Borderline Hyper-reactivity: Compared to What?

One of my complaints about the research literature on the so called “hyper-reactivity” of patients with borderline personality disorder (BPD) is that the authors of such studies almost always look at the quality and frequency of their subjects’ responses without ever looking at what they are responding to.  Since mood instability is the most central part of the definition of the disorder, of course they will have more reactions. By definition, they’ve been selected for it!

 

Two recent studies show that patients with BPD really don’t seem as different from others as one might expect. They both provide strong evidence for my point of view. One showed that the specific reactions to interpersonally threatening stimuli of patients with BPD  is not all that different from those of anybody else.  It looked at skin conductance responses (SCR, a measure of stress) in patients and healthy controls.  The second investigated whether or not patients with other psychiatric disorders responded differently. They found that they all sort of responded the same, in spite of the fact that - once again  - the source and severity of the environmental events which triggered the patients was ignored.

Here’s some descriptions from the study abstracts.

1.   Hillmann K; Mancke F; Herpertz SC; Jungkunz M; Olsson A; Haaker J; Bertsch   K. Psychopathology. 53(2):84-94, 2020. Intact Classical Fear Conditioning to Interpersonally Threatening Stimuli in Borderline Personality Disorder.

 

Threat hypersensitivity is regarded as a central mechanism of deficient emotion regulation, a core feature of patients with borderline personality disorder (BPD). In this study, patients with BPD showed larger conditioned prolonged conditioned skin conductance responses (SCR) (a measure of stress) and subjective stress and expectancy ratings  to interpersonally non-threatening and neutral than interpersonally threatening stimuli, while interpersonally threatening stimuli elicited higher SCR compared to non-threatening or neutral stimuli in healthy controls. 

While the overall the results suggest no alterations in fear conditioning to generally aversive stimuli in BPD, it’s quite interesting than when someone in the environment is non threatening, patients with BPD react with MORE stress. One possible explanation: the people around them most of the time are more likely to attack them when most  other people would have let their guard down.

2.  Kockler TD; Santangelo PS; Limberger MF; Bohus M; Ebner-Priemer UW, Specific or transdiagnostic? The occurrence of emotions and their association with distress in the daily life of patients with borderline personality disorder compared to clinical and healthy controls.
Psychiatry Research 284, 11262, 2020).

 The authors wanted to see if hyper-reactivity to stress was specific to BPD or was seen as much in other disorders. Using e-diaries, they compared patients with BPD, normal controls, patients with bulimia, and those with PTSD. The majority of the comparisons (anxiety, sadness, shame, disgust, jealousy, guilt, interest) revealed transdiagnostic patterns, which means that the same reactivity was seen in the other disorders. The only major exception was that patients with BPD exhibited anger more frequently than any of the clinical groups or in healthy control. 

As mentioned, nothing was looked at concerning what the anger was about. So maybe anyone would be angry if exposed to whatever it was the patients with BPD had been exposed to. 

Borderline Personality Disorder: Why They Don't “Get Used to It.”

At the annual meeting of the American Psychiatric Association in New York this year, I learned about a new finding from one study with patients who exhibit borderline personality disorder (BPD). The same finding also applied, although to a lesser degree, to those with avoidant personality disorder (AVD), which is pretty much identical to the diagnosis of Social Phobia.  I suspect that the reasons for the similar findings may be different for the two disorders.

The finding involved a part of the brain called the Amygdala. This little doohickey is central to a lot of brain functions, but in particular, it is the center for the body’s “fight or flight” response. I always though it fascinating  that the amygdala also has specific cells which respond only to one’s own mother (or other primary female attachment figure) and nothing and nobody else, and other specific cells which respond only to one’s father (or other primary male attachment figure). 

Although one cannot prove such things, this fact suggests to me that primary attachment figures may be the most potent of all of the environmental triggers to fear-based flight or fight reactions. They are certainly more powerful that a therapist can ever be for doing so, for instance.

The finding may relate to one of the primary symptoms of BPD, which goes by a variety of names. In the actual DSM criteria, it is described as “affective instability, or marked reactivity of mood (e.g., intense episodic dysphoria, irritability, or anxiety usually lasting a few hours and only rarely more than a few days.)” It is also called high reactivity, and lay people often label it hypersensistivity. In psychological tests, it is called neuroticism. Clearly, amygdala activation is intrinsic to this phenomenon.

Therapists have a tendency to think that patients with BPD over-react because they misperceive the behavior of others as being emotional slights, when the behavior is not at all meant as such. In fact, these therapists do not even know to what exactly the patient may be reacting to, or alternatively, that sometimes patients with BPD feign such reactions in order to provoke a specific response in others in order to recruit them to be enablers of the patients’ spoiler role.

For example, one patient would go ballistic if anyone ever even implied that her mother might have been a loving parent. Of course, if one knew all the horrible things her mother had done to her, one could easily see why she would find such a comment annoying - to say the least!

