Conduct Disorder

在研究的最后，贾天野团队基于多个大规模影像队列数据和病例数据，证实青少年队列中确定的NP因子在多个发育时期都对精神症状有重要影响，包括前青春期（ABCD，9-10岁）、青少年期（IMAGEN，14岁） 世界卫生组织2022年发布的一份报告显示：2019年，全球有近10亿人患有精神疾病，青少年的患病率更是高达14%[1]。精神疾病的诊疗，迫切需要一场大转变。 然而，与其他疾病相比，精神疾病很复杂，而且还存在多种精神疾病并发的现象。例如，有研究发现，在14-17岁的青少年患者群体中，有27.9%达到了多种精神疾病的诊断标准[2]。 剑桥大学神经学家Barbara Sahakian教授认为，不同的精神疾病背后可能存在着一个共有的神经机制[3]。 近日，由复旦大学类脑智能科学与技术研究院贾天野领衔的研究团队，在著名期刊《自然·医学》发表的研究论文[4]表明，他们可能找到了这个共有机制。 他们基于几个大型临床神经影像队列的数据，确定并验证了一个多种神经疾病共有的神经基础——神经精神病理学（NP）因子。这个NP因子是神经影像定义的一种神经特征，而且这个受遗传影响的神经病理因子可能代表了前额叶大脑神经回路的延迟发育，导致执行控制功能不佳。 这一研究成果或能解释为什么有些人会遭受多种精神疾病的影响，并可能在将来帮助识别高风险人群。 论文首页截图 接下来咱们就一起来看看这个研究是如何展开的。 在正式介绍研究过程之前，有必要先了解一下著名的欧洲青少年影像遗传学纵向队列——IMAGEN队列，NP因子就是基于这个队列找到的。 IMAGEN队列于2007年2月启动，是全球第一个多中心遗传神经影像学研究队列。队列在欧洲8个中心招募2000名14岁的青少年随访至22岁，并对他们进行全面的行为和神经心理学特征、功能和结构神经影像学以及全基因组关联分析[5]。IMAGEN队列的发起人是计算神经科学家Gunter Schumann，他在2021年底全职加盟复旦大学类脑智能科学与技术研究院，也是本研究的参与者之一。 基于IMAGEN队列（N=1750，其中882人是女孩），贾天野团队构建了多认知维度的任务态功能连接组，并进一步利用连接组预测模型得到了四种内化精神症状（抑郁、焦虑、特定恐惧症和进食障碍）和四种外化精神症状（孤独症、注意力缺陷多动障碍、对立违抗性障碍和品行障碍）的大脑特征。 紧接着，他们将跨疾病的稳定假说、纵向随访数据与纵向稳定的跨内化精神症状和外化精神症状的大脑特征相整合，成功构建了由大脑功能连接定义的NP因子。他们证实，NP因子能够用于预测外化精神症状和内化精神症状，并能够在多个发育时间点稳定一致地预测跨疾病精神症状。 NP因子发现过程 为了进一步解析NP因子的生物学功能，贾天野团队分析了NP因子在脑区水平和网络水平的神经解剖学分布。他们发现，NP因子主要位于前额叶环路，包括上内侧额叶网络、凸显网络和额顶网络。 他们还分析了NP因子与多种行为表型之间的关系，发现NP因子主要与执行控制功能相关的行为表型有关，包括智力、风险调整和工作记忆表现等。 NP因子的神经生物学特征 贾天野团队还分析了NP因子与神经疾病之间的关系，他们发现，NP因子所在的前额叶环路在青少年大脑发育过程表现出连接强度减弱的趋势，但是精神疾病共病症状严重的个体中，却表现出更少的连接强度减弱。 实际上，之前的研究已经发现，在青春期，随着年龄的增长大脑会经历突触修剪和突触稳定的成熟过程，这会导致前额叶功能连接减弱，目的是为了提高大脑信息传递的效率[6]。 贾天野团队注意到，这种连接减弱（从14岁到19岁）在NP因子得分较高的个体中被明显抑制，这表明NP因子得分高的个体的神经回路成熟的轨迹不典型。他们认为，前额叶环路NP因子的过度连接可能是大脑发育延迟的结果。 值得注意的是，贾天野团队发现，NP因子与IGSF11基因（有助于突触维持）上一个跨疾病的单核苷酸多态性位点（rs6780942）有关系，并且该基因的表达水平从青少年期至成年期逐渐减少。 以上研究数据表明， NP因子代表了一种前额叶发育延迟的神经内表型，它能够广泛影响外化和内化精神症状。 NP因子的遗传分析 在研究的最后，贾天野团队基于多个大规模影像队列数据和病例数据，证实青少年队列中确定的NP因子在多个发育时期都对精神症状有重要影响，包括前青春期（ABCD，9-10岁）、青少年期（IMAGEN，14岁）、青年期（IMAGEN，19岁）和成年期（HCP，33岁）。 总的来说，研究人员认为，NP因子是前额叶发育紊乱的神经内表型，其能够帮更深入地解析跨精神症状的神经精神病理机制，有助于提高我们对个体化精神医学的认识。此外，这一研究成果对于精神疾病共病的早期诊断和治疗具有重要意义，为精神疾病的精准治疗提供了新的思路和方向。 据了解，贾天野团队将依托复旦张江国际脑库和国内大型青少年心理健康合作队列，开展NP因子在精神健康干预和治疗方面的临床应用研究，为精神健康领域的分层诊疗提供更多的有效工具和方法。 复旦大学类脑智能科学与技术研究院博士后谢超为论文第一作者，通讯作者为复旦大学贾天野青年研究员。剑桥大学、复旦大学特聘教授Trevor Robbins，复旦大学Gunter Schumann教授、贾天野青年研究员、冯建峰教授为本文做出同等贡献。 参考文献： [1].https://www.who.int/news/item/17-06-2022-who-highlights-urgent-need-to-transform-mental-health-and-mental-health-care [2].Kessler RC, Avenevoli S, McLaughlin KA, et al. Lifetime co-morbidity of DSM-IV disorders in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A). Psychol Med. 2012;42(9):1997-2010. doi:10.1017/S0033291712000025 [3].https://www.cam.ac.uk/research/news/problems-with-pruning-brain-connections-linked-to-adolescent-mental-health-disorders [4].Xie C, Xiang S, Shen C, et al. A shared neural basis underlying psychiatric comorbidity. Nat Med. 2023. doi:10.1038/s41591-023-02317-4 [5].Schumann G, Loth E, Banaschewski T, et al. The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology. Mol Psychiatry. 2010;15(12):1128-1139. doi:10.1038/mp.2010.4 [6].Lee FS, Heimer H, Giedd JN, et al. Mental health. Adolescent mental health--opportunity and obligation. Science. 2014;346(6209):547-549. doi:10.1126/science.1260497

