MAY PPAR GAMMA BE SIGNIFICANT IN BIPOLAR DISORDER ONLY IN THE PRESENCE OF METABOLIC SYNDROME?

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) has a key role in regulating both neurogenesis and various metabolic processes, including adipogenesis and glucose homeostasis. In this study, it was aimed to compare the serum PPARγ levels and metabolic syndrome (MetS) parametres of patients with Bipolar Disorder (BD) diagnosed manic-depressive-euthymic episodes with those of healthy subjects. SUBJECTS AND METHODS: We included 121 male patients with BD type I, 44 in mania, 35 in depression and 42 in euthymic state, and 41 healthy controls. Serum PPARγ levels, inflammation indicators (CRP, neutrophil, leukocyte, and albumin) and Mets parametres were measured. RESULTS: There were no statistically significant differences between the groups in terms of PPARγ values. PPARγ serum level is highest in the control group and then euthymic, manic and depressive episodes continue to decrease, respectively. However, there was a significant difference between the depressive group with MetS and without MetS in terms of serum PPARγ levels. A statistically significant correlation was found between PPARγ and the other serum markers such as low-density lipoprotein (p=0.022), HbA1c (p=0.002), neutrophils levels (0.001), white blood cell (p=0.025), and clinical features such as age at first treatment (p=0.024), age at first episode (p=0.039), and smoking (0.013). CONCLUSIONS: We suggest that PPARγ may be a key factor in the BD depressive group with MetS. Not finding any relationship between the PPARγ levels and the episode of BD may be related with the absence of MetS in the individuals. MetS parametres must also be considered if PPARγ is to be evaluated in the future investigations.

Resolvin D1 as a novel anti-inflammatory marker in manic, depressive and euthymic states of bipolar disorder.

Background: Resolvin D1 (RvD1) is a soluble mediator, which is the metabolite of docosahexaenoic acid (DHA), an omega-3 fatty acid. It is thought that RvD1 may contribute to the etiology of bipolar disorder (BD) because of its anti-inflammatory and antidepressant effect. In this study, it was aimed to compare the serum RvD1 levels of patients with BD diagnosed manic-depressive-euthymic episodes with those of healthy subjects. The secondary objective of this study is to investigate the relationship between RvD1 measures and inflammatory markers.Methods: We included 121 male patients with BD type I, 44 in a mania, 35 in depression and 42 in euthymic state, and 41 healthy controls. Serum RvD1 levels and inflammation indicators (CRP, neutrophil, leukocyte, and albumin) were measured.Results: When the RvD1 values of patients were compared, the median (interquartile range) RvD1 value was 11.2 (5.2) for manic patients, 11.2 (6.6) for depressive patients, 9.6 (5.6) for euthymic patients and 8.4 (7.7) for the control group. There were statistically significant differences between the groups in terms of RvD1 values (p < .001). After adjustment for age and current state with ANCOVA, there were statistically significant differences between manic vs. control groups and depression vs. control groups (p < .001, p=.047). Also mean CRP measures (p=.029) and neutrophil counts (p=.009) were significantly correlated with log transformed RvD1 levels.Conclusions: Our results of increased anti-inflammatory RvD1 during manic and depressive states suggest RvD1 may serve as a delayed resolvent possibly improving inflammatory imbalance. Further research is needed to confirm our findings.

Does Blood Flow Change according to Mood? Blood Rheology in Bipolar Disorder.

OBJECTIVE: Bipolar disorder (BD) is associated with increased rates of cardiovascular diseases. There is growing evidence that blood viscosity may have a common role, correlated with well-known major risk factors that promote cardiovascular disease. In this study we aimed to investigate the whole blood viscosity (WBV) in different stages of BD. METHODS: A total of 121 bipolar patients and 41 age-gender matched healthy controls were included. Forty-four of bipolar patients were in manic, 35 were depressed and 42 were in euthymic state. WBV was calculated from hematocrit and total plasma protein according to Simone's formula at low and high shear rates (LSR and HSR). RESULTS: WBV at HSR of manic group was 16.91±1.01, depressive group was 17.23±0.80, euthymic group was 17.63±0.95, and control group was 17.52±0.71 (p =0.001). WBV at LSR of manic depressive, euthymic and control group were 53.10±20.58, 60.30±17.02, 8.91±20.33, and 62.01±19.28, respectively (p =0.001). Both WBV at HSR and LSR of manic group was significantly lower than that of the euthymic and control groups (p =0.001 and 0.010 respectively for HSR, p =0.001 and 0.011 respectively for LSR). WBV was significantly positively correlated with lipid profile except high density lipoprotein (HDL). CONCLUSION: Our results demonstrate a decrement in blood viscosity in manic episode compared with euthymics and controls. Positive correlation of blood viscosity with lipid parameters (except HDL), and negative correlation with number of previous manic episodes suggest that manic episode has favorable effect on cardiovascular risk regarding to blood viscosity.

