OBJECTIVE:Suicidal ideation is an uncommon symptom than can emerge during antidepressant treatment. The biological basis of treatment-emergent suicidal ideation is unknown. Genetic markers may shed light on the causes of treatment-emergent suicidal ideation and help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, or specialty care. METHOD: A clinically representative cohort of outpatients with major depressive disorder who enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated withcitalopram under a standard protocol for up to 14 weeks. DNA samples from 1,915 participants were genotyped for 768 single-nucleotide polymorphisms in 68 candidate genes. Allele and genotype frequencies were compared between the 120 participants who developed treatment-emergent suicidal ideation and those who did not. RESULTS: Two markers were significantly associated with treatment-emergent suicidal ideation in this sample (marker rs4825476, p=0.0000784, odds ratio=1.94; permutation p=0.01; marker rs2518224, p=0.0000243, odds ratio=8.23; permutation p=0.003). These markers reside within the genes GRIA3 and GRIK2, respectively, both of which encode ionotropic glutamate receptors. CONCLUSIONS: Markers within GRIK2 and GRIA3 were associated with treatment-emergent suicidal ideation during citalopram therapy. If replicated, these findings may shed light on the biological basis of this potentially dangerous adverse event and help identify patients at increased risk.
RCT Entities:
OBJECTIVE: Suicidal ideation is an uncommon symptom than can emerge during antidepressant treatment. The biological basis of treatment-emergent suicidal ideation is unknown. Genetic markers may shed light on the causes of treatment-emergent suicidal ideation and help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, or specialty care. METHOD: A clinically representative cohort of outpatients with major depressive disorder who enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 1,915 participants were genotyped for 768 single-nucleotide polymorphisms in 68 candidate genes. Allele and genotype frequencies were compared between the 120 participants who developed treatment-emergent suicidal ideation and those who did not. RESULTS: Two markers were significantly associated with treatment-emergent suicidal ideation in this sample (marker rs4825476, p=0.0000784, odds ratio=1.94; permutation p=0.01; marker rs2518224, p=0.0000243, odds ratio=8.23; permutation p=0.003). These markers reside within the genes GRIA3 and GRIK2, respectively, both of which encode ionotropic glutamate receptors. CONCLUSIONS: Markers within GRIK2 and GRIA3 were associated with treatment-emergent suicidal ideation during citalopram therapy. If replicated, these findings may shed light on the biological basis of this potentially dangerous adverse event and help identify patients at increased risk.
Authors: Thomas G Schulze; Martin Alda; Mazda Adli; Nirmala Akula; Raffaella Ardau; Elise T Bui; Caterina Chillotti; Sven Cichon; Piotr Czerski; Maria Del Zompo; Sevilla D Detera-Wadleigh; Paul Grof; Oliver Gruber; Ryota Hashimoto; Joanna Hauser; Rebecca Hoban; Nakao Iwata; Layla Kassem; Tadafumi Kato; Sarah Kittel-Schneider; Sebastian Kliwicki; John R Kelsoe; Ichiro Kusumi; Gonzalo Laje; Susan G Leckband; Mirko Manchia; Glenda Macqueen; Takuya Masui; Norio Ozaki; Roy H Perlis; Andrea Pfennig; Paola Piccardi; Sara Richardson; Guy Rouleau; Andreas Reif; Janusz K Rybakowski; Johanna Sasse; Johannes Schumacher; Giovanni Severino; Jordan W Smoller; Alessio Squassina; Gustavo Turecki; L Trevor Young; Takeo Yoshikawa; Michael Bauer; Francis J McMahon Journal: Neuropsychobiology Date: 2010-05-08 Impact factor: 2.328
Authors: J Scott Templin; Sun Jung Bang; Mariano Soiza-Reilly; Charles B Berde; Kathryn G Commons Journal: Brain Res Date: 2012-04-04 Impact factor: 3.252