MONDAY, May 1, 2023 -- Growing numbers of American kids and teens are cutting or burning themselves, banging their heads against walls, pulling out their hair and even trying to die by suicide. But figuring out who is at highest risk for harming themselves has been a daunting challenge. Until now. Researchers report they have developed risk profiles that can help doctors pinpoint which kids or teens are in the most danger. "The U.S. is in the midst of a mental health crisis, with mental health diagnoses and hospitalizations surging over the past few years, and many of these hospitalizations are for self-harm events or concern for future self-harm," said study author Dr. James Antoon , an assistant professor of pediatrics and hospital medicine at Monroe Carell Jr. Children's Hospital at Vanderbilt University in Nashville, Tenn. “Self-harm is a big bucket of events from mild things like cutting on the arms or thighs to taking so much Tylenol that you die on purpose or jumping out of a window, and we wanted to find out which kids require hospitalization and more intensive treatment and monitoring," he said. There’s a pronounced shortage of in-patient hospital beds for kids with mental health issue in the United States, which makes the situation even more dire. Knowing which kids are at the highest risk can help make better use of these limited resources, Antoon noted. So, his team developed four risk profiles for serious self-harm based on age, gender and psychiatric and medical conditions. Of nearly 1,100 children hospitalized for psychiatric reasons at two children’s hospitals from April 2016 to March 2020, 37% were there for self-harm. The researchers found that boys aged 10 to 13 with ADHD, bipolar disorder, autism spectrum disorder or another developmental disorder were 80% more likely to engage in serious self-harm behavior that requires hospitalization. Meanwhile, teen girls aged 14 to 17 with depression and anxiety, substance- and trauma-related disorders, and personality and eating disorders were also at high risk for serious self-harm, the study showed. Suicide attempts comprised the majority of serious self-harm behaviors in the study. In a counterintuitive finding, kids who were at moderate risk for serious self-harm didn’t necessarily have depression, Antoon said. “It is assumed that if you are suicidal, you must be depressed, but there are other things that can drive self-harm and suicide, including anxiety disorders,” he noted. The study was published online May 1 in the journal Pediatrics . There are many reasons kids and teens will try to harm themselves, said Elizabeth Bailey , director of clinical services at the 3East Boys Intensive Program at McLean Hospital in Boston. “It can serve to help individuals self-regulate