MICA:Translational validation of 5HT7 antagonists for the treatment of cognitive impairment in bipolar disorder: a proof of concept neuroimaging study

双相情感障碍是一种严重的心理健康问题，其中人们反复经历抑郁和兴高采烈的情绪。双相情感障碍影响了英国约120万人，每年花费约52亿英镑。大约60%的双相情感障碍患者的注意力和记忆力出现问题，称为认知障碍，这极大地影响了工作和保持关系的能力。目前还没有有效的药物治疗双相情感障碍患者所经历的认知障碍。然而，阻断一种称为5 HT 7受体的大脑化学受体的药物可能是一种有希望的新治疗方法。本研究的主要目的是了解一种名为JNJ-18038683的药物对大脑活动和认知能力的影响，该药物可特异性阻断5 HT 7受体。我们将检查JNJ-18038683在有认知障碍证据的双相情感障碍患者和健康人群中的作用。我们计划这样做，以确定JNJ-18038683是否影响在执行注意力和记忆任务时发生的大脑活动，以及JNJ-18038683是否纠正大脑活动和认知能力的损伤。我们计划招募34名双相情感障碍患者和34名健康人参加这项研究。每个参与研究的人都将被仔细筛选是否适合，然后将完成测量认知表现的注意力和记忆功能测试。然后，他们将服用10 mg JNJ-18038683一周，并在两周停药期后转换为安慰剂一周，反之亦然。一些受试者将首先服用JNJ-18038683，一些受试者将首先服用安慰剂，受试者和研究工作人员都不知道服用了哪种药物。我们将研究JNJ-18038683和安慰剂对每个治疗阶段第7天脑活动和认知能力的影响。大脑活动将使用一种称为磁共振成像（MRI）的大脑扫描来测量，这种扫描可以产生非常详细的大脑结构和功能图像。我们将通过要求受试者在扫描仪中完成思维和情绪任务，然后分析由此产生的大脑活动水平，研究JNJ-18038683和安慰剂如何影响MRI扫描期间的大脑活动水平。我们计划通过比较JNJ-18038683和安慰剂治疗第7天的脑活动水平，评估JNJ-18038683是否改变这些任务期间产生的脑活动，以及JNJ-18038683是否使双相情感障碍患者的脑活动正常化。我们还将通过比较JNJ-18038683和安慰剂治疗第7天的记忆和注意力测试结果，评估JNJ-18038683是否改善认知能力。我们希望这些结果将支持进一步的大型临床治疗研究的发展。当研究完成后，我们将在科学期刊上发表其结果，并通过新闻发布会和社交媒体将其传达给双相情感障碍患者，心理健康专业人员和公众。总体而言，我们预计本研究将使我们更好地了解5 HT 7阻滞剂（如JNJ-18038683）治疗双相情感障碍患者认知障碍的潜力，我们希望这将导致新治疗方法的开发。

Bipolar disorder is a serious mental health problem in which people experience repeated episodes of depression and elated mood. Bipolar disorder affects around 1.2 million people in the UK and costs around £5.2 billion per year. Around 60% of people with bipolar disorder experience problems with their attention and memory, known as cognitive impairment, which greatly affects the ability to work and hold relationships. Currently there are no effective drug treatments for cognitive impairment experienced by people with bipolar disorder. However, drugs which block a type of brain chemical receptor, called the 5HT7 receptor, may be a promising new treatment. The main aim of this study is to understand the effect of a medication called JNJ-18038683, which specifically blocks the 5HT7 receptor, on brain activity and cognitive performance. We will examine the effect of JNJ-18038683 in people with bipolar disorder who show evidence of cognitive impairment and also in healthy people. We plan to do this to determine whether JNJ-18038683 affects brain activity which occurs whilst performing attention and memory tasks, and whether JNJ-18038683 corrects impairments in brain activity and cognitive performance. We plan to recruit 34 people with bipolar disorder and 34 healthy people to take part in the study. Each person taking part in the study will be carefully screened for suitability and will then complete tests of attention and memory function which measures cognitive performance. They will then take 10mg JNJ-18038683 for one week and will be switched to placebo for one week, or vice versa, after a two-week drug free period. Some participants will take JNJ-18038683 first and some will take placebo first, and neither participants nor the staff running the study will know which medication has been taken. We will study the effects of JNJ-18038683 and placebo on brain activity and cognitive performance on day 7 of each treatment period. Brain activity will be measured using a brain scan called magnetic resonance imaging (MRI) which produces very detailed images of the structure and function of the brain. We will examine how JNJ-18038683 and placebo affects the levels of brain activity during the MRI scan by asking participants to complete thinking and mood tasks in the scanner and then analysing the level of brain activity this produces. We plan to assess whether JNJ-18038683 changes brain activity produced during these tasks, and in people with bipolar disorder whether JNJ-18038683 normalises brain activity, by comparing brain activity levels on day 7 of JNJ-18038683 and placebo treatments. We will also assess whether JNJ-18038683 improves cognitive performance by comparing memory and attention test results on day 7 of JNJ-18038683 and placebo treatments. We hope that these results will support the development of further large clinical treatment studies. When the study is complete we will publish its results in scientific journals and communicate this to people with bipolar disorder, mental health professionals and to the general public through press briefings and social media. Overall, we anticipate that this study will allow us to better understand the potential of 5HT7 blockers such as JNJ-18038683 for the treatment of cognitive impairment in people with bipolar disorder which we hope will lead to the development of new treatments.