. 2016 Aug 12;19(8):pyw012.

doi: 10.1093/ijnp/pyw012. Print 2016 Aug.

The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders

Tzu-Yun Wang¹, Sheng-Yu Lee¹, Shiou-Lan Chen¹, Yi-Lun Chung¹, Chia-Ling Li¹, Yun-Hsuan Chang¹, Liang-Jen Wang¹, Po See Chen¹, Shih-Heng Chen¹, Chun-Hsien Chu¹, San-Yuan Huang¹, Nian-Sheng Tzeng¹, Tsai-Hsin Hsieh¹, Yen-Chu Chiu¹, I Hui Lee¹, Kao-Chin Chen¹, Yen Kuang Yang¹, Jau-Shyong Hong¹, Ru-Band Lu²

Affiliations

¹ Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Drs T.-Y.W., S.-Y.L., S.-L.C., Ms Y.-L.C. Drs C.-L.L.,Y.-H.C., and P.S.C. , Ms T.-H.H., Drs I.H.L., K.-C.C., Y.K.Y., and R.-B.L.); Institute of Behavioral Medicine (Drs Y.K.Y. and R.-B.L.), and Institute of Allied Health Sciences (Dr Y.-H.C. and R.-B.L.), College of Medicine, and Addiction Research Center (Drs P.S.C., I.H.L, K.C.C., Y.K.Y., and R.-B.L.), National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (Dr S.-Y.L.); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University(KMU), Lipid Science and Aging Research Center, KMU, Kaohsiung, Taiwan (Dr S.-L.C.); Department of Psychiatry, Tri-Service General Hospital, School of Medicine, and Student Counseling Center (Dr N.-S.T.), National Defense Medical Center, Taipei, Taiwan (Dr S.-Y.H.); Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan (Dr L.-J.W.); Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan (Dr Y.K.Y.); Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan (Dr R.-B.L.); Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC (Drs S.-H.C. and J.-S.H.); Deprtment of Psychology, Asia University, Taichung, Taiwan (Dr Y.-H.C.); Institute of Molecular Medicine (Dr C.-H.C.) , and Institute of Basic Medical Sciences (Ms Y.-L.C.), College of Medicine, National Cheng Kung University, Tainan, Taiwan ; Department of Biomedical Science and Environmental Biology, School of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan (Ms Y.-C.C.).
² Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Drs T.-Y.W., S.-Y.L., S.-L.C., Ms Y.-L.C. Drs C.-L.L.,Y.-H.C., and P.S.C. , Ms T.-H.H., Drs I.H.L., K.-C.C., Y.K.Y., and R.-B.L.); Institute of Behavioral Medicine (Drs Y.K.Y. and R.-B.L.), and Institute of Allied Health Sciences (Dr Y.-H.C. and R.-B.L.), College of Medicine, and Addiction Research Center (Drs P.S.C., I.H.L, K.C.C., Y.K.Y., and R.-B.L.), National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (Dr S.-Y.L.); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University(KMU), Lipid Science and Aging Research Center, KMU, Kaohsiung, Taiwan (Dr S.-L.C.); Department of Psychiatry, Tri-Service General Hospital, School of Medicine, and Student Counseling Center (Dr N.-S.T.), National Defense Medical Center, Taipei, Taiwan (Dr S.-Y.H.); Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan (Dr L.-J.W.); Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan (Dr Y.K.Y.); Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan (Dr R.-B.L.); Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC (Drs S.-H.C. and J.-S.H.); Deprtment of Psychology, Asia University, Taichung, Taiwan (Dr Y.-H.C.); Institute of Molecular Medicine (Dr C.-H.C.) , and Institute of Basic Medical Sciences (Ms Y.-L.C.), College of Medicine, National Cheng Kung University, Tainan, Taiwan ; Department of Biomedical Science and Environmental Biology, School of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan (Ms Y.-C.C.). rblu@mail.ncku.edu.tw.

PMID: 26865313
PMCID: PMC5006191
DOI: 10.1093/ijnp/pyw012

The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders

Tzu-Yun Wang et al. Int J Neuropsychopharmacol. 2016.

. 2016 Aug 12;19(8):pyw012.

doi: 10.1093/ijnp/pyw012. Print 2016 Aug.

