Indices of insulin resistance and glucotoxicity are not associated with bipolar disorder or major depressive disorder, but are differently associated with inflammatory, oxidative and nitrosative biomarkers.

BACKGROUND: Insulin resistance (IR) is a key factor in diabetes mellitus, metabolic syndrome (MetS) and obesity and may occur in mood disorders and tobacco use disorder (TUD), where disturbances of immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways are important shared pathophysiological pathways. METHODS: This study aimed to a) examine IR and ß-cell function as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity and ß cell function (HOMA-B) and glucotoxicity (conceptualized as increased glucose levels versus lowered HOMA-B values) in 74 participants with major depressive disorder (MDD) and bipolar disorder, with and or without MetS and TUD, versus 46 healthy controls, and b) whether IR is associated with IO&NS biomarkers, including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), plasma advanced oxidation protein products (AOPP), C-reactive protein (CRP), haptoglobin (Hp) and uric acid. RESULTS: Mood disorders are not associated with changes in IR or glucotoxicity, although the number of mood episodes may increase IR. 47.8% of the variance in HOMA-IR is explained by AOPP and body mass index (BMI, both positively) and NOx, Hp and TUD (all inversely). 43.2% of the variance in HOMA-B is explained by NOx, Hp and age (all inversely associated) and higher BMI and sex. The glucotoxic index is strongly associated with NOx, Hp and BMI (positively), male gender and lower education. LIMITATIONS: This is a cross-sectional study and therefore we cannot draw firm conclusions on causal associations. CONCLUSIONS: Activated IO&NS pathways (especially increased Hp and NOx) increase glucotoxicity and exert very complex effects modulating IR. Mood disorders are not associated with increased IR.

Genetic polymorphisms in glutathione-S-transferases are associated with anxiety and mood disorders in nicotine dependence.

BACKGROUND: Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence. MATERIALS AND METHODS: Smokers were recruited at the Centre of Treatment for Smokers. The instruments were a sociodemographic questionnaire, Fagerström Test for Nicotine Dependence, diagnoses of mood disorder and nicotine dependence according to DSM-IV (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Anxiety disorder was assessed based on the treatment report. Laboratory assessment included glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), which were detected by a multiplex-PCR protocol. RESULTS: Compared with individuals who had both GSTM1 and GSTT1 genes, a higher frequency of at least one deletion of the GSTM1 and GSTT1 genes was identified in anxious smokers [odds ratio (OR)=2.21, 95% confidence interval (CI)=1.05-4.65, P=0.034], but there was no association with bipolar and unipolar depression (P=0.943). Compared with nonanxious smokers, anxious smokers had a greater risk for mood disorders (OR=4.67; 95% CI=2.24-9.92, P<0.001), lung disease (OR=6.78, 95% CI=1.95-23.58, P<0.003), and suicide attempts (OR=17.01, 95% CI=2.23-129.91, P<0.006). CONCLUSION: This study suggests that at least one deletion of the GSTM1 and GSTT1 genes represents a risk factor for anxious smokers. These two genes may modify the capacity for the detoxification potential against oxidative stress.