Conduct Disorder

FRIDAY, July 26, 2024 -- There are widespread brain structural alterations apparent in conduct disorders, mostly in surface area, according to a study published in the August issue of The Lancet Psychiatry . Yidian Gao, Ph.D., from the University of Birmingham in the United Kingdom, and colleagues examined brain structural correlates of conduct disorders among those aged 18 years or younger. Individual participant data were collected from 1,185 young people with conduct disorder and 1,253 typically developing young people (mean age, 13.5 years). The researchers found that the conduct disorder group had lower surface area in 26 cortical regions and lower total surface area relative to typically developing young people. Differences were seen in cortical thickness in the caudal anterior cingulate cortex and the banks of the superior temporal sulcus. Smaller amygdala, nucleus accumbens, thalamus, and hippocampus volumes were also seen in the conduct disorder group. After adjustment for attention-deficit/hyperactivity disorder comorbidity or intelligence quotient, most differences remained significant. There were no group-by-sex or group-by-age interactions seen. Between Diagnostic and Statistical Manual of Mental Disorders -defined conduct disorder subtypes, few differences were found. However, more widespread differences were seen for individuals with high callous-unemotional traits versus controls than for those with low callous-unemotional traits. "These findings provide further evidence that brain alterations could contribute to conduct disorder," the authors write. "This underrecognized disorder warrants greater consideration in research, including longitudinal studies exploring neurodevelopmental trajectories and additional subtyping approaches." Several authors disclosed ties to the biopharmaceutical industry. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

WEDNESDAY, July 17, 2024 -- Defiance, tantrums, aggression: All signs of a condition called conduct disorder, which Mental Health America says affects up to 16% of boys and 9% of girls. Now, research is revealing real differences in the brain structure of children and youths with conduct disorder, compared to those without the condition. Specifically, the study of the brains of people ages 7 through 21 found that the brain's outer layer, the cerebral cortex, was smaller than is typical for people with conduct disorder. “Conduct disorder has among the highest burden of any mental disorder in youth," noted study co-author Dr. Daniel Pine . "However, it remains understudied and under-treated." "Understanding brain differences associated with the disorder takes us one step closer to developing more effective approaches to diagnosis and treatment, with the ultimate aim of improving long-term outcomes for children and their families," said Pine. He's chief of the Section on Development and Affective Neuroscience at the National Institute of Mental Health (NIMH). The new study was published July 16 in the journal Lancet Psychiatry . In their research, Pine and his colleagues used MRI scans to examine the brains of about 2,400 children and youth who'd enrolled in 15 different studies from around the world. About half of the participants had been diagnosed with conduct disorder while the other half had not. The scans looked specifically at the thickness of each person's cerebral cortex, as well as the volume of deeper "subcortical" brain regions. Compared to kids and young adults unaffected by conduct disorder, those with the condition differed in terms of the thickness of their cerebral cortices. They also "had lower volume in several subcortical brain regions, including the amygdala, hippocampus and thalamus," according to a news release from the NIMH. These regions are known to be key to behavioral regulation. In prior studies, the prefrontal cortex and amygdala had already been implicated as playing possible roles in conduct disorder, but the new study has pinpointed other brain regions. No differences in terms of brain changes were noted between girls and boys with conduct disorder. However, young people with more severe forms of conduct disorder -- for example, they had low levels of empathy, remorse or guilt -- tended to display the largest brain differences on MRI, the research team said. According to the authors, the new study is the largest to date and supports the notion that physical changes in the brain might drive conduct disorder. "The study also provides novel evidence that brain changes are more widespread than previously shown, spanning all four lobes and both cortical and subcortical regions," according to the NIMH news release. The good news: The findings could give researchers a new foothold in pursuing the cause and treatment of conduct disorder, the team said. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

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