion of how alterations occurring perinatally can manifest themselves in adolescence, producing schizophrenia. Chapter 4, by Wood et al., covers cognitive development in adolescence, addressing how early lesions may affect executive functions and working memory which usually come “on line” during that time. They propose that those cognitive functions that mature around the same time as when symptoms of schizophrenia begin to emerge are more impaired that those cognitive functions that mature earlier. Allin et al., in Chapter 5, explain why the Kennard principle, which states that the earlier the brain lesion, the less likely disturbed behavior occurs, may not be applicable. They cite evidence from behavioral and cognitive outcome studies of very preterm birth. Behavioral and structural brain abnormalities are detectible in adolescents, challenging the assumptions of plasticity.

Part II, Etiological Factors, is a heterogeneous section covering a broad range of topics, from the molecular, such as the discussion of transcriptomes in Chapter 12 by Lewis, Mirnics, and Levitt, and Pariante and Cotter's review in Chapter 6 of glucocorticoid involvement in major psychiatric disorders, to broad environmental factors such as social class, discussed by Boydell et al. in Chapter 13. In Chapter 7, Eliez and Feinstein cover the velo-cardio-facial syndrome. In this genetic disorder an extremely high percentage of individuals (up to 30%) develop schizophrenia or schizoaffective disorder by young adulthood. In Chapter 8, McDonald and Murray use structural MRI to look at putative endophenotypes for schizophrenia. Chapter 9 on nutritional factors was very intriguing. Mahadik describes how essential polyunsaturated fatty acids and antioxidants can improve clinical outcome in schizophrenia patients. Unfortunately, the author never exactly explained which clinical outcome factors improved. Petronis' Chapter 10 on epigenetics and structural abnormalities echoes Heinrichs' recent review, explaining why structural abnormalities seen in neuroimaging are not more helpful from a diagnostic or etiological standpoint. According to Petronis, “From the epigenetic point of view, age- and hormone-dependent neurochemical changes rather than structural changes in the brain are the main disease mechanisms” (p. 187). A particularly excellent and thought-provoking Chapter 13 by Boydell et al. on social factors and development explores a number of adverse environmental factors associated with an increased risk of schizophrenia, such as poor parenting, early parental loss, child abuse, urban versus rural upbringing, and ethnic minority status. Chapter 14 by Chen and Murray carefully considers the drug and schizophrenia “chicken and egg” question on how drug abuse interacts with familial and developmental factors in the etiology of schizophrenia. In Chapter 11, Cannon, Dean, and Jones review prenatal and perinatal risk factors for schizophrenia, such as place or time of birth, infection, malnutrition, prenatal stress, and obstetric complications and assign a relative risk or odds ratio for each.

In Part III on Pathophysiology, Grace reviews dysregulation of the dopamine system in Chapter 15 and Benes reviews the interaction between GABA and dopamine in the limbic circuitry as a possible cause for schizophrenia in Chapter 16. Melchitzky and Lewis review thalamocortical circuitry in the pathophysiology of schizophrenia in Chapter 17. Chapter 18 by Craig et al. on X chromosome, estrogen, and brain development is particularly interesting and well written. They review how normal brain development differs for males and females across the lifespan, and how these differences might account for respective differences in prevalence and age of onset in schizophrenia. Chapter 20 by Jarskog et al. reviews the mostly weak evidence for a neurodegenerative as opposed to a neurodevelopment model of schizophrenia. In Chapter 21, Kreipke et al. review the similarities and differences found with neuroimaging in obsessive-compulsive disorder, attention deficit disorder, and schizophrenia, suggesting commonalities between ADHD and schizophrenia. Lawrie (Ch. 19) summarizes the evidence for premorbid structural abnormalities.

Part IV, Clinical Implications, is very brief, with three chapters that only begin to address this topic. Several of the chapters in earlier sections offered ideas on prevention and treatment. In Chapter 22, Kravariti et al. ask the question, “Can one identify preschizophrenia children?” They review the motor and cognitive markers and conclude that one cannot reliably identify children based on these markers. Chapter 23 by Keshavan reviews the methodology of studies of individuals at high risk for developing schizophrenia. This chapter might fit better in the section on etiological factors instead of clinical implications. Finally, Chapter 24 by Keshavan and Cornblatt attempts to integrate the neurodevelopmental, neurodegenerative, and pre- and post-natal data based on a unifying theme involving glutamate. They also review the sparse literature on preventive projects, which are still underway and inconclusive but tremendously important and deserving of more attention. This last chapter did a very nice job of integrating much of the evidence, some of it seemingly contradictory, to implicate glutamate as the unifying factor.

In his forward to the book, Michael Rutter stated that this book “is not light bedtime reading” (p. xv). Indeed it is not. This reviewer needed to invoke her distant knowledge of biochemistry and genetics to appreciate the points made in the first chapter on genes and brain development, as well as other chapters in the book that focused primarily on molecular mechanisms. At great risk of being trite, reading this book reminded this reviewer of the analogy of the three blind men and the elephant. Certainly not because the scientists who have written in this book have single-mindedly argued for their neurodevelopmental theory of how schizophrenia emerges, but rather because this reviewer felt like the blind men after reading each chapter. Each chapter led down a slightly different path, a plausible cause for schizophrenia, but never revealed the “elephant” in its entirety. After reading the book, this reviewer was very intrigued, yet, even more bewildered regarding the pathophysiology and etiology of schizophrenia, one of the most tragic and disabling psychiatric diseases. In part, this reflects the current state of the scientific literature on schizophrenia, in which one may develop via several pathways, both genetic and environmental. However, part of the reason for the sense of discontinuity is that chapters seemed to be written independently and would have benefited from more editorial input for a thematic and organizational perspective with a consistent voice. Some redundancy was apparent (e.g., three chapters on neuroimaging) and, at times, contradictory. One final chapter that reviewed and integrated all of the seemingly disparate findings would have been useful. This would have helped this “blind” reviewer “see” the neuropathogenesis of schizophrenia more coherently, and would have increased the readability of this very impressive volume of work. This book is highly recommended as an addition to the libraries of those professionals involved in clinical care or research with individuals with severe psychiatric disability. It is dense, thought provoking, and worth the effort.