or control overwhelming emotions, escape from feelings of being numb or empty or punish themselves, and [it] also serves as a form of unspoken communication to others about one’s suffering," said Bailey, who was not involved with the study. But it's not always easy to spot the signs of self-harm in kids, as they hide evidence by wearing long sleeves to cover scars on their arms or other methods, she said. Still, there are some things to look out for. "A typically outgoing and social child who suddenly withdraws, or an academically driven and achieving child who stops completing assignments for a sustained period of time may be cause for concern,” Bailey said. Self-harming behaviors are often portrayed as problems for girls and women in the media, added Anna Precht , program director at 3East Boys Intensive Program. “The finding that the highest risk profile is characterized by boys aged 10-13 with anxiety and depression, as well as other psychiatric disorders including externalizing behaviors like ADHD and conduct disorder, highlights the importance of assessing for self-harm behaviors across diagnostic and gender presentations," said Precht, who was not part of the new research. If you are concerned that your child is engaging in self-harm, contact a psychologist, social worker or pediatrician, she advised. Help is available. “Dialectical Behavior Therapy [a type of talk therapy based on cognitive behavioral therapy] helps people to understand what factors contribute to self-injurious behaviors [as well as other problematic behaviors] and teaches skills for managing emotions more effectively,” Precht said. “This a treatment that has been shown to be effective in treating these behaviors and has been adapted for teens and their families.” Sources James Antoon, MD, PhD, MPH, assistant professor, pediatrics, hospital medicine, Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tenn. Elizabeth Bailey, PsyD, director, clinical services, 3East Boys Intensive Program, McLean Hospital, Boston Anna Precht, PsyD, program director, 3East Boys Intensive Program, McLean Hospital Pediatrics , May 1, 2023 Posted May 2023

该研究利用从青春期到成年早期2000人的大型纵向随访队列（IMAGEN），并结合任务态功能连接组学和大脑-行为预测模型，确定了一个可表征长期跨精神健康风险（即跨外化和内化症状）的神经精神病理学NP因子 据世界卫生组织（WHO）统计，全球10-19岁的青少年人群中，有七分之一患有精神健康障碍；中国2021年的一项调查结果显示，6-16岁的在校学生中，抑郁、焦虑等精神障碍总患病率为17.5%。大量的临床研究发现，随着青春期的发育，满足多个精神障碍诊断标准的共病患者越来越普遍。如何确定多种精神障碍之间共有的神经病理学起源，并深入解析其神经生物学机制，将为精神健康领域的跨疾病精准诊疗提供重要的临床指导。 复旦大学类脑智能科学与技术研究院贾天野领衔的国际研究团队在国际顶尖医学期刊 Nature Medicine 上发表了题为：A Shared Neural Basis Underlying Psychiatric Comorbidity 的研究论文。 该研究不仅揭示了广泛存在的精神障碍共病现象的神经病理学基础，同时为跨疾病诊断及分层治疗提供了重要的理论基础。 该研究利用从青春期到成年早期2000人的大型纵向随访队列（IMAGEN），并结合任务态功能连接组学和大脑-行为预测模型，确定了一个可表征长期跨精神健康风险（即跨外化和内化症状）的神经精神病理学NP因子（Neuropsychopathological Factor）。 该因子在多个独立大型群体队列数据中（ABCD和HCP）都获得了验证，并能够泛化到静息状态连接组和临床样本上（ADHD-200和STRATIFY/ESTRA）。研究团队进一步整合行为、影像和基因等多维度生物数据，发现NP因子与突触维持相关基因的突变有关，其可能导致了前额叶环路的发育紊乱，并进而引起了执行功能受损。 这一重大发现将有助于开发全新的针对精神障碍共病的干预措施，特别是为从青少年时期开始的早期心理预防提供更多的科学依据。