Genetics of emergent suicidality during antidepressive treatment--data from a naturalistic study on a large sample of inpatients with a major depressive episode.
Factors contributing to treatment-emergent suicidal ideation (TESI) using antidepressants have been in the focus of recent research strategies. We investigated previously established clinical predictors of TESI and combined these with several polymorphisms of candidate genes in patients with major depressive disorder. Common polymorphisms involved in the tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), serotonin transporter, monoamine oxidase A (MAOA) and brain-derived neurotrophic factor (BDNF) were investigated in a naturalistic inpatient study of the German research network on depression. We compared patients showing TESI with non-TESI suicidal patients and with non-suicidal patients using univariate tests to detect relevant factors, which were further tested in logistic regression and CART (Classification and Regression Trees) analyses. Of the 269 patients, TESI occurred in 22 patients (17 female), 117 patients were defined as non-TESI suicidal patients, and 130 patients were classified as non-suicidal. When comparing cases with both control groups we found the TPH2 rs1386494 (C/T) polymorphism to be moderately associated with TESI (Univariate tests: TESI vs. non-suicidality: p=0.005; adjusted: p=0.09; TESI vs. non-TESI suicidal patients: p=0.0024; adjusted: p=0.086). This polymorphism remained the only significant genetic factor in addition to clinical predictors in logistic regression and CART analyses. CART analyses suggested interactions with several clinical predictors. Haplotype analyses further supported a contribution of this polymorphism in TESI. The TPH2 rs1386494 (C/T) polymorphism might contribute to the genetic background of TESI. This polymorphism has been previously associated with committed suicide and major depressive disorder. The small number of cases warrants replication in larger patient samples. Lack of a placebo control group hampers definite conclusions on an association with antidepressive treatment.
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336 Munich, Germany. Richard.musil@med.uni-muenchen.de
Richard
R
Musil
Peter
P
Zill
Florian
F
Seemüller
Brigitta
B
Bondy
Sebastian
S
Meyer
Ilja
I
Spellmann
Wolfram
W
Bender
Mazda
M
Adli
Isabella
I
Heuser
Robert
R
Fisher
Wolfgang
W
Gaebel
Wolfgang
W
Maier
Marcella
M
Rietschel
Dan
D
Rujescu
Rebecca
R
Schennach
Hans-Jürgen
HJ
Möller
Michael
M
Riedel
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D008995:Monoamine Oxidase / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D059020:Suicidal Ideation; D013406:Suicide, Attempted / Q000706:statistics & numerical data*; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D044465:White People / Q000235:genetics
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human