Further Support for the Involvement of Genetic Variants Related to the Serotonergic Pathway in the Antidepressant Response in Children and Adolescents After a 12-Month Follow-Up: Impact of the HTR2A rs7997012 Polymorphism

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Grant support

This work was supported by the Alicia Koplowitz Foundation; the Spanish Ministry of Health, Instituto Carlos III, Fondo de Investigacion Sanitaria (FIS) (PI041239); and FEDER-Union Europea. Support was also given by the Agencia de Gestio d'Ajuts Universitaris i Recerca'' (AGAUR) of the Generalitat de Catalunya'' to the Child Psychiatry and Psychology Group'' (2014 SGR 489) and to the Clinical Pharmacology and Pharmacogenetics Group'' (2014 SGR 436).

Analysis of institutional authors

Rodríguez Ferret, NataliaAuthorGasso, PatriciaAuthorBlazquez, AnaAuthorRodriguez, NataliaAuthorBoloc, DanielAuthorTorres, TeresaAuthorMas, SergiAuthorLafuente, AmaliaAuthorLazaro, LuisaCorresponding Author

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Article

Publicated to:Journal Of Child And Adolescent Psychopharmacology. 28 (10): 711-718 - 2018-07-05 28(10), DOI: 10.1089/cap.2018.0004

Authors: Gasso, Patricia; Blazquez, Ana; Rodriguez, Natalia; Boloc, Daniel; Torres, Teresa; Mas, Sergi; Lafuente, Amalia; Lazaro, Luisa;

Affiliations

Ctr Invest Biomed Red Salud Mental CIBERSA, Barcelona, Spain - Author

Hosp Clin Barcelona, Dept Child & Adolescent Psychiat & Psychol, Inst Neurosci, Villarroel 170, E-08036 Barcelona, Spain - Author

Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain - Author

Univ Barcelona, Dept Basic Clin Practice, Pharmacol Unit, Barcelona, Spain - Author

Univ Barcelona, Dept Med, Barcelona, Spain - Author

Abstract

Objective: Fluoxetine is an effective and well-tolerated pharmacological treatment for children and adolescents with major depressive disorder (MDD). However, a high percentage of patients do not respond. There is a substantial genetic contribution to this variable clinical outcome. Based on previous genetic results of our group and given the lack of pharmacogenetics studies of antidepressant response with a long follow-up period, we evaluated the influence of single nucleotide polymorphisms (SNPs) in genes related to the serotonergic pathway on remission and recovery in children and adolescents diagnosed with MDD after 12 months of initiating fluoxetine treatment. Methods: The assessment was performed in 46 patients. All of them were visited at least once a month during the 12-month follow-up. Psychiatrists interviewed patients and their parents to explore clinical improvement. A total of 75 genotyped SNPs in 10 candidate genes were included in the genetic association analysis with remission and recovery. Bonferroni correction for multiple testing was applied to avoid false positive results. Results: The HTR2A rs7997012 SNP was significantly associated after Bonferroni correction with clinical improvement. Particularly, the homozygotes for the major allele (GG) showed the highest percentage of remitters and the highest score reductions on the Clinical Global Impressions-Severity (CGI-S) scale. Moreover, although the results were on the border of statistical significance, the GG homozygotes also tended to experience fewer readmissions during the follow-up period Conclusions: These results provide more evidence of the involvement of genetic variants related to the serotonergic pathway in the antidepressant response. Studies with larger cohorts are needed to integrate all relevant variants into clinical predictors of antidepressant response.

Keywords

associationchildrenclinical improvementdepressionfluoxetinehtr2apharmacogeneticsreceptorrelapsereliabilityscheduleschizophreniasnpversionAdolescentAntidepressive agentsAssociationChildChildrenClinical improvementDepressionDepressive disorder, majorFemaleFluoxetineGenetic variationHtr2aHumansK-sads-plMajor depressive disorderMaleMetaanalysisPharmacogeneticsPolymorphism, single nucleotidePsychiatric status rating scalesReceptors, serotonin, 5-ht2ReliabilityRemission inductionScheduleSchizophreniaSnpTreatment outcome

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Child And Adolescent Psychopharmacology due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2018, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Pediatrics, Perinatology and Child Health.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations from Scopus Elsevier, it yields a value for the Field-Weighted Citation Impact from the Scopus agency: 1.32, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

Field Citation Ratio (FCR) from Dimensions: 3.11 (source consulted: Dimensions Apr 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-04-30, the following number of citations:

WoS: 8
Scopus: 15
Europe PMC: 4
OpenCitations: 14

Impact and social visibility

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Gassó Astorga, Patricia) and Last Author (Lázaro García, Luisa).