Evaluation of the role of MAPK1 and CREB1 polymorphisms on treatment resistance, response and remission in mood disorder patients

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• 作者：Raffaella Calati^a ; Concetta Crisafulli^b ; Martina Balestri^c ; Alessandro Serretti^c ; ^{alessandro.serretti@unibo.it} ; Edoardo Spina^d ; Marco Calabrò ; ^b ; ^d ; ^e ; Antonina Sidoti^b ; Diego Albani^f ; Isabelle Massat^g ; Peter Hö ; fer^h ; Daniela Amitalⁱ ; Alzbeta Juven-Wetzler^j ; Siegfried Kasper^h ; Joseph Zohar^j ; Daniel Souery^k ; Stuart Montgomery^l ; Julien Mendlewicz^m
• 关键词：TRD ; Treatment Resistant Depression ; SNPs ; Single Nucleotide Polymorphisms ; MDD ; Major Depressive Disorder ; BD ; Bipolar Disorder ; MAPK1 ; Mitogen activated protein kinase 1 ; CREB1 ; Cyclic AMP responsive element binding protein 1 ; TRD-W ; Treatment Resistant
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2013
• 出版时间：1 July, 2013
• 年：2013
• 卷：44
• 期：Complete
• 页码：271-278
• 全文大小：259 K

文摘

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.