The mixed features of DSM-5

DSM digest

Mixed-mood states are, as the name implies, heterogeneous in nature, and have probably been recognised, in one form or another, since the early 1800s. As the 19th century came to a close, Weygandt, Kraepelin and Hecker described admixtures of excited and agitated symptoms, such as increased psychomotor activity, prolixity, irritability and flight of ideas, occurring against the backdrop of a depressive syndrome. Importance was attached to understanding mixed states, even though they did not belong to any specific model for psychiatric classification of mood disorders. But clinically, mixed states were conspicuous and hence formed part of Kraepelin’s manic-depressive illness, in which he gave priority to recurrence of mood disorders and their longitudinal course – as opposed to polarity (Malhi and Berk, 2014).

Puzzlingly, the Diagnostic and Statistical Manual of Mental Disorders (DSM)* favoured polarity, and did so to such an extent that the common-sense longitudinal perspective to diagnosis was all but lost. This partly explains why the Diagnostic and Statistical Manual of Mental Disorders–First and Second Editions (DSM-I and II) made little or no attempt to recognise or accommodate mixed states, and instead subsumed them within manic-depressive reactions and mixed manic-depressive illness as part of ‘major affective disorders for which a specific diagnosis has not been made’. In noticeable contrast, the Diagnostic and Statistical Manual of Mental Disorders–Third Edition (DSM-III) recognised mixed mood states as a ‘subtype’, but placed them within a newly coined diagnosis, termed ‘bipolar disorder’ – and thus labelled them as ‘bipolar disorder-mixed’.

This resurgence of interest in mixed states and recognition of their diagnostic importance was triggered in part by the publication of the Research Diagnostic Criteria (Spitzer et al., 1978). However, in both DSM-III and the Diagnostic and Statistical Manual of Mental Disorders–Third Edition, Revised (DSM-III-R), mixed states were, by definition, limited to mania, and this meant that depressive mixed states (arguably more common than manic mixed states) were still not recognised. Remarkably, the Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition (DSM-IV) failed to rectify this aberration even though it created the ‘mixed episode’. The problem with this newly concocted descriptor and its definition in the Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition, Text Revision (DSM-IV-TR) was that it required concurrence of a full major depressive and manic episode – a condition seldom observed in clinical practice. In addition, a mixed episode could not capture depressive mixed states that occur in the absence of mania – further limiting its usefulness both clinically and for the purposes of research.

To redress this, the Diagnostic and Statistical Manual of Mental Disorders–Fifth Edition (DSM-5) removed mixed episodes and instead introduced mixed features as a specifier. This lowers the threshold for diagnosis considerably and permits the recognition of mixed states in both bipolar depression and mania. Indeed, the specifier can even be applied to major depression – thus enabling a tangible nexus between unipolar and bipolar mood disorders. However, the threshold of any three symptoms among a checklist of many, and the exclusion of the defining core features of a mixed state on the basis that they do not sufficiently differentiate mania and depression, is a cause for concern. The potential manifestations of mixed states as defined by the DSM-5 specifier will be myriad and a mixed state diagnosis will fail to correlate to a specific aetiology, or inform potential treatment (Malhi, 2013).

In addition to these putative diagnostic limitations, the clinical detection of mixed states is problematic, particularly early in the course of the illness or when episodes are frequent or marked by prolonged affective instability. Responses to treatment (treatment-induced euphoria and dysphoria) and treatment non-responsiveness, along with stress-related and substance use comorbidities, further obfuscate detection and complicate diagnosis. Failure to detect this ‘state’ is likely to culminate in the implementation of inappropriate and perhaps even harmful treatment strategies. These risks underscore the need to better operationalise the clinical diagnosis of mixed states and to adopt a more logical and meaningful approach to defining them. Perhaps alongside clinical studies, exploration of the neurobiology of mixed states is necessary to more thoroughly characterise and understand the phenomenon.

In this vein, we propose that rather than regarding mixed states as a diagnostic dilemma and a hindrance to successful treatment, they be considered an opportunity to reframe the nosology of mood disorders and perhaps to identify a more accurate model of emotional dysfunction (Goldberg, 2014). Mixed states may represent much more than the simple interplay between mania and depression, but rather may be an altogether separate entity. Alternatively, mixed states are perhaps the consequence of different types of dysfunction within separate domains, such as anxiety, psychomotor activity, motivation and energy. Remodelling mood disorders drawing on neuroscientific knowledge and technology, such as neuroimaging and genetics, is likely to yield a deeper understanding of emotional processing and its aberrations than the examination of patterns of mood instability alone.

The publication of Research Domain Criteria (RDoC) alongside DSM-5 substantiates this view. It promotes the perspective that some conditions are transdiagnostic and that limiting research to clinical phenotypes precludes the identification of aetiology and the mechanisms that govern treatment responsiveness.

International Classification of Diseases and Related Health Problems–Eleventh Edition (ICD-11), scheduled for publication in 2017, still has the opportunity to develop a clinically meaningful classification of mixed states (Carroll, 2014) but, in the meantime, DSM-5 definitions are likely to amplify the already widespread heterogeneity among mood disorder diagnoses and do little to advance our appreciation of potential causes and cures.