Science and Psychiatry: Groundbreaking Discoveries in Molecular Neuroscience

Psychiatrists have a noble tradition of revisiting and teaching the classic papers that revolutionized the field, such as the works of Sigmund Freud, Jean Piaget, or Wilhelm Reich. In this tradition, American Psychiatric Publishing has published a compilation of several of the scientific papers written by one of the modern giants in the field: Solomon Snyder, M.D.

Snyder pioneered and then dominated the integration of brain science into psychiatry, primarily through defining how drugs work in the brain. Snyder published his first scientific paper nearly 50 years ago, and the arc of Snyder’s scientific career coincides with massive advances in our understanding of the brain. When he started his research career as a medical student, only five or six substances were considered to be neurotransmitters in the brain. Now hundreds of substances serve as signaling molecules in the brain, and some of the most unconventional of these were discovered by Snyder.

The book opens with a brief autobiographical essay by Snyder. Unbeknownst to many, Snyder excelled at classical guitar in high school and even studied under Andrés Segovia. Although he was drawn to a career in classical music, his choice to ultimately go into biomedical research had less to do with his interest in scientific matters and much more to do with his excitement and gratification over the process of discovery—that is, doing science. His attraction to psychiatry was based upon his enjoyment of philosophy in college. Psychiatry, he believed, might be a specialty in which the life of the mind meets medicine. The book closes with an essay by Snyder entitled “The Audacity Principle in Science,” in which he reflects on scientific creativity and mentoring, with particular reference to his mentor, Nobel Prize winner Julius Axelrod, Ph.D.

Between these two essays, Snyder has selected several of his seminal scientific articles, each of which is preceded by an introduction from a distinguished scientist that places the article in context. (I myself started my research career in Snyder’s laboratory and wrote one of the introductory essays.) For the nonscientist, this format provides a helpful sense of context and illuminates the true novelty of Snyder’s research. Commentators include Eric Kandel, Eric Nestler, Charles Nemeroff, George Aghajanian, Carol Tamminga, Herbert Meltzer, Robert Post, Anne Young, Samuel Barondes, and Nancy Andreasen.

Snyder is an excellent scientific writer, so it is fun and instructive to visit papers written up to 35 years ago. The discovery of the opiate receptor led logically in Snyder’s fertile mind to the discovery of its natural agonist, endogenous opioid peptides. The demonstration that antipsychotic medications act upon dopamine D ₂ receptors shed light on the mechanisms of their therapeutic action and side effects. The characterization of serotonin transport in pinched-off nerve terminals prepared from brain tissue provided a precise target for rational drug design that has since been exploited by the pharmaceutical industry to discover Prozac, among other drugs. The elusive therapeutic action of the mood stabilizer lithium was clarified by characterizing the disposition of an intracellular signaling molecule, inositol triphosphate.

Snyder pushed the limits of what was defined as a neurotransmitter. He demonstrated the important role in the brain of nitric oxide, a gas that diffuses from its neuronal site of synthesis across neuronal membranes to activate cyclic nucleotide synthesis in adjacent cells. He characterized the role of D-serine (virtually all amino acids in animals are L-stereoisomers), which is released from glial cells and acts as a co-agonist of the brain’s major excitatory receptor, the NMDA receptor. He links these bizarre, atypical neurotransmitters to diverse disease processes such as impotence, stroke, and schizophrenia.

Snyder has published more than a thousand scientific papers over a period of nearly 50 years. He is the most highly cited biomedical scientist in the world. Furthermore, his h -index, a value that takes into account the number of papers that are highly cited, is 191 (191 of his papers were cited at least 191 times), the highest in all research (1) . Snyder has a record of being an extraordinary mentor. He has mentored over 100 doctoral students and postdoctoral fellows who now hold scientific leadership positions in psychiatry, neurology, pharmacology, neuroscience, and the pharmaceutical industry. He writes passionately about the mentoring process: the back and forth between mentor and mentee that leads to the out-of-the-box scientific advances that characterized his career. This book provides a very personal and readable introduction to the writings of one of the giants in modern psychiatry and neuroscience. After you read it, it should be placed on the shelf next to Freud’s The Interpretation of Dreams .