title: Evaluation of the role of MAPK1 and CREB1 polymorphisms on treatment resistance, response and remission in mood disorder patients.
abstract: Treatment resistant depression (TRD) is a significant clinical and public health problem. Among others, neuroplasticity and inflammatory pathways seem to play a crucial role in the pathomechanisms of antidepressant efficacy. The primary aim of this study was to investigate whether a set of single nucleotide polymorphisms (SNPs) within two genes implicated in neuroplasticity and inflammatory processes (the mitogen activated protein kinase 1, MAPK1 (rs3810608, rs6928, rs13515 and rs8136867), and the cyclic AMP responsive element binding protein 1, CREB1 (rs889895, rs6740584, rs2551922 and rs2254137)) was associated with antidepressant treatment resistance (according to two different definitions), in 285 Major Depressive Disorder (MDD) patients. As secondary aims, we investigated the genetic modulation of the same SNPs on response, remission and other clinical features both in MDD patients and in a larger sample including 82 Bipolar Disorder (BD) patients as well. All patients were screened in the context of a European multicenter project. No association between both the investigated genes and treatment resistance and response was found in MDD patients. However, considering remission, higher rates of CREB1 rs889895 GG genotype were reported in MDD patients. Moreover, MAPK1 rs8136867 AG genotype was found to be associated with remission in the whole sample (MDD and BD). Present results suggest that some genetic polymorphisms in both CREB1 and MAPK1 could be associated with treatment remission. Although further research is needed to draw more definitive conclusions, such results are intriguing since suggest a potential role of two genes implicated in neuroplasticity and inflammatory processes in symptom remission after antidepressant treatment.
authors.affiliation: IRCCS Centro S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Calati
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.forename: Martina
authors.initials: M
authors.lastname: Balestri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.forename: Marco
authors.initials: M
authors.lastname: Calabrò
authors.forename: Antonina
authors.initials: A
authors.lastname: Sidoti
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.forename: Isabelle
authors.initials: I
authors.lastname: Massat
authors.forename: Peter
authors.initials: P
authors.lastname: Höfer
authors.forename: Daniela
authors.initials: D
authors.lastname: Amital
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Juven-Wetzler
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Joseph
authors.initials: J
authors.lastname: Zohar
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
authors.forename: Stuart
authors.initials: S
authors.lastname: Montgomery
authors.forename: Julien
authors.initials: J
authors.lastname: Mendlewicz
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D061218:Depressive Disorder, Treatment-Resistant / Q000235:genetics; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D019964:Mood Disorders / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D000928:Antidepressive Agents; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1