The study I am discussing here is by Harold Koenigsberg and others (Journal of the American Psychiatric Association 171:82-90, January 2014). Study participants were asked to look at a series of pictures with either highly negative or neutral content, and the activation of the amygdala and another region of the brain called the dorsal anterior cingulate was measured using a specific type of brain scan. The subjects also subjectively rated their emotional responses to the pictures. 

Exposure to these pictures and these measurements were then repeated. Repeated only once, I’m afraid. The study would have been a lot more powerful if they had repeated the exposure several times.

The changes in emotional arousal and brain activation after a repeat viewing of the negative images was small but signficantly different between patients with BPD or AVD and the "normal" control subjects.  

The brains of the controls seemed to habituate, while those of the patients with BPD did not.  Habituation means that the controls got used to or became accustomed to the awful pictures, and their arousal levels decreased from what it had been after the initial viewing.

If anything, the emotional arousal of patients with BPD actually increased with the repeat viewing.

This finding, if it can be replicated, might seem to indicate that the brains of those with BPD are abnormal in this regard. However, as I have ranted in the past, a difference is not automatically indicative of an abnormality. In fact, it may be a conditioned response that is highly adaptive in particular environments.

In the case of patients with BPD in particular, they invariable grow up in chaotic family environments in which “getting used” to the chaos and not reacting to it when one needs to could be hazaradous to their and their family’s health, as described in my post on Error Management Theory.  If the chaos continues, such individuals need to pay even more attention to it, not less. 

This new research finding fits my ideas about that to a tee.

Is Marketing Drugs for Non-FDA Approved Uses Free Speech?

A recent ruling by a three-judge panel of the Court of Appeals for the Second Circuit in Manhattan threatens to legalize the marketing of snake oil without any restrictions. It maintains that the marketing  of pharmaceuticals by drug companies for conditions for which the FDA has not approved them is free speech!

Considering the ruling of the Supreme Court in the Citizens United case, many of us are highly concerned that if the lower court ruling is appealed and ends up there, that the current court will concur, and this will become the law of the land.

U.S. Supreme Court

As my colleague Ken Harvey says, only in America.

I have posted here several times about the huge fines levied against big Pharma drug companies for marketing psychiatric and other medical drugs for uses in conditions for which the FDA has not approved them as safe and effective. For a summary, see my last post on the subject.

Once a medication is FDA-approved for any indication, doctors are absolutely free to prescribed it for any other condition they see fit, but pharmaceutical companies are not allowed to market the drugs for these other conditions. This is important because pharmaceutical companies can run poorly-constructed studies that show that a drug might help this or that condition, and if there were no law against it, use their various marketing techniques and financial inducements to get doctors to prescribe the drug to larger and larger populations of patients.

Many of these powerful marketing techniques have been described by me in a series of previous posts (the last one being my post of August 7, 2012). The profits to be gained by so-called off-label marketing are enormous, and completely dwarf even the billion dollar plus fines levied by the U.S. Department of Justice. The fines are considered to be just a cost of doing business by Big Pharma.

This situation has also led to an explosion of disease mongering, in which the definitions of disorders like bipolar disorder for which certain drugs are FDA-approved are expanded beyond all reason (see my posts of 10/20/12 and 8/13/11).

The damage to patients, especially in the field of psychiatry, has been particularly horrendous. People with family and behavioral problems who are in desperate need of psychotherapy are instead given only drugs, many with potentially toxic side effects.  Patients unfortunately are all to eager to buy in to the proposition that their emotional problems or those of their children are merely the result of some brain dysfunction rather than their own behavioral difficulties.

(Disclaimer for the anti-medication lot: of course some psychiatric conditions do indeed result from brain dysfunction, and for those medication is the primary and most effective treatment, and psychotherapy is next to worthless. Which ones are those?  Read this blog! Also, medications can control anxiety and emotional reactivity so that psychotherapy becomes even more effective).

Just as an aside, readers may wonder if I think it should be illegal for doctors to prescribe medications for non-FDA approved indications. This is a complicated question, because of the crazy way the FDA in the U.S. works. For example, we know that if one SSRI antidepressant (Prozac, Paxil, Zoloft, Lexapro, Luvox, Viibrid) works for, say obsessive compulsive disorder, then they all do.

However, once one drug company does the studies that result in their getting an approval from the FDA for their product for this indication, the other drug companies have no financial incentives for doing studies with their own product. Doing the studies is expensive, and they know doctors know about the if one-then all idea, so they will use the other me-too drugs off label. I don't see anything wrong with doctors doing so in properly diagnosed patients (which, BTW, is unfortunately a big "if" nowadays).

Also, sometimes there is widespread clinical experience that shows that a given drug is effective for a certain indication for which studies have not led to FDA approval for that indication. For instance, many of us have successfully used SSRI antidepressants in patients with borderline personality disorder to decrease their emotional reactivity (neuroticism). The drugs do not stop the hyper-responsiveness that these patients show to problematic interactions, but they do raise the bar. It takes a higher level of stress to get them into a state of dysregulation than it would in an unmedicated state.  Hardly a cure, but still very useful.

There have been many studies to show that SSRI's do this, some performed by Emil Cocarro, a highly respected researcher. But so far, no drug company has, for a variety of reasons, made a petition to the FDA for this indication.

