Hsu Tien-Wei, Chu Che-Sheng, Tsai Shih-Jen, Bai Ya-Mei, Su Tung-Ping, Chen Tzeng-Ji, Chen Mu-Hong, Liang Chih-Sung
Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Neuropsychobiology. 2022;81(6):539-549. doi: 10.1159/000526984. Epub 2022 Nov 18.
Evidence has suggested an association between bacterial infection and increased risk of subsequent major mental disorders (MMDs). Whether such association varies with different pathogens remains unclear. We aimed to investigate the risk of subsequent MMDs after exposure to bacterial pathogens in children and adolescents.
Between 1997 and 2012, we enrolled a nationwide cohort of 14,024 children and adolescents with hospitalized bacterial infection, and noninfected controls were 1:4 matched for demographics. There were 11 investigated pathogens, namely, Streptococcus, Staphylococcus, Pseudomonas, Klebsiella, Hemophilus, Mycoplasma, Tuberculosis, Meningococcus, Escherichia, Chlamydia, and Scrub typhus. The primary outcomes were the subsequent risk of seven MMDs, namely, autism spectrum disorder (ASD), attention-deficiency hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), tic disorder, schizophrenia, bipolar disorder, and depressive disorder. The secondary outcomes were the subsequent risk of exposure to psychotropic medications.
Pooled bacterial infection was associated with increased risk of the six MMDs - ASD (reported as hazard ratios with 95% confidence intervals: 13.80; 7.40-25.75), ADHD (6.93; 5.98-8.03), OCD (3.93; 1.76-8.76), tic disorder (6.19; 4.44-8.64), bipolar disorder (2.50; 1.28-4.86), and depressive disorder (1.93; 1.48-2.51) - and exposure to four psychotropic medications, including ADHD drugs (11.81; 9.72-14.35), antidepressants (2.96; 2.45-3.57), mood stabilizers (4.51; 2.83-7.19), and atypical antipsychotics (4.23; 3.00-5.96) compared to controls. The associations among MMDs and specific pathogens varied. Importantly, Streptococcus was associated with the most MMDs (six MMDs), and ADHD was associated with eight bacterial pathogen infections.
After bacterial infection, the risk of MMDs increased in children and adolescents compared to controls, and such associations varied with different pathogens. Future studies are warranted to validate our study findings and investigate the potential mechanisms.
有证据表明细菌感染与后续发生重大精神障碍（MMD）的风险增加之间存在关联。这种关联是否因不同病原体而异仍不清楚。我们旨在调查儿童和青少年接触细菌病原体后发生后续MMD的风险。
在1997年至2012年期间，我们纳入了一个全国性队列，其中有14024名因细菌感染住院的儿童和青少年，并按照1:4的比例为其匹配了未感染的对照人群，匹配因素为人口统计学特征。共调查了11种病原体，分别为链球菌、葡萄球菌、假单胞菌、克雷伯菌、嗜血杆菌、支原体、结核杆菌、脑膜炎球菌、大肠杆菌、衣原体和恙虫病立克次体。主要结局是七种MMD的后续发病风险，即自闭症谱系障碍（ASD）、注意力缺陷多动障碍（ADHD）、强迫症（OCD）、抽动障碍、精神分裂症、双相情感障碍和抑郁症。次要结局是接触精神药物的后续风险。
与对照组相比，合并细菌感染与六种MMD的发病风险增加相关，这六种MMD分别为ASD（报告的风险比及95%置信区间为：13.80；7.40 - 25.75）、ADHD（6.93；5.98 - 8.03）、OCD（3.93；1.76 - 8.76）、抽动障碍（6.19；4.44 - 8.64）、双相情感障碍（2.50；1.28 - 4.86）和抑郁症（1.93；1.48 - 2.51），以及与四种精神药物的接触相关，这四种精神药物包括ADHD药物（11.81；9.72 - 14.35）、抗抑郁药（2.96；2.45 - 3.57）、心境稳定剂（4.51；2.83 - 7.19）和非典型抗精神病药物（4.23；3.00 - 5.96）。MMD与特定病原体之间的关联各不相同。重要的是，链球菌与最多的MMD（六种MMD）相关，而ADHD与八种细菌病原体感染相关。
与对照组相比，儿童和青少年在细菌感染后发生MMD的风险增加，且这种关联因不同病原体而异。未来有必要开展研究以验证我们的研究结果并探究潜在机制。
