Prolactin as a biomarker for treatment response and tardive dyskinesia in schizophrenia subjects: old thoughts revisited from a genetic perspective

Abstract

Previous studies investigated whether prolactin (PRL) serum level was a biomarker of antipsychotic response, schizophrenia symptomatology, and tardive dyskinesia. Most of the findings support that antipsychotic drugs modulate PRL levels but PRL is not a steady indicator. Recent results suggest a genetic effect of PRL and PRL receptor (PRLR) polymorphisms in PRL levels indicating that independently of antipsychotic therapy subjects could have altered PRL levels due to their genetic background.We evaluated whether PRL and PRLR variants were associated with treatment outcome and tardive dyskinesia. We observed no association of PRL/PRLR polymorphism with treatment response (best genotypic results include PRL rs849885 and PRLR rs4703509 permuted p=0.326). Regarding tardive dyskinesia, the major allele of PRL rs37364 was nominally associated with risk for tardive dyskinesia in the European ancestry sub-sample (permuted p=0.183). Although we reported no significant associations, it is definitely worthy of investigation to see if together (genetic variants in the PRL system and PRL serum measures) could be a reliable biomarker for antipsychotic response and TD prevalence. Our results suggest that more studies in this context are required to shed light in the molecular mechanisms underlying antipsychotic response and tardive dyskinesia occurrence.

Prolactin and Psychopathology in Schizophrenia: A Literature Review and Reappraisal

“…They found that the G allele was significantly more common in patients, particularly in males, and pointed out that this variation was similar to that reported in autoimmune diseases. Souza et al [53] examined the association between the prolactin and prolactin receptor (PRLR) genes and both tardive dyskinesia and treatment response but failed to find a significant association in either case.…”

Review of serum prolactin levels as an antipsychotic‐response biomarker

“… 50 In a preliminary study done in patients with SZ, genetic variation at the prolactin and prolactin receptor loci were not associated with: 1) prolactin serum levels; 51 2) patients who do not respond to antipsychotic treatment; or 3) patients who have tardive dyskinesia. 52 Serum prolactin levels are primarily under dopaminergic control and increase in response to D2 antagonists such as haloperidol, blockade of monoamine transporters that decrease extracellular dopamine such as reserpine, but do not change significantly in response to partial D2 agonists such as aripiprazole. 53 …”

Alterations in Expression and Function of Phosphodiesterases in Huntington’s Disease

“…The existence of PDE4B gene variants was examined in a population of 169 Caucasian patients taking antipsychotic medication. Two PDE4B variants associated with tardive dyskinesia and two additional variants associated with female-specific tardive dyskinesia were discovered (Souza et al, 2011). However, correction for multiple testing eliminated these variants as being truly genetically associated with the tardive dyskinesia observed in schizophrenia.…”