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    • Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study

    Translational Psychiatry（2024）

    Department of Psychiatry | Univ Calif San Diego | Charite Univ Med Berlin | Dokkyo Med Univ | NIMH | Discipline of Psychiatry | Unit of Clinical Pharmacology | Univ Barcelona | Geneva Univ Hosp | Karolinska Inst | Tech Univ Dresden | Univ Paris Cite | Med Univ Graz | Department of Health Sciences Research | The Neuromodulation Unit | Department of Psychiatry & Center of Sleep Disorders | Univ Bonn | Campus for Ageing and Vitality | Douglas Mental Health University Institute | Psychiatric Genetic Unit | Department of Psychiatry and Behavioral Sciences | Ludwig Maximilians Univ Munchen | Department of Adult Psychiatry | Department of Psychiatry and Psychology | Mental Illness Research Theme | Pôle de Psychiatrie Générale Universitaire | Biometric Psychiatric Genetics Research Unit | Mood Disorders Center of Ottawa | Georg August Univ Gottingen | Natl Inst Mental Hlth | Inserm U955 | Univ Lorraine | Laboratory for Molecular Dynamics of Mental Disorders | Department of Psychiatry and Psychotherapeutic Medicine | Institute of Epidemiology and Preventive Medicine | Gothenburg Univ | Hop Albert Chenevier Henri Mondor | Department of Pharmacy | Department of Medical Sciences and Public Health | Department of Clinical Neurosciences | Department of Biomedicine | School of Psychiatry | Neurosciences Section | National Institute of Mental Health | Ludwig-Maximilians-University of Munich | Department of Biomedical Sciences | Goethe Univ | Heidelberg Univ | Montreal Neurological Institute and Hospital | Bipolar Center | The University of Queensland | Department of Mental Health

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    Abstract
    Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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    Linkage Disequilibrium
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    【要点】：该研究通过多组学复制实验发现，在双相情感障碍中对锂的反应与焦点粘附和PI3K-Akt网络有关。
    

    【方法】：研究者通过网络传播方法在独立样本中复制了先前的多组学研究成果。
    

    【实验】：在International Consortium on Lithium Genetics (ConLiGen)的2039名患者基因组关联研究中，研究者发现焦点粘附和PI3K-Akt通路的功能富集，但未发现与细胞外基质通路有关联。结果显示，在双相情感障碍中，锂的反应可能受到神经生长锥缺陷和PI3K-Akt信号的影响，而不是细胞外基质蛋白。
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