Comparing clinical responses and the biomarkers of BDNF and cytokines between subthreshold bipolar disorder and bipolar II disorder.
Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naïve patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacological treatment (valproic acid, fluoxetine, risperidone, lorazepam). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical responses at baseline and at weeks 0, 1, 2, 4, 8, and 12. Inflammatory cytokines (tumour necrosis factor [TNF]-α, transforming growth factor [TGF]-β1, interleukin [IL]-6, IL-8 and IL-1β) and BDNF levels were also measured. Mixed models repeated measurement was used to examine the therapeutic effect and changes in BDNF and cytokine levels between the groups. HDRS and YMRS scores significantly (P < 0.001) declined in both groups, the SBP group had significantly lower levels of BDNF (P = 0.005) and TGF-β1 (P = 0.02). Patients with SBP and BP-II respond similarly to treatment, but SBP patients may have different neuroinflammation marker expression.
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Tzu-Yun
TY
Wang
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Sheng-Yu
SY
Lee
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University (KMU), Lipid Science and Aging Research Center, KMU, Kaohsiung, Taiwan.
Shiou-Lan
SL
Chen
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Deprtment of Psychology, Asia University, Taichung, Taiwan.
Yun-Hsuan
YH
Chang
Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Liang-Jen
LJ
Wang
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.
Po See
PS
Chen
Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC, USA.
Shih-Heng
SH
Chen
Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chun-Hsien
CH
Chu
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
San-Yuan
SY
Huang
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.|Student Counseling Center, National Defense Medical Center, Taipei, Taiwan.
Nian-Sheng
NS
Tzeng
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chia-Ling
CL
Li
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
Yi-Lun
YL
Chung
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Tsai-Hsin
TH
Hsieh
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.
I Hui
IH
Lee
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.
Kao Chin
KC
Chen
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.|Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan.
Yen Kuang
YK
Yang
Neurobiology Laboratory, NIH/NIEHS, Research Triangle Park, NC, USA.
Jau-Shyong
JS
Hong
Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.|Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
Ru-Band
RB
Lu
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000627:therapeutic use; D010919:Placebos; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D010919:Placebos; D014635:Valproic Acid; D003915:Dextromethorphan; D008559:Memantine