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• W2945170936 abstract "Everything has been thought of before, but the problem is to think of it again. Just prior to a tsunami, the water curiously recedes – and on occasion, this draws unsuspecting onlookers to explore the beach further and venture inquisitively towards imminent danger. This early warning sign is particularly treacherous because it is counterintuitive, contrasting to the fearful roar that precedes a wall of fast approaching water. However, the tsunami itself is also only a sign, and meanwhile the event that it represents – an earthquake, quietly tears apart the seabed deep beneath the ocean's surface. Analogous to this, the foundation of psychiatry is experiencing its own earthquake, and the early warning signs – signalling that there are deep-seated fractures within the structure of our classificatory systems are already here. In psychiatry, the description ‘early warning sign’ usually refers to the incipience of mental illness – such as bipolar disorder 1. Being attuned to such signals is helpful in clinical practice for detecting the emergence of an episode of illness (e.g. depression or mania) – either de novo or when the individual relapses. However, in this editorial, we employ the term more broadly – to describe the failure of current taxonomies to properly accommodate mixed states. We contend that mixed states simply do not fit – and argue, that this inability to adequately incorporate mixed states is a consequence of it simply not being possible. This is because the basis upon which our classificatory models have been devised is fundamentally flawed. This criticism applies to both DSM and ICD, but for brevity we'll use DSM-5 as an exemplar. Mixed states are by no means new, in fact they were originally described more than a century ago by Weygandt and Kraepelin 2, 3. The definition of mixed states by these ‘clinician-researchers’ arose out of meticulous observations of patients, ostensibly suffering from mood disorders, who did not fall readily into neat categories of mania or depression. They described six kinds of mixed states comprising different degrees of activity, cognition and emotion. In contrast, DSM focused predominantly on mood and created a ‘bipolar model’ with depression and mania at each end respectively. On this single axis, mixed presentations could only be captured as a mixed episode, requiring symptoms fulfilling the criteria for both mania and depression to be met. In practice, the simultaneous occurrence of both mania and depression is clearly not feasible, and at best unlikely, so this definition remained entrenched through to DSM-IV. Consequentially, mixed episodes which were codable and regarded as distinct from episodes of depression or mania were instead subsumed by the latter 4. Hence, data specific to mixed episodes is largely lacking, and that which does exist, is fragmented and difficult to interpret. To circumnavigate the difficulty of diagnosing mixed states, DSM-5 replaced mixed episodes with mixed features. But, the problem with this approach is twofold: first, by losing the ability to code for mixed episodes the potential for capturing epidemiological and phenomenological data that would better define the prevalence and character of mixed presentations has been lost. The second is that the putative ‘solution’ has not addressed the key problem and has, in fact, created many more difficulties. The introduction of mixed features is problematic because the definition simply requires three or more features from the opposite pole. However, which symptoms are needed is not specified and in fact key symptoms have been accorded much less importance on the basis that they are overlapping and fail to discriminate 5. The shift from mixed episodes to features is critical. Mixed symptoms were previously essential to the diagnosis – indeed, they characterised the mixed state. As features, they are far less important and no longer integral to the diagnosis. Hence, in the DSM-5, it is only possible to code mixed features in the context of an episode of depression or mania. They cannot be coded or even recorded separately. This change alone not only devalues the importance of mixed symptoms and presentations, it also provides no option to capture or regard mixed states as a separate entity. Added to this, the lack of specificity as to which symptoms typify mixed states means that any number of varied presentations can qualify as having mixed features. In practice, mixed presentations of symptoms are common and of considerable concern because they do not respond to standardised treatments as well as purer presentations 6. Mixed mood states highlight the limitations of the DSM approach, namely dichotomising mood disorders along a single domain. In this framework, there is no real capacity to conceive of mixed states because depression and mania are by definition at the opposite ends of the mood spectrum and are therefore mutually exclusive. This approach has created an unworkable model of mood disorders. We have argued previously that an additional concern of DSM-5 is that mixed features further diminish the role of important symptoms such as distractibility, irritability and psychomotor agitation (collectively referred to as DIP), which likely represent the core features of mixed presentations 4, 7. But perhaps, the more substantive issue is the incorporation of additional domains so that alongside mood; cognition and activity are given equal importance. This model has been articulated as the ACE model and draws attention to activity, cognition and emotion as distinct domains that collectively provide a three-dimensional space within which the symptoms of mood can be mapped 8. It ensures a more accurate characterisation of symptoms and provides depth to our taxonomy by literally adding dimensions. This holistic approach is in keeping with real-world clinical observations of mixed states, and modelling mood disorders in this manner also provide a potential explanation for phenomena such as switching and the emergence of treatment-induced mixed symptoms/mania. Conceiving mood disorders as multidimensional (see Fig. 1) provides insight into potential mechanisms. For instance, it is possible to see how asynchrony among symptoms along different domains can generate various mixed states while still accommodating the purer forms of depression and mania. The ACE model also fits with mood disorders being regarded as a true spectrum comprising varying contributions of activity, cognition and emotional symptoms. Interestingly, the model may also be useful for understanding the aetiology of mixed states, which can emerge via a number of mechanisms. When longitudinally tracking a mood disorder in which there are episodes of depression and mania (typical/classic bipolar disorder), it is likely that when transitioning directly between poles without an intervening period of euthymia there will be a brief period when symptoms from both poles coexist and the clinical presentation appears to be that of a mixed state (see Fig. 2a). This is essentially a transitional mixed state that has occurred naturally. Conceivably, in some instances, the ‘process’ may stall and the individual remains in a mixed state. A mixed presentation may also occur when a treatment – typically an antidepressant – triggers symptoms from one particular domain, such as activity, more so than other domains (see Fig. 2b). This produces ‘uncoupling’ of the domains and asynchrony that manifests as a mixed state. Such concepts as to the aetiology of mixed states are only possible if mood disorders are conceptualised using this multidimensional model. The adoption of a more sophisticated approach to mixed states is also more likely to facilitate the development of more specific treatments. This is particularly important, given that presently mixed states respond poorly to most available treatments, and are more likely to eventuate in treatment resistance and suicide. In conclusion, mixed mood states are an important ‘early warning sign’. Their widespread presence in clinical practice is a clear and strong signal that there is a fundamental problem with our current classification of mood disorders. Our illogical adherence to a model that emphasises only one domain above all others, and misguided belief in a dichotomy of two poles of illness, will prevent us from ever making an advance. If we are to truly achieve a deep understanding of mood disorders, and develop treatments that provide targeted and sustained improvement – then models that are closer approximations of reality and have true depth are needed. Therefore, it is time to heed the clarion call and begin revising our taxonomy. The authors received no financial support for the research, authorship and/or publication of this article. G.S.M. has received grant or research support from National Health and Medical Research Council, Australian Rotary Health, NSW Health, American Foundation for Suicide Prevention, Ramsay Research and Teaching Fund, Elsevier, AstraZeneca, Janssen-Cilag, Lundbeck, Otsuka and Servier; and has been a consultant for AstraZeneca, Janssen-Cilag, Lundbeck, Otsuka and Servier. EB declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article." @default.
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• W2945170936 title "Mixed states: an early warning sign of profound problems in our taxonomy?" @default.
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