In Search of Madness: Schizophrenia and Neuroscience is a concise but thorough and even-handed review of the current status of research in schizophrenia. It is an amalgam of research studies distributed across numerous domains relevant to schizophrenia and represents a much expanded version of his 1993 review article in the American Psychologist. In particular, the book synthesizes aspects of neuropsychological functioning, genetic, behavioral and genetic markers, and the neurochemistry of schizophrenia with information on etiology and overt symptoms of the illness. One potentially controversial and central feature of this book is Heinrich's argument that schizophrenia is not one single illness but a heterogeneous syndrome. Heinrichs' rationale for conducting research on the studies is to exemplify the discrepancies between what researchers claim to be “common symptoms” of schizophrenia. For each topic covered, Heinrichs and colleagues combined all relevant research studies between 1980 and 1999 and performed a meta-analysis to better explain the overall status of such research. For example, regarding attention deficits on the Continuous Performance Test, he grouped all studies together between 1980 and 1999 and matched the studies according to patient sample (schizophrenia patients and controls) and measure used (the Identical Pairs version of the CPT). He then calculated the effect size to determine the variance attributed to the identified construct. This meticulous method was employed for each phenomenon that was examined.

In the first chapter, Heinrichs explicitly states his purpose is to challenge the belief that a comprehensive understanding of schizophrenia is within reach by investigating the successes and failures of current research across a variety of domains germane to schizophrenia. He provides case examples of three very different individuals who have the same diagnosis of schizophrenia. These individuals come from very diverse backgrounds, with differing social support systems, different childhoods, differing circumstances and, very different symptoms—at least for something that is identified as the same illness in all three individuals. Throughout the book, Heinrichs incorporates these vignettes and their inconsistencies to illustrate his point that schizophrenia manifests itself in a variety of ways and is not likely a single disease state.

Heinrichs goes on to explain the organization of the book—a logical progression from symptoms and diagnosis to premorbid functioning and encompassing chapters on illness markers, neuroanatomical differences, and neurochemistry. After providing empirical support for his views, he critiques current theories of schizophrenia. In a final chapter, he integrates the current research findings of schizophrenia neuroscience and provides a cohesive picture of the conjectures he made in his book.

In addition, Heinrichs identifies his audience and intended readers. He explains that his manuscript is intended for students and researchers alike who are seeking a complete and integrated summary of current research regarding the neuroscience of schizophrenia, and “anyone who has been moved by madness in some way and is willing to be moved again by reading this book” (p. 12).

Overall, Heinrichs did an outstanding job of documenting evidence that schizophrenia is a heterogeneous disorder. Time and time again, he describes published, peer-reviewed evidence that supports this notion that there are many different subgroups of schizophrenia. For instance, he provided evidence of schizophrenia patients who never shared the same symptoms. He explained that there are some individuals who have the typical positive symptoms, such as delusions and hallucinations, but no negative symptoms. Conversely, he provided other evidence of individuals who suffered with only negative symptoms, such as restrained affect and poverty of speech.

Aside from these apparent discrepancies in cases, the majority of the book consists of evidence supportive of more cognitive or biological differences. In the chapter on markers of schizophrenia, he examines research on a variety of putative markers for the development of psychosis, e.g., the validity of digit span, the Continuous Performance Test(s), backward visual masking, eye tracking abnormalities, and evoked brain potentials. Globally, Heinrichs argues that there is, in fact, “no convincing attention-related or psychophysiological marker for schizophrenia” (p. 85). The next chapter addresses executive incompetence and the inconsistencies found in frontal lobe functioning of people with schizophrenia. He presents numerous examples on various frontal lobe tasks and neuroimaging techniques that are designed to identify people with thought disorders or brain damage. Some individuals with schizophrenia will show functioning or neuroanatomical deficits in one area, while other schizophrenia patients will not. Also, he provides a critical analysis of the problems of the testing instruments themselves, reporting much evidence to suggest that our tools are not as precise when identifying complex deficits in brain functioning or structure, as we may optimistically believe.

