Montejo Laura, Sole Brisa, Fico Giovanna, Kalman Janos L, Budde Monika, Heilbronner Urs, Oliva Vincenzo, De Prisco Michele, Martin-Parra Sara, Ruiz Andrea, Martinez-Aran Anabel, Adorjan Kristina, Falkai Peter, Heilbronner Maria, Kohshour Mojtaba Oraki, Reich-Erkelenz Daniela, Schaupp Sabrina K, Schulte Eva C, Senner Fanny, Vogl Thomas, Anghelescu Ion-George, Arolt Volker, Baune Bernhard T, Dannlowski Udo, Dietrich Detlef E, Fallgatter Andreas J, Figge Christian, Juckel Georg, Konrad Carsten, Reimer Jens, Reininghaus Eva Z, Schmauß Max, Wiltfang Jens, Zimmermann Jörg, Vieta Eduard, Papiol Sergi, Schulze Thomas G, Torrent Carla
Bipolar and Depressive Disorders Unit, Hospital Clinic de Barcelona, Barcelona, Spain; Fundació Clínic per la Recerca Biomèdica-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
Bipolar and Depressive Disorders Unit, Hospital Clinic de Barcelona, Barcelona, Spain; Fundació Clínic per la Recerca Biomèdica-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Barcelona, Spain.
Eur Neuropsychopharmacol. 2025 Mar;92:29-37. doi: 10.1016/j.euroneuro.2024.12.001. Epub 2024 Dec 22.
Older Adults with Bipolar Disorder (OABD) represent a heterogeneous group, including those with early and late onset of the disorder. Recent evidence shows both groups have distinct clinical, cognitive, and medical features, tied to different neurobiological profiles. This study explored the link between polygenic risk scores (PRS) for bipolar disorder (PRS-BD), schizophrenia (PRS-SCZ), and major depressive disorder (PRS-MDD) with age of onset in OABD. PRS-SCZ, PRS-BD, and PRS-MDD among early vs late onset were calculated. PRS was used to infer posterior SNP effect sizes using a fully Bayesian approach. Demographic, clinical, and cognitive variables were also analyzed. Logistic regression analysis was used to estimate the amount of variation of each group explained by standardized PRS-SCZ, PRS-MDD, and PRS-BD. A total of 207 OABD subjects were included (144 EOBD; 63 LOBD). EOBD showed higher PRS-BD compared to LOBD (p = 0.005), while no association was found between age of onset and PRS-SCZ or PRS-MDD. Compared to LOBD, EOBD individuals also showed a higher likelihood for suicide attempts (p = 0.01), higher presence of psychotic symptoms (p = 0.003), higher prevalence of BD-I (p = 0.002), higher rates of familiarity for any psychiatric disorder (p = 0.004), and lower processing speed measured with Trail-Making Test part A (p = 0.03). OABD subjects with an early onset showed a greater genetic burden for BD compared to subjects with a late onset. These findings contribute to the notion that EOBD and LOBD may represent different forms of OABD, particularly regarding the genetic predisposition to BD.
老年双相情感障碍患者（OABD）是一个异质性群体，包括疾病早发和晚发的患者。最近的证据表明，这两组患者具有不同的临床、认知和医学特征，与不同的神经生物学特征相关。本研究探讨了双相情感障碍（PRS-BD）、精神分裂症（PRS-SCZ）和重度抑郁症（PRS-MDD）的多基因风险评分与OABD发病年龄之间的联系。计算早发和晚发患者的PRS-SCZ、PRS-BD和PRS-MDD。使用全贝叶斯方法，通过PRS推断后验单核苷酸多态性效应大小。还分析了人口统计学、临床和认知变量。采用逻辑回归分析估计标准化PRS-SCZ、PRS-MDD和PRS-BD对每组变异的解释量。共纳入207例OABD患者（144例早发双相情感障碍患者；63例晚发双相情感障碍患者）。与晚发双相情感障碍患者相比，早发双相情感障碍患者的PRS-BD更高（p = 0.005），而发病年龄与PRS-SCZ或PRS-MDD之间未发现关联。与晚发双相情感障碍患者相比，早发双相情感障碍患者自杀未遂的可能性也更高（p = 0.01），精神病症状的发生率更高（p = 0.003），双相I型障碍的患病率更高（p = 0.002），任何精神障碍的家族发病率更高（p = 0.004），以及在连线测验A部分测量的处理速度更低（p = 0.03）。与晚发患者相比，早发OABD患者显示出更大的双相情感障碍遗传负担。这些发现支持了早发双相情感障碍和晚发双相情感障碍可能代表OABD不同形式的观点，特别是在双相情感障碍的遗传易感性方面。
