At the edge of the bipolar spectrum: primacy of affective over psychotic symptoms or vice versa?

Abstract

Strakowski et al should be congratulated upon this very comprehensive and well balanced essay of pros and cons about a broadening of diagnostic criteria for bipolar disorder. They very well point out potential benefits for otherwise insufficiently treated patients, but also that, given our lack of a full understanding of the biological basis, such a broadening might be premature in treatment research. So far, we still have a long way to go if we want to define groups of mental disorder by shared genetic underpinnings or biological markers, and thus we rely on phenomenology and derived categorizations when we conduct treatment research. And, in my opinion, these categorizations still need to be strict, reliable and largely unaltered over time, until we find better (and tested) definitions. With rising placebo response rates in randomized clinical trials and subsequent narrowing of drug-placebo differences, it becomes increasingly difficult to identify specific benefits of a drug, e.g. against core manic symptoms. Allowing, for example, patients into trials whose “mania” manifests itself just by agitation and irritability may give rise to large numbers of subjects with maniform features which are in fact related to substance use or personality. As a consequence, we would not expect a drug to differentiate from placebo unless it probably has a strong sedative component, but would we consider this as a true and specific antimanic agent? Strakowski et al also make it quite clear that bipolar disorder has a huge overlap of symptoms and features with other major mental disorders. Besides the grey zone that does (or does not) divide bipolar disorder from other affective, or more generalized, emotional states, a fascinating question is the relationship of bipolar disorder and schizophrenia. As Strakowski et al point out, a future trend might be, “based on risk factor and clinical history considerations, that bipolar disorder may be better classified with schizophrenia in a psychotic cluster than with unipolar depression in an emotional cluster”. But, how valid is the clinical observation of psychotic symptoms to serve as a basis of categorical clustering, and are they not more likely subsidiary to emotional processes? Looking back, for many decades bipolar disorder has been an orphan of psychiatry, whereas schizophrenia was considered the most important challenge. At the beginning of last century, it was still well accepted that all psychotic symptoms arise from mood dysregulation 1. In the post-Kraepelinian area, diagnostic habits continuously shifted towards schizophrenia, putting much more weight on psychotic than affective symptoms. Kraepelin’s successor Schneider reports that the ratio of patients diagnosed with schizophrenia vs. cyclothymia at the Munich hospital between 1934 and 1936 was greater than 5:1, while in the same department 35 years earlier Kraepelin had stated that 10-15% of hospital admissions were suffering from manic-depressive illness 2. Whereas it was hard to neglect the obvious existence of (unipolar) depression, bipolar disorder was almost cut down to clinical (and research) insignificance. This tendency of overdiagnosing schizophrenia at the expense of bipolar disorder continued well into the 1970s 3. Now the pendulum seems to swing back the other way. Lake and Hurwitz 4 questioned the validity of the diagnosis of schizophrenia, postulating that a single disease, a mood disorder with a broad spectrum of severity, accounts for functional psychoses. Compared to schizophrenia, and despite all limitations, diagnostic criteria for bipolar disorder may still have a better validity 5. Schneiderian first-rank symptoms (FRS) are not exclusive to schizophrenia; they also occur in some bipolar patients 6, although they may be more frequent and more severe in patients with schizophrenia than bipolar disorder. Schizophrenia patients with FRS during the acute phase are more likely to have poorer long-term outcome than those who do not have these symptoms. However, the same is true also for bipolar patients exhibiting FRS 7. But what really matters in end is how we can improve our bipolar patient’s life. Strakowski et al make it clear that the categorical vs. spectrum discussion is not a academic one in an ivory tower, but has clinical significance: “People with bipolar disorder are identified from the general population in order to assign therapies that will alleviate their suffering (i.e., symptoms), ideally through evidence-based treatment guidelines developed from past studies of similar individuals”.