In the past few decades we have learned a great deal about proteins and nucleic acids, the molecular building blocks of all biological systems. This knowledge is being applied in many branches of medicine. The goal of this book is to show its impact on our view of mental illness and its treatment.

Until recently, few people have been thinking about the connections between molecules and mental illness, because to do this requires familiarity with two very different intellectual and professional traditions. Myopportunity to combine them came during my postdoctoral training at the National Institutes of Health (NIH) between 1960 and 1963. When I arrived at NIH, I had completed medical school and was thinking of embarking on a career in psychiatry. But I also wanted to learn more about fundamental biology by working in a laboratory. At NIH I met Gordon Tomkins, who was deeply committed to relating basic science to medicine and had founded a department to achieve this goal. Gordon was bursting with knowledge and enthusiasm about the infant field of molecular biology and was convinced that it would ultimately explain almost everything (which, to me, meant even psychiatry).

To provide a taste of molecular biology, Gordon arranged for me to become the second postdoctoral fellow in the then tiny laboratory of Mar-shall Nirenberg. I began there immediately before Marshall`s discovery that a synthetic nucleic acid, called poly U, could act as an artificial genetic message. Within months I became an industrious student of poly U, while Marshall went on to work with other synthetic nucleic acids, ultimately deciphering the genetic code by which nucleic acid sequences are translated into the language of proteins. It was obvious to me, and to everyone else, that Marshall`s work was monumental; and within a few years it was honored with a Nobel prize. The experience was an extraordinarily exciting introduction to the laboratory, and supported Gordon`s belief that, if you study things at the molecular level, anything is possible. I was hooked.

After a year in Gordon`s laboratory in which I began to use molecular techniques to study the mechanism for storing memories in the brain, I went on to psychiatric training and have worked in both psychiatry and basic biological sciences ever since. Although the integration of these fields has progressed more slowly than I would have liked, the pace is picking up. This book is designed to provide enough essential information about biology and psychiatry for readers unfamiliar with both fields to appreciate how they are coming together.

In writing this book I have been greatly aided by the advice of many colleagues and friends and have enjoyed the benefit of working with an extraordinary group of professionals at Scientific American Library. Two people I wish to single out for special thanks are my editor, Sonia Deviatory, and my assistant Anne Poirier, who each made invaluable contributions. My daughters Elizabeth and Jessica, both more comfortable with words than with molecules, were often my target audience. "Recapitulation (in Verse)" is especially for them. I hope you like it too.

Samuel H. Barondes

Sausalito, California

October 1992

In the six years since the publication of the first edition of this book there has been a dramatic increase in interest in the biological basis of mentaldisorders. This is mainly the result of the widespread acceptance of therapeutic drugs that were developed on the basis of knowledge about brain molecules. Of these drugs, fluoxetine (Prozac) and related compounds have become immensely popular as treatments for depression and anxiety disorders. Effective new medications have also been introduced for the treatment of schizophrenia and manic-depressive illness.

The other big change in the past six years is in public awareness that there are inherited vulnerabilities to many mental disorders. This is one consequence of a more general change: the accumulation of information about the structure and individual variations in human DNA. Although it was known for centuries that forms of mental illness run in families, powerful new technologies are making it possible to identify the specific genes and gene variants that playa role in a particular disorder. Identification of these genes will revolutionize our approach to the diagnosis and prevention of mental illness. They will also lead to the creation of still more effective drug treatments.

The present edition of this book has been updated to reflect these new developments in pharmacology and genetics. By presenting the material in historical context, and as an outgrowth of basic principles, I have tried to provide a broad foundation for understanding this evolving field. This will make it easier to follow the many more discoveries about molecules and mental illness that are just around the corner.

Samuel H. Barondes

Sausalito, California

January 1999