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Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.
Amare, Azmeraw T; Schubert, Klaus Oliver; Hou, Liping; Clark, Scott R; Papiol, Sergi; Cearns, Micah; Heilbronner, Urs; Degenhardt, Franziska; Tekola-Ayele, Fasil; Hsu, Yi-Hsiang; Shekhtman, Tatyana; Adli, Mazda; Akula, Nirmala; Akiyama, Kazufumi; Ardau, Raffaella; Arias, Bárbara; Aubry, Jean-Michel; Backlund, Lena; Bhattacharjee, Abesh Kumar; Bellivier, Frank; Benabarre, Antonio; Bengesser, Susanne; Biernacka, Joanna M; Birner, Armin; Brichant-Petitjean, Clara; Cervantes, Pablo; Chen, Hsi-Chung; Chillotti, Caterina; Cichon, Sven; Cruceanu, Cristiana; Czerski, Piotr M; Dalkner, Nina; Dayer, Alexandre; Del Zompo, Maria; DePaulo, J Raymond; Étain, Bruno; Jamain, Stephane; Falkai, Peter; Forstner, Andreas J; Frisen, Louise; Frye, Mark A; Fullerton, Janice M; Gard, Sébastien; Garnham, Julie S; Goes, Fernando S; Grigoroiu-Serbanescu, Maria; Grof, Paul; Hashimoto, Ryota; Hauser, Joanna; Herms, Stefan.
Afiliação
  • Amare AT; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
  • Schubert KO; South Australian Academic Health Science and Translation Centre, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia.
  • Hou L; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
  • Clark SR; Northern Adelaide Local Health Network, Mental Health Services, Adelaide, SA, Australia.
  • Papiol S; Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
  • Cearns M; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
  • Heilbronner U; Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
  • Degenhardt F; Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.
  • Tekola-Ayele F; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
  • Hsu YH; Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
  • Shekhtman T; Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen, Göttingen, Germany.
  • Adli M; Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
  • Akula N; Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • Akiyama K; HSL Institute for Aging Research, Harvard Medical School, Boston, MA, USA.
  • Ardau R; Program for Quantitative Genomics, Harvard School of Public Health, Boston, MA, USA.
  • Arias B; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
  • Aubry JM; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
  • Backlund L; Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
  • Bhattacharjee AK; Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
  • Bellivier F; Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
  • Benabarre A; Unitat de Zoologia i Antropologia Biològica (Dpt. Biologia Evolutiva, Ecologia i Ciències Ambientals), Facultat de Biologia and Institut de Biomedicina (IBUB), University of Barcelona, CIBERSAM, Barcelona, Spain.
  • Bengesser S; Department of Psychiatry, Mood Disorders Unit, HUG - Geneva University Hospitals, Geneva, Switzerland.
  • Biernacka JM; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
  • Birner A; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Brichant-Petitjean C; Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
  • Cervantes P; INSERM UMR-S 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France.
  • Chen HC; Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
  • Chillotti C; Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for bipolar affective disorder, Medical University of Graz, Graz, Austria.
  • Cichon S; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Cruceanu C; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
  • Czerski PM; Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for bipolar affective disorder, Medical University of Graz, Graz, Austria.
  • Dalkner N; INSERM UMR-S 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France.
  • Dayer A; The Neuromodulation Unit, McGill University Health Centre, Montreal, QC, Canada.
  • Del Zompo M; Department of Psychiatry & Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan.
  • DePaulo JR; Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
  • Étain B; Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
  • Jamain S; Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
  • Falkai P; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
  • Forstner AJ; Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland.
  • Frisen L; Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for bipolar affective disorder, Medical University of Graz, Graz, Austria.
  • Frye MA; Department of Psychiatry, Mood Disorders Unit, HUG - Geneva University Hospitals, Geneva, Switzerland.
  • Fullerton JM; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
  • Gard S; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
  • Garnham JS; INSERM UMR-S 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France.
  • Goes FS; Inserm U955, Translational Psychiatry laboratory, Fondation FondaMental, Créteil, France.
  • Grigoroiu-Serbanescu M; Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.
  • Grof P; Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
  • Hashimoto R; Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
  • Hauser J; Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
  • Herms S; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Mol Psychiatry ; 26(6): 2457-2470, 2021 06.
Article em En | MEDLINE | ID: mdl-32203155
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Bipolar / Transtorno Depressivo Maior Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Austrália
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Bipolar / Transtorno Depressivo Maior Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Austrália