Mind games

Eric R Kandel offers the latest thinking on mental health and neuroscience, writes Alan Jasanoff

Disorders of the mind have meant different things to different people at different times. In Plato’s Phaedrus, Socrates extols divinely inspired madness in mystics, lovers, poets and prophets; he describes these disturbances as gifts of the gods, rather than maladies. Premodern Europeans more commonly despised the insane, but barely distinguished them from others their society rejected; madmen were imprisoned alongside beggars, blasphemers and prostitutes. Some modern cultures have notions of mental disorder that seem almost as strange to us; syndromes with names like latah, amok and zar defy traditional classifications of Western psychiatry and often call for spiritual rather than medical responses.

Our own culture’s conception of the varieties of mental illness took shape first from a deck of cards curated by the pioneering German psychiatrist Emil Kraepelin over a century ago. Each of the cards contained an abstract of a patient’s medical history, and by grouping them according to similarities he observed among the cases, Kraepelin delineated for the first time some of the major categories physicians now use to diagnose psychiatric diseases. Since the 1980s, Kraepelin’s characterisations of psychosis, mania and depression have been virtually codified in the

Diagnostic and Statistical Manual of Mental Disorders, the clinician’s bible for evaluating patients. Kraepelin was a staunch critic of psychoanalysis and an advocate for understanding mental phenomena in strictly biological terms – attitudes now also ascendant in psychiatric biomedicine.

Kraepelin’s ideas permeate The Disordered Mind, Eric Kandel’s engaging new overview of contemporary thinking about the intersection of mental health and neuroscience. Kandel’s chief aim is to explore “how the processes of the brain that give rise to our mind can become disordered, resulting in devastating diseases that haunt humankind,” and he declares at the outset his intention to weave Kraepelin’s story throughout. The book’s very structure emulates the organisation of a neo-kraepelinian diagnostic manual, with a succession of chapters devoted to conditions including schizophrenia, bipolar disorder and autism. Kraepelin’s lasting influence can be felt in the way Kandel reduces these mental conditions chiefly to microscopic causative factors in the nervous system. According to Kandel, mental illnesses are simply brain disorders, and all variations in behavior “arise from individual variations in our brains.”

Kandel was awarded a 2000 Nobel Prize in Medicine or Physiology for his discovery of molecular processes that underlie learning and memory. In addition to running laboratories at NYU and then Columbia, he has co-written successive editions of the massive and widely used textbook Principles of Neural Science ,a testament to the same encyclopedic knowledge that is on display in this book.

His well-constructed narrative smoothly blends historical perspective and first-person accounts with explanations of recent experiments. In a chapter on dementia, for instance, he introduces us to the classic brain pathology studies of Alois Alzheimer; he tells the celebrated story of patient H.M., whose 1953 brain surgery destroyed his capacity to form new declarative memories; and he guides us through some of his own research on learning in invertebrates and animal models of Alzheimer’s disease. In another chapter, on gender identity, Kandel nicely juxtaposes autobiographical accounts from the late Ben Barres, a prominent neuroscientist who began his life as Barbara, against genetic

studies of sexual dimorphisms in mice and humans.

Kandel is particularly focused on the importance of genetics. Here the author again parallels Kraepelin, who stressed the contribution of heritable “degeneracy” to mental disorders. Kandel credits advances in human genetics and genetic models of disease in animals in large part for our modern appreciation of the brain’s role in mental illness. But the sober truth, some of which emerges elsewhere in the book, is that the relationships between genes and most psychiatric diseases are still far from clear. The majority of implicated genes are only weakly correlated with disease. The world’s economically costliest mental illness, major depressive disorder, has yet to be tied convincingly to any genes. Even where a gene seems to influence brain cell biology in defined ways – as with the remarkable schizophrenia related C 4 gene Kandel features– the connection between cellular hallmarks and high-level psychiatric symptoms remains mysterious.