Treatment Resistant Depression and Borderline Personality Disorder

On October 18, 2013, John Gunderson, perhaps the most internationally recognized expert on borderline personality disorder (BPD), wrote a piece in the American Psychiatric Association’s newspaper, Psychiatric News. He opined that many if not the majority of cases of treatment resistant depression (TRD - depression that does not respond to antidepressant drugs) may in fact be undiagnosed cases of patients with BPD.  This opinion is totally consistent with my own clinical experience.

John Gunderson, M.D.

Of course, the psychiatric-industrial-Pharma complex immediately went on the offensive. On his Medscape blog, Nassir Ghaemi - a fan of  bipolar m.a. - wrote a two part rebuttal. He expressed the opinion, asserted and not backed by any particular review of the literature, that the DSM criteria for BPD are invalid. In the past, he has also expressed the belief that the DSM duration criteria for manic and hypomanic episodes in bipolar disorder are far too restrictive, and seems to liberally substitute his own personal criteria for these disorders in his arguments

He goes on to assert that the “…bland, broad DSM definition allows Dr Gunderson and other borderline experts to diagnose the condition in a large chunk of persons with mood illness, not just bipolar illness but also simple depression, since depression entails relationship problems, is often associated with irritability and paranoia, frequently involves mood reactivity, often involves suicidal attempts, and can also entail nihilistic thoughts of feeling abandoned or empty.”

Nassir Ghaemi, M.D.

As I shall discuss a little later, these symptoms, when all taken together as a group, are not typical for your average run-of-the-mill case of Major Depressive Disorder (MDD), but are extremely typical of depression in BPD.

Dr. Ghaemi's statement here is misleading, because, while any given patient with major depression and no BPD may indeed have any one or two of these characteristics, they usually do not have almost all of them together. Omitting mention of this pertinent fact is a tactic frequently employed in arguments from the everyone-who-is-moody-is-bipolar crowd.

As a reference for his assertion, Ghaemi cites a study by Angst, who is another bipolar disease monger whose circular pseudo-logic I dissected in a previous post.  

Ghaemi then goes on to focus on one of Gunderson’s statements in his article: Gunderson cited a study that showed that the presence of BPD was a major predictor of persistence of depression over time in a sample of persons who met MDD criteria.

I agree with Dr. Ghaemi that such a study does not prove, in isolation and by itself, that BPD is the most common cause of TRD, as there could very well be very many other even more common causes.

His impeccable logic: “It does not follow that if x makes y worse, then most cases of treatment resistant y are examples of x. Substance abuse makes the course of MDD worse; but it does not follow - it is scientifically incorrect and illogical - to then conclude that most cases of TRD are cases of substance abuse, end of story."

Of course, the fact that Gunderson cited this one particular study did not mean that he thought he was providing a complete literature review, but Ghaemi seems to be implying that Gunderson is saying that this one study is the only evidence he is relying upon - which he didn’t say. There are a host of studies, btw, that show that severe personality disorders are often predictive of a poor response to all sorts of psychiatric medications for all sorts of psychiatric disorders.

Ghaemi himself, on the basis of some highly questionable studies, opines that the most common cause of TRD is “unrecognized bipolarity.” He of course cites references produced by his fellow bipolar m.a. disease mongers in Hagop Akiskal’s incredibly biased Journal of Affective Disorders.

Their logic has always been a one or another version of the following:

Treatment resistant depression is often accompanied by symptoms such as racing thoughts or  hyperactivity

Racing thoughts, hyperactivity, and other such symptoms can look vaguely similar to symptoms of mania

Therefore, such patients must be bipolar

This is every bit as invalid as the logic that Ghaemi is attributing to Gunderson. In fact, anxiety disorders can and do produce, superficially, all of the symptoms that Ghaemi and his buddies attribute to an underlying “bipolarity.” When looked with a more discerning eye, of course, the symptoms of anxiety disorders and mania look very, very different.

A certain type of anxiety mixed with depression, is, as I shall discuss in a bit, one of the major qualitative factors that distinguish depression in BPD from other types of depression. I think the articles that Ghaemi is quoting are not only consistent with what Gunderson is arguing, but could have been used by him as clear evidence for his main thesis!

I have met Professor Gunderson. I think he is more than capable of telling the difference between BPD and bipolar disorder. 

It’s not subtle.

