Mixed Episodes Redux

Earlier in a post titled Mixed Episodes we discussed the DSM definition of a mixed episode and we discussed some other ways of viewing mixed episodes.  Adding to that discussion is a recent article:

Swann et al. Bipolar Mixed States: An International Society for Bipolar Disorders Task Force Report of Symptom Structure, Course of Illness, and Diagnosis. Am J Psychiatry. 170:31-42, 2013.

This article is the result of discussions and several conferences involving a long list of people who appear on the author list of the paper.  The point of the article is best summarized by its conclusion:

Components of what are considered manic and depressive states can combine in bipolar disorder. Mixed features may be associated with illness course and treatment response characteristics distinct from more exclusively depressive or manic states. Clinical characteristics, including co-occurring conditions, suicidal behavior, anxiety, poor treatment outcome, and severely recurrent and complicated course, appear stable across definitions and criteria for mixed states. The importance of recognizing and monitoring mixed features during a hypomanic, manic, or depressed episode is highlighted by their relationship to recurrent course, treatment resistance, co-occurring substance use, and potential for suicidality.

The article does give a specific clinical algorithm for identifying mixed states, similar to the algorithms that the DSM gives.  The primary type of episode is identified (manic or depressive) with concomitant identification of an episode as mixed if it has sufficiently many non-overlapping symptoms from the 'opposite' type of episode.  Symptoms are said to be non-overlapping if they are unlikely to occur in both non-mixed depression and non-mixed mania.

There were several interesting sets of symptoms brought up by the article.  The authors segregate symptoms as to whether they are manic or depressive.  Then they segregate mixed episodes as to whether they are primarily manic or primarily depressive.

The authors say that manic symptoms of maniac mixed episodes are "greater mood lability and irritability and decreased grandiosity, euphoria, pressured speech, and need for sleep ," and depressive symptoms of manic mixed episodes are "dysphoric mood, anxiety, excessive guilt, and suicidality" are symptoms of mixed episodes.    In depressive episodes, manic symptoms include "irritable mood, distractibility, racing thoughts, and increased talking."

There is a collection of symptoms that the authors say characterize mixed episodes regardless of the primary categorization (into mania or depression) of the mixed episode.  These include "anxiety, agitation, or psychosis."  About anxiety the authors say

Anxiety has been shown to correlate with depressive symptoms in manic episodes, with manic symptoms in depressive episodes, and with the degree to which symptoms were mixed regardless of polarity. This pervasive role of anxiety is consistent with mixed states being driven by hyperarousal. 

Agitation is a combination of hand-ringing and uninhibited impulsive action.  Psychosis, as we know, is typified by thought disorder, including paranoia, delusions, and hallucination.  Psychosis is thought by the authors to be present primarily in either manic or mixed episodes.

While this article represents a step forward in terms of diagnostic tools for bipolar, I have reservations about it.  This article makes heavy use of the binary description of bipolar while simultaneously breaking the binary thinking and expanding it to be trinary.  The authors want to have their cake (the dichotomy) and eat it (make it trinary), too.  Also, they assume that one can always identify a primary episode type.  I suspect this last assumption is based on circular logic.  I think there are examples of episodes not having a clearly distinguishable primary type, and yet these episodes should still be classified as being bipolar episodes.

I am an example of a person having episodes that fall between the diagnostic cracks.  This has previously been discussed in the post titled My Diagnosis or Lack of One.  One comforting thing about the article mentioned above is that I finally find a description that matches my experiences.  This is comforting, because I know that I am not the only one who experiences the combination of symptoms that I experience.  In particular, my episodes have been marked by anxiety, agitation, and psychosis.  According to the authors it would seem that I have been having mixed bipolar episodes.  However, I find this categorization of my episodes to be unsatisfactory.  The popular conception of bipolar is wedded to the idea of a dichotomy between mania and depression.  My experience has nothing to do with such a dichotomy.  I experience no highs, no extreme lows.  On the other hand, the drugs that help me also help people with the traditional bipolar.  So, it seems to me that we are missing some important biological connection between patients exhibiting these disparate sets of symptoms.

The analysis performed by the authors is on individuals who are incontrovertibly diagnosed as bipolar, according to the binary definition of bipolar.  Then the authors take these people and group their symptoms into the binary categories of mania and depression. The authors then use that grouping of categories to decide whether an episode is primarily manic or primarily depressive.  Does this sound like circular logic?  They first assumed there were categories for mania and depression, then used patients diagnosed according to this dichotomy to establish whether symptoms and subsequently episodes were primarily manic or depressive. The correct statement of their argument goes something like this: if there exist two poles for the bipolar disease, then there is a grouping of symptoms into the two poles and a subsequent categorization of episodes into primary types of mania and depression.  But the classification of episodes cannot provide evidence for episodes having a primary manic or depressive categorization, unless we first assume that there is a dichotomy matching the labels mania and depression, making the logic circular.

Another problem with the article is that most reasonable experiments involving phenotype data would yield the result that there is a mixed trait.  This is because such a study would be based on the false binary assumption that there are two clusters of phenotypes.  I can take any cases (individuals with a disease) having any binary disease along with a set of multiple symptoms that have some noise (meaning that the symptoms do not exactly predict the presence of the disease).  The binary analysis described above can be performed whereby the cases are grouped into two poles based on some of the symptoms.  Most certainly, since there is noise, there will be symptoms that do not segregate exactly with the two poles as they are defined by a few of the symptoms. As a result it will seem as if there are cases with 'mixed' symptoms.  And the 'mixed' symptoms would be an artifact of the incorrect assumption that there is a dichotomy describing the disease.

It would seem that the simplest explanation for the presence of mixed episodes is that we have a collection of noisy symptoms that do not describe a disease having binary poles.  This would be an application of Occam's razor where we reject the introduction of a more complicated mixed bipolar model involving manic, depressive, mixed manic, and mixed depressive episodes, and we instead entertain simpler models which not based on a binary description of the disease symptoms.  For example, if we are committed to having phenomenological diagnostic tools, we could diagnose bipolar and schizophrenia from a single bucket of symptoms.  The diagnostic algorithm would be something like the following: if a person has at least 6 of the symptoms displayed in an episodic fashion then they might benefit from lifestyle changes, therapy, and anti-pychotic and mood-stabilizing drugs.  This approach would better reflect what we know about these diseases than current approaches based on false dichotomies.

Such approaches could facilitate investigations into the biology of these diseases, perhaps recognizing that there are changes in the brains of people with bipolar and schizophrenia.  Maybe our current biological studies are inhibited by the ascertainment bias that comes from our insistence on a separation between mania and depression.  Perhaps we would discover biological diagnostic tools faster if we were to discard the notion that there is a polar distinction between mania and depression.  In a similar vain, perhaps the distinction between schizophrenia and bipolar is something that needs to be reconsidered as well.  Perhaps there is a common biological basis for both schizophrenic episodes and mixed episodes.

I see that the biggest weakness of this article is that it clings to the idea that there are two poles of bipolar.  While the article seems at first glance to break the binary by introducing a definition of mixed episodes, a closer look reveals that the authors diagnosis of mixed episodes only reinforce a possibly false dichotomy between mania and depression.  It is certainly not the case that there are two main types of episodes; this thinking seems to me to be an artifact of our attempt to understand this disease by categorization.  It is time to move beyond the binary or trinary thinking and look for a biological basis from which to diagnose this disease.