Giagulli Vito Angelo, Campone Beatrice, Castellana Marco, Salzano Ciro, Fisher Alessandra Daphne, de Angelis Cristina, Pivonello Rosario, Colao Annamaria, Pasquali Daniela, Maggi Mario, Triggiani Vincenzo
Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, Interdisciplinary Department of Medicine, University of Bari, School of Medicine, Policlinico, Bari, Italy.
Psychiatric Unit Department of Health Science, University of Florence, Italy.
Endocr Metab Immune Disord Drug Targets. 2019;19(2):109-115. doi: 10.2174/1871530318666180703160250.
Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy (47, XXY) and cause of male hypergonadotropic hypogonadism. It is characterized by an extreme clinical heterogeneity in presentation, including infertility, hypogonadism, language delay, metabolic comorbidities, and neurocognitive and psychiatric disorders. Since testosterone is known to have organizational, neurotrophic and neuroprotective effects on brain, the condition of primary hypogonadism could play a role. Moreover, given that KS subjects have an additional X, genes on the extra-chromosome could also exert a significant impact. The aim of this narrative review is to analyze the available literature on the relationship between KS and neuropsychiatric disorders.
To extend to the best of published literature on the topic, appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined.
Both morphological and functional studies focusing on the brain showed that there were important differences in brain structure of KS subjects. Different psychiatric disorders such as Schizophrenia, autism, attention deficit hyperactivity disorder, depression and anxiety were frequently reported in KS patients according to a broad spectrum of phenotypes. T supplementation (TRT) was not able to improve the psychotic disorders in KS men with or without overt hypogonadism.
Although the risk of psychosis, depression and autism is increased in subjects with KS, no definitive evidence has been found in studies aiming at identifying the relationship between aneuploidy, T deficit and the risk of psychiatric and cognitive disorders in subjects affected by KS.
克兰费尔特综合征（KS）是最常见的性染色体非整倍体疾病（47, XXY），也是男性高促性腺激素性性腺功能减退的病因。其临床表现具有高度的临床异质性，包括不育、性腺功能减退、语言发育迟缓、代谢合并症以及神经认知和精神障碍。由于已知睾酮对大脑具有组织、神经营养和神经保护作用，原发性性腺功能减退的状况可能起了一定作用。此外，鉴于KS患者有一条额外的X染色体，该额外染色体上的基因也可能产生重大影响。本叙述性综述的目的是分析关于KS与神经精神障碍之间关系的现有文献。
为了全面涵盖关于该主题的已发表文献，在PubMed中确定并搜索了适当的关键词和医学主题词（MeSH）。最后，查阅了原始文章和综述的参考文献。
针对大脑的形态学和功能研究均表明，KS患者的大脑结构存在重要差异。根据广泛的表型，KS患者经常出现不同的精神障碍，如精神分裂症、自闭症、注意力缺陷多动障碍、抑郁症和焦虑症。睾酮补充治疗（TRT）无法改善有或无明显性腺功能减退的KS男性的精神障碍。
尽管KS患者患精神病、抑郁症和自闭症的风险增加，但在旨在确定非整倍体、睾酮缺乏与受KS影响患者的精神和认知障碍风险之间关系的研究中，尚未找到确凿证据。
