Atypical Features and Bipolar Disorder.

Bipolar Disorder (BD) features with various of clinical symptoms, leading to the misdiagnosis of major depressive disorder (MDD). The atypical features (ATFs) are regarded as one of valuable index to identify BD from depressed patients. The ATFs should be helpful to the differential diagnose of the two diseases. In this forum, we discussed the issue of the relation between the ATFs and BD.

Bipolar disorder (BD), a severe mental illness with high disability and recurrence rates, has been listed as the 12th leading cause of disability.[ The recurrence rate of bipolar disorder is approximately 90%. BD brings considerable challenges to the patients, their families and society at large.[ The clinical symptoms at the onset of the depressive episode of BD have many similarities with the symptoms of major depressive disorder (MDD). These similarities increase the rate of misdiagnoses of BD and MDD in clinical practice. Several studies in Americans showed that the incidence of the bipolar spectrum, including bipolar I disorder (BP I), bipolar II disorder (BP II) and cyclothymic disorder, ranged from 1.5% to 6%.[A Chinese study found that the incidence of BPI and BP II were 0.1% and 0.3%, respectively.[ Another Chinese study aimed at screening individuals with BD who had previously been diagnosed with MDD found that approximately 20.8% of individuals who had been diagnosed with MDD should have been diagnosed as BD.[ Because of the misdiagnoses and early detection difficulties, it takes nearly ten years for individuals with BD to receivea correct diagnoses and the related mood stabilizer medications.[ So the early detection problems related to BD diagnosis urgently need to be solved.

The Diagnostic and Statistical Manual of the American Psychiatric Association, Fourth Edition (DSM-IV) defined the atypical features (ATFs) of BD and related disorders as showing the main feature of ‘mood reactivity’ and four adjunct features including ‘significant weight gain or increase in appetite’, ‘hypersomnia’, ‘leaden paralysis’ and ‘a long-standing pattern of interpersonal rejection sensitivity’.[ In 2005, Akiskal suggested that atypical depression was a variant of BP II or should be treated as a bridging state between unipolar depression and BP II.[ Stewart held the same opinion: whether individuals during the onset of a depressive episode had ATFs or not could be a potential indicator for predicting BD, thus helping us discriminate between BP II and MDD.[

Many studies compared the ATFs differences between individuals with unipolar depression and individuals duringthe onset period of a depressive episode of BD in recent years. These results show that there are significantly higher incidences of individuals during the onset period of a depressive episode of BD who have accompanying ATFs than individuals with MDDwho have accompanying ATFs.[ In addition, many other studies found that there were certain correlations between the clinical characteristics of individuals with ATFs and those with BD. One study showed that there were significantly higher incidences of overweight individuals (BMI>25) with BD having ATFs than normal-weight individuals with BD having ATFs.[ Moreover, studies by Akiskal and colleagues suggested that there is a dose-response relationship between the number of ATFs and the family history of individuals with BD: with increasing items of ATFs, family loading for BD is increased.[ Another study showed that ATFs did not only exist for individuals with BD during the onset of the depressive episode, but also at the onset of the manic episode. The incidence rate of ATFs was 9.1%, and the proportion was even higher among individuals with the mixed state accompanying ATFs. The results imply that ATFs could be a characteristic index but not a state index.[

Meanwhile, a three-year clinical follow-up study by Stephen and colleagues showed that 5% of individuals diagnosed as MDD at first depressive episode would eventually be reassigned to BD. There was no statistical difference between individuals with reassignments and those with no reassignment on accompanying ATFs.[ The reasons for heterogeneity of several study results may be that: (a) as suggested by Mitchell and colleagues, individuals with BD, MDD or severe mood dysregulation could all have ATFs. The significant differences of ATFs among the three illnesses only represent the differences of mean incidences. ATFs are not only special in BD;[ (b) different studies had different definitions for ATFs and different ways of organizing symptom items. Even now, controversies over the standards remain,[ especially in ‘mood reactivity’. DSM-IV, Text Revision (DSM-IV-TR) treated mood reactivity as an essential symptom for diagnosing patients with ATFs as mood reactivity better described ATFs than the adjunct items and, thus, mood reactivity should be more correlated with ATFs than the adjunct items. Another study showed that apart from mood reactivity, the incidences of significant weight gain or increase in appetite, hypersomnia, leaden paralysis and a long-standing pattern of interpersonal rejection sensitivity among individuals with BD were higher than those of individuals with MDD; the results of hypersomnia and a long-standing pattern of interpersonal rejection sensitivity reached statistical differences. There was no significant difference between individuals with mood reactivity and those with no mood reactivity for other clinical characteristics.[ One study showed that there was no correlation between mood reactivity and the other five adjunct items. It was hard to distinguish individuals with different types of depressive disorders from demographics and other clinical characteristics based on whether they were having mood reactivity or not.[Moreover, different studies had different specific items of ATFs between BD and MDD.[

In summary, ATFs may be relevant risk factors of BD and therefore can function as symptoms for early warning and detection of the illness. For further confirmation of the relationship between the specific items of ATFs and BD, we need more studies, especially longitudinal ones, to investigate the differences of ATFs between MDD and BD.