Stoddard Joel, Tseng Wan-Ling, Kim Pilyoung, Chen Gang, Yi Jennifer, Donahue Laura, Brotman Melissa A, Towbin Kenneth E, Pine Daniel S, Leibenluft Ellen
Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Colorado, Anshutz Medical Campus, Aurora2Section on Bipolar Spectrum Disorders, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
Section on Bipolar Spectrum Disorders, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
JAMA Psychiatry. 2017 Jan 1;74(1):95-103. doi: 10.1001/jamapsychiatry.2016.3282.
Psychiatric comorbidity complicates clinical care and confounds efforts to elucidate the pathophysiology of commonly occurring symptoms in youths. To our knowledge, few studies have simultaneously assessed the effect of 2 continuously distributed traits on brain-behavior relationships in children with psychopathology.
To determine shared and unique effects of 2 major dimensions of child psychopathology, irritability and anxiety, on neural responses to facial emotions during functional magnetic resonance imaging.
DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional functional magnetic resonance imaging study in a large, well-characterized clinical sample at a research clinic at the National Institute of Mental Health. The referred sample included youths ages 8 to 17 years, 93 youths with anxiety, disruptive mood dysregulation, and/or attention-deficit/hyperactivity disorders and 22 healthy youths.
The child's irritability and anxiety were rated by both parent and child on the Affective Reactivity Index and Screen for Child Anxiety Related Disorders, respectively. Using functional magnetic resonance imaging, neural response was measured across the brain during gender labeling of varying intensities of angry, happy, or fearful face emotions. In mixed-effects analyses, the shared and unique effects of irritability and anxiety were tested on amygdala functional connectivity and activation to face emotions.
The mean (SD) age of participants was 13.2 (2.6) years; of the 115 included, 64 were male. Irritability and/or anxiety influenced amygdala connectivity to the prefrontal and temporal cortex. Specifically, irritability and anxiety jointly influenced left amygdala to left medial prefrontal cortex connectivity during face emotion viewing (F4,888 = 9.20; P < .001 for mixed model term). During viewing of intensely angry faces, decreased connectivity was associated with high levels of both anxiety and irritability, whereas increased connectivity was associated with high levels of anxiety but low levels of irritability (Wald χ21 = 21.3; P < .001 for contrast). Irritability was associated with differences in neural response to face emotions in several areas (F2, 888 ≥ 13.45; all P < .001). This primarily occurred in the ventral visual areas, with a positive association to angry and happy faces relative to fearful faces.
These data extend prior work conducted in youths with irritability or anxiety alone and suggest that research may miss important findings if the pathophysiology of irritability and anxiety are studied in isolation. Decreased amygdala-medial prefrontal cortex connectivity may mediate emotion dysregulation when very anxious and irritable youth process threat-related faces. Activation in the ventral visual circuitry suggests a mechanism through which signals of social approach (ie, happy and angry expressions) may capture attention in irritable youth.
精神疾病共病使临床护理变得复杂，并干扰了阐明青少年常见症状病理生理学的努力。据我们所知，很少有研究同时评估两种连续分布的特质对患有精神病理学儿童脑-行为关系的影响。
确定儿童精神病理学的两个主要维度——易怒和焦虑，对功能磁共振成像期间对面部情绪的神经反应的共同和独特影响。
设计、背景和参与者：在国立精神卫生研究所的一个研究诊所，对一个大型、特征明确的临床样本进行横断面功能磁共振成像研究。转诊样本包括8至17岁的青少年，93名患有焦虑、情绪失调和/或注意力缺陷多动障碍的青少年以及22名健康青少年。
分别由父母和孩子根据情感反应指数和儿童焦虑相关障碍筛查量表对儿童的易怒和焦虑进行评分。使用功能磁共振成像，在对不同强度的愤怒、快乐或恐惧面部情绪进行性别标记时，测量全脑的神经反应。在混合效应分析中，测试易怒和焦虑对杏仁核功能连接以及对面部情绪激活的共同和独特影响。
参与者的平均（标准差）年龄为13.2（2.6）岁；在纳入的115名参与者中，64名是男性。易怒和/或焦虑影响杏仁核与前额叶和颞叶皮质的连接。具体而言，在观看面部情绪时，易怒和焦虑共同影响左侧杏仁核与左侧内侧前额叶皮质的连接（F4,888 = 9.20；混合模型项的P <.001）。在观看强烈愤怒的面孔时，连接性降低与高水平的焦虑和易怒相关，而连接性增加与高水平的焦虑但低水平的易怒相关（Wald χ21 = 21.3；对比的P <.001）。易怒与几个区域对面部情绪的神经反应差异相关（F2, 888≥13.45；所有P <.001）。这主要发生在腹侧视觉区域，相对于恐惧面孔，与愤怒和快乐面孔呈正相关。
这些数据扩展了之前仅对易怒或焦虑青少年进行的研究，并表明如果单独研究易怒和焦虑的病理生理学，研究可能会错过重要发现。当非常焦虑和易怒的青少年处理与威胁相关的面孔时，杏仁核-内侧前额叶皮质连接性降低可能介导情绪失调。腹侧视觉回路的激活表明一种机制，通过该机制社交接近信号（即快乐和愤怒表情）可能会吸引易怒青少年的注意力。
