Development of Brain Abnormalities in Bipolar Disorder

描述(由申请人提供)：双相情感障碍(BD)存在于大约1%的人口中。对于患有BD的人、他们的家人和社区来说，痛苦是巨大的，因为发作可能会导致关系丧失、经济困难和高自杀风险。青春期的发病高峰表明，了解这一时期大脑异常的发展可能是理解BD生物学的关键；然而，对青少年BD的研究很少。此外，青少年BD的诊断和治疗是从成人推断出来的；然而，尚不清楚青少年BD和成人BD之间的脑异常是否有所不同。因此，对青少年BD患者脑发育的研究具有重要意义，因为它可以为阐明其病理生理机制，改善早期发现和治疗，从而改善预后提供关键信息。 杏仁核和眼眶额叶皮质是共同处理情绪的大脑结构，与成人BD的临床前、脑损伤、成像和尸检研究有关。我们的横断面试点工作表明，杏仁核缺陷在青春期早期就存在，并在BD患者持续到成年，但眼眶前额叶缺陷在青春期期间进展，与大脑发育的正常区域序列平行。这项拟议的研究使用结构和功能磁共振成像来测量40名BD青少年杏仁核和眶前皮质的纵向变化(超过2年)，并与40名健康对照组进行比较。我们还将扩大我们的初步研究，该研究为修改编码CATECO I-O-甲基转移酶和5-羟色胺转运体启动子蛋白的基因对BD杏仁核的影响提供了证据。据我们所知，这是此类作品中的第一部。创新包括：测试一种新的神经发育假说，该假说得到了重大横断面工作的支持，首次对青少年BD进行了前瞻性纵向研究；以及关于BD相关基因的等位基因变异对大脑异常的修正影响的综合神经成像和遗传学研究。

DESCRIPTION (provided by applicant): Bipolar disorder (BD) is present in about 1% of the population. Suffering is great for individuals with BD, their families and communities, as episodes can lead to relationship loss, economic hardship, and a high suicide risk. The peak onset in adolescence suggests that understanding the development of brain abnormalities during this period may be pivotal to understanding the biology of BD; yet, studies of BD in adolescents are rare. Furthermore, diagnosis and treatment of BD in adolescents are extrapolated from adults; yet, it is not known whether brain abnormalities differ between adolescents and adults with BD. Thus, study of brain development in adolescents with BD is important because it could provide information key to elucidating its pathophysiology, and improvements in early detection and treatment and therefore prognosis. The amygdala and orbitofrontal cortex are brain structures that work together to process emotions and that are implicated by preclinical, brain lesion, imaging and postmortem studies in adult BD. Our cross-sectional pilot work suggests that amygdala deficits are present by early adolescence and are sustained into adulthood in BD, but that orbitofrontal deficits progress over adolescence paralleling the normal regional sequence of brain development. The proposed study employs structural and functional magnetic resonance imaging to measure longitudinal changes (over 2 years) in amygdala and orbitofrontal cortex in 40 adolescents with BD, compared to 40 healthy controls. We will also extend our pilot investigation which provides evidence for modifying influences of allelic variation in the genes encoding catechoI-O-methyl transferase and a serotonin transporter promotor protein on the amygdala in BD. To the best of our knowledge this is the first work of its kind. Innovations include: testing a novel neurodevelopmental hypothesis supported by significant cross sectional work, with the first prospective longitudinal study of adolescent BD; and integrated neuroimaging and genetic study of modifying influences of allelic variation in genes implicated in BD on brain abnormalities.