Reward and stress: Developing neuroimaging biomarkers for bipolar depression

双相情感障碍（BD）是英国发病率和死亡率的重要原因，对个人和社会都是昂贵的。双相情感障碍与预期寿命减少约10年，自杀死亡风险增加15倍有关。尽管双相抑郁症（包括双相I型或II型患者）很重要，但介导抑郁症的大脑机制尚不清楚，也没有可靠的生物标志物来支持疾病分层或预测治疗反应。以前双相抑郁的神经影像学研究通常集中在双相II型障碍上。双相情感障碍的研究已经检查了相对于健康对照、单极抑郁症和BD-I的BP-II障碍的结构和功能改变。虽然早期的研究表明结构改变，但ENIGMA联盟对1700多名双相情感障碍患者的分析并未支持BD-II在皮质下体积或皮质指标上的任何差异。对于功能性神经影像学研究，一个相对清晰的画面出现了功能失调的情绪和奖励回路以及双相情感障碍的额顶叶异常，包括BD-II。双相情感障碍患者所经历的抑郁症状令人痛苦，并增加了自我伤害的风险。双相抑郁症患者通常不能享受他们的生活，在奖励和动机方面经历困难，并且通过地塞米松-促肾上腺皮质激素释放激素挑战（DEX-CRH）测试显示出异常的应激激素反应。DEX-CRH是HPA轴功能的综合测试。在所有可用的神经内分泌功能测试中，DEX/CRH测试已被证明是检测抑郁症患者HPA轴异常最敏感的工具。目前，对于异常的大脑信号是如何引起症状的，以及这些症状是如何与应激激素反应联系在一起的，人们知之甚少。应激恢复能力受损和下丘脑-垂体-肾上腺皮质（HPA）轴功能紊乱被认为在重度抑郁症（MDD）和BD中起关键作用。神经影像学方法提供了无创检查中枢神经系统对急性心理应激源反应的变化的机会。在这种情况下，基于任务的功能磁共振成像（fMRI）是有用的，因为它允许探索在健康和精神疾病人群中涉及压力反应和下丘脑轴调节的网络。一些研究要么利用应激诱导来引发神经和神经内分泌反应，要么调查了外源性皮质醇对脑功能和静息状态测量的影响。然而，据我们所知，还没有研究将DEX/CRH和fMRI联合应用于双相或重度抑郁症患者。通过检测双相抑郁症患者与重度抑郁症患者和健康对照者在亚一般扣带-边缘-杏仁核通路中情绪、努力和奖励处理脑活动的差异，识别双相抑郁症的功能MRI （fMRI）神经成像生物标志物。此外，为了检查在情绪障碍参与者组（BD或MDD）中检测到的fMRI信号损伤程度是否与Dex/CRH测试测量的HPA轴异常相关。

Bipolar disorder (BD) is an important cause of morbidity and mortality in the UK, and is costly to both the individual and society. Bipolar disorder is associated with around a ten-year reduction in life expectancy and a fifteen-fold increased risk of death by suicide. Despite the importance of bipolar depression (which includes people with both bipolar I or II disorder), the brain mechanisms which mediate depression are very poorly understood and no reliable biomarkers exist to support disease stratification or predict treatment response. Previous neuroimaging studies on bipolar depression have typically focused on bipolar II disorder. Studies in bipolar disorder have examined both structural and functional alterations in BP-II disorder relative to healthy controls, unipolar depression, and BD-I. While earlier studies suggested structural changes, the ENIGMA consortium analysis of over 1700 individuals with bipolar disorder did not support any differences in either subcortical volumes or cortical metrics for BD-II. For functional neuroimaging studies, a relatively clear picture emerges of dysfunctional emotion and reward circuitry as well as fronto-parietal abnormalities in bipolar disorder, including BD-II. Depressive symptoms experienced by people with bipolar disorder are distressing and increase self-harm risks. People with bipolar depression often don't enjoy their lives, experience difficulties with reward and motivation, and show abnormal stress hormone responses measured by the dexamethasone - corticotropin releasing hormone challenge (DEX-CRH) test. The DEX-CRH is an integrated test of HPA axis function. Of all the available neuroendocrine function tests, the DEX/CRH test has proven to be the most sensitive tool for detecting an HPA axis abnormality in depressed individuals. For now, little is known about how abnormal brain signalling causes symptoms and how these are linked to stress hormone responses. Impaired stress resilience and disturbances in hypothalamic-pituitary-adrenocortical (HPA) axis function have been suggested to play key roles in major depressive disorder (MDD) and BD. Neuroimaging methods offer the opportunity to non-invasively examine the changes that take place in the central nervous system in response to an acute psychological stressor. Task-based fMRI can be useful in this context, as it allows the exploration of the networks involved in the stress response and in the regulation of the HPA axis, both in healthy and in psychiatric populations. Some studies have either employed stress induction to elicit neural and neuroendocrine responses or have investigated the effect of externally administered cortisol on brain function and resting state measures. However, to the best of our knowledge, no studies have combined administration of the DEX/CRH and fMRI in depressed individuals with BD or MDD. To identify functional MRI (fMRI) neuroimaging biomarkers of bipolar depression by examining differences in emotional, effort and reward processing brain activity in the subgenual cingulate-limbic-amygdala pathway in people with bipolar depression compared to people with MDD and healthy controls. Additionally, to examine whether the extent of impairments in fMRI signals detected in the mood disorder participant groups (BD or MDD) correlates with abnormalities in the HPA axis as measured by the Dex/CRH test.