Neurochemistry of Schizophrenia and Depression

It used to be that the major hypotheses of schizophrenia and depression were limited to excess dopamine in schizophrenia and lower levels of noradrenaline and serotonin (and an overactive hypothalamic-pituitary-adrenal [HPA] axis) in depression. It is clear that the decade of the brain has produced a wealth of data. We are no longer studying schizophrenia subtypes with changes in dopamine, γ-aminobutyric acid (GABA), glutamate, opioid, serotonin, or acetylcholine. All these systems may be involved in the pathophysiology of these disorders. The biochemistries of schizophrenia and depression have become so complex that it is hard to make sense out of the data unless we understand the different systems and their interactions. It is hard for the uninitiated to deal with all this without some guidance. Not to mention those of us who spend a lifetime studying the biochemical and clinical aspects of these disorders.

Aman Kahn reviews the literature of the different neurotransmitter systems from acetylcholine to vasopressin, from cholecystokinin to sigma receptors, from a multisystem perspective. He points out the many biochemical differences and similarities between schizophrenia and depression. He takes the reader systematically through the different putative neurotransmitter system hypotheses. Every system is briefly discussed followed by a review of the findings, regardless of whether they are traditional neurotransmitter or neuropeptide systems. What I particularly liked about the book was a discussion of how and with which other systems a given neurotransmitter system interacts and how that potentially affects our present conceptualizations. The author in his review reveals that almost all systems have produced positive findings in both disorders. He also points at promising areas of further research.

For example, although primarily studied in affective disorders, the HPA axis is frequently found to be abnormal in schizophrenia. Plasma HVA, which reflects only 30% or more brain dopamine metabolism, is considered to be a good marker of central dopamine activity. On the other hand, plasma GABA, 95% of which comes from the brain, is highly understudied in both depression and schizophrenia. The limited pursuit of single neurotransmitter systems has not addressed major areas of clinical interest such as the difference between unipolar and bipolar depression.

A book like this cannot be complete. The task of judging all the available literature from the last 25 years and making sense of it or providing new insights is daunting. Although extensive references are in the back of each chapter, it is unavoidable that we miss some of our favorite studies. I hope that second messengers, immune and membrane abnormalities, and mania can be included in the biochemical review of the two disorders in future editions. A minor irritant in an overall well-appreciated book is the many misspellings of names in the text. Fortunately, the references themselves are correct.

Aman Kahn has made an important contribution. While we are waiting for clarification of the genetic underpinnings of these complex disorders and their altered biochemistries, a review like this will have to do. Many would-be and experienced students of the brain will find this a useful book.