Department of Psychiatry and Behavioral Sciences, Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, CA.
Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA.
J Dev Behav Pediatr. 2024;45(4):e365-e371. doi: 10.1097/DBP.0000000000001279. Epub 2024 Jul 10.
Klinefelter syndrome (KS) is the most common sex-chromosome aneuploidy (47,XXY), affecting 1 in 500 male participants. The phenotype of male participants with KS includes both physical features, such as tall stature and testicular insufficiency, and behavioral alterations, including difficulties in social functioning, anxiety, and depression. Studies examining underlying neural alterations associated with the behavioral phenotype, however, are sparse. We aimed to address this gap in knowledge using functional magnetic resonance imaging in conjunction with an emotion processing paradigm.
Functional magnetic resonance imaging was conducted on 38 children and adolescents with KS ( Mage = 12.85, SD = 2.45) and 47 typical developing (control) boys ( Mage = 12.04, SD = 1.82) as they completed a facial emotion processing task. Group differences in activation occurring during the processing of angry versus neutral faces were examined while controlling for age.
The results indicated that relative to typically developing boys, boys with KS exhibited anomalous increases in activation of frontal, temporal, and occipital cortices. Within the KS group, secondary analyses indicated that greater activation in these regions was associated with more internalizing symptoms (e.g., anxiety, depression, withdrawn behaviors) and greater social impairments (e.g., social cognition, social communication, social motivation, social communication and interaction, functional communication).
The findings from this study indicate a possible neural correlation for difficulties in social and emotional function in KS and add to a growing body of research aimed at increasing our understanding of neural biomarkers in this condition. Future studies that examine the influence of testosterone-replacement therapy on these differences are warranted.
克氏综合征（KS）是最常见的性染色体非整倍体（47，XXY），影响每 500 名男性参与者中的 1 名。KS 男性参与者的表型包括身体特征，如身材高大和睾丸功能不全，以及行为改变，包括社交功能障碍、焦虑和抑郁。然而，研究检查与行为表型相关的潜在神经改变的研究很少。我们旨在使用功能磁共振成像结合情绪处理范式来解决这一知识空白。
对 38 名 KS 儿童和青少年（Mage = 12.85，SD = 2.45）和 47 名典型发育（对照组）男孩（Mage = 12.04，SD = 1.82）进行功能磁共振成像，当他们完成面部情绪处理任务时。在控制年龄的情况下，检查处理愤怒与中性面孔时发生的激活的组间差异。
结果表明，与典型发育男孩相比，KS 男孩的额、颞和枕叶皮层的激活异常增加。在 KS 组中，二次分析表明，这些区域的更大激活与更多的内化症状（例如，焦虑、抑郁、退缩行为）和更大的社交障碍（例如，社会认知、社会沟通、社会动机、社会沟通和互动、功能性沟通）相关。
本研究的结果表明，KS 中社交和情绪功能困难可能存在神经相关性，并为旨在增加我们对该病症神经生物标志物理解的越来越多的研究做出了贡献。未来研究应检查睾酮替代疗法对这些差异的影响。
