Bipolar disorder — a “one-state” mood disorder?

Researchers at the National Institute of Mental Health’s Intramural Research Program recently reported progress in their search for a scientific mode of diagnosing mood disorder (E.D. Ballard and colleagues, Journal of Affective Disorders 231:51-57, 2018)—one that may be independently validated by dint of diverse genetic markers and ultimately, the alleles of genes inherited by those diagnosed.

The authors’ sample consisted of 41 inpatients with bipolar depression, who represented a subgroup of 119 patients (with unipolar major depression or bipolar depression), who had been enrolled in a randomized, double-blind antidepressant comparison of ketamine and placebo. The authors’ experimental approach consisted of including each of the ratable items of some of the best known and most extensively used depression rating scales (the Montgomery-Asberg Depression Rating Scale, the Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Snaith-Hamilton Pleasure Rating Scale), identifying the individual items on each rating scale whose decrements best correlated with antidepressant response overall, and then combining them into a new rating instrument with fewer items that correlated more strongly and replicably with antidepressant activity than did the longer, better established rating scales from which it was derived.

Eight item-factors from the four rating instruments provided optimal “fit” with the data pertaining to overall clinical response: depressed mood, tension, negative cognition, impaired sleep, suicidal thoughts, reduced appetite, anhedonia, and amotivation (not further elaborated),

Aware of the limitations of a small sample unvalidated for factor structure against an independent sample, and aware that findings derived from their sample of treatment-resistant patients undergoing an experimental treatment may not be generalizable to a “naturalistic” sample from the general population, the authors nevertheless believe that their experimental approach may yield “more refined…(mood rating scores)” for assessing dimensional symptoms whose “structure” may reflect dimensionality of “underlying pathophysiology” more closely than do current categorical diagnostic criteria. (Obiter: The authors’ factors seem adaptable to assessing a “one-state” mood disorder distributed along dimensionalities, whose cross-sectional points, relative to one another, may result in a cleaner cut of Occam’s Razor than that made by a disorder of two poles oriented in opposite “directions.” If, for example, the authors had included “fatigue,” a combination of presence of sleep impairment without fatigue would comport with a hypomanic or manic state, especially if corroborated by lack of anhedonia and no impairment of motivation; addition of depressed mood could comport with depressive mixed state (dysphoric manic spectrum. Even simpler, because reduced need for sleep is rare (occurring in hypomania or mania, hypercortisolemic and hyperthyroid states, and stimulant intoxication), its inclusion could rule mania spectrum symptoms in or out (sleep impairment without reduced need for sleep—that is, fatigue, is characteristic of depressive spectrum symptoms). Other items could strongly corroborate mania or depressive spectrum disorders, rendering even eight items more than needed. If expressed and received meaning of language were successfully addressed (standardized), lexical variance minimized or eliminated, and greater reliance placed on observables than on reportables, fewer than eight factors may be adequately informative without adding ambiguity)

Consistent with the notion that the authors’ items need designate no more than one (affective dysregulation) disorder with diverse presentations rather than the two clinically and mechanistically distinct constructions that they and us (psychiatry, generally) have perennially promoted as a bipolar disorder is a recently published re-analysis of the STEP-BD study (Z Mousavi and colleagues, Journal of Affective Disorders 236136-139, 2018), wherein acute response and long-term outcome of depressed patients with bipolar disorder were similar during treatment with coadministered antidepressants and mood-stabilizers, regardless of whether their penultimate clinical states had been depressed, hypomanic or manic, or euthymic. Again, it would seem (by virtue of Occam’s blade) that what we have constructed as distinctive poles of a bipolar disorder need, by the logic of empirical findings, be no more than a unidimensional affective dysregulation disorder comprising a single cluster of affective and somatic symptoms.



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