Title:A Genetic Dissection of Antipsychotic Induced Movement Disorders
Volume: 20
Issue: 3
Author(s): C. Crisafulli, A. Drago, A. Sidoti and A. Serretti
Affiliation:
Keywords:
Gene, genetic variations, extrapyramidal symptoms, antipsychotics
Abstract: Background. Antipsychotic medications (APM) are the first line pharmacological treatment for psychotic disorders and other
behavioral disorders. Nevertheless, their use causes a number of side effects, including extrapyramidal symptoms (EPS). EPS decrease
the efficacy of the antipsychotic treatments by causing poorer compliance to the treatment, stigma and a poorer quality of life for patients.
Genetic studies hold the potential to unravel the molecular underpinnings of the EPS induced by APM but results are not conclusive and
are far to be used in clinical practice despite decades of research. A more sophisticated selection of the list of genetic mutations explaining
the genetic variance of EPS induced by APM could help in the definition of a personalized treatments for patients. Moreover, it
would increase the quality of the current treatments with APM. Methods: We reviewed the literature searching for the genetic association
studies focused on dystonia, parkinsonism, akathisia and tardive dyskinesia. Moreover, we reviewed the current biological knowledge of
the APM induced side effects. Finally, we provide a reasoned list of candidate genes and their genetic variations, with the aim of identifying
a list of candidates for APM induced EPS genetic investigations. Results: Variations located within PIK3CA (phosphoinositide-3-
kinase, catalytic, alpha polypeptide), PLA2G4A (phospholipase A2, group IVA, cytosolic, calcium-dependent), PRKCA (protein kinase
C, alpha), PRKACG (Phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma), ERK-1 (extracellular signalregulated
kinase 1 (MAPK3)), ERK-2 (extracellular signal-regulated kinase 2 (MAPK1)), GNAS (guanine nucleotide binding protein (G
protein), alpha stimulating activity polypeptide 1), PLCB1 (phospholipase C, beta 1 (phosphoinositide-specific)) and ITPR1 (inositol
1,4,5-triphosphate receptor type 1) were found to be relevant for APM induced EPS. Some of the genes are classical candidates for this
kind of research, others were never investigated. For each of these genes we provide a list of variations that balances the limitations of
multitesting with the advantages of the tagging approach. Conclusions: We undertook a review of the literature about the APM induced
EPM to provide some rational genetic candidates to be tested in further genetic investigations.