In the next chapter Heinrichs reviews the functioning of selective memory, emotion, concentrating most of his efforts around the temporal lobe and concluding that a link between schizophrenia and the temporal lobes has not been definitively proven at present. Much evidence shows that many individuals with schizophrenia suffer problems indicative of substantially impaired temporal lobe processing, but also numerous patients exhibit little to no impairment within this region. While impaired temporal lobe functioning is indeed found in patients with schizophrenia, it does not appear to be a necessary component of schizophrenia.

Next, Heinrichs explores the neurochemistry that has long been implicated for its crucial role in schizophrenia. He begins by describing the advent of psychotropic medications, primarily chlorpromazine (Thorazine) and its role as an impetus for the study of neurochemical abnormalities in the disease and then summarizes findings surrounding various neurotransmitters found in the brain, particularly dopamine, serotonin, and glutamate. Not surprisingly, there is some evidence that neurotransmitter abnormalities and numbers of receptors differ between schizophrenia patients with differing sets of symptoms, however, “the neurochemical effect sizes are too modest and too variable to support causal evidence for a single illness” (p. 182). An important chapter concerns the clues that scientists can obtain from studying at-risk children, mostly those who had a first-degree biological relative with the disorder. This invaluable area of study, unfortunately, is under-researched. Heinrichs briefly reviews the current thought regarding genetic influence of schizophrenia yet explains that it has been more thoroughly reviewed elsewhere (see Gottesman, 1991). He then tackles a variety of assertions such as, many people with schizophrenia were born in winter months and that viruses, which tend to proliferate in cold seasons, may have caused their condition; or birth complications—forceps, premature births and other perinatal conditions. Following a critical and broad analysis of previous research in these areas, Heinrichs found no conclusive evidence that any of the aforementioned perinatal complications can be found in the developmental history of all, or even most, patients, but rather play a peripheral role, at best, in schizophrenia's etiology.

Perhaps, Heinrichs asserts, the key to understanding schizophrenia will not be found by gathering more empirical data at present, but by evaluating the current theories that address schizophrenia. In order to be considered a good, solid theory, various conditions regarding the disorder must be addressed: neurogenesis, symptoms, etiology, onset, and heterogeneity. According to Heinrichs, only three current theories, all formulated around the diathesis-stress model, address these crucial aspects: Paul Meehl's theory of schizotaxia and schizotypy, Weinberger's neurodevelopmental theory, and Walker and Diforio's neural diathesis-stress theory. He asserts that all of these theories provide us with helpful information; yet none is completely satisfactory in its explanation of schizophrenia. Heinrichs acknowledges that theory construction is an enormously daunting and complex task because “the theorist has to stay true to what is known about the illness but also propose new concepts that lead to predictions that can be tested” (p. 247).

Finally, Heinrichs summarizes current knowledge of schizophrenia and proposes alternative categorizations for schizophrenia. He notes the numerous ways to group the illness (i.e., positive vs. negative symptoms, biological vs. behavioral abnormalities, or the subgroups observed for DSM–IV diagnosis); only time will tell which one proves to be correct. He supports divisions based on biological findings since these “lie closer than behavior to the neurogenesis of the illness” (p. 269). The pleasantly surprising aspect of this chapter was the reflective, brilliant criticism of applying the medical model to neurosciences—especially coming from a prominent neuroscientist. Possibly, he asserts, the capabilities of our current understanding and application of scientific principles is not accurate enough to uncover the intricacies of an illness as complex as schizophrenia. “[S]tudying diverse conditions as a single disease state is guaranteed to produce inconsistent findings that apply to some patients and not others. Everyone pays lip service to the heterogeneity problem, but only a small number of researchers do more and actually study multiple illness models of schizophrenia” (p. 276).

In summary, In Search of Madness: Schizophrenia and Neuroscience is a superb piece of writing. The material is presented in a straightforward, thoughtful manner, is easy to follow, and interesting to read. The text integrates empirical scientific findings with compassionate and thoughtful scrutiny to produce a candid portrait of schizophrenia. Heinrichs comes across as a lucid, articulate, yet empathic scientist who offers thoughtful analysis to complex questions and hypotheses. This book is highly recommended to anyone interested in schizophrenia. Students and researchers are encouraged to challenge their conceptualizations of schizophrenia by reading this book. Perhaps over time, together, we can uncover its complexity. Until that time, “madness is among us and diminishes to the extent that we care for those who endure it” (p. 276).