Decreased circulating urokinase plasminogen activator receptor (uPAR) concentration in acute episodes of bipolar disorder; could it be a reflection of axonal injury?

INTRODUCTION: In recent years, the role of inflammation in the pathogenesis of Bipolar Disorder (BD) has been studied thoroughly. Urokinase-type plasminogen activator receptor (uPAR) is one of the molecules, whose concentration is of predictive value with regards to an ongoing inflammation and tissue regeneration, and it is hypothesized that it may also be altered in Bipolar Disorder. In this study, it is aimed to compare the levels of serum soluble uPAR during the manic, depressive and euthymic states of cases diagnosed with bipolar disorder, with healthy individuals. MATERIALS AND METHODS: Forty-four BD patients at manic state (BD-m), 35 BD patients at depressive state (BD-d), 42 euthymic patients (BD-e) and 41 healthy controls (HC) who were similar with the diseased subjects regarding age and smoking status included in the study. Serum soluble uPAR levels of patients and healthy controls were measured. RESULTS: The main finding of our study is that serum soluble uPAR levels are lower in patients diagnosed with BD either in depressive (BD-d) or in manic state (BD-m) than in BD patients in euthymic state (BD-e) or in healthy controls (HC). There was no significant difference in serum soluble uPAR concentrations between BD-m and BD-d s or between BD-e and HC with regards to serum soluble uPAR concentrations. CONCLUSIONS: Urokinase-type plasminogen (uPA) is a molecule which is an element of uPAR system and the molecules collectively take role in inflammation, tissue regeneration and axonal regeneration within the Central Nervous System (CNS). It has previously suggested in some studies that there may be a decrease in axonal density or axonal dysfunction in CNS in bipolar individuals. Accordingly, one may say that the low concentrations of soluble uPAR measured in our bipolar patients either at depressive or at manic state is due to the diminished regulatory role of soluble uPAR on axonal regeneration in CNS of BD cases.

Atherogenic index of plasma as a cardiovascular risk marker in manic, depressive, and euthymic stages of bipolar disorder.

OBJECTIVE: Individuals with bipolar disorder (BD) frequently suffer from cardiovascular disease (CVD), and it is a leading cause of mortality. Clinicians use routine laboratory tests, including a lipid profile, to predict cardiovascular risk. In addition, a particular lipid ratio, the atherogenic index of plasma (AIP), is a sensitive, new parameter that can be used to assess highrisk groups. To our knowledge, this is the first study evaluating cardiovascular risk via AIP in different stages of BD. METHODS: The study group consisted of male patients with BD who were in a manic, depressive, or euthymic state, and age- and gender-matched healthy controls. Lipid profiles were analyzed and the AIP parameter of logarithm of triglyceride (TG) / high-density lipoprotein cholesterol (HDLc) was calculated for all of the participants. The significance level was set at p<0.05. RESULTS: A total of 44 BD patients experiencing a manic episode, 35 depressive BD patients, 42 euthymic patients, and 41 healthy controls matched for age, gender, and smoking status were enrolled in the study. The AIP level was significantly different between groups (p=0.009). Pairwise comparisons of the groups revealed that the AIP level of depressive patients was significantly higher than that of the manic, euthymic, and control groups (p=0.013, p=0.048, and p=0.021, respectively). The AIP level was positively correlated with body mass index, waist circumference, metabolic syndrome, total cholesterol, low-density lipoprotein, and triglyceride level, and was negatively correlated with the HDLc level. CONCLUSION: In this study, male BD patients in a depressive episode demonstrated an increase in cardiovascular risk. The significant correlations between AIP and other conventional cardiovascular risk factors indicate that AIP may be more useful to identify individuals with BD at high risk for CVD than absolute lipid parameters.