TY  - JOUR
A1  - Baune, Bernhard T.
A1  - Konrad, Carsten
A1  - Grotegerd, Dominik
A1  - Suslow, Thomas
A1  - Birosova, Eva
A1  - Ohrmann, Patricia
A1  - Bauer, Jochen
A1  - Arolt, Volker
A1  - Heindel, Walter
A1  - Domschke, Katharina
A1  - Schöning, Sonja
A1  - Rauch, Astrid V.
A1  - Uhlmann, Christina
A1  - Kugel, Harald
A1  - Dannlowski, Udo
T1  - Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain
JF  - Journal of Neuroinflammation
N2  - Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. 
Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e. g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (-174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = -10, z = -15; F(2,286) = 8.54, p(uncorrected) = 0.0002; p(AlphaSim-corrected) = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. 
Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.
KW  - aging brain
KW  - hippocampal neurogenesis
KW  - cholinergic neurons
KW  - neurothrophic factor
KW  - Alzheimers disease
KW  - neurite outgrowth
KW  - inflammatory cytokines
KW  - major depression
KW  - nervour system
KW  - dentate gyrus
KW  - genetics
KW  - inflammation
KW  - interleukin 6
KW  - neuroprotection
KW  - voxel-based morphometry
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130804
VL  - 9
IS  - 125
ER  - 
TY  - JOUR
A1  - Hennings, Johannes M.
A1  - Kohli, Martin A.
A1  - Czamara, Darina
A1  - Giese, Maria
A1  - Eckert, Anne
A1  - Wolf, Christiane
A1  - Heck, Angela
A1  - Domschke, Katharina
A1  - Arolt, Volker
A1  - Baune, Bernhard T.
A1  - Horstmann, Sonja
A1  - Brückl, Tanja
A1  - Klengel, Torsten
A1  - Menke, Andreas
A1  - Müller-Myhsok, Bertram
A1  - Ising, Marcus
A1  - Uhr, Manfred
A1  - Lucae, Susanne
T1  - Possible Associations of NTRK2 Polymorphisms with Antidepressant Treatment Outcome: Findings from an Extended Tag SNP Approach
JF  - PLoS ONE
N2  - Background: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment.
Methods: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples.
Results: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (\(P_{corr}\) = .018, \(P_{corr}\) = .015 and \(P_{corr}\) = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients.
Conclusions/Limitations: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies.
KW  - brain
KW  - bipolar disorder
KW  - mood disorder
KW  - treatment response
KW  - genome-wide association
KW  - major depressive disorder
KW  - neurotrophic factor gene
KW  - VAL66MET polymorphism
KW  - sequence variations
KW  - messenger RNA
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130924
VL  - 8
IS  - 6
ER  - 
TY  - JOUR
A1  - Manchia, Mirko
A1  - Adli, Mazda
A1  - Akula, Nirmala
A1  - Arda, Raffaella
A1  - Aubry, Jean-Michel
A1  - Backlund, Lena
A1  - Banzato, Claudio E. M.
A1  - Baune, Bernhard T.
A1  - Bellivier, Frank
A1  - Bengesser, Susanne
A1  - Biernacka, Joanna M.
A1  - Brichant-Petitjean, Clara
A1  - Bui, Elise
A1  - Calkin, Cynthia V.
A1  - Cheng, Andrew Tai Ann
A1  - Chillotti, Caterina
A1  - Cichon, Sven
A1  - Clark, Scott
A1  - Czerski, Piotr M.
A1  - Dantas, Clarissa
A1  - Del Zompo, Maria
A1  - DePaulo, J. Raymond
A1  - Detera-Wadleigh, Sevilla D.
A1  - Etain, Bruno
A1  - Falkai, Peter
A1  - Frisén, Louise
A1  - Frye, Mark A.
A1  - Fullerton, Jan
A1  - Gard, Sébastien
A1  - Garnham, Julie
A1  - Goes, Fernando S.
A1  - Grof, Paul
A1  - Gruber, Oliver
A1  - Hashimoto, Ryota
A1  - Hauser, Joanna
A1  - Heilbronner, Urs
A1  - Hoban, Rebecca
A1  - Hou, Liping
A1  - Jamain, Stéphane
A1  - Kahn, Jean-Pierre
A1  - Kassem, Layla
A1  - Kato, Tadafumi
A1  - Kelsoe, John R.
A1  - Kittel-Schneider, Sarah
A1  - Kliwicki, Sebastian
A1  - Kuo, Po-Hsiu
A1  - Kusumi, Ichiro
A1  - Laje, Gonzalo
A1  - Lavebratt, Catharina
A1  - Leboyer, Marion
A1  - Leckband, Susan G.
A1  - López Jaramillo, Carlos A.
A1  - Maj, Mario
A1  - Malafosse, Alain
A1  - Martinsson, Lina
A1  - Masui, Takuya
A1  - Mitchell, Philip B.
A1  - Mondimore, Frank
A1  - Monteleone, Palmiero
A1  - Nallet, Audrey
A1  - Neuner, Maria
A1  - Novák, Tomás
A1  - O'Donovan, Claire
A1  - Ösby, Urban
A1  - Ozaki, Norio
A1  - Perlis, Roy H.
A1  - Pfennig, Andrea
A1  - Potash, James B.
A1  - Reich-Erkelenz, Daniela
A1  - Reif, Andreas
A1  - Reininghaus, Eva
A1  - Richardson, Sara
A1  - Rouleau, Guy A.
A1  - Rybakowski, Janusz K.
A1  - Schalling, Martin
A1  - Schofield, Peter R.
A1  - Schubert, Oliver K.
A1  - Schweizer, Barbara
A1  - Seemüller, Florian
A1  - Grigoroiu-Serbanescu, Maria
A1  - Severino, Giovanni
A1  - Seymour, Lisa R.
A1  - Slaney, Claire
A1  - Smoller, Jordan W.
A1  - Squassina, Alessio
A1  - Stamm, Thomas
A1  - Steele, Jo
A1  - Stopkova, Pavla
A1  - Tighe, Sarah K.
A1  - Tortorella, Alfonso
A1  - Turecki, Gustavo
A1  - Wray, Naomi R.
A1  - Wright, Adam
A1  - Zandi, Peter P.
A1  - Zilles, David
A1  - Bauer, Michael
A1  - Rietschel, Marcella
A1  - McMahon, Francis J.
A1  - Schulze, Thomas G.
A1  - Alda, Martin
T1  - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report
JF  - PLoS ONE
N2  - Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. 
Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. 
Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). 
Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
KW  - age
KW  - observer agreement
KW  - prophylactic lithium
KW  - mapping susceptibility genes
KW  - mood disorders
KW  - onset
KW  - association
KW  - reliability
KW  - morality
KW  - illness
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130938
VL  - 8
IS  - 6
ER  -