OBJECTIVES: Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have described earlier the association between treatment-emergent suicidal ideation (TESI) and markers in genes encoding glutamate receptor subunits GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. METHODS: A clinically representative cohort of outpatients with nonpsychotic major depressive disorder 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 90 White participants who developed TESI and a sex-matched and race-matched equal number of treated participants who denied any suicidal ideas were genotyped with 109 365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. RESULTS: One marker was found to be associated with TESI in this sample at the experiment-wide adjusted P less than 0.05 level (marker rs11628713, allelic P = 6.2x10, odds ratio = 4.7, permutation P = 0.01). A second marker was associated at the experiment-wide adjusted P = 0.06 level (rs10903034, allelic P = 3.02x10, odds ratio = 2.7, permutation P = 0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. CONCLUSION: Together with our earlier report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event.
OBJECTIVES: Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have described earlier the association between treatment-emergent suicidal ideation (TESI) and markers in genes encoding glutamate receptor subunits GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. METHODS: A clinically representative cohort of outpatients with nonpsychotic major depressive disorder 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 90 White participants who developed TESI and a sex-matched and race-matched equal number of treated participants who denied any suicidal ideas were genotyped with 109 365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. RESULTS: One marker was found to be associated with TESI in this sample at the experiment-wide adjusted P less than 0.05 level (marker rs11628713, allelic P = 6.2x10, odds ratio = 4.7, permutation P = 0.01). A second marker was associated at the experiment-wide adjusted P = 0.06 level (rs10903034, allelic P = 3.02x10, odds ratio = 2.7, permutation P = 0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. CONCLUSION: Together with our earlier report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event.
Authors: M H Trivedi; A J Rush; H M Ibrahim; T J Carmody; M M Biggs; T Suppes; M L Crismon; K Shores-Wilson; M G Toprac; E B Dennehy; B Witte; T M Kashner Journal: Psychol Med Date: 2004-01 Impact factor: 7.723
Authors: Maurizio Fava; A John Rush; Madhukar H Trivedi; Andrew A Nierenberg; Michael E Thase; Harold A Sackeim; Frederic M Quitkin; Steven Wisniewski; Philip W Lavori; Jerrold F Rosenbaum; David J Kupfer Journal: Psychiatr Clin North Am Date: 2003-06
Authors: Gonzalo Laje; Silvia Paddock; Husseini Manji; A John Rush; Alexander F Wilson; Dennis Charney; Francis J McMahon Journal: Am J Psychiatry Date: 2007-10 Impact factor: 18.112
Authors: A John Rush; Madhukar H Trivedi; Hicham M Ibrahim; Thomas J Carmody; Bruce Arnow; Daniel N Klein; John C Markowitz; Philip T Ninan; Susan Kornstein; Rachel Manber; Michael E Thase; James H Kocsis; Martin B Keller Journal: Biol Psychiatry Date: 2003-09-01 Impact factor: 13.382
Authors: A John Rush; Maurizio Fava; Stephen R Wisniewski; Philip W Lavori; Madhukar H Trivedi; Harold A Sackeim; Michael E Thase; Andrew A Nierenberg; Frederic M Quitkin; T Michael Kashner; David J Kupfer; Jerrold F Rosenbaum; Jonathan Alpert; Jonathan W Stewart; Patrick J McGrath; Melanie M Biggs; Kathy Shores-Wilson; Barry D Lebowitz; Louise Ritz; George Niederehe Journal: Control Clin Trials Date: 2004-02