探索双相情感障碍中锂反应的遗传学。

Exploring the genetics of lithium response in bipolar disorders.

作者信息

Herrera-Rivero Marisol, Adli Mazda, Akiyama Kazufumi, Akula Nirmala, Amare Azmeraw T, Ardau Raffaella, Arias Bárbara, Aubry Jean-Michel, Backlund Lena, Bellivier Frank, Benabarre Antonio, Bengesser Susanne, Bhattacharjee Abesh Kumar, Biernacka Joanna M, Birner Armin, Cearns Micah, Cervantes Pablo, Chen Hsi-Chung, Chillotti Caterina, Cichon Sven, Clark Scott R, Colom Francesc, Cruceanu Cristiana, Czerski Piotr M, Dalkner Nina, Degenhardt Franziska, Del Zompo Maria, DePaulo J Raymond, Etain Bruno, Falkai Peter, Ferensztajn-Rochowiak Ewa, Forstner Andreas J, Frank Josef, Frisén Louise, Frye Mark A, Fullerton Janice M, Gallo Carla, Gard Sébastien, Garnham Julie S, Goes Fernando S, Grigoroiu-Serbanescu Maria, Grof Paul, Hashimoto Ryota, Hasler Roland, Hauser Joanna, Heilbronner Urs, Herms Stefan, Hoffmann Per, Hou Liping, Hsu Yi-Hsiang, Jamain Stephane, Jiménez Esther, Kahn Jean-Pierre, Kassem Layla, Kato Tadafumi, Kelsoe John, Kittel-Schneider Sarah, Kuo Po-Hsiu, Kusumi Ichiro, König Barbara, Laje Gonzalo, Landén Mikael, Lavebratt Catharina, Leboyer Marion, Leckband Susan G, Maj Mario, Manchia Mirko, Marie-Claire Cynthia, Martinsson Lina, McCarthy Michael J, McElroy Susan L, Millischer Vincent, Mitjans Marina, Mondimore Francis M, Monteleone Palmiero, Nievergelt Caroline M, Novák Tomas, Nöthen Markus M, O'Donovan Claire, Ozaki Norio, Papiol Sergi, Pfennig Andrea, Pisanu Claudia, Potash James B, Reif Andreas, Reininghaus Eva, Richard-Lepouriel Hélène, Roberts Gloria, Rouleau Guy A, Rybakowski Janusz K, Schalling Martin, Schofield Peter R, Schubert Klaus Oliver, Schulte Eva C, Schweizer Barbara W, Severino Giovanni, Shekhtman Tatyana, Shilling Paul D, Shimoda Katzutaka, Simhandl Christian, Slaney Claire M, Squassina Alessio, Stamm Thomas, Stopkova Pavla, Streit Fabian, Tekola-Ayele Fasil, Thalamuthu Anbupalam, Tortorella Alfonso, Turecki Gustavo, Veeh Julia, Vieta Eduard, Viswanath Biju, Witt Stephanie H, Zandi Peter P, Alda Martin, Bauer Michael, McMahon Francis J, Mitchell Philip B, Rietschel Marcella, Schulze Thomas G, Baune Bernhard T

机构信息

Department of Psychiatry, University of Münster and Joint Institute for Individualisation in a Changing Environment (JICE), University of Münster and Bielefeld University, Albert-Schweitzer-Campus 1, Building A9, 48149, Münster, Germany.

Department of Psychiatry and Psychotherapy, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.

出版信息

Int J Bipolar Disord. 2024 Jun 12;12(1):20. doi: 10.1186/s40345-024-00341-y.

DOI:10.1186/s40345-024-00341-y

PMID:38865039

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11169116/

Abstract

BACKGROUND

Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.

RESULTS

We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.

CONCLUSIONS

Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

摘要

背景

锂盐（Li）仍是双相情感障碍（BP）的首选治疗药物。其心境稳定作用有助于减轻双相情感障碍患者的躁狂、抑郁和自杀风险的长期负担。它还被证明对包括睡眠和心血管疾病在内的疾病相关状况有有益影响。然而，根据临床表现，双相情感障碍诊断亚型（如双相I型和双相II型）内部和之间对锂盐治疗的个体反应存在差异。此外，长期锂盐治疗与不良副作用有关，这些副作用令人担忧且会导致患者不依从治疗，包括患甲状腺和肾脏疾病等慢性疾病的风险。近年来，锂盐遗传学联盟（ConLiGen）的研究发现了一些导致双相情感障碍患者锂盐治疗反应变异性的遗传因素。在此，我们利用ConLiGen队列（N = 2064）来研究双相情感障碍中锂盐效应的遗传基础。为此，我们研究了锂盐反应及相关基因如何与精神症状以及合并症的多基因负荷相关联，特别着重于识别双相I型和双相II型之间的差异。

结果

我们发现，用阿尔达量表衡量，锂盐治疗的临床反应与双相I型患者的躁狂、抑郁、物质和酒精滥用、精神病及自杀观念负担减轻相关，而在双相II型患者中仅与抑郁负担减轻相关。我们的基因分析表明，对锂盐更强的临床反应与双相I型而非双相II型中较低的糖尿病和高血压多基因负荷适度相关。此外，我们的结果表明，一些先前与双相情感障碍中锂盐反应变异性相关的基因与精神症状学，特别是躁狂和抑郁发作次数，以及与包括糖尿病、高血压和甲状腺功能减退在内的合并症多基因负荷存在差异关联。