Bipolar spectrum: just broadening or an integration between categories and dimensions?
Authors: GIOVANNI B. CASSANO, VALENTINA MANTUA, ANDREA FAGIOLINI
Journal: World Psychiatry (2011)

In their thoughtful paper, Strakowski et al review the extensive literature regarding the benefits and risks of broadening the boundaries of bipolar disorders. According to the authors, the adoption of a bipolar spectrum model, not adequately supported by research evidence, is premature. While we underscore that DSM categories are rarely based on research evidence, we agree with the authors. We believe that keeping a more conservative approach, until new insights into underlying biological mechanisms allow a more rationale change of the borders among different diagnoses and among threshold and subthreshold symptoms, ensures that the existing categories maintain the current levels of diagnostic reliability and acceptable levels of communication among clinicians and researchers. Nevertheless, we need to acknowledge that the current diagnostic system does not adequately take into account the subthreshold phenomenology, which limits the possibility of considering its influence in the disease course. In a recent paper, the lifetime prevalence of subthreshold bipolarity in the general population has been estimated to be 1.4% 1. Among the multiple borders of bipolar spectrum, three appear to have clinical relevance. The first is the widely accepted schizophrenia/bipolar I continuum. Electroconvulsive therapy, lithium and atypical antipsychotics have contributed to the progressive erosion of the schizophrenia borders, to the advantage of bipolar spectrum diagnoses. The continuum schizophrenia-schizoaffective-mixed-psychotic bipolar-unipolar psychotic, initially supported by treatment response, found recent support from molecular genetics and imaging data. Indeed, the motor and cognitive disturbances, ranging from retardation to catatonic excitement, as well as the cognitive decay in chronic mania and the so-called negative symptoms, may represent a common ground between mood disorders and schizophrenia. In our opinion, the identification of subtypes may be facilitated by a clustering process rather than a simple comparison between two diagnoses. Such a process will need biomarkers that are more likely to be associated with psychopathological dimensions than with current diagnostic categories. The second border is the bipolar/ “unipolar” depression continuum, which is still the target of a remarkable research effort initiated by the pioneering work of H. S. Akiskal, who proposed different subtypes of bipolarity. Our data and clinical experience emphasize the relevance of subthreshold bipolarity, that consists of multiple dimensions spanning the entire bipolar/unipolar continuum. Most of these dimensions, such as psychomotor activation and retardation, suicidality, irritability, diurnal variation and need for sleep, can be measured by means of a traditional clinical evaluation, aided by questionnaires that assess the lifetime presence of typical, atypical, precursor and residual symptoms and signs. Such an approach may contribute to increasing the validity and the diagnostic accuracy while preserving the current criteria for bipolar II disorder. In a large sample of patients with bipolar and unipolar disorder we demonstrated the ability of a “psychomotor activation” dimension to identify subgroups of subjects with a progressively higher likelihood of belonging to the bipolar category 2. Only 25 patients with unipolar depression out of 571 (4.4%) were misclassified by classification tree analysis as belonging to bipolar II disorder group. Moreover, in a sample of 291 SCID-diagnosed unipolar patients 3, 9 patients (8 treated with selective serotonin reuptake inhibitors and one with interpersonal psychotherapy) developed an episode of mania or hypomania during the course of the study. When we examined their pre-treatment factor scores on the lifetime MOODS questionnaire, we found that 8 out of 9 exceeded at least one of the thresholds on psychomotor activation, mixed instability or suicidality measured by this questionnaire. A third border of the bipolar spectrum is subthreshold bipolarity which may be observed in a variety of disorders, including anxiety, eating and personality disorders. In these cases, mood dysregulation may be secondary as well as primary and genetically independent. This is similar to what we observe for medical illnesses. For instance, myocardial infarction, kidney failure and pulmonary edema can be progressive manifestations of a single disease or represent three relatively independent disorders. Therefore, it appears to be hazardous to include different categories such as anxiety or eating disorders in the bipolar spectrum, since they often stand in a relationship of comorbidity. Genetic research has moved through models with growing levels of complexity: from “one disorder-one gene” to “one disorder-multiple genes” and finally to a model envisioning a group of genes controlling one or more psychological or psychopathological trans-nosographic dimensions. In conclusion, the clinical validity of a diagnosis should include the ability to predict evolution, establish prognosis and inform treatment choice. Such goals are better achieved when nosography is linked to biological mechanisms. Therefore, we agree with the need to retain the current categories until more insight into their etiology is achieved and until valid biological markers are identified and can be utilized in clinical practice. This would avoid problems that result from rapid and continuous changes in diagnoses and classification. However, it must be noted that the present categories do not consider the halo of subthreshold and atypicality that surrounds each of them. An integration of the categorical classification with a dimensional approach could improve the ability to measure bipolarity and predict the progression to bipolar disorder. Subthreshold bipolarity, though a strong predictor, does not necessarily warrant a change in diagnosis. Given our poor ability to predict which individuals with major depression will develop hypomania or mania, close longitudinal monitoring remains the best tool for an early diagnosis of patients whose major depressive disorder moves toward a bipolar diagnosis 4.