Dr. Ghaemi shows such limited understanding of BPD that I suspect that, in all likelihood, he has never or rarely sat down with such patients in long-term psychotherapy and painstakingly dissected the environmental and interpersonal context in which their depressive symptoms come and go.

Another person who, like myself, has done this with patients is my colleague, academic psychiatrist Ken Silk. He did a far more complete literature search [“The Quality of Depression in BPD and the Diagnostic Process.” Silk, K. Journal of Personality Disorders 24 (1), 2/2010] than was presented in the discussions by either Dr. Ghaemi or Dr. Gunderson.

Kenneth Silk, M.D.

He points out that, rather than restricting the diagnosis of MDD to those who clearly display a biologic depression - the cases that used to respond to tricyclic antidepressants back when they were the dominant drugs - the diagnosis has spread along with the assumption that most presentations of depression are some form of major depression and, even if not MDD, should respond to antidepressants. The term depression is now used in academic discussions to refer to a mood rather than an actual diagnostic construct.

He lists the qualitative difference between the symptoms of MDD and those of depressed BPD’s. Besides the fact that the BPD patients meet criteria for BPD, not to mention that they also exhibit the family dynamics typical of those with the disorder, the quality of their depression is characterized by the following [My comments in italics]:

1.      A“mad-bad” depression closely tied to anger and hostile behavior.

2.      Mood symptoms that are very sensitive to interpersonal situations in which the patient feels abandoned, lonely, or empty in the absense [or in the presence for that matter] of a longed-for important other.

3.      Depressed moods can come on quickly and disappear quickly [the opposite of true MDD] depending on the reactions of an attachment figure.

 

4.      The depression is at times more closely related to chronic self-criticism and a feeling of intrinsic “badness” than in MDD without BPD.

 

5.      It is associated with chronic self destructive behavior [including self-injurious behavior like cutting].

 

6.      It is associated with a loss of gratification and frustration.

 

7.      Recovery from BPD facilitates recovery from MDD when it is co-occurring, rather than the other way around.

 

8.      The depression often comes from exhaustion and demoralization from repeated unsuccessful battles with chronic and overwhelming anxiety. [BPD often is accompanied by panic disorder].

9.      Patients with BPD often exhibit impulsive aggression (a hair trigger leading to rage). [Patients with true major depression, especially of the melancholic variety, tend not to show this characteristic at all. They are usually extremely passive because they do not have the energy to strike out].

Important questions glossed over by Dr. Ghaemi include: in what context do symptoms appear? How attached is the low mood to specific interpersonal events? Is affective dysregulation (high reactivity to interpersonal problems) prominent? 

An important additional point is that these qualitative differences in depression  that Dr. Silk lists are not measured clearly by any of the standard symptom rating scales used in the vast majority of psychiatric studies. Therefore, citing any studies which employ these instruments in this debate is sort of irrelevant to the basic question. 

A few final caveats.  People with BPD can still have depression that does respond to an antidepressant. And even when the depression in BPD does not improve with SSRI antidepressants directly, other symptoms such as panic attacks can improve dramatically with these drugs (especially if the SSRI is combined with certain benzodiazepines).  SSRI’s can also decrease reactivity by raising the bar, so to speak, so that it takes somewhat more extreme behavior by an attachment figure to create a severe emotional reaction. 

In patients in which either or both of these two things happen, their depression may improve indirectly because of the effects of the drug on the other symptoms, as opposed to in MDD, in which the decrease in low mood is a direct effect of the drugs.

Finally, patients can also have both BPD and true bipolar disorder. In fact, patients with bipolar disorder, when not in the midst of a manic or a depressive episode (when they are euthymic), can have just about any psychological or psychiatric reaction or personality issue in addition to bipolar disorder.  That is because, when they are euthymic, they are basically just like anyone else! 

Writers in the Journal of Affective Disorders just love to merely assume that any emotional reaction a patient with bipolar disorder has simply must be due to the underlying bipolar disorder.  What hogwash.

Counting Symptoms that Don’t Count, Part II: Compared to What?

In my blogpost of July 24, 2010, Counting Symptoms That Don’t Count, I wrote.

