Bipolar spectrum: has its time come?
Authors: ELLEN FRANK
Journal: World Psychiatry (2011)

Strakowski et al carefully assess the risks versus benefits of broadening the diagnosis of bipolar disorder and conclude that “until research findings can provide better insight into the validity of a broader conception of bipolar disorder, clinical expansion to a ‘spectrum’ concept should be considered with caution”. They argue that such expansion should await evidence that the concept, and clear definition thereof, lead to improvements in treatment development or in our understanding of etiopathogenesis. As the authors point out, one problem is that there are currently multiple definitions of “bipolar spectrum” and it is not clear that the risks and benefits associated with adopting one of these concepts are necessarily the same as adopting another of these concepts. Retracing the recent history of psychiatric diagnosis may help us to understand why we find ourselves having this debate. As Hyman points out 1, roughly coincident with the advent of disorder-specific pharmacotherapies and psychotherapies, Western psychiatry moved from very vague disorder constructs to a focus on reliability. This focus provided a shared language that facilitated an explosion of controlled research on these new medications and psychotherapies which continues to this day; however, it also had the effect of reifying the categories. Those categories then became the basis for studies of genetics and other biomarkers such as the cognitive ones discussed by Strakowski et al, as well as those identified in various forms of neuroimaging. And, therein, lies the problem. In most cases, each of these study methods finds some evidence to suggest that the distinct categories are correct and some evidence for a bipolar spectrum, however defined. Thus, to some extent our very reliable categories can be considered to have been a barrier to understanding the etiology of mental disorders and to the development of new approaches to treating them. The US National Institute of Mental Health (NIMH), in its Research Domain Criteria (RDoC) Project 2, is currently taking a completely different approach to this conundrum by looking at five domains believed to be relevant to mental disorders (negative valence systems including fear/extinction, stress/distress and aggression; positive valence systems including reward seeking and reward/habit learning; cognitive systems including attention, perceptions, working memory, declarative memory, language behavior and cognitive [effortful] control; systems for social processes including imitation, theory of mind, social dominance, facial expression identification, attachment/separation feat and self-representation areas; and arousal regulatory systems including arousal and regulation and resting state activity) across seven increasingly broad units of analysis (genes, molecules, cells, circuits, physiology, behavior and self-reports). This approach is intended to be complementary to the diagnostic developments taking place in the DSM-5 and ICD-11. The primary intention of the RDoC is to advance science, while the DSM and ICD must serve multiple purposes, including clinical decision-making, clinical record-keeping, regulatory decision-making and forensics. Thus, the NIMH approach may eventually provide a better way of understanding which aspects of “bipolarity”, however defined, are common across the “bipolar spectrum”, however defined. Working from the RDoC perspective, there would be nothing problematic about the fact that bipolar I disorder and bipolar disorder “not elsewhere classified” or NEC (the new term being proposed for what was formerly “not otherwise specified” or NOS) are similar with respect to the genes related to reward-seeking, but different with respect to the genes related to cognitive control. Concern about benefits and risks would not be relevant. Rather, the focus would be on understanding what combination of genes, coupled with what combination of life experiences, leads to the reward-seeking unmodulated by any sort of cognitive control that is characteristic of full-blown mania in one individual and to the modulated reward-seeking that is characteristic of mild hypomania in another individual. There is little doubt that efforts to date to understand the genetic basis of major psychiatric disorders such as schizophrenia and bipolar disorder, despite their very high heritabilities, have been hampered by our categorical diagnostic approaches (and, early on, by the naïve hope that we were dealing with Mendelian traits). An approach such as the one being proposed for the RDoC, which avoids the category vs. spectrum dichotomy, seems more likely to bear fruit in terms of understanding etiology. How it might relate to our understanding of treatment effects and to the development of improved treatments is, perhaps, less clear. Having had the opportunity to treat patients with mood and anxiety disorders through most of the psychopharmacologic era and virtually all of the disorder-specific psychotherapy era, I have witnessed an evolution from more specific pharmacotherapies (e.g., tricyclic antidepressants and typical antipsychotics) to ones that seem to treat a broad range of conditions (e.g., atypical antipsychotics and the SSRIs/SNRIs). Likewise, psychotherapies originally developed for unipolar depression have now been adapted to the needs of those with anxiety disorders and bipolar disorders. It occurs to me that a better understanding of for whom our treatments work might be obtained by “dismantling” our current disorder groups and subgroups in the way the RDoC proposes and using the RDoC parameters in sophisticated analyses of treatment moderation and mediation. Once we have those answers, a final step could be figuring out how to define useful categories that represent combinations of the RDoC parameters. Then, broadening our constructs might not be as risky as it currently appears.