Dr. Emil F. Cocarro

I would be very much opposed to any action that would limit my ability to help my patients in this way. Unfortunately, many of my colleagues listen to drug company propaganda and use drugs in ways that are very inappropriate. I'm not sure what the solution to this quandary is, but of one thing I am certain: allowing Big Pharma to market drugs for unapproved indications ain't it.

Debunking De Biederman

Joseph Biederman, the Harvard guru who advocates for the use of antipsychotic medication on children, is a psychiatrist who almost single-handedly started the current craze of psychiatrists and primary care doctors diagnosing acting-out children as having bipolar disorder.  I discussed in previous posts some of the issues involved both in Dr. Biederman's behavior and in the diagnosis of "pediatric bipolar disorder," particularly in my post of March 9, 2010, Recipe for Producing Frequent Temper Tantrums in Children.



Dr. Joseph Biederman

Dr. Biederman argued that the symptoms of bipolar disorder in children are very different from those of adult bipolar disorder.  In particular, he said that manic or depressed mood episodes, required by the DSM to last for a minimum of four to seven days in adults for mania and two weeks for bipolar depression, could last for mere minutes in children. Symptoms of bipolar disorder seen in children but not in adults, he opined, included temper tantrums and "explosive irritability."  Not that he had any clear scientific evidence connecting such symptoms to adult bipolar disorder. I'm guessing he just pulled these ideas out of his butt.

Tantrums, rage, emotional instabilty, low frustration tolerance and the like are all symptoms of borderline personality disorder in adults.  These types of symptoms fall under the rubric of affective instability or mood dysregulation, also called neuroticism by personality theorists. 

Individuals high on this variable get depressed, anxious, or angry quite easily and take much longer to calm down than average person. Patients with borderline personality disorder are frequently misdiagnosed as bipolar in the world of today's psychiatry (see my post of April 7, 2010, Borderline or Bipolar?).

Is similar diagnostic bungling being seen today with out of control children who exhibit affective instability?  Well, according to a new review of all of the existing studies in the February 2011 edition of the American Journal of Psychiatry by Ellen Leibenluft, the anwer is quite clearly yes.

From the abstract: "An emerging literature compares children with severe mood dysregulation and those with bipolar disorder in longitudinal course, family history, and pathophysiology. Longitudinal data in both clinical and community samples indicate that nonepisodic irritability in youths is common and is associated with an elevated risk for anxiety and unipolar depressive disorders, but not bipolar disorder, in adulthood.

Data also suggest that youths with severe mood dysregulation have lower familial rates of bipolar disorder than do those with bipolar disorder. While youths in both patient groups have deficits in face emotion labeling and experience more frustration than do normally developing children, the brain mechanisms mediating these pathophysiologic abnormalities appear to differ between the two patient groups."

In the absence of validated biological laboratory tests for a psychiatric disorder, the time course of symptoms, clustering of the symptoms in close family members, and differences in brain physiology and mental abilities on various mental tasks are the most important indirect ways of assessing whether two similar appearing psychiatric syndromes have something important in common. In each of these ways, comparing short-term affective instability to the longer term symptoms seen in bipolar disorder shows that the phenomena are not the same thing.

It is also important to note that irritability is a criterion for at least six different psychiatric diagnoses in children (manic episode, oppositional defiant disorder, generalized anxiety disorder, dysthymic disorder, posttraumatic stress disorder, and major depressive episode).

Of course, not even Leibenluft discusses the possibility that -  just maybe - affective instability in children is reactive to a chaotic family environment.  Interestingly, in an interview in the January 21, 2011 Psychiatric News, she was quoted as saying, "The phrase we commonly hear from parents is that they have to 'walk on eggshells.'"

 

Translation: the kids in these families are determining what the adults do or say, not the other way around.  A situation in which parents seem to be afraid of their own children is very bad for children, who tend to badly need to be taken care of and given limits by their adult caretakers - despite the kids' protestations to the contrary.  There is very strong evidence from the attachment literature that such situations actually create affective instability in children.

So what might Biederman's answer be to this new data?  Amazingly, according the Leibenluft, Biederman's research group and some other groups maintain that it is "nonetheless reasonable to apply a bipolar diagnosis to children with such a clinical presentation. One important argument for this position is that children with severe nonepisodic irritability manifest severe mood symptoms and are as severely impaired as those with classic bipolar disorder, but without a diagnosis of bipolar disorder their access to the mental health services they need might be limited."  (p.129-130).

Wow. In other words, we should label kids who actually have behavior problems as having bipolar disorder, so instead of doing family therapy, we can treat them with sedating drugs that have not been approved as safe or efficacious in children, and which have a lot of potentially extremely serious toxic side effects (metabolic syndrome) in people including death. 

An amazing display of sick, twisted phony logic worthy of Ann Coulter.

(See a great review of the issues involved in the case of a child named Rebecca Riley who died at the hands of parents who were trying to bilk the psychiatric disability system.  It also shows how easy it is to fool some psychiatrists).