When a new patient with depression enters your practice, you face a diagnostic dilemma. If you miss bipolar disorder (BD), and prescribe an antidepressant, you can do harm. But if you call a unipolar depression "bipolar," you may also do harm, because lithium, anticonvulsants, and atypical antipsychotics carry significant risk as both short- and long-term treatments. In addition, the label of "BD" currently carries much more stigma than the term "depression."

Many concerns have been raised about the overdiagnosis of BD,^1,2 especially in child and adolescent psychiatry.³ In the very young, this diagnosis is particularly difficult: the differential is broad; the stigma is particularly burdensome and potentially long-lasting; and treatments pose their gravest risk, especially given the potential duration of exposure and unknown developmental effects. At the same time, systematic review of existing data support the opposite concern—that of continued underdiagnosis of BD—at least in adults.^4,5

Why is our profession simultaneously concerned about overdiagnosis and underdiagnosis? This paradox stems in part from limitations of the DSM system. A categorical system is, by its nature, forced to create divisions that include some patients and exclude others, even if there is no recognizable juncture of separation. It cannot identify patients whose symptoms and signs fall below official thresholds yet who will eventually manifest a bipolar outcome over time and in their response to treatment. By contrast, a diagnostic approach that can recognize varying degreesof bipolarity (usually referred to as a "dimensional system") avoids the problem of potentially arbitrary division. However, it creates other problems, including a lack of precise boundaries with resultant increased interobserver variation (at minimum) and substantial logistical problems (eg, coding). Moreover, a major overhaul in our diagnostic system would create its own chaos, which is a significant barrier against change.

Nonmanic bipolar markers
Nevertheless, mood researchers increasingly emphasize the importance of nonmanic bipolar markers (also known as "external validating features"⁶ or colloquially as "soft signs"). These illness features, enumerated below, are statistically associated with an eventual bipolar course. In an example of this trend, the International Society for Bipolar Disorders recently convened 25 bipolar specialists to prepare literature reviews for each of several problematic aspects of bipolar diagnosis, requesting specific recommendations for interim changes in DSM-IV. Scheduled for publication in mid-2007, these reviews include examinations of the lower boundary of hypomania in BDII⁶; presence of nonmanic bipolar markers in patients who present with depression⁷ and mixed states⁸; and the diagnostic implications of a bipolar spectrum perspective.⁹ All of these emphasize the diagnostic importance of nonmanic bipolar markers.

However, this is not a new concept. Pies¹⁰ examined bipolar recognition from Aristotle to Kraepelin, demonstrating that the latter's broad view of bipolarity had deep historical roots. Nevertheless, an important transition in diagnostic thought came 5 years ago with a review by Ghaemi and colleagues¹¹ in which they summarized data supporting the use of 11 nonmanic markers in the process of diagnosing bipolar disorder:

• Repeated (4 or more) episodes of major depression.
• Early age at onsetof mood disturbance (before age 25).¹
• Family historyof BD, particularly a first-degree relative.
• Hyperthymicpersonality.
• Atypical depression (hypersomnia, hyperphagia, leaden anergy, rejection hypersensitivity).
• Brief episodes of major depression, eg, lasting less than 3 months.
• Psychosis.
• Postpartumonset.
• Hypomaniawhen patient is given an antidepressant.
• Loss of patient responseto an antidepressant agent.
• Three or moreantidepressant agents ineffective.

This approach was also adopted by Mitchell and colleagues,⁷ who proposed using these features to adjust the probability of BD when patients present with depression, independent of the assessment of manic symptoms. These nonmanic bipolar markers have also been incorporated into a diagnostic system that is currently being tested in the Systematic Treatment Enhancement Program for Bipolar Disorder.¹² The Bipolarity Index organizes nonmanic bipolar markers into 5 dimensions (easier to remember and document than 11 soft signs):

1. Hypomania or mania.
2. Family history of mood and substance use problems.
3. Patient's age at the onset of mood symptoms.
4. Illness course and other features generally only visible over time.
5. Response to medications (antidepressants and mood stabilizers).

The index thus places 4 additional dimensions of bipolarity alongside the DSM-IV criteria, openly changing the diagnostic question from "Does the patient have bipolar disorder?" to "How much bipolarity does the patient have?"¹³

Another system for memorizing and routinely assessing nonmanic bipolar markers was recently prepared by Pies¹⁴; his whiplashED mnemonic appears in Table 1.