Q. I appreciate your learned thoughts on the subject of BPD. I too have a strong negative reaction to the presumption that individuals with mental problems are somehow "fixable" with a course of talk therapeutic treatments, and agree that neuropsychopharmacological "adjustments" can be enormously helpful. But I also have a problem with simply saying the problem is "biological" or "chemical". Every psychological/behavioral phenomenon -- normal and abnormal, pleasant and painful -- is biological/chemical, without exception. And all are systematically modifiable with pharmacological intervention -- adjustments of levels of brain neurochemicals. The behavioral intelligence system (and it's mind) isn't a somatic organ designed to serve a specific predetermined function. It is designed to be an ever-adapting interface between the individual organism and it's environment. When we're talking about this neurohormonal system, I don't think it's particularly informative to say a set of phenomena results from "a chemical imbalance". What would constitute balance in a complex biochemical system designed to function by ever changing levels of chemicals in response to external and internal environmental factors. Every aspect of the intelligence system's function is dependent on ever-changing increases and decreases in neurotransmitters and hormones. So, for example when a person's life is going great and they're on top of their game, their serotonin levels are high; when their life hits the skids and everything isn't going great, their serotonin levels are low. The change in serotonin level results in the selection of different subsets of experiential information, so that the behavior currently being generated is informed by experiential data that was stored when the person was at the same social level. It's always easier to think about such phenomena in nonhuman primates. If we record the positioning in the social hierarchy of all members of a troop of rhesus monkeys, and then assess serotonin levels, the highest level belongs to the alpha monkey and the lowest to the omega, and there's a one-to-one relationship between level of social positioning and serotonin levels, all the way down the line. Using SSRIs and serotonin antagonists, one can completely manipulate the social hierarchy by increasing or decreasing serotonin levels. Or, in a more natural demonstration, one can simply wait until a lesser monkey has a lucky accident and one-ups the alpha; there will be a resulting increase in the lucky monkey's serotonin level and a concomitant decrease in the alpha's. When a monkey's serotonin level is low, information subsets selected for are those that are yoked with that level of serotonin. As a consequence, the animal will "know" to behave in a more submissive way, and in that way will survive in the hope of a better tomorrow. We could say the omega monkey has "low self esteem", and if the state persisted (or if we couldn't identify the predisposing life event) we could say he was suffering from "depression". And we could say that this was due to "a chemical imbalance" -- that is, a nonnormatively low level of serotonin. But we'd be missing the point. Increasing and decreasing dopaminergic and noradrenergic systems also grossly modulate the intelligence system as a function of experience in the environment. And, as I perhaps immodestly suggested, I think I have some understanding of the phenomena we would call depression and mania, as well as some of the so-called "personality disorders" within one pretty cogent and comprehensive framework that aligns well with the neuroscientific evidence. I believe that BPD is absolutely the most difficult phenomenon to understand, and to treat. I applaud you in your work, and would be very interested in knowing what medication you have found to most effective n the treatment of most cases of BPD. If a gene complex has been identified as being associated with BPD symptomatology, that would be useful to know; unfortunately, it doesn't tell us what the gene is actually coding for (and it is unlikely that it codes for gross cognitive, affective and/or behavioral phenomena, nor does it imply that the gene ballistically "produces" BPD or a neurological anomaly that supports BPD symptomatology. We have so much to learn . . . Also, the fact that adopted individuals raised by normal adoptive parents display symptoms of BPD is interesting and suggestive of innate cause. But the finding of normal siblings of patients with BPD is much less informative. The social environment of siblings living together is radically different from their individualistic perspective (though it looks identical to those of us peering through the window). They're forced to vie for distinctive niches in the small, closed biological market of the family. Indeed, monozygotic twins reared apart show much more significant similarity on various dimensions than those raised together in the same family -- quite a counterintuitive finding . . . Finally (and this really will be it for today :) I think its important to recognize that "learning" IS a change in the biological substrate, and that early learning establishes what are usually lifelong patterns in the processing of behavioral/psychological information. In theory, at least, behavioral tendencies can be changed because the system remains modifiable on line (you're just always fighting an uphill battle against a lifelong accretion of information networks that are countering your attempts). Hopefully, the recognition that the information-processing pathways of the human neocortex are constructed in an on-line fashion as a function of an individual's ongoing experience in the environment will eventually enable us to discard the dichotomous "nature versus nurture" framework. Again, thank you for taking the time to respond to my inquiry, and best of luck in your continuing endeavors to treat and understand the heartbreaking condition of BPD.

A. I have been following the monkey data closely for over 10 years. I agree with you that in monkeys, serotonin increases result in happier or higher functioning monkeys. That is the whole point of using SRIs in BPD. It works. Regardless of what society does, where they live, or what their life experiences, they have an illness called BPD that needs treated. If you use medications, people function a lot better. That said, I do not believe serotonin is the cause of the illness. Like sugar in diabetes, it is a measure of something being wrong. Essentially, low serotonin can equate to BPD. BPD is, however, a clinical diagnosis. Low serotonin does not guarantee the presence of BPD, nor does normal serotonin guarantee its absence. The medications do not work through serotonin or we would be using a lot less than we are. We are way over what we need to block serotonin reuptake, but lesser amounts will not help. My favorite meds are Effexor XR, Zoloft, and Serzone. All the SRIs (Zoloft, Prozac, Paxil, Celexa, and Luvox) work. I like Zoloft because you can measure levels and see if it is enough to work. Effexor XR has less side effects than the SRIs, esp. sexual dysfunction, and seems to work in a higher percentage of folks with BPD than the SRIs. It may be 10% better. Serzone is great if they do not have OCD. It is the cheapest and has no sexual dysfunction of note.

I find your learning paradigm pedantic. Of course our brain has constant chemical changes. We would die otherwise. The problem is that once emotional responses are laid down, they stay that way (see data from NYU neurochemistry section). They are hard-wired. I would love to see a therapy that works to remove these behaviors. I have not. If therapy worked, there would be not need to use medications. Whether the BPD-behaviors are learned or genetic is a moot point. It is unequivocal that chemical changes occur that are permanent. So our job is to fix them. I cannot change a person's childhood. Even if they were molested and this is the cause of the problem, there is not much to do but fix the chemistry. Adopted apart twin studies argue for the genetics being somehow a factor.

Finally, I find the current concepts in therapy illogical. I believe therapy will help, but I am not a believer that it will come from the types we are currently using. Therapy should be logical, and based on a premise that is testable. If one were to use cognitive therapy--an individuals ability to cognitively understand and process data-- this would be illogical. Why can folks with BPD do everything else in their lives logically, e.g. wear shorts in the summer because it is hot, learn to not swim outside in the winter because it is cold, eat when hungry, not soil themselves, aspire to nice amenities, and even swallow when they have spittle in their mouths, but not be able to stop other uncomfortable behaviors that are part of the illness for more pleasant ones? The learning model does not fit. Hopefully, someone will develop ways of treating this illness psychotherapeutically. I follow it as a medical illness because it is based on all the data I have seen. In all other medical illnesses, you do therapy after you fix what is physically wrong.

We do a disservice to those afflicted with BPD by suggesting they can talk their ways out of the illness. It implies they are just in need of having their thinking straightened out. It is like talking to a diabetic to lower their blood sugar. Clear grounds for malpractice. I have all my patients in therapy because it gives them another way to get some better. I also do not mind if they try meditation, acupuncture, vitamins, whatever, as long as they are doing what is known to work. If there is no data that it helps or hurts, it may be worth a try if they only get 1% better. Medications work without question. Not using them in a patient with BPD is a horrific transference issue by the therapist at least or severe narcissism at worse.