Authors

Affiliations

¹ Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Drs T.-Y.W., S.-Y.L., S.-L.C., Ms Y.-L.C. Drs C.-L.L.,Y.-H.C., and P.S.C. , Ms T.-H.H., Drs I.H.L., K.-C.C., Y.K.Y., and R.-B.L.); Institute of Behavioral Medicine (Drs Y.K.Y. and R.-B.L.), and Institute of Allied Health Sciences (Dr Y.-H.C. and R.-B.L.), College of Medicine, and Addiction Research Center (Drs P.S.C., I.H.L, K.C.C., Y.K.Y., and R.-B.L.), National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (Dr S.-Y.L.); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University(KMU), Lipid Science and Aging Research Center, KMU, Kaohsiung, Taiwan (Dr S.-L.C.); Department of Psychiatry, Tri-Service General Hospital, School of Medicine, and Student Counseling Center (Dr N.-S.T.), National Defense Medical Center, Taipei, Taiwan (Dr S.-Y.H.); Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan (Dr L.-J.W.); Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan (Dr Y.K.Y.); Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan (Dr R.-B.L.); Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC (Drs S.-H.C. and J.-S.H.); Deprtment of Psychology, Asia University, Taichung, Taiwan (Dr Y.-H.C.); Institute of Molecular Medicine (Dr C.-H.C.) , and Institute of Basic Medical Sciences (Ms Y.-L.C.), College of Medicine, National Cheng Kung University, Tainan, Taiwan ; Department of Biomedical Science and Environmental Biology, School of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan (Ms Y.-C.C.).
² Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Drs T.-Y.W., S.-Y.L., S.-L.C., Ms Y.-L.C. Drs C.-L.L.,Y.-H.C., and P.S.C. , Ms T.-H.H., Drs I.H.L., K.-C.C., Y.K.Y., and R.-B.L.); Institute of Behavioral Medicine (Drs Y.K.Y. and R.-B.L.), and Institute of Allied Health Sciences (Dr Y.-H.C. and R.-B.L.), College of Medicine, and Addiction Research Center (Drs P.S.C., I.H.L, K.C.C., Y.K.Y., and R.-B.L.), National Cheng Kung University, Tainan, Taiwan; Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (Dr S.-Y.L.); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University(KMU), Lipid Science and Aging Research Center, KMU, Kaohsiung, Taiwan (Dr S.-L.C.); Department of Psychiatry, Tri-Service General Hospital, School of Medicine, and Student Counseling Center (Dr N.-S.T.), National Defense Medical Center, Taipei, Taiwan (Dr S.-Y.H.); Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan (Dr L.-J.W.); Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan (Dr Y.K.Y.); Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan (Dr R.-B.L.); Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC (Drs S.-H.C. and J.-S.H.); Deprtment of Psychology, Asia University, Taichung, Taiwan (Dr Y.-H.C.); Institute of Molecular Medicine (Dr C.-H.C.) , and Institute of Basic Medical Sciences (Ms Y.-L.C.), College of Medicine, National Cheng Kung University, Tainan, Taiwan ; Department of Biomedical Science and Environmental Biology, School of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan (Ms Y.-C.C.). rblu@mail.ncku.edu.tw.

PMID: 26865313
PMCID: PMC5006191
DOI: 10.1093/ijnp/pyw012

Abstract

Objective: Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder. To investigate biological markers of cytokines and brain-derived neurotrophic factor between bipolar I, bipolar II, and other specified bipolar disorder with short duration hypomania may support the association with inflammatory dysregulation and bipolar disorder and, more specifically, provide evidence for other specified bipolar disorder with short duration hypomania patients were similar to bipolar II disorder patients from a biological marker perspective.

Methods: We enrolled patients with bipolar I disorder (n=234), bipolar II disorder (n=260), other specified bipolar disorder with short duration hypomania (n=243), and healthy controls (n=140). Their clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokine (tumor necrosis factor-α, C-reactive protein, transforming growth factor-β1, and interleukin-8) and brain-derived neurotrophic factor levels were measured in each group. Multivariate analysis of covariance and linear regression controlled for possible confounders were used to compare cytokine and brain-derived neurotrophic factor levels among the groups.

Results: Multivariate analysis of covariance adjusted for age and sex and a main effect of diagnosis was significant (P<.001). Three of the 5 measured biomarkers (tumor necrosis factor-α, transforming growth factor-β1, and interleukin-8) were significantly (P=.006, .01, and <.001) higher in all bipolar disorder patients than in controls. Moreover, covarying for multiple associated confounders showed that bipolar I disorder patients had significantly higher IL-8 levels than did bipolar II disorder and other specified bipolar disorder with short duration hypomania patients in multivariate analysis of covariance (P=.03) and linear regression (P=.02) analyses. Biomarkers differences between bipolar II disorder and other specified bipolar disorder with short duration hypomania patients were nonsignificant.

Conclusion: The immunological disturbance along the bipolar spectrum was most severe in bipolar I disorder patients. Other specified bipolar disorder with short duration hypomania patients and bipolar II disorder patients did not differ in these biological markers.

Keywords: BDNF; bipolar I disorder; bipolar II disorder; bipolar spectrum disorder; cytokines; subthreshold bipolarity.

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Figures

**Figure 1.**
Scatter plot of plasma interleukin-8 (IL-8) levels with representative linear regression of plasma IL-8 levels in the bipolar spectrum disorders (covarying for age, sex, disease duration, comorbidity, Hamilton Depression Rating Scale [HDRS], and Young Mania Rating Scale [YMRS] scores).

See this image and copyright information in PMC

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The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders

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The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders

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