1. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2. Department of Medical Research, Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan
3. Department of Genomic Medicine, Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan
4. Department of Psychiatry, Chimei Medical Center, Tainan, Taiwan
5. Department of Health, Jianan Mental Hospital, Tainan, Taiwan
6. Department of Applied Life Science and Health, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
7. Department of Psychiatry, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan
8. Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
9. Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
10. Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
* Equal contributors.
Several studies have been suggested that immunity plays a part in neurodevelopment and schizophrenia pathogenesis. Early age of onset in schizophrenia is associated with genetic factors which affect neurodevelopment. This study aims to identify immune abnormalities associated with neurodevelopmental impairments in early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) patients. We determined the plasma levels of six cytokines (IL-1β, IL-4, IL-6, IL-10, IL-12 and TNF-α) in schizophrenia patients and healthy controls. Measurements included neurological soft signs (NSS) to distinguish and subgroup those with neurodevelopmental impairments. The study included 210 schizophrenia patients, which were divided into 84 EOS and 126 AOS patients, as well as 122 healthy controls. We observed significant differences in levels of IL-4, IL-6 and IL-10 between EOS and AOS patients. The results demonstrated the area under ROC curve (AUC) of the IL-4 in EOS and healthy controls was 0.81. Moreover, these results indicated that AUC of the IL-4 and the combination of IL-4, IL-6 and IL-12 in EOS with NSS and healthy controls were 0.91 and 0.95. These cytokines are altered in EOS and schizophrenia patients with neurodevelopmental impairments and demonstrated good classification abilities. These findings manifested that both pro- and anti-inflammatory cytokines are contributed to the clinical and pathophysiological features of schizophrenia. Future works are expected to explore potential genetic effectors and predictors as well as therapeutic directions in personalized medicine for early-onset schizophrenia.
Keywords: schizophrenia, early-onset, immune dysregulation, neurodevelopment, discriminant analysis.