cinanserin and Bipolar-Disorder

Reduced brain serotonin transporter (SERT) has been demonstrated in bipolar disorder (BD). The aim of this study was to explore the potential role of cytokines on reduced SERT in BD.. Twenty-eight BD type I patients and 28 age- and gender-matched healthy controls (HCs) were recruited. Single photon emission computed tomography with the radiotracer 123I ADAM was used for SERT imaging. Regions of interest included the midbrain, thalamus, putamen and caudate. Seven cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1α (IL-1α), IL-1β, IL-4, IL-6 and IL-10, were measured using an enzyme linked immune-sorbent assay.. SERT availability in the midbrain and caudate was significantly lower in BD compared to HCs. IL-1β was significantly lower, whereas IL-10 was significantly higher in BD compared to HCs. Multiple linear regression analyses revealed that there were associations between cytokines, IL-1α, IL-1β, IL-6 and SERT availability in the midbrain but not in the thalamus, putamen and caudate. Furthermore, linear mixed effect analyses demonstrated that these associations were not different between HCs and BD.. While many cytokines have been proposed to be important in the pathophysiology of BD, our results demonstrated that significant associations between cytokines and SERT availability may explain the role of cytokines in mood regulation. However, these associations were not different between HCs and BD, which imply the role of these cytokines is not specific for BD.

Topics: Adult; Bipolar Disorder; Brain; Cinanserin; Cytokines; Female; Functional Neuroimaging; Humans; Male; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon; Young Adult

Converging evidence indicates the hypothalamus-pituitary-adrenal axis and serotonergic neurons exert reciprocal modulatory actions. Likewise, brain-derived neurotrophic factor (BDNF) has been implicated as a growth and differentiation factor in the development of serotonergic neurons. The aim of this study was to examine the interaction of cortisol and BDNF on serotonin transporter (SERT) in bipolar disorder (BD). Twenty-eight BD and 28 age- and gender-matched healthy controls (HCs) were recruited. (123)I-ADAM with single-photon emission computed tomography (SPECT) was applied for measurement of SERT availability in the brain, which included the midbrain, thalamus, putamen and caudate. Ten milliliters of venous blood was withdrawn, when the subject underwent SPECT, for the measurement of the plasma concentration of cortisol and BDNF. SERT availability was significantly decreased in the midbrain and caudate of BD compared with HCs, whereas plasma concentration of cortisol and BDNF did not show a significant difference. The linear mixed-effect model revealed that there was a significant interaction of group and cortisol on SERT availability of the midbrain, but not BDNF. Linear regression analyses by groups revealed that cortisol was associated with SERT availability in the midbrain in the HCs, but not in BD. Considering previous studies, which showed a significant association of cortisol with SERT availability in the HCs and major depressive disorder (MDD), our result replicated a similar finding in HCs. However, the negative finding of the association of cortisol and SERT availability in BD, which was different from MDD, suggests a different role for cortisol in the pathophysiology of mood disorder.

Topics: Adult; Bipolar Disorder; Brain; Brain-Derived Neurotrophic Factor; Case-Control Studies; Cinanserin; Female; Humans; Hydrocortisone; Linear Models; Magnetic Resonance Imaging; Male; Protein Binding; Radiochemistry; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon

Previous positron emission tomography studies have demonstrated that serotonin transporter (SERT) binding in the midbrain is decreased in the depressive state of bipolar disorder (BD). The aim of this study was to assess SERT binding in the midbrain of patients in a euthymic state of BD.. Twenty-eight healthy controls and 24 patients in a euthymic state of medicated BD were recruited. Euthymic state was defined as Montgomery-Asberg Depression Rating Scale scores < 10 and Young Mania Rating Scale scores < 7 within a consecutive eight-week period. Single photon emission computed tomography with the radiotracer (123)I-ADAM was used to measure SERT binding in the midbrain. An equilibrium ratio model was used for data analysis. Specific uptake ratio (SUR), which represents availability of SERT binding in the midbrain, was the primary measurement outcome.. The averaged SURs were not different between healthy controls and BD patients in euthymic state (p = 0.27). However, a three-way ANCOVA analysis comparing SURs in healthy controls, bipolar I disorder (BD I) patients, and bipolar II disorder (BD II) patients, covarying education duration and sex, showed that the averaged SURs were significantly lower in BD I than BD II patients and healthy controls (p = 0.042). The decreased SURs in BD I patients were well correlated with duration of illness (R = -0.742, p = 0.014) only.. Our findings demonstrate that there is differential biological regulation in BD I and BD II patients after stable treatment, which may support the existence of a dichotomy in BD.

Topics: Analysis of Variance; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Brain; Cinanserin; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Protein Binding; Psychiatric Status Rating Scales; Serotonin Antagonists; Serotonin Plasma Membrane Transport Proteins; Tomography, Emission-Computed, Single-Photon