Impact of COMT, DIRAS2, and LPHN3 on emotional processing in ADHD

COMT、DIRAS2 和 LPHN3 对 ADHD 情绪处理的影响

• 批准号: 258696339
• 负责人: Professor Dr. Thomas Ethofer
• 金额: --
• 依托单位: Universitätsklinik für Psychiatrie und Psychotherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/258696339?language=en
• 关键词: Impact; COMT; DIRAS2; LPHN3; emotional

Attention deficit hyperactivity disorder (ADHD) is highly heritable and its core symptoms including inattention, hyperactivity, and impulsivity can also be present in adulthood severly compromising the quality of life of affected individuals. For ADHD patients, processing of emotional signals is particularly challenging: On the one hand, impaired judgments of non-verbal emotional signals in voices and faces have been shown in both children and adults with ADHD. On the other hand, such socially relevant signals have the potential to act as distractors that can interfere with cognitive tasks. Recent results using functional magnetic resonance imaging (fMRI) demonstrated increased responses in the amygdala of children with ADHD during judgment of emotional faces. The neural correlates of the disturbed perception of emotional signals in adult ADHD as well as their genetic origins, however, are unknown so far. Genetic imaging studies in healthy participants could demonstrate a crucial role for the val158met genotype of the catecholamin-O-methyl transferase (COMT) during processing of emotional stimuli. Furthermore, it has been shown that the high-activity COMT genotype leading to decreased dopaminergic activity in the prefrontal cortex is associated with impaired social cognition and antisocial behavior. At behavioral level, a significant genetic impact on social behavior has been recently described in ADHD for the ADHD-associated genes GTP-binding RAS-like 2 gene (DIRAS2) and latrophilin 3 (LPHN3). It is the aim of this project to identify endophenotypes in ADHD which are associated with impaired social cognition. To this end, we plan to combine structural and functional MRI with molecular genetics (imaging genetics). Successful prediction of impaired social cognition based on genetic and neuroimaging risk factors might open a window for an early and individualized therapy in this patient group.

注意力缺陷多动障碍 (ADHD) 具有高度遗传性，其核心症状包括注意力不集中、多动和冲动，也可能在成年后出现，严重影响患者的生活质量。对于多动症患者来说，处理情绪信号尤其具有挑战性：一方面，患有多动症的儿童和成人都表现出对声音和面部非语言情绪信号的判断受损。另一方面，此类与社会相关的信号有可能成为干扰认知任务的干扰因素。最近使用功能磁共振成像（fMRI）的结果表明，多动症儿童在判断情绪面孔时杏仁核的反应增强。然而，成人多动症患者情绪信号感知紊乱的神经相关性及其遗传起源目前尚不清楚。对健康参与者的基因成像研究可以证明儿茶酚胺-O-甲基转移酶 (COMT) 的 val158met 基因型在情绪刺激的处理过程中发挥着至关重要的作用。此外，研究表明，导致前额皮质多巴胺能活性降低的高活性 COMT 基因型与社会认知受损和反社会行为有关。在行为水平上，最近描述了 ADHD 相关基因 GTP 结合 RAS 样 2 基因 (DIRAS2) 和 latrophilin 3 (LPHN3) 对 ADHD 社会行为的显着遗传影响。该项目的目的是确定 ADHD 中与社会认知受损相关的内表型。为此，我们计划将结构和功能 MRI 与分子遗传学（影像遗传学）相结合。基于遗传和神经影像学危险因素成功预测社会认知受损可能为该患者群体的早期个体化治疗打开一扇窗。

项目成果

CACNA1C risk variant affects microstructural connectivity of the amygdala

• DOI: 10.1016/j.nicl.2019.101774
• 发表时间: 2019-03
• 期刊: NeuroImage : Clinical
• 作者: K. Koch;Sophia Stegmaier;Lena Schwarz;M. Erb;Mara Thomas;K. Scheffler;D. Wildgruber;V. Nieratschker;T. Ethofer

Properties of face localizer activations and their application in functional magnetic resonance imaging (fMRI) fingerprinting

• DOI: 10.1371/journal.pone.0214997
• 发表时间: 2019-04
• 期刊: PLoS ONE
• 影响因子: 3.7
• 作者: Lena Schwarz;B. Kreifelts;D. Wildgruber;M. Erb;K. Scheffler;T. Ethofer

Neurobiology of knowledge and misperception of lyrics

知识的神经生物学和歌词的误解

• DOI: 10.1016/j.neuroimage.2016.03.080
• 发表时间: 2016
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Beck Lidén;Krüger O;Schwarz L;Kardatzki B;Scheffler K;Ethofer T
• 通讯作者: Ethofer T

Neural correlates of processing emotional prosody in unipolar depression

• DOI: 10.1002/hbm.24185
• 发表时间: 2018-08
• 期刊: Human Brain Mapping
• 影响因子: 4.8
• 作者: K. Koch;Sophia Stegmaier;Lena Schwarz;M. Erb;M. Reinl;K. Scheffler;D. Wildgruber;T. Ethofer

Are you laughing at me? Neural correlates of social intent attribution to auditory and visual laughter

• DOI: 10.1002/hbm.24806
• 发表时间: 2019-10-22
• 期刊: HUMAN BRAIN MAPPING
• 影响因子: 4.8
• 作者: Ethofer, Thomas;Stegmaier, Sophia;Wildgruber, Dirk
• 通讯作者: Wildgruber, Dirk