She was an Ivy League–educated woman working in a freelance profession, bright and verbal, and she showed up on time for treatment four times a week for the better part of a year.

She was also impulsive, prone to outbursts of furious rage, lacked a stable sense of identity or a clear direction in life, and had a history of troubled and broken relationships—symptoms that seemed to fall within the domain of what at the time, in the mid 1970s, had only fairly recently been termed "borderline personality disorder" (BPD).

At the Columbia University Psychoanalytic Center, she was assigned to John Oldham, M.D., then an analyst-in-training under the supervision of the internationally renowned Otto Kernberg, M.D. The latter was a pioneer in what was called "character pathology" and had been among the first to study and write about borderline pathology in depth.

Kernberg described what he called "borderline personality organization," a theoretical type of intrapsychic structure. In his formulation, patients with BPD used primitive defenses to bolster a diffuse sense of identity, though their reality testing remained (with the exception of high-stress circumstances) intact; it was a formulation that fit the name, denoting an illness that inhabited a "border" between the psychoses and what were at the time called "neuroses."

So the prescription was classical psychoanalysis, calling for the patient to free associate while lying on the couch. "At first, she was friendly and cooperative, always on time and eager to talk about herself," Oldham recalled. "She engaged in the treatment and seemed to be benefitting from it."

A couple of months into treatment, however, the patient made an announcement. "She said to me, ‘Here I am doing just what I've always done. I blithely rush into a relationship without even thinking about it, and I don't know you at all. How do I know I can trust you?’"

She began to demand of Oldham information about himself and about his training and blamed him for what she perceived as a treatment that wasn't working. "She became convinced I was keeping secrets from her and told me the problem was that I had been trained in a ‘fly-by-night’ school," he said. "In time, she would become absolutely enraged at me, regardless of what I said. And when I didn't give her an answer she wanted, it became proof that once again she had landed in the clutches of someone who was another disappointment and who might actually harm her."

The treatment and what had appeared to be a promising therapeutic relationship ended abruptly when the patient relocated to another part of the country. For Oldham the case remains an object lesson in how not to treat a patient with BPD.

"Under no circumstances would I treat her today with psychoanalysis," Oldham said. "Some patients with BPD have too much mistrust and too fragile a sense of identity to tolerate the sensory deprivation that is part of psychoanalysis. They need eye contact, reassurance, lots of dialogue, and the sense of working with someone within an active partnership."

Since then, Oldham—who is president-elect of APA, senior vice president and chief of staff at the Menninger Clinic, and a member of APA's DSM-5 Work Group on Personality and Personality Disorders—has been a pioneer in research on, and treatment of, personality disorders generally and BPD in particular. He was co-project director of the borderline research group at New York Hospital, Westchester Division, from 1982 to 1984 and a co-investigator on a study of familial transmission of DSM-III personality disorders published in the July 1982 Archives of General Psychiatry. BPD was added to the DSM in its third edition, DSM-III.

Although Oldham has hundreds of books, chapters, editorials, and peer-reviewed articles to his credit, he singles out the multisite Collaborative Longitudinal Personality Disorders Study (CLPS), led over many years by John Gunderson, M.D., and Andrew Skodol, M.D., as particularly important. Oldham served as co-principal investigator of the Columbia site of this NIMH-funded longitudinal study during its early phase.

CLPS is a naturalistic study of long-term outcome that has exponentially advanced the understanding of BPD and personality disorders generally as hybrids of stable personality traits and intermittently expressed symptomatic behaviors that may frequently remit over time (see Why Are You the Way You Are?).

The period since the first "trial-and-error" years of treating borderline patients has seen a rapid expansion of knowledge about the genetic and neurobiological correlates of BPD and the evolution of the understanding of BPD as a disorder with heritable traits, predisposing to emotional dysregulation and impaired impulse control, often compounded by early environmental trauma.

And the period has seen the development of several forms of psychotherapy proven effective including dialectical behavior therapy; mentalization-based therapy, transference-focused therapy, schema-focused therapy, supportive psychotherapy, systems training for emotional predictability and problem solving (STEPPS), and general psychiatric management with dynamicallty oriented therapy.

The new insights about BPD upend some early assumptions that have endured to this day about the illness. Oldham noted, for instance, that personality disorders like BPD were originally categorized as Axis II disorders in part because they were viewed as life sentences, an expression of "who you are" as opposed to "a disorder you have."

"I would place the personality disorders in Axis I," Oldham said. "There is no conceptual justification to have them in a separate place and viewed as fundamentally different from other mental illnesses. These conditions, like those in Axis I, are the result of the combination of heritable biological risk factors and environmental stress."

Oldham explained that the most recent research has suggested that BPD is characterized by genetic risk factors that predispose individuals to two distinctive traits, or endophenotypes—impulsive aggression and affective instability—which in the presence of environmental risk factors can lead to the phenotype recognized as borderline personality.

"Just as it may run in the family to be at risk for diabetes or heart disease, so it can run in the family to be at risk for borderline personality," Oldham told Psychiatric News.

The environmental traumas that are likely to produce the phenotype of BPD are neglect, abuse, or massive stress, typically early in childhood. So the theoretical construct articulated by Kernberg 40 years ago remains salient and has informed the psychotherapies that have proven effective in randomized, controlled trials.

Additionally, evidence from functional magnetic resonance imaging has shown that patients with BPD have hyperactivity in the limbic areas of the brain, especially the amygdala, and hypoactivity in the prefrontal cortex and related areas that ordinarily have strong corticolimbic connectivity.

Oldham likened the amygdala to the engine of a car "running hot," thereby causing the patient with BPD to be hypersensitive to stimuli and inclined to over-interpret or misinterpret social cues or facial expressions. Meanwhile, the hypoactive prefrontal cortex, which should normally act like the brakes of a car, diminishes the patient's capacity to reconsider or modulate aggressive impulses.

"So with borderline patients, the engine is running hot, and the brakes don't work," he said. And all of the psychotherapies that have been shown in randomized, controlled trials to be effective work to retrain, as it were, these habits of the borderline personality—demonstrable instance, Oldham said, of "psychotherapy acting as a biological treatment to change the brain."

But it takes time. "We are seeing converging evidence that psychotherapy works for BPD, but it's not a quick fix," he said. "What I tell families is that the challenge is engaging in treatment for the long term, because the key variable is time. The patients who don't benefit are those who don't stay in the treatment long enough."

So far and fast has the field come since BPD was first described that much about the disorder, including its classification within the emerging DSM-5 and even its name, is being reconsidered. Ultimately this evolution that has led to a far more sympathetic understanding of the "person behind the illness"—a person who in another day was described in DSM-III with such pejoratives as "social contrariness" and "consistently using others for one's own ends"—and of the eminently treatable nature of the condition.

"These patients can be difficult to treat," Oldham said, "but it is the illness that produces the behavior, not the person."

The second in this series will profile Glen Gabbard, M.D., who has united psychoanalytic insights with the latest genetic and neurobiological research on personality disorders.