Bipolar Disorder and Dopamine Dysfunction: An Indirect Approach Focusing on Tardive Movement Syndromes in a Naturalistic Setting
van Rossum I, Tenback D, van Os J
BMC Psychiatry. 2009;9:16
Summary
European Mania in Bipolar Evaluation of Medication (EMBLEM) was a 2-year prospective, observational study performed in 14 European countries to evaluate outcomes of pharmacologic treatment of mania. Dysfunction in dopamine-containing pathways may underlie the pathophysiology of bipolar disorder (BD) independent of drug therapy. The investigators in this observational study, therefore, developed an indirect approach to evaluate dopaminergic dysfunction in patients with BD, using proxy markers of tardive movement syndromes.
The study sample consisted of 3459 eligible patients with BD who were evaluated during 2 years of follow-up for tardive dyskinesia and tardive dystonia (TDD) and for other symptoms linked with dopamine, including prolactin-related adverse effects and bipolar symptoms. During follow-up, TDD occurred in 4.1% of patients and was independently linked with more severe bipolar symptoms, including hallucinations/delusions, other extrapyramidal symptoms, amenorrhea, sexual dysfunction, and prolactin-related adverse drug effects, as well as to antipsychotic use.
Viewpoint
Not surprisingly, this study confirmed the previously documented association of TDD with antipsychotic use. Of interest, the findings also suggest generalized dysregulation of dopaminergic function in BD because development of TDD was associated with various other dopamine proxy markers. In schizophrenia, the association between extrapyramidal symptoms and TDD has been well documented, but a link between psychosis severity and TDD was not previously reported in patients with bipolar disorder. The proxy measures reported in the present study suggest generalized dopaminergic dysfunction involving the mesolimbic and the tuberoinfundibular tracts.
Study limitations include the reliance on proxy measures of dopaminergic transmission, a lack of data on the use of other medications or other factors that could affect dopaminergic pathways, and the inability to address the underlying mechanisms. Dose adjustments for lithium and other medications may also have affected the findings. Additional research involving neuroimaging and animal
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