Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

被引：59

作者：

Amare, Azmeraw T. ^{[1
,2
]}

Schubert, Klaus Oliver ^{[1
,3
]}

Hou, Liping ^{[4
]}

Clark, Scott R. ^{[1
]}

Papiol, Sergi ^{[5
,6
]}

Cearns, Micah ^{[1
]}

Heilbronner, Urs ^{[5
,7
]}

Degenhardt, Franziska ^{[8
,9
]}

Tekola-Ayele, Fasil ^{[10
]}

Hsu, Yi-Hsiang ^{[11
,12
]}

Shekhtman, Tatyana ^{[13
]}

AdIi, Mazda ^{[14
]}

Akula, Nirmala ^{[4
]}

Akiyama, Kazufumi ^{[15
]}

Ardau, Raffaella ^{[16
]}

Arias, Barbara ^{[17
,18
]}

Aubry, Jean-Michel ^{[19
]}

Backlund, Lena ^{[20
,21
]}

Bhattacharjee, Kumar ^{[13
]}

Bellivier, Frank ^{[22
]}

Benabarre, Antonio ^{[23
]}

Bengesser, Susanne ^{[24
]}

Biernacka, Joanna M. ^{[25
,26
]}

Birner, Armin ^{[24
]}

Brichant-Petitjean, Clara ^{[22
]}

Cervantes, Pablo ^{[27
]}

Chen, Hsi-Chung ^{[28
,29
]}

Chillotti, Caterina ^{[16
]}

Cichon, Sven ^{[8
,9
,30
]}

Cruceanu, Cristiana ^{[31
]}

Czerski, Piotr M. ^{[32
]}

Dalkner, Nina ^{[24
]}

Dayer, Alexandre ^{[19
]}

Del Zompo, Maria ^{[33
]}

DePaulo, J. Raymond ^{[34
]}

Etain, Bruno ^{[22
]}

Jamain, Stephane ^{[35
]}

Falkai, Peter ^{[6
]}

Forstner, Andreas J. ^{[8
,9
,30
,36
]}

Frisen, Louise ^{[20
,21
]}

Frye, Mark A. ^{[26
]}

Fullerton, Janice M. ^{[37
,38
]}

Gard, Sebastien ^{[39
]}

Garnham, Julie S. ^{[40
]}

Goes, Fernando S. ^{[34
]}

Grigoroiu-Serbanescu, Maria ^{[41
]}

Grof, Paul ^{[42
]}

Hashimoto, Ryota ^{[43
,44
]}

Hauser, Joanna ^{[32
]}

Herms, Stefan ^{[8
,9
,30
]}

机构：

[1] Univ Adelaide, Sch Med, Discipline Psychiat, Adelaide, SA, Australia

[2] SAHMRI, South Australian Acad Hlth Sci & Translat Ctr, Adelaide, SA, Australia

[3] Northern Adelaide Local Hlth Network, Mental Hlth Serv, Adelaide, SA, Australia

[4] NIMH, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA

[5] Ludwig Maximilians Univ Munchen, IPPG, Univ Hosp, Munich, Germany

[6] Ludwig Maximilian Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany

[7] Georg August Univ Gottingen, Univ Med Ctr UMG, Dept Psychiat & Psychotherapy, Gottingen, Germany

[8] Univ Bonn, Inst Human Genet, Bonn, Germany

[9] Life & Brain Ctr, Dept Genom, Bonn, Germany

[10] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA

[11] Harvard Med Sch, HSL Inst Aging Res, Boston, MA 02115 USA

[12] Harvard Sch Publ Hlth, Program Quantitat Genom, Boston, MA USA

[13] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA

[14] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Campus Charite Mitte, Berlin, Germany

[15] Dokkyo Med Univ, Dept Biol Psychiat & Neurosci, Sch Med, Mibu, Tochigi, Japan

[16] Hosp Univ Agcy Cagliari, Unit Clin Pharmacol, Cagliari, Italy

[17] Univ Barcelona, Fac Biol, Dept Biol Evolut Ecol & Ciencies Ambientals, Unitat Zool & Antropol Biol, Barcelona, Spain

[18] Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain

[19] Hug Geneva Univ Hosp, Dept Psychiat, Mood Disorders Unit, Geneva, Switzerland

[20] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[21] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden

[22] Univ Paris Diderot, Grp Hosp St Louis Lariboisiere F Widal, AP HP, INSERM UMR S 1144,Dept Psychiat & Med Addictol, Paris, France

[23] Univ Barcelona, Hosp Clin, Inst Neurosci, IDIBAPS,CIBERSAM,Bipolar Disorder Program, Barcelona, Catalonia, Spain

[24] Med Univ Graz, Dept Psychiat & Psychotherapeut Med, Res Unit Bipolar Affect Disorder, Graz, Austria

[25] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[26] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA

[27] McGill Univ, Neuromodulat Unit, Hlth Ctr, Montreal, PQ, Canada

[28] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei, Taiwan

[29] Natl Taiwan Univ Hosp, Ctr Sleep Disorders, Taipei, Taiwan

[30] Univ Hosp Basel, Dept Biomed, Human Genom Res Grp, Basel, Switzerland

[31] McGill Univ, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada

[32] Poznan Univ Med Sci, Psychiat Genet Unit, Poznan, Poland

[33] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy

[34] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA

[35] Fdn FondaMental, Translat Psychiat Lab, Inserm U955, Creteil, France

[36] Univ Basel, Dept Psychiat UPK, Basel, Switzerland

[37] Neurosci Res Australia, Sydney, NSW, Australia

[38] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia

[39] Hop Charles Perrens, Serv Psychiat, Bordeaux, France

[40] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada

[41] Alexandru Obregia Clin Psychiat Hosp, Biometr Psychiat Genet Res Unit, Bucharest, Romania

[42] Mood Disorders Ctr Ottawa, Ottawa, ON, Canada

[43] Osaka Univ, Mol Res Ctr Childrens Mental Dev, United Grad Sch Child Dev, Osaka, Japan

[44] Osaka Univ, Dept Psychiat, Grad Sch Med, Osaka, Japan

[45] Univ Lorraine, Serv Psychiat & Psychol Clin, Ctr Psychotherap Nancy, Nancy, France

[46] Natl Taiwan Univ, Coll Publ Hlth, Dept Publ Hlth, Taipei, Taiwan

[47] Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan

[48] RIKEN, Lab Mol Dynam Mental Disorders, Ctr Brain Sci, Saitama, Japan

[49] Univ Hosp Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany

[50] Poznan Univ Med Sci, Dept Adult Psychiat, Poznan, Poland

来源：

MOLECULAR PSYCHIATRY | 2021年 / 26卷 / 06期

基金：

瑞士国家科学基金会; 澳大利亚国家健康与医学研究理事会; 瑞典研究理事会; 英国医学研究理事会; 加拿大健康研究院;

关键词：

PHARMACOLOGICAL-TREATMENTS; PROPHYLACTIC LITHIUM; AUGMENTATION; RISK; PREDICTORS; GENETICS; EFFICACY; POLARITY; THERAPY; AGENTS;

D O I：

10.1038/s41380-020-0689-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi(+)Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

引用

页码：2457 / 2470

页数：14

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