“So what does a doctor who spends so little time with a patient do to save time? I mean besides completely ignoring the patient's relationships, history of trauma, humanity, etc…Well, one thing they can do is ask only about symptoms, and blindly accept the patient's yes or no answer without even checking to see if the patient understands the difference between a transient mood state and a psychiatric symptom. Better yet, before the doctor even sees the patient, he or she can have the patient fill out a symptom checklist, and base his diagnosis entirely on that. (Of course, his secretary could make a diagnosis doing that, so the patient really wouldn't even have to talk to the doctor at all).”

The inappropriate use of self report tests designed to screen patients as actual diagnostic instruments has become even more of an issue than ever. As you may recall from earlier posts, such instruments are purposely designed to cast a wide net so as not to miss someone in need of treatment, and as such, they snare many patients who do not, in fact, need treatment. 

As managed care is tightening its ever present grip, full psychiatric diagnostic interviews are being marginalized. This is especially true in the so call “collaborative care” models, in which psychiatrists merely advise primary care physicians without necessarily seeing the patient themselves. 

Fellow blogger George Dawson, M.D. beautifully describes the problems with the use of a depression screening instrument in wide use called the PHQ-9:  “…let's talk about what is really happening here.  This is all about a patient coming in and being given a PHQ-9 depression screening inventory…  It generally takes most patients anywhere from 1 - 3 minutes to check off the boxes.  Conceivably that could lead to a diagnosis of depression in a few more minutes in the primary care clinic.  At that point the patient enters the antidepressant algorithm and they are they are officially being treated [they may be given an antidepressant on the basis of the pHQ-9 results alone - DA]. The care manager reports the PHQ-9 scores of those who do not improve to the "supervising" psychiatrist and gets a recommendation to modify treatment."

No determination of whether the symptoms are clinically significant. No determination of whether the symptoms reported are merely relatively normal reactions to adverse environmental events. No nothing.

To appreciate why symptom checklists are so problematic, I need to discuss something called a Likert Scale. A Likert Scale asks the patient to “rate” a symptom by level of severity, frequency, importance, or how strongly the test taker agrees with a statement. There is usually a 4 to 7 point scale with a  number attached.  Examples:

Not at all - 0

Several days - 1

More than half the days - 2

Nearly every day -3

(the PHQ-9 Likert Scale)

Very Frequently = 5

Frequently = 4

Occasionally =3

Rarely = 2

Never  =1

Not difficult at all = 0

Somewhat difficult = 1

Very difficult = 2

Extremely difficult =3

Very Important = 5

Important = 4

Moderately Important =3

Of Little Importance =2

Unimportant =1

Notice that the questions are asking the test taker to make a judgment about a symptom, but do not really define each level. It is therefore up to the test taker to decide whether the symptom occurs “often” or is “difficult” compared to some standard. But compared to what? Most people will use their own experience as reference points, and apply the terms according to this subjective standard.

So how is this a problem? Well, for depression inventories, most people have never seen someone with a severe melancholic depression who is thinking, moving and talking at a snail’s pace and who is totally and constantly overwhelmed with his or her depression all day every day for weeks at a time.  

Having never seen this, the average person does not know how bad depressive symptoms can be – unlike an experienced psychiatrist who has seen the whole gamut of depressed feelings. They therefore will not compare themselves to that, which is actually the relevant comparison!

So each test taker is, in effect, creating his or her own scale. What seems like "often" to them might not seem like very often at all to someone else. This makes the results next to meaningless for making a real diagnosis.

For those interested in statistics, the issue was neatly summed up by John Knight, a commenter on a Psychology Today Blog Post that criticized another post I had written.  He wrote:

“Firstly, there is nothing more subjective than self-reporting. How on earth can we treat what a client reports as objective data? Can any patient really detach themselves and report their... 'status' objectively, and interpret their symptoms and place scores on a Likert-type scale in the same manner as everyone else? What about the issue of the relationship to the practitioner? Can a patient be trusted to report objectively without trying to spare the practitioner's feelings? Or the opposite - what if they are annoyed and want to give negative feedback to someone they don't like?

Secondly, these Likert-type scales are often being processed as interval-level data rather than ordinal data. For the statistically uninitiated, ordinal data generally consists of "an arbitrary numerical scale where the exact numerical quantity of a particular value has no significance beyond its ability to establish a ranking over a set of data points" (thank you Wikipedia), whereas interval data will be something like degrees, metres, kilometres, and so on.

