Elsevier

The Lancet

Volume 381, Issue 9878, 11–17 May 2013, Pages 1663-1671
The Lancet

Series
Bipolar disorder diagnosis: challenges and future directions

https://doi.org/10.1016/S0140-6736(13)60989-7Get rights and content

Summary

Bipolar disorder refers to a group of affective disorders, which together are characterised by depressive and manic or hypomanic episodes. These disorders include: bipolar disorder type I (depressive and manic episodes: this disorder can be diagnosed on the basis of one manic episode); bipolar disorder type II (depressive and hypomanic episodes); cyclothymic disorder (hypomanic and depressive symptoms that do not meet criteria for depressive episodes); and bipolar disorder not otherwise specified (depressive and hypomanic-like symptoms that do not meet the diagnostic criteria for any of the aforementioned disorders). Bipolar disorder type II is especially difficult to diagnose accurately because of the difficulty in differentiation of this disorder from recurrent unipolar depression (recurrent depressive episodes) in depressed patients. The identification of objective biomarkers that represent pathophysiologic processes that differ between bipolar disorder and unipolar depression can both inform bipolar disorder diagnosis and provide biological targets for the development of new and personalised treatments. Neuroimaging studies could help the identification of biomarkers that differentiate bipolar disorder from unipolar depression, but the problem in detection of a clear boundary between these disorders suggests that they might be better represented as a continuum of affective disorders. Innovative combinations of neuroimaging and pattern recognition approaches can identify individual patterns of neural structure and function that accurately ascertain where a patient might lie on a behavioural scale. Ultimately, an integrative approach, with several biological measurements using different scales, could yield patterns of biomarkers (biosignatures) to help identify biological targets for personalised and new treatments for all affective disorders.

Introduction

Psychiatric illnesses are usually primarily diagnosed by careful assessment of behaviour combined with subjective reports of abnormal experiences to group patients into disease categories. However, these categories mask substantial heterogeneity. For example, a diagnosis of schizoaffective disorder is often given to people with episodes of both affective and psychotic symptoms, either alternating or occurring together, which casts some doubt on the traditional dichotomy delineating affective and psychotic disorders into discrete illness categories.1 In the absence of definitive and objective biomarkers of pathophysiological processes underlying behaviours associated with conventionally defined psychiatric illness categories, and because of the heterogeneity within, and considerable overlap between, these behaviours, appropriate diagnosis and treatment are difficult for many psychiatric illnesses. Bipolar disorder is an especially good example of a group of psychiatric illnesses that are difficult to diagnose accurately. For example, although this disorder, along with other psychiatric illnesses, is one of the ten most debilitating of all non-communicable diseases,2, 3 misdiagnosis of the illness as recurrent unipolar depression occurs in 60% of patients seeking treatment for depression.4, 5 We emphasise the main reasons for the challenges in diagnosis of bipolar disorder in clinical practice, describe future clinical and biological directions for improving the accuracy of diagnosis, and discuss novel approaches that are moving towards a conceptualisation of bipolar disorder and unipolar depression along an affective disorders continuum.

Section snippets

Bipolar disorder definitions

The origins of the categorical approach to psychiatric illness lie in the classic work of the founders of modern psychiatry, such as Emil Kraepelin. Kraepelin proposed a dichotomy between psychiatric illnesses characterised by regularly recurring episodes of notable changes in affect; and illnesses characterised by abnormal cognitions, beliefs, and experiences (ie, psychotic symptoms), which usually manifested in early adulthood and persisted throughout life.6 Kraepelin referred to the first

Why is bipolar disorder so difficult to diagnose accurately?

Bipolar disorder types I and II are especially difficult to diagnose accurately in clinical practice, particularly in their early stages. Only 20% of patients with bipolar disorder who are experiencing a depressive episode are diagnosed with the disorder within the first year of seeking treatment,5 and the mean delay between illness onset and diagnosis is 5–10 years.10 A major reason for the difficult diagnosis is the challenge of differentiating bipolar disorder type I or II from unipolar

Clinical strategies to improve diagnosis of bipolar disorder in depressed patients

Several changes have been recommended for the bipolar disorder section in DSM-5. First, bipolar disorder and related disorders have their own chapter. Second, the diagnostic criteria for bipolar disorder now include both changes in mood and changes in activity or energy. Previously, the diagnosis of a mixed mood episode required a patient to simultaneously meet the full criteria for both mania and major depression. A new specifier with mixed features has replaced the earlier criteria, and thus

Biological approaches to identification of bipolar disorder: use of neuroimaging to identify neural circuit biomarkers of the disease

The aforementioned approaches could detect clinical features suggestive of a bipolar disorder diagnosis that might have otherwise been undetected during standard clinical assessment (panel 2). However, these clinical approaches alone cannot identify objective biomarkers that represent the underlying pathophysiologic processes that vary between bipolar disorder and unipolar depression. The identification of such biomarkers could provide biological measures to inform diagnosis of bipolar disorder

Neural circuitry abnormalities that differentiate bipolar disorder depression from unipolar depression

Surprisingly, the extent to which functional and structural abnormalities in emotion, reward, and emotion regulation neural circuitries can distinguish bipolar disorder from unipolar depression has not been well studied.38 Thus, whether objective neuroimaging biomarkers can be identified in these circuitries to distinguish these illnesses is unclear.

Nevertheless, some evidence from a few neuroimaging studies comparing patients with bipolar disorder (predominantly type I) depression versus those

Dimensional approaches

The clinical challenges in differentiation between bipolar disorder and unipolar depression have led to substantial debate about the phenomenological and pathophysiological associations between them. Discussion continues about whether these illnesses might be better represented as an affective disorders continuum, with variable expressions of vulnerability to hypomania or mania contributing to different phenotypes and various types of recurrent illness.47, 48, 49, 50, 51 For example, recent

Conclusions

Recent evidence from field trials indicates that DSM-5 criteria might help to increase the accuracy of bipolar disorder type I diagnosis, one reason for which could be the less stringent criteria for mixed episodes. However, bipolar disorder, and bipolar disorder type II in particular, remains difficult to diagnose accurately in clinical practice, largely because of its frequent misdiagnosis as unipolar depression in depressed patients, since the diagnostic criteria for depressive episodes are

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