Inflammation’s Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naïve Patients with Bipolar II Disorder

<div><p></p><p>Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP) and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117) diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma cytokines (TNF-α, CRP, IL-6, and TGF-β) were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (<i>P</i> = 1.7E-7) and triglyceride (<i>P</i> = 0.005) levels. Changes in plasma TGF-β1 were significantly associated with changes in BMI (<i>P</i> = 8.2E-6), cholesterol (<i>P</i> = 0.004), and triglyceride (<i>P</i> = 0.006) levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (<i>P</i> = 0.003) levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (<i>P</i> = 0.006) and TNF-α (<i>P</i> = 0.039) levels. Plasma CRP and TGF-β1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology of clinical symptoms and metabolic disturbance in BP-II.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01188148" target="_blank">NCT01188148</a>.</p></div

Correlation of changes in metabolic profiles and cytokines before and after 12 weeks of pharmacological treatment.

<p>CRP: C-reactive protein; TGF-β1: transforming growth factor β1; TNF-α: tumor necrosis factor α; IL-6: interleukin 6.</p>**<p><b><i>P</i></b><0.001.</p

Mean HDRS score, YMRS score, and cytokine and metabolic profiles before and after pharmacological treatment.

<p>VPA: valproate; HDRS: Hamilton Depression Rating Scale; YMRS: Young Mania Rating Scale; CRP: C-reactive protein; TGF-β1: transforming growth factor β1; TNF-α: tumor necrosis factor α; IL-6: interleukin 6.</p

Consort flow chart of recruitment.

<p>Consort flow chart of recruitment.</p