A Likert-type scale is ordinal data, but weak arguments and statistical trickery are being employed to treat it as interval data, which is easier to process and looks more scientifically impressive.

To lay off the accountant language for a moment, many CBT practitioners are treating patient self-reports with the same kind of measurable, real-world objectivity that one would treat degrees celsius, metres, kilometres, and so on. That is quite simply disgusting, and should trouble the conscience of any scientist willing to employ the method.”

Another problem is that instruments like the PHQ-9 ask questions about how many days a week a person experiences a symptom, but do not ask how long the symptoms last on a given day when present, let alone about the circumstances in which a symptom makes an appearance.

Let’s look at the questions, and I’d like the reader to envision two scenarios. The first is the melancholic depressive described above. The other is a man who gets involved and preoccupied with his duties at work and feels fine there, but every night after he gets home he becomes embroiled in a continuing conflict with his wife, who is threatening divorce, and only then starts to become extremely upset. 

I think the reader will see how it is quite possible that both of these very different individuals might answer the PHQ-9 questions in almost the exact same way, and come out with identical scores. The first would benefit from an antidepressant. The other would not, and probably needs marriage counseling instead.

PHQ-9 Patient Depression Questionnaire

Over the last 2 weeks, how often have you been bothered by any of the following problems.

Not at all - 0

Several days - 1

More than half the days - 2

Nearly every day -3

1. Little interest or pleasure in doing things

2. Feeling down, depressed, or hopeless

3. Trouble falling or staying asleep, or sleeping too much

4. Feeling tired or having little energy

5. Poor appetite or overeating

6. Feeling bad about yourself—or that you are a failure or

have let yourself or your family down

7. Trouble concentrating on things, such as reading the

newspaper or watching television

8. Moving or speaking so slowly that other people could

have noticed. Or the opposite - being so figety or

restless that you have been moving around a lot more

than usual

9. Thoughts that you would be better off dead, or of

hurting yourself

add columns

TOTAL:

10. If you checked off any problems, how difficult have these problems made it for you to do your work take care of things at home, or get along with other people?

Not difficult at all

Somewhat difficult

Very difficult

Extremely difficult

Copyright © 1999 Pfizer Inc.

Oh gee, look at who came up with this scale. A drug company. How convenient!!

Disease Mongering in a Respected Journal and Plausible Deniability

In my post of August 31, 2011, Plausible Deniability, I illustrated how doctors under the sway of pharmaceutical companies widely distribute a completely invalid “take home message” to readers of journal articles and those who listen to academic-sounding presentations, while simultaneously providing themselves with an “out” so that they can deny doing just that.  Some of these strategies have been created from information gathered from the drug company marketing departments' intensive research into physicians and the way they think (see post: Physicians As Unwitting Research Subjects, 1/3/12). 

Apparently, these strategies are widely disseminated to physicians and researchers working with Pharma.  They are just too common.  A great example occurred in a rebuttal to a letter to the editor that I and several of my partners in crime (Peter I. Parry, Robert Purssey, Glen I. Spielmans, Jon Jureidini, Nicholas Z. Rosenlicht, David Healy, and Irwin Feinberg) managed to get published in the June 2012 issue of the Archives of General Psychiatry.  The Archives is considered one of the two top journals in psychiatry.

The letter was highly critical of a study that was published in a previous issue.  The article was one I blogged about in a previous post (More Disease Mongering in a Respected Journal, 8/13/11).  The gist of our published letter was described in that post, and I will not repeat it here.

However, let me use the rebuttal to our letter, printed in the same issue of the Archives, to illustrate how the authors avoid actually addressing the criticisms in the letter and deny that they meant to conclude from their "study" that which was highly implied by their journal article.  The latter issue is what I previously referred to as plausible deniability. 

Please keep in mind that when journals publish letters to the editor that are critical of one of their published studies, they allow the authors of the original study to respond to the criticisms, but that is where it ends.  They do not give letter writers the chance to respond in the journal to the rebuttal.  (It is a situation similar to that of reporters at a presidential press conference who are not allowed to ask follow-up questions).  So I’m doing it here.  Next to what they wrote in said rebuttal, I will provide my own commentary.

