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David Baxter PhD

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The Roots of Problem Personalities
By Andreas Meyer-Lindenberg, Scientific American Mind
April, 2009

Scientists are peering into the brains of people with borderline personality disorder and finding clues to the roots of this disabling illness

Glenn Close?s unforgettably vivid portrayal in the movie Fatal Attraction gave viewers a front-row look at the damaging mental illness known as Borderline Personality Disorder (BPD). By itself, this ailment accounts for up to 10 percent of patients under psychiatric care and 20 percent of those who have to be hospitalized. The defining characteristic is pervasive instability in the patient?s life, especially in relationships. People who suffer from BPD also have difficulty controlling their impulses and regulating their emotions. Their behavior exerts a tremendous toll not only on themselves but also on their friends and colleagues, as well as on the health care system.

Despite the importance of this disorder, surprisingly little is known about what brain mechanisms might underlie it. Over the past few years, however, scientists have found intriguing hints. Structural imaging studies have indicated, for example, that parts of the brain?s limbic system, which regulates various aspects of emotion, are abnormally small in patients with BPD, and the areas that appear most reduced in volume govern negative moods. Investigations of functional abnormalities show that these same limbic areas?including the amygdala?tend to be hyperactive. Some researchers theorize that the smaller size of limbic structures reflects a loss of inhibitory neurons, which might mean these patients? brains have a weaker rein on behavior and negative emotions, leading to impulsivity and overly negative reactions to events.

In a 2008 paper in Science, neuroscientist Brooks King-Casas and his colleagues at the Baylor College of Medicine showed that aside from lacking emotional restraint, individuals with BPD have problems correctly perceiving social gestures from others. In addition, the team has illuminated an additional brain structure that plays an important role in the disease.

The researchers took an innovative game theory approach to probe the roots of the disturbed interpersonal communication characterizing the disorder. This technique, which involves the use of interactive competitions to gain insights into human social behavior and decision making, also holds promise for investigating other types of social interactions and interpersonal pathologies.

Investing in Trust
In King-Casas?s study, pairs of people exchanged money over 10 rounds of a game. Each pair consisted of an investor, who decided on an amount of money to front?knowing those funds would triple?and a trustee, who received the expanded sum and could decide how much of it to keep and how much to pay back. If the investor chose to advance $10, then the trustee would have $30 to split ($10 ? 3) between himself or herself and the investor. In this experiment, some transactions occurred between two mentally healthy individuals; in other exchanges, the trustee (but not the investor) suffered from BPD.

Although this game is at first glance only about money, it actually probes the nature of cooperation and the development of trust, both of which require sensing and responding to the social messages implied by a colleague?s behavior. Thus, a socially sensitive trustee realizes that being gen*erous builds trust?and will also pay off, because an investor is likely to respond in future rounds with increased investments. Such cooperation produces mutual profits much greater than if the investor just keeps most of the money for himself or herself. On the other hand, an investor who does not trust the other player will not put in much money, and as a result both members of the pair will be less well off.

Monetary offerings were uniformly high early on, but in later rounds investors were offering significantly less to the trustees with BPD than to the mentally healthy trustees, pointing to a breakdown of trust and cooperation in exchanges involving partners with BPD. Although trust fragments even in normal relationships, the mentally healthy trustees restored confidence through a ?coaxing? strategy, in which they encouraged wary investors with generous returns, which are a sign of trustworthiness. Healthy players used this strategy twice as often as individuals with BPD did, indicating that people who have this disorder lack the social skills essential for establishing and maintaining cooperative relationships.

Self-Centered Brains
To find out why the players with BPD behaved this way, the researchers used neuroimaging to study brain activation of trustees confronted with a small investment, which usually signals a lack of trust on the investor side. The functional magnetic resonance imaging scans revealed a crucial difference between BPD trustees and healthy players. In healthy subjects, a region of the brain called the anterior insula seemed to neurally represent the investment level, so that small contributions from a partner corresponded to a large activation in the trustee?s brain, and vice versa. In the brains of BPD subjects, however, no such relation existed.

As expected from earlier work, activity in this same brain area also mirrored the amount of money a trustee was about to return to the investor, so that a large amount of insula activation in the trustee?s brain predicted a small payment from the trustee. In this case, however, both players with BPD and healthy volunteers displayed the same neural pattern. Thus, although in healthy subjects the insula encoded both ?distrustful? offers from investors and ?stingy? repayments, the insula activity in people with BPD reflected only their own actions. Their impairment seemed to selectively concern the portrayal of the other player.

The anterior insula has long been associated with the representation of unpleasant bodily sensations such as pain. In addition, many studies have shown that this area strongly responds to uncomfortable social contact, including interactions that seem unfair, frustrating or risky. This body of work suggests that the anterior insula tracks information about the intentions and behavior of others and colors them with a feeling of discomfort. If that interpretation is accurate, then one reason BPD subjects may be impaired in maintaining cooperation is that they do not have the ?gut feeling? (resulting from the anterior insula signal) that there is a problem with the relationship. Unable to detect the breakdown of trust, BPD sufferers do not work to repair it and are less likely to trust others at all.

Genetic Roots
This exciting finding prompts many new questions. The first is: What causes this abnormal brain activity? Most research indicates that BPD commonly arises from a combination of a genetic predisposition and severe trauma in early childhood. Not everyone who is traumatized as a child gets BPD, but a combination of risk genes may heighten the impact of trauma on the developing brain.

Although no one has identified specific genes that cause BPD, many of the personality components of the ailment, including impulsiveness and aggression, are highly heritable. Moreover, researchers have linked genetic variants, such as those involved in the neurotransmission of serotonin, to the disorder. (Selective serotonin reuptake inhibitors such as Prozac, however, are not effective treatments for BPD, according to a recent study.) It would be of high interest to determine whether these genetic variants compromise the structure and function of the anterior insula. Because no brain region operates in isolation, neuroscientists should aim to fully characterize the brain network of which the insula is a part.

Beyond BPD, scientists may want to apply the game theory strategy used in this study to other severe mental illnesses, such as schizophrenia or autism, in which social dysfunction plays a pivotal role. Researchers, patients and therapists should all welcome such an advance.
 
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