Putative role of immune reactions in the mechanism of tardive dyskinesia

The term extrapyramidal disorders is most often used for conditions such as Parkinson's disease or Huntington's disease, but also refers to a group of extrapyramidal side effects of antipsychotics (EPS), such as tardive dyskinesia (TD). After a brief description of some clinical features of TD, this article summarizes the relatively scarce results of research on a possible link between mainly cytokine levels and TD. This data was found by systematically searching Pubmed and Embase. The limitations of these types of studies are a major obstacle to interpretation. After describing relevant aspects of the neuroinflammatory response and the neuroanatomical backgrounds of EPS, a new hypothesis for the origin of TD is presented with emphasis on dysfunctions in the striosomal compartment of the striatum and the dorsal diencephalic connection system (DDCS). It is postulated that (partly immunologically-induced) increase in oxidative stress and the dopamine-dependent immune response in classic TD proceed primarily via the DDCS, which itself is activated from evolutionarily older parts of the forebrain. Neuroinflammatory responses in the choroid plexus of the third ventricle may contribute due to its proximity to the habenula. It is concluded that direct evidence for a possible role of inflammatory processes in the mechanism of TD is still lacking because research on this is still too much of a niche, but there are indications that warrant further investigation.