We are pleased to respond to the points raised by Allen et al, some of which take material out of context and quote news media articles beyond our control. For example, the letter states that “The message is that almost half the patients with a major depressive episode have undiagnosed bipolar disorder and are ‘not receiving necessary mood stabilizer treatment.’” The authors are well aware of exactly how the news media were going to interpret their study.  Ditto doctors who read the article.  The drug companies have apparently taught these authors that readers will routinely ignore the disclaimers that they list next in their rebuttal – a case of plausible deniability.  The article is designed to give a very specific “take home message.”  The success of this strategy is illustrated by those very news stories over which they are now saying they have no control.  Of course they don’t need to have direct control to achieve this goal.

Our actual statements are: "Based on these studies and the major differences in treatment guidelines for MDD [major depressive disorder] and bipolar disorder, we recommend that, among patients with MDEs [major depressive episodes], the presence of bipolar features, including all those with significant predictive value reported in this study, should be investigated carefully before a decision is made to prescribe antidepressants. If patients exhibit bipolar symptoms that impair everyday functioning, treatment with a mood stabilizer or an atypical antipsychotic may be useful." The take home message from what they “actually said:” exactly what we said it was.  This paragraph subtly equates "bipolar features" with agitation seen in major depressive disorder - a fact nowhere in evidence.  


This conflation is even more pronounced in the abstract of the article (the short summary at the beginning of the article which is usually the only thing that most busy physicians actually read). The introduction states "Many patients with major depressive episodes who have an underlying but unrecognized bipolar disorder receive pharmacologic treatment with ineffective regimens that do not include mood stabilizers."  This sounds like the article is going to demonstrate unrecognized signs of bipolar disorder and will "orient" anyone who reads the whole thing to think along those lines.

They assert that “The study’s findings are based on a ‘bipolar specifier’ requiring ‘no minimum duration of symptoms’ and ‘no exclusion criteria,’ ” and that “Any subject who came to psychiatric attention with an angry, agitated, or elated response to environmental triggers or psychoactive substances might have met criteria for ‘bipolarity.’ ”  

The criteria, stated in the “Methods” section of our article,1(p793) were (1) an episode of elevated mood, an episode of irritable mood, or an episode of increased activity with (2) at least 3 of the symptoms listed under Criterion B of the DSM-IV-TR …The minimum duration of symptoms required for a hypomanic episode was 1 day. Here the authors are flat out contradicting themselves! I quote from the original article itself: “No minimum duration of symptoms was required and no exclusion criteria were applied.” (page 793).  And exclusion criteria in the article do not exclude active drug abusers, which we brought up and the authors just ignore in their rebuttal.

 We assessed the duration reported for hypomanic episodes in 5 groups. Among subjects with major depressive episode with hypomanic episodes, 7.8% reported episodes of 1 day’s duration; 2 to 3 days’ duration was more frequent than 4 to 6 days.  Even if they did have a minimum duration criteria, the DSM criteria for even a hypomanic episode is four days.  Really, one day? In patients who met criteria for major depressive disorder?  Riiiight.

…associated with (3) at least 1 of the 3 following consequences: unequivocal and observable change in functioning uncharacteristic of the person’s usual behavior, marked impairment in social or occupational functioning observable by others, or requiring hospitalization or outpatient treatment.  Neither the article nor the rebuttal tells us how the study doctors made the determination that there was an unequivocal  “change in functioning uncharacteristic of the person’s usual behavior. “  Especially since under their rules you only have to agitated for a day, and if you took cocaine or had a big fight with your mother, you might have an unequivocal change in your “usual” functioning. What the phrase is supposed to mean is that the patient’s functioning has unequivocally changed under any and all environmental contingencies.  They would have to be more reactive than they usually are to all unpleasant situations to a similar degree. 

So how do would the study doctors know this?  Did they take the patient’s or a family member’s word for it?  I can tell you beyond a shadow of a doubt that patients rarely really understand what psychiatrists mean by this phrase.  The only way a doctor can know this is the case is to observe the patients several times over several weeks, both during and outside of the specified time period.  


Even a close approximation would require taking an extensive psychosocial history including evaluating current environmental stresses as well as an exploration of the nature, past history of, and current status of the subjects relationships with spouses, lovers, parents, and children.  Maybe they did that, but I doubt it, because doctors like these tend to denigrate the importance of such factors in favor of “disease” explanations.  And it would take a LOT of time.

No exclusion criteria for manic/hypomanic episodes associated with antidepressant or other drug use were applied. So people who got agitated from a side effect of an antidepressants were not excluded by their own admission.  Someone gets a side effect from a drug, and that proves they are manic? 

Importantly, the initial eligibility criterion was that patients have presented to clinical settings for evaluation and treatment of a major depressive episode per DSM-IV-TR criteria. These sequential criteria, applied by senior psychiatrists in each country, are entirely inconsistent with the assertion that the psychiatrists conducting the assessments enrolled “any subject who came to psychiatric attention with an angry, agitated, or elated response to environmental triggers.” 


The statement that 23.2% of subjects experienced elevated or irritable mood triggered by antidepressants did not “define the subjects as having ‘bipolar disorder.’” Rather,it addresses the DSM A criteria, which are essential, but not sufficient, for diagnosis of bipolar disorder. As Figure 1 in our article shows, mood lability while taking antidepressants occurred in 55.8% of bipolar specifier–positive vs 23.0% of bipolar specifier–negative subjects (odds ratio, 1.7;95% CI, 1.4-2.0) and mania/hypomania while taking antidepressants occurred in 37.2% of bipolar specifier–positive vs 3.4% of bipolar specifier–negative subjects (odds ratio, 5.7; 95% CI, 4.4-7.5).  Sorry, but with this paragraph the authors are still implying that their subjects MAY be bipolar, and assumes precisely what the article is supposed to show – that a patient who is agitated when depressed could have a manic symptom.  So if patients with an agitated depression are more likely to become more agitated on an antidepressant than depressed patients without agitation, that is supposed to show that they might be bipolar?  Only by circular reasoning.

Allen et al view their position as part of a “debate” about the “ever-widening bipolar spectrum.” We consider data, not debates, as central to the progress in the scientific understanding of mood disorders.  Ha!  This is a brazenly outrageous statement. The “debate” is specifically ABOUT "data" like theirs – both its validity and what it means.

They make several references to borderline personality disorder. The BRIDGE study assessed for comorbid diagnoses in all subjects. Five hundred thirty-two patients (9.3%)met DSM-IV-TR criteria for borderline personality disorder. This large sample provides an opportunity to analyze patients who met borderline criteria vs those who did not. We are completing a manuscript that will provide useful evidence on this subject. Maybe they should have said this in the original article.  But we know from the work of Zimmerman and others (My Psychology Today blogpost 12/11/11) that many patients who have borderline personality disorder are misdiagnosed.

Allen et al cast unseemly aspersions that the BRIDGE study was a vehicle to promote sales of an antipsychotic drug sold by sanofi-aventis. sanofi-aventis has no antipsychotic with an indication for bipolar disorder.  Here the study authors are being complete weasels.  The misleading point is contained in the phrase “with an indication for bipolar disorder.”  What they say is literally true - in the United States. Unfortunately, Sanofi does have an antipsychotic drug called amisulpiride (brand name, Solian). In fact, in the United States, it is not FDA-approved for any indication, let alone for bipolar disorder.   


However, Solian is approved and widely marketed in Europe and Australia, and at least according to Wikipedia, used for bipolar disorder.  (This may be why the study was conducted overseas). In addition, Sanofi also sells a preparation of depakote, which while an anticonvulsant and not an antipsychotic, is widely used in both actual and misdiagnosed bipolar disorder. 

Besides, as I described in my post of 6/12/12, marketing for off-label uses of drugs for bipolar disorder is unequivocally rampant.  Maybe the authors didn’t know this?  NOT.

We know of no evidence that this was the case at any stage of development and execution of the BRIDGE study. Sanofiaventis ceased financial support for analyses of the study in 2010. All work subsequently conducted has been achieved by our local funds. The drug company got out of the game just in time for the authors to claim they were not biased due to the funding source. Actually, the original article says “The sponsor of this study (sanofi aventis) was involved in the study design, conduct, monitoring, data analysis, and preparation of the report.” 


In addition, all of the clinicians recruited for the study received fees, on a per patient basis, from Sanofi-Aventis in recognition of their participation in the study. The key lead authors, all with significant Pharma connections, did not disclose their other pharmaceutical company ties.  These authors: Allan H. Young, MD, Jules Angst, MD, Jean-Michel Azorin, MD, Eduard Vieta, MD, Guilio Perugi, MD, Alex Gamma, PhD, Charles L. Bowden, MD.  


They should be ashamed of themselves.