title: Influence of GRIK4 genetic variants on the electroconvulsive therapy response.
abstract: Several lines of evidence have shown the involvement of the glutamatergic system in the function of electroconvulsive therapy (ECT). In particular, patients with treatment resistant depression (TRD) and chronic depression have lower levels of glutamate/glutamine than controls, and ECT can reverse this deficit. Genetic factors might contribute to modulating the mechanisms underlying ECT. This study aimed to evaluate the relationship between three polymorphisms (rs1954787, rs4936554 and rs11218030) of the glutamate receptor ionotropic kainate 4 (GRIK4) gene and responsiveness to ECT treatment in a sample of one hundred individuals, TRD or depressive Bipolar Disorder patients resistant to pharmacological treatments. The results revealed that GRIK4 variants were significantly associated with the response to ECT. In particular, we found that patients carrying the G allele of the GRIK4 rs11218030 had a significantly poorer response to ECT (p=2.71×10(-4)), showing five times the risk of relapse after ECT compared to the AA homozygotes. Analogously, patients carrying the GG rs1954787 genotype and rs4936554A allele carriers presented a double risk of lack of response after ECT (p=0.013 and p=0.040, respectively). In conclusion, the current study provides new evidence, indicating that some GRIK4 variants modulate the response to ECT in patients with depression resistant to treatment, suggesting a role for kainate receptor modulation.
authors.affiliation: Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy. Electronic address: alessandra.minelli@unibs.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Minelli
authors.affiliation: Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Congiu
authors.affiliation: Department of Neuroscience, Fatebenefratelli Foundation, AFaR Division, Fatebenefratelli Hospital-Isola Tiberina, Rome, Italy.
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Ventriglia
authors.affiliation: Psychiatric Hospital "Villa Santa Chiara", Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolomasi
authors.affiliation: Genetic Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Bonvicini
authors.affiliation: Psychiatric Hospital "Villa Santa Chiara", Verona, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Abate
authors.affiliation: Department of Philosophy, Education, Psychology University of Verona, Verona, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sartori
authors.affiliation: Psychiatric Hospital "Villa Santa Chiara", Verona, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Gainelli
authors.affiliation: Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Brescia, Italy; Genetic Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
mesh_terms: D000483:Alleles; D061218:Depressive Disorder, Treatment-Resistant / Q000235:genetics* / Q000628:therapy*; D004565:Electroconvulsive Therapy; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018092:Kainic Acid Receptors / Q000235:genetics*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D018092:Kainic Acid Receptors; C514872:GRIK4 protein, human
keywords: ECT; Electroconvulsive therapy; GRIK4 polymorphisms; Glutamate; Major depressive disorder; Treatment resistant depression