Table of Contents

Volume 1, Issue 6                                                                                              June, 2015

Classic Study of the month

Bipolar or unipolar?

The modern founder of the bipolar/unipolar dichotomy revisits the idea

This paper is not a study itself, but rather a brief  two-page summary of fifty years of wisdom.  It bears careful reading. 

The Zurich cohort study

Let’s set the stage.  Jules Angst is a Swiss psychiatrist who has been at the forefront of research in mood illnesses for half a century.  In his youth, he studied at the home of Carl Jung, in addition to being trained by the most prominent mood researchers in Europe.  In the 1950s, he started a prospective outcome study that would be the largest and longest cohort study in mood research.  The Zurich Cohort was collected in 1959-1963, consisting of all patients admitted to the psychiatric hospital in Zurich with diagnoses of unipolar depression or bipolar illness.  406 patients were identified and followed prospectively at 5 year intervals for over 40 years; they have now been followed until the almost the entire cohort has died. Angst’s group also followed and compared outcomes with a normal general population comparison group from Zurich of 4547   persons initially enrolled in 1979 and followed for 20-30 years.

In other words, Angst’s Zurich cohort study is the Framingham heart study of psychiatry.  It is a classic well-designed observational study where people are followed for a very very long time to see what happens to them. 

Contrast his efforts with almost all other studies in psychiatry.  Most drug treatment studies are 8 weeks long.  The “long” studies rarely last longer than one year.   

One might say, without exaggeration, that 99% of all published psychiatric treatment or outcome studies are one year or less in duration. But you treat your patients for years, sometimes decades. Where’s your evidence for what happens to them over years and years. The Zurich study is the best such evidence: we are referring to 20 years, 30 years, even 40 years of outcome data here - not one year, and certainly not 8 weeks. 

1966: For bipolar/unipolar 

After getting his study started in 1959-1963, Angst had collected about 5 years worth of data, which he published in a classic paper in 1966.  The same year, an independent researcher, Carlo Perris, published a similar study. Both men were looking at whether bipolar and unipolar mood illness could be distinguished based on the accepted diagnostic validators of genetics and course. Obviously they differed in symptoms of mania versus depression, but did those differences matter?  Kraepelin had said: No. And for 70 years, Kraepelin’s view had held sway.

Angst and Perris independently found otherwise; they said: Yes. Their data showed that bipolar illness had more genetic loading of mania and mood illness than unipolar illness; they found that the course of the two conditions was different as well, with earlier age of onset and more but briefer episodes in bipolar than unipolar illness.

Angst likes to tell the story that when he told senior figures in mood research about his findings, their initial reaction was: This can’t be right. It goes against what Kraepelin said.  

2014: Against bipolar/unipolar 

Fast forward from 1966 to 2014:  about half a century.  Angst’s 1966 results of five years of follow-up were used as central to the radical changes of DSM-III in 1980.  Bipolar disorder and major depressive disorder (MDD) became official. Our definitions of those conditions have barely changed in the last 50 years.

Then 50 years later, with DSM-5, Angst was invited as a consultant to the Mood Disorders Task Force. He presented, not five, but 50 years of research, with the exact same cohort. He presented the same research data, but much better. And he now found, with much longer follow-up, that he had been mistaken in his 1966 report:  The 50 year follow-up finds that there is not a clear distinction between bipolar and unipolar illness on many diagnostic validators. 

In this review paper, Angst summarizes his findings, and places them in the context of other research over the past decades.  

He finds that manic symptoms do not radically separate from depressive symptoms in the diagnostic validators of course and genetics.  Many people have mild manic symptoms which have the same course and genetics as persons with more severe manic symptoms.  For instance, the hypomania threshold of 4 days is disproven by the Zurich cohort, where 1-3 days of mild manic symptoms led to the same course and genetic findings as with one week or longer of manic symptoms.  Similarly, the presence of mild manic symptoms all the time, with no episodes at all,  has been identified in the mood temperament of “hyperthymia.” The same has been shown in the opposite polarity with dysthymia; and with both polarities with cyclothymia.  And these mood temperaments are found in many normal persons in the general population, who do not have full mood episodes of any kind, whether manic, hypomanic, or depressed.  Such persons often have relatives with those mood episodes, however.

In sum, with the longest follow up over decades, Angst has concluded that there is a spectrum of mood symptoms, rather than a clear dichotomy of categories. We can still talk of categories as shorthand clinically, and at the extremes they may differ substantially: Severe unipolar elated mania is quite different than severe unipolar depression. But there are many variations in between; and the variations are the rule.

In 2014, Angst went to the DSM-5 committee with better, stronger, more valid results than he had in 1966, and the reaction was the same:  This can’t be right; it goes against what DSM-III/IV said.  

Angst speaks now of two spectra: one of severity, and one of polarity.  Some patients are a little bipolar but severely so; others are very bipolar but less severely so. Some are very unipolar but mildly so; and so on.  There are many variations to mood, and the simple polarity distinction of DSM-III to 5, which was based to a great degree on the Zurich cohort, has been disproven by the same research study’s longer and more valid database.  

The PL Bottom Line

  • The Zurich cohort initially supported the DSM dichotomy of bipolar/unipolar illness.
  • The same cohort study now disproves that simplistic dichotomy, and supports a spectrum approach based on both severity and polarity. 

PL Reflection

All interpretations are hypotheses, which must be forever tested and revised if unsatisfactory. That’s why a change of mind in a scientist, particularly a great scientist, is not a sign of weakness, but of greatness. 

                                         Ernst Mayr (adapted)

Meet our expert EDITORIAL BOARD, composed of clinicians and researchers from around the world. 

Subscribe to the RSS feed below to follow our "What's new" blog posts