Spechler Philip A, Chaarani Bader, Orr Catherine, Mackey Scott, Higgins Stephen T, Banaschewski Tobias, Bokde Arun L W, Bromberg Uli, Büchel Christian, Quinlan Erin Burke, Conrod Patricia J, Desrivières Sylvane, Flor Herta, Frouin Vincent, Gowland Penny, Heinz Andreas, Ittermann Bernd, Martinot Jean-Luc, Nees Frauke, Orfanos Dimitri Papadopoulos, Poustka Luise, Fröhner Juliane H, Smolka Michael N, Walter Henrik, Whelan Robert, Schumann Gunter, Garavan Hugh, Althoff Robert R
University of Vermont, Burlington; Vermont Center on Behavior and Health, University of Vermont, Burlington.
University of Vermont, Burlington; Vermont Center on Behavior and Health, University of Vermont, Burlington.
J Am Acad Child Adolesc Psychiatry. 2019 Nov;58(11):1092-1103. doi: 10.1016/j.jaac.2019.01.021. Epub 2019 Apr 17.
To characterize the structural and functional neurobiology of a large group of adolescents exhibiting a behaviorally and emotionally dysregulated phenotype.
Adolescents aged 14 years from the IMAGEN study were investigated. Latent class analysis (LCA) on the Strengths and Difficulties Questionnaire (SDQ) was used to identify a class of individuals with elevated behavioral and emotional difficulties ("dysregulated"; n = 233) who were compared to a matched sample from a low symptom class (controls, n = 233). Whole-brain gray matter volume (GMV) images were compared using a general linear model with 10,000 random label permutations. Regional GMV findings were then probed for functional differences from three functional magnetic resonance imaging (fMRI) tasks. Significant brain features then informed mediation path models linking the likelihood of psychiatric disorders (DSM-IV) with dysregulation.
Whole-brain differences were found in the right orbitofrontal cortex (R.OFC; p < .05; k = 48), with dysregulated individuals exhibiting lower GMV. The dysregulated group also exhibited higher activity in this region during successful inhibitory control (F = 7.53, p < .05). Path analyses indicated significant direct effects between the likelihood of psychopathologies and dysregulation. Modeling the R.OFC as a mediator returned modest partial effects, suggesting that the path linking the likelihood of an anxiety or conduct disorder diagnoses to dysregulation is partially explained by this anatomical feature.
A large sample of dysregulated adolescents exhibited lower GMV in the R.OFC relative to controls. Dysregulated individuals also exhibited higher regional activations when exercising inhibitory control at performance levels comparable to those of controls. These findings suggest a neurobiological marker of dysregulation and highlight the role of the R.OFC in impaired emotional and behavioral control.
描述表现出行为和情绪失调表型的一大群青少年的结构和功能神经生物学特征。
对来自IMAGEN研究的14岁青少年进行调查。使用长处与困难问卷(SDQ)的潜在类别分析(LCA)来识别一类行为和情绪困难程度较高的个体(“失调组”;n = 233),并将其与低症状组的匹配样本(对照组,n = 233)进行比较。使用具有10,000次随机标签置换的一般线性模型比较全脑灰质体积(GMV)图像。然后从三个功能磁共振成像(fMRI)任务中探究区域GMV结果的功能差异。显著的脑特征随后为将精神疾病(DSM-IV)的可能性与失调联系起来的中介路径模型提供信息。
在右侧眶额皮质(R.OFC;p <.05;k = 48)发现全脑差异,失调个体的GMV较低。在成功的抑制控制过程中,失调组在该区域也表现出更高的活动(F = 7.53,p <.05)。路径分析表明精神病理学可能性与失调之间存在显著的直接影响。将R.OFC建模为中介产生了适度的部分影响,表明将焦虑或品行障碍诊断的可能性与失调联系起来的路径部分地由这一解剖特征所解释。
与对照组相比,一大样本的失调青少年在R.OFC中的GMV较低。在与对照组相当的表现水平上进行抑制控制时,失调个体在该区域也表现出更高的激活。这些发现提示了失调的一种神经生物学标志物,并突出了R.OFC在情绪和行为控制受损中的作用。