A genetic dissection of antipsychotic induced movement disorders

C. Crisafulli, A. Drago, A. Sidoti, A. Serretti

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)312-330
Number of pages19
JournalCurrent Medicinal Chemistry
Volume20
Issue number3
Publication statusPublished - Jan 2013

Fingerprint

Dissection
Movement Disorders
Antipsychotic Agents
Genes
Phosphatidylinositols
Class Ia Phosphatidylinositol 3-Kinase
Group IV Phospholipases A2
Phosphotransferases
Phospholipase C beta
Protein Kinase C-alpha
Inositol 1,4,5-Trisphosphate Receptors
Psychomotor Agitation
Guanine Nucleotides
Dystonia
Mitogen-Activated Protein Kinase 1
Genetic Association Studies
Parkinsonian Disorders
Therapeutics
GTP-Binding Proteins
Research

Keywords

  • Antipsychotics
  • Extrapyramidal symptoms
  • Gene
  • Genetic variations

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Crisafulli, C., Drago, A., Sidoti, A., & Serretti, A. (2013). A genetic dissection of antipsychotic induced movement disorders. Current Medicinal Chemistry, 20(3), 312-330.

A genetic dissection of antipsychotic induced movement disorders. / Crisafulli, C.; Drago, A.; Sidoti, A.; Serretti, A.

In: Current Medicinal Chemistry, Vol. 20, No. 3, 01.2013, p. 312-330.

Research output: Contribution to journalArticle

Crisafulli, C, Drago, A, Sidoti, A & Serretti, A 2013, 'A genetic dissection of antipsychotic induced movement disorders', Current Medicinal Chemistry, vol. 20, no. 3, pp. 312-330.
Crisafulli C, Drago A, Sidoti A, Serretti A. A genetic dissection of antipsychotic induced movement disorders. Current Medicinal Chemistry. 2013 Jan;20(3):312-330.
Crisafulli, C. ; Drago, A. ; Sidoti, A. ; Serretti, A. / A genetic dissection of antipsychotic induced movement disorders. In: Current Medicinal Chemistry. 2013 ; Vol. 20, No. 3. pp. 312-330.
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