What the hell is it? Does anyone really know?

by John McManamy


IN mid-2006, at a session of the International Society of Bipolar Disorders conference in Edinburgh, the conversation started to get particularly interesting. Nick Craddock MD, PhD of Cardiff University was discussing genetic susceptibility to psychosis. The gene research, which he and others have been involved in, is pointing to some apparent common ground between bipolar and schizophrenia. Clearly, some "nosological" (diagnostic classification) rethinking was in order.

Various psychiatrists in the audience kept referring to the pioneering diagnostician, Emil Kraepelin. Psychiatrists and others seeking to reform the DSM are leading a sort of "back to Kraepelin" movement that would tear down the artificial diagnostic boundaries now existing between bipolar disorder and what we presently classify as certain types of unipolar depression.

But Dr Craddock was working the other side of the spectrum, and here Kraepelin posed an obstacle. One of Kraepelin’s great achievements was to separate what he called manic-depression (what we now call bipolar and recurrent depression) and dementia praecox (what we now call schizophrenia) into two illnesses. The distinction (what Dr Craddock calls "the dichotomous view") has served psychiatry well over the years, but recent gene studies are beginning to demand a second look.



Then someone mentioned Kraepelin one time too many, and the frustration in Dr Craddock’s response was evident. The gist of his remarks amounted to something along these lines: Why the fascination with Kraepelin? You don’t hear historical figures referred to with such reverence in other branches of medicine. Other branches of medicine work with hard science.

In an article in the June 2007 World Psychiatry, Dr Craddock summarily dispatched Kraepelin:

Theoretical constructs in science, including diagnoses in medicine, have a finite lifespan and should be discarded when the weight of research data against them becomes critical and when more satisfactory alternatives become apparent.

A discussion of Kraepelin "is not of direct relevance to contemporary clinical psychiatry."

The Double-Whammy Gene

One of the gene studies Dr Craddock referred to was Neuregulin 1 (NRG1), involved in glutamate signaling. The gene was first implicated with schizophrenia in an Icelandic population. In 2005, Dr Craddock and his colleagues found similar evidence of susceptibility in a bipolar sampling. Further teasing out of the data found that in the bipolar subjects, the effect of the NRG1 gene variation was most marked in cases with predominantly mood-incongruent psychotic features. In the population with schizophrenia, the effect was greatest in the subset which had experienced mania.

In other words, psychosis is not just psychosis. We have psychosis that is linked to mania. Some of us  may also have what may be best described as "free-floating" psychosis, independent of mania. In his article, Dr Craddock suggests that NRG1 may be a sort of double-whammy psychosis gene. Those with the wrong variation are prone to get blindsided by two types of psychosis.




The Case for Schizoaffective

Dr Craddock suggests that this gene variation, plus others, could shed light on the controversial hybrid diagnosis known as schizoaffective disorder. Dr Craddock contends that, given that various "psychosis genes" have been identified in both bipolar and schizophrenia, the current definition of schizoaffective disorder is too narrow to be clinically useful. A broader definition, he contends, would give researchers and clinicians something to work with.

Deconstructing Psychosis

In 2006, The American Psychiatric Association, in conjunction with WHO and the NIMH, hosted a planning session involving leading bipolar and schizophrenia experts.

Following the presentations, the gathering broke out into two groups. The first group recommended (among other things) replacing the current diagnostic categories with a "general psychosis syndrome" that would cover schizophrenia, schizoaffective, delusional, and brief psychotic disorders, bipolar disorder, and psychotic depression, and reducing the criterion for schizophrenia from six months to one month.



The second group would keep the bipolar/schizophrenia distinction, but urged the possibility of more subcategories (with a pressing need to improve the definition of schizoaffective) and the need for a dimensional approach to psychosis and mood disorders.

Two years later, a panel of the International Society for Bipolar Disorders (ISBD) recommended eliminating the designation, schizoaffective, in its entirety and substituting it with additional specifiers to schizophrenia, bipolar Ibipolar II, and major depression

Taking Dr Craddock, the two APA groups, and the ISBD into account, we have four different points of view and at least three wildly diverging opinions. The strong implication is that there is no expert consensus for what constitutes schizoaffective, other than it represents a wholly unsatisfactory hybrid diagnosis. The people in charge of coming up with the DSM-5 (of 2013) threw up their hands in despair and (with one minor textual adjustment) left intact the 30-year-old DSM-IV version.

What the DSM Says

The DSM maintains that schizoaffective is distinct from both bipolar and schizophrenia, but acknowledges that there are no "absolute boundaries."

In schizoaffective, "there must be a mood episode that is concurrent with active-phase symptoms of schizophrenia." This is different than a "mood disorder with psychotic features" or "mood symptoms in schizophrenia."

Not that it's easy to tell. Is a psychotic feature, for instance, congruent (more likely to be mood-related) or incongruent (more likely to be schizophrenia-related)? And is any given depression a mood disorder phenomenon or schizophrenia phenomenon?

Confounding matters is the discomforting reality that schizoaffective is a moving target - the relative proportion of mood to psychotic symptoms may change over the course of the disturbance, not to mention over the long term. Not surprisingly, most patients who receive an initial diagnosis of schizoaffective are later diagnosed with something else.

The operative phrase to the DSM-5 schizoaffective diagnosis is:

There is either a Major Depressive Episode, a Manic Episode, or a Mixed Episode concurrent with symptoms that meet Criterion A for Schizophrenia.

Criterion A lists other symptoms besides psychosis, and calls for a minimum time of one month. (There is a Criterion C for schizophrenia, which mandates a six-month minimum for "continuous signs of the disturbance," but there is no reference to this in the schizoaffective diagnosis.)

Schizoaffective, then, is basically short-form schizophrenia (ie with periods of remission) punctuated by relatively brief overlays of depression or mania (the DSM minimum for mania, for instance, is one week). The assumption with schizoaffective is that it is highly likely that there will be long periods when the schizophrenia symptoms manifest with no mood symptoms, and indeed this is a DSM requirement.

Thus, schizophrenia symptoms can appear without mood symptoms, and mood symptoms can also appear without schizophrenia symptoms, but - big but - the DSM demands a two-week period sometime over the lifetime of the individual where schizophrenia symptoms existed without the mood symptoms.

Does this sound like schizophrenia to you? Short form or not? Say, schizophrenia, usually with mood symptoms? Is schizoaffective, then, a euphemism diagnosis for clinicians too chicken to tell their patients the truth? It appears that way.

Meanwhile, Back in the Real World

There appears to be more going on with schizoaffective than just "mania with psychotic features" (as part of the Bipolar I diagnosis) or "major depression with psychotic features" (as part of the depression diagnosis). Instead, it appears the other way around, a schizophrenia-like condition where psychosis and other cognitive impairments predominate, "with mood features."

But is your psychiatrist smart enough to make that distinction, and does it matter? A few questions you need to be asking:

  1. Is your psychiatrist using the diagnosis to bring your clinical condition into sharper relief? In other words, has a competent clinician who really knows you figured out that your bipolar comes with serious complications? And if so, is he or she ready to work with you - including spending extra time with you - in helping you manage?
  2. Or has your psychiatrist basically given up on you? In other words, is your diagnosis a result of the frustration of a lazy clinician who barely knows you and has already written you off as untreatable?
  3. Or is your psychiatrist over-reacting? In other words, is your diagnosis the result of a lazy clinician who barely knows you and assumes that anything that even remotely resembles psychosis must be connected to schizophrenia or schizoaffective? In other words, are you about to be over-treated and over-medicated?

What's in a name? Sometimes nothing. Sometimes everything.

See also: Psychosis in Mania. 

Rewritten June 18, 2016


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