A Nobel Laureate Asks What Makes a ‘Disordered Mind’

THE DISORDERED MIND
What Unusual Brains Tell Us About Ourselves
By Eric R. Kandel
304 pp. Farrar, Straus & Giroux. $30.

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 characterizations 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 passionate advocate for understanding mental phenomena in strictly biological terms — attitudes now also ascendant in psychiatric biomedicine.

Kraepelin’s ideas permeate “The Disordered Mind: What Unusual Brains Tell Us About Ourselves,” 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 organization 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 N.Y.U. 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. Kandel’s well-constructed narrative smoothly blends historical perspective and first-person accounts with explanations of recent experiments. In a chapter on dementia, for instance, Kandel introduces us to the classic brain pathology studies of Alois Alzheimer (a close colleague of Emil Kraepelin); 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.

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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. Although he discusses a variety of basic science approaches, he gives pride of place to analyses involving genes and their associated molecules. Kandel’s enthusiasm for genetics reflects the current priorities of many psychiatric researchers, but it also drives him to occasional exaggerations. His exuberant verdict, that “decoding the human genome has shown us how genes dictate the organization of the brain and how changes in genes influence disorders,” is extraordinarily premature.

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 C4 gene Kandel features — the connection between cellular hallmarks and high-level psychiatric symptoms remains mysterious. It is notoriously difficult to find relevant animal models to help make this connection (psychotic mice are hard to spot), which means the more arduous research of humans continues. And while genetic techniques may be an excellent bet for psychiatric science, whether there will be payoffs in the clinic is far from certain.

Apart from potential medical benefits, however, Kandel believes that biological studies of the mind “offer the possibility of a new humanism, one that merges the sciences, which are concerned with the natural world, and the humanities, which are concerned with the meaning of human experience.” Neurobiology may indeed be well poised to promote this kind of synthesis. Kandel himself bridges science and humanities in a chapter on the link between mental illness and artistic creativity. He also tries to reconcile Kraepelin-style biologism with more humanistically oriented psychotherapy, correctly assailing the false dichotomy between these two approaches, which in practice both act on the brain.

But the new humanism Kandel admirably invites might require something more drastic as well: a departure from purely brain-focused views of mental life. This is because all of human experience depends intimately on interactions within and around us that causally affect our brains and minds at every moment. It is misleading to suppose, with Kandel, that “every activity we engage in, every feeling and thought that gives us our sense of individuality, emanates from our brain.” Nature does not see the brain as a prime mover.

Interestingly, recent genetic findings themselves support a broader view of mental health. No common psychiatric condition is fully heritable, meaning that the environment always plays a role. There are many indications that the brain’s interactions with the rest of the body, either during development or later in life, can have a major impact on health. The idea that mental disorders can arise from sources outside the head is actually nothing new — the most devastating psychiatric illness of the 19th century was caused by bacterial syphilis, a sexually transmitted disease that only secondarily affects the brain. The fact that genes that signal an increased risk of autism, schizophrenia and bipolar disorder are often shared (as Kandel notes) further suggests that mental illnesses are not as distinct from one another as previously thought, challenging the outcome of Kraepelin’s card game and reminding us of the cultural heritage that frames psychiatric research.

The cultural norms surrounding mental health are also increasingly questioned by “neurodiversity” advocates. Like Socrates, they argue that people with unusual brains and minds should be celebrated for their traits, rather than overly medicalized and stigmatized. Acknowledging this view in no way strikes at the need to find treatments for truly debilitating mental problems, or at the significance of the groundbreaking research Kandel covers in his excellent book. It does, however, highlight the need to consider our brains in the social, environmental and bodily contexts in which they operate — contexts that help make us who we are, in both sickness and health.