Ultrasound-guided superficial cervical plexus block under dexmedetomidine sedation versus general anesthesia for carotid endarterectomy: a retrospective pilot study.

Background: Carotid endarterectomy (CEA) has been performed under regional and general anesthesia (GA). The general anesthesia versus local anesthesia for carotid surgery study compared the two techniques and concluded that there was no difference in perioperative outcomes. However, since this trial, new sedative agents have been introduced and devices that improve the delivery of regional anesthesia (RA) have been developed. The primary purpose of this pilot study was to compare intraoperative hemodynamic stability and postoperative outcomes between GA and ultrasound-guided superficial cervical plexus block (UGSCPB) under dexmedetomidine sedation for CEA. Methods: Medical records from 43 adult patients who underwent CEA were retrospectively reviewed, including 16 in the GA group and 27 in the RA group. GA was induced with propofol and maintained with sevoflurane. The UGSCPB was performed with ropivacaine under dexmedetomidine sedation. We compared the intraoperative requirement for vasoactive drugs, postoperative complications, pain scores using the numerical rating scale, and the duration of hospital stay. Results: There was no difference between groups in the use of intraoperative antihypertensive drugs. However, intraoperative inotropic and vasopressor agents were more frequently required in the GA group (p<0.0001). In the GA group, pain scores were significantly higher during the first 24 h after surgery (p<0.0001 between 0-6 h, p<0.004 between 6-12 h, and p<0.001 between 12-24 h). The duration of hospital stay was significantly more in the GA group (13.3±4.6 days in the GA group vs. 8.5±2.4 days in the RA group, p<0.001). Conclusion: In this pilot study, intraoperative hemodynamic stability and postoperative outcomes were better in the RA compared to the GA group.

Solar radiation increases suicide rate after adjusting for other climate factors in South Korea.

OBJECTIVE: Previous studies have indicated that suicide rates have significant seasonal variations. There is seasonal discordance between temperature and solar radiation due to the monsoon season in South Korea. We investigated the seasonality of suicide and assessed its association with climate variables in South Korea. METHOD: Suicide rates were obtained from the National Statistical Office of South Korea, and climatic data were obtained from the Korea Meteorological Administration for the period of 1992-2010. We conducted analyses using a generalized additive model (GAM). First, we explored the seasonality of suicide and climate variables such as mean temperature, daily temperature range, solar radiation, and relative humidity. Next, we identified confounding climate variables associated with suicide rate. To estimate the adjusted effect of solar radiation on the suicide rate, we investigated the confounding variables using a multivariable GAM. RESULTS: Suicide rate showed seasonality with a pattern similar to that of solar radiation. We found that the suicide rate increased 1.008 times when solar radiation increased by 1 MJ/m2 after adjusting for other confounding climate factors (P < 0.001). CONCLUSION: Solar radiation has a significant linear relationship with suicide after adjusting for region, other climate variables, and time trends.

Outdoor artificial light at night, obesity, and sleep health: Cross-sectional analysis in the KoGES study.

Obesity is a common disorder with many complications. Although chronodisruption plays a role in obesity, few epidemiological studies have investigated the association between artificial light at night (ALAN) and obesity. Since sleep health is related to both obesity and ALAN, we investigated the association between outdoor ALAN and obesity after adjusting for sleep health. We also investigated the association between outdoor ALAN and sleep health. This cross-sectional survey included 8526 adults, 39-70 years of age, who participated in the Korean Genome and Epidemiology Study. Outdoor ALAN data were obtained from satellite images provided by the US Defense Meteorological Satellite Program. We obtained individual data regarding outdoor ALAN; body mass index; depression; and sleep health including sleep duration, mid-sleep time, and insomnia; and other demographic data including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking status and consumption of caffeine or alcohol before sleep. A logistic regression model was used to investigate the association between outdoor ALAN and obesity. The prevalence of obesity differed significantly according to sex (women 47% versus men 39%, p < 0.001) and outdoor ALAN (high 55% versus low 40%, p < 0.001). Univariate logistic regression analysis revealed a significant association between high outdoor ALAN and obesity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.14-1.35, p < 0.001). Furthermore, multivariate logistic regression analyses showed that high outdoor ALAN was significantly associated with obesity after adjusting for age and sex (OR 1.25, 95% CI 1.14-1.37, p < 0.001) and even after controlling for various other confounding factors including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking, consumption of caffeine or alcohol before sleep, delayed sleep pattern, short sleep duration and habitual snoring (OR 1.20, 95% CI 1.06-1.36, p = 0.003). The findings of our study provide epidemiological evidence that outdoor ALAN is significantly related to obesity.

G protein ß3 subunit polymorphism and long-term prognosis of functional dyspepsia.

BACKGROUND/AIMS: A link between G protein ß3 (GNB3) polymorphism and functional dyspepsia (FD) has been suggested. The aim of this study was to determine the role of GNB3 polymorphism in the long-term prognosis of FD in Koreans. METHODS: FD patients and normal healthy controls were recruited from patients who visited our center between December 2006 and June 2007. All of the subjects completed Rome III questionnaires before undergoing upper