Shrinks (31 page)

Whereas psychoanalysis attempted to unearth impulses deeply buried in the unconscious, Beck was interested in the thoughts circling around and around in the waking consciousness. Whereas psychoanalysis attempted to uncover the historic motives behind troubling emotions, Beck scrutinized the immediate experience of a person’s emotions. Whereas psychoanalysis was ultimately pessimistic, seeing neurotic conflict as the price for existing in a social world, Beck remained upbeat, suggesting that if people were willing to work hard on their problems, they could eliminate their neurotic tendencies.

CBT had an energizing and liberating effect on the field. Unlike psychoanalysis, which placed restrictions on the therapist’s conduct and was undefined and open-ended, possibly lasting for years, CBT had a defined set of instructions for therapists, entailed a finite number of sessions, and established specific goals. CBT’s therapeutic effects were soon validated in controlled experiments that compared the effects of CBT with a placebo and with different forms of psychoanalysis when treating depression, making CBT the first “evidence-based psychotherapy”—a form of talk therapy proven to work through a blind experiment. Since then, numerous studies have validated CBT’s effectiveness as a treatment for many mental disorders, including anxiety disorders, obsessive-compulsive disorder, and ADHD.

The unexpected success of CBT opened the door to other kinds of evidence-based psychotherapy by showing that it was possible to treat patients more quickly and effectively than traditional psychoanalysis allowed. In the 1970s, two Yale faculty members created “interpersonal psychotherapy,” a form of talk therapy for depressed patients that encourages patients to regain control of their moods and their lives. In the late 1980s, dialectical behavioral therapy, a highly focused form of psychotherapy for patients with borderline personality disorder, was created by a psychologist who suffered from the disorder herself. In 1991, two psychologists introduced motivational interviewing, a psychotherapeutic technique for treating addiction that fosters motivation.

Tim Beck’s venture beyond the rigid precepts of psychoanalysis to explore the true nature of neurotic depression through experimentation enabled him to create a unique form of psychotherapy that improved the lives of millions of patients. By doing so, he demonstrated that rigorous science was not solely the purview of biological psychiatrists but could also be wielded to dramatic effect by psychodynamic psychiatrists.

Too Many Genes, Too Few Genes

By the mid-1980s, psychiatry was using more effective forms of psychotherapy, more effective psychopharmaceuticals, and more effective brain imaging. The field of neuroscience was rapidly gaining strength. There was growing acceptance among psychiatrists that people suffering from mental illness had something wrong in their brain—especially severe mental illnesses that previously required institutionalization, like schizophrenia, bipolar disorder, autism, and depression. But if something was wrong with your mentally ill brain, then where did this wrongness come from? Were you born to it? Or was it forged within you by your experiences in life? The answer turned out to be quite different than anyone expected.

The relationship between genes and mental illness did not interest the Freudians (who emphasized the role of childhood experiences) or the social psychiatrists (who emphasized the role of family and cultural environments). But in the early 1960s, a physician-scientist named Seymour Kety decided to investigate the genetic basis of mental illness, following up on the work of the German psychiatrist Franz Kallman. It had been known for centuries that mental illness ran in families—but families have many things in common that are not genetic, such as wealth, religion, and table manners, that come from a shared or common environment. The first question Kety attempted to answer seemed straightforward enough: Is schizophrenia primarily caused by genes or the environment?

Using Danish health registries, Kety found that the rate of schizophrenia in the population was about 1 percent, while the rate among individuals with at least one family member with schizophrenia was 10 percent. His data also revealed that if both your parents had schizophrenia, then you had a 50 percent chance of developing schizophrenia yourself. Similarly, if you had an
identical
twin with schizophrenia, then you also had a 50 percent chance of being schizophrenic, but if your
fraternal
twin had schizophrenia then your chance of being schizophrenic was only 10 percent. Thus, it seemed that the more genes you shared with a schizophrenic, the more likely you were to develop the disorder—though this correlation was clearly not perfect. After all, identical twins share 100 percent of the same genes, so if there was a “schizophrenia gene” in one twin, it should presumably be found in the other.

Citing this fact, many critics took Kety’s finding as strong evidence that schizophrenia was primarily environmental, arguing that the greater incidence of schizophrenia within families with at least one schizophrenic member was due to an unhealthy domestic environment rather than anything genetic. To settle the question of schizophrenia’s genetic basis, Kety started a new study. He identified individuals with schizophrenia who had been adopted at birth and examined the rates of schizophrenia among both adoptive and biological relatives. He found higher rates of schizophrenia in the biological relatives, but not in the adoptive families. He also found that children born to a mother with schizophrenia but reared in an adoptive family developed schizophrenia at the same rate as those reared by the biological mother with schizophrenia. These findings demonstrated that schizophrenia was at least partially due to one’s genetic endowment, and not solely due to environmental factors like “double-binding mothers” or poverty.

Similar studies of other disorders quickly followed, showing that autism, schizophrenia, and bipolar disorder featured the highest heritability among mental disorders, while phobias, eating disorders, and personality disorders featured the lowest. Yet even though the epidemiologic studies carried out by Kety and other researchers seemed to demonstrate that a predisposition toward mental illnesses could be inherited, the findings posed a number of genetic puzzles. For one thing, even monozygotic twins—individuals with identical sets of genes—didn’t always develop the same mental illness. Further complicating the picture was the fact that sometimes schizophrenia skipped entire generations, only to reemerge later in the family tree. And sometimes, schizophrenia appeared in individuals with no family history of the disease at all. All of this also held true with depression and bipolar disorder.

Another riddle was presented by the fact that individuals with schizophrenia or autism were less likely to form romantic relationships, marry, and have children compared to people without mental illnesses, yet the frequency of both disorders in the population remained relatively constant or increased over time. As the role of genetics gained prominence in biomedical research in the 1980s, psychiatrists became convinced that these strange patterns of inheritance would be explained once scientists discovered the fabled pot of gold at the end of the genetic rainbow: a specific gene (or gene mutation) that caused a specific mental illness.

Psychiatrists began searching for mental illness genes in unique, geographically isolated or founder populations like the Old Order Amish and among aboriginal peoples in Scandinavia, Iceland, and South Africa with all the fervor of miners headed for the Klondike gold rush. The first report of a mental illness gene came in 1988 from a team of British scientists led by geneticist Hugh Gurling. Gurling’s team reported that they had “found the first concrete evidence for a genetic basis to schizophrenia” residing on chromosome 5. But Gurling’s gene proved to be fool’s gold: Other scientists could not replicate his finding with DNA from other schizophrenic patients. This reversal of fortune was to become a recurring and deeply frustrating pattern in psychiatric genetics.

By the 1990s, researchers had succeeded in identifying specific genes that caused illnesses like cystic fibrosis, Huntington’s disease, and Rett syndrome, but psychiatric researchers were unable to pinpoint any specific gene associated with any mental illness. Psychiatrists began to experience an unsettling sense of déjà vu: More than a century earlier, using the cutting-edge technology of the era (the microscope), biological psychiatrists had been unable to identify any gross anatomical basis for mental illness, even though they were certain it must exist
somewhere
. And now it seemed to be happening again with genetics.

But in 2003, two game-changing events occurred. First, the Human Genome Project was completed, mapping the entire set of genes encoded in human DNA. This was soon followed by the invention of a stunning new genetic technique known as representational oligonucleotide microarray analysis (ROMA). Prior to ROMA, molecular geneticists analyzed genes by determining the sequence of nucleotides in a given gene to see if any nucleotide was missing or out of place (called single nucleotide polymorphisms, or SNPs). ROMA, in contrast, scanned a person’s entire genome at once and tabulated the number of copies of a specified gene, revealing whether a person had too many copies of the gene or too few.

Michael Wigler, a biologist working at Cold Spring Harbor Laboratory, invented ROMA as a method to study cancer. But he quickly realized its implications for understanding mental illness, and with the help of geneticist Jonathan Sebat, Wigler began applying ROMA to the DNA of patients with autism, schizophrenia, and bipolar disorder. Before ROMA, the question that psychiatric geneticists asked was, “Which specific genes cause mental illness?” But ROMA reframed the question as: “Can too many (or too few) copies of a healthy gene cause mental illness?”

Using ROMA, Wigler and Sebat were able to examine a wide array of genes in mentally ill patients’ DNA and compare them to the genes in healthy persons. They targeted genes that produced proteins essential to healthy brain functions, such as a gene that produced a protein forming part of a neurotransmitter receptor or guided the formation of neural connections. Their research paid off almost immediately. They found that mentally ill patients possessed the same brain-related genes in their DNA as their mentally healthy counterparts, but the patients possessed either
more copies
or
fewer copies
of these genes than healthy people. Wigler had discovered the genome’s Goldilocks phenomenon: To have a healthy brain, not only did you need the right kind of genes, but you needed a “just right” number of these genes—neither too numerous nor too scarce.

Wigler’s new methodology divulged other unexpected insights. While most genetic mutations in the DNA of patients with autism, schizophrenia, and bipolar disorder were specific to each illness, some genetic mutations were shared by two or more disorders, meaning that some manifestly different mental disorders shared common genetic factors. ROMA research also revealed a possible explanation for the sporadic nature of mental illness within families, such as how it skipped entire generations and sometimes appeared in only one identical twin: While a particular brain-related gene might get passed on to one’s offspring (or appear in both twins), the number of copies of that gene could vary. Sometimes, copies of a gene were spontaneously created or deleted within the DNA of the sperm or egg cells. Even though twins shared 100 percent of the same
type
of genes, they didn’t share 100 percent of the same
number of copies
of these genes.

Wigler’s findings also provided a possible explanation for why older men and women are more likely to have children with mental conditions like autism or Down syndrome. Their egg and sperm cells have been genetically dividing and replicating for a longer period of time than in young parents, so they are more likely to introduce extra or fewer copies of genes into their children’s DNA, since genetic replication errors accumulate over time and are more likely to occur than a mutation creating an entirely new gene.

As psychiatry progressed through the first decade of the twenty-first century, buoyed by the emergent technologies of brain imaging, neuroscience, and genetics as well as the proliferation of new pharmacological advances and psychotherapy, the once-stagnant field of psychiatry showed all the signs of a profession undergoing intellectual rejuvenation.

A New Kind of Psychiatry

When I first saw Jenn in 2005, the doctors couldn’t figure out exactly what was wrong with her. A twenty-six-year-old woman born to an affluent family who had enjoyed a privileged upbringing, Jenn had attended private school in Manhattan and then a liberal arts college in Massachusetts, which is where her behavior first became problematic.

During her junior year, she became suspicious and guarded and stopped socializing with her friends. She began to exhibit severe mood swings. She was friendly and pleasant one day but volatile and nasty the next, often hurling caustic insults over minor provocations. Eventually her hostility and volatility became so disruptive that the college implored her parents to have her seen by a psychiatrist. They obeyed, taking her to a leading psychiatric facility in the Northeast, where she was promptly admitted. But when she was discharged she did not follow through with her aftercare appointments or take her prescribed medication. She relapsed repeatedly, leading to multiple hospitalizations, and with every relapse she got worse. What made her situation even more daunting was that each time she was admitted, the doctors seemed to give her a different diagnosis, including schizophrenia, schizoaffective disorder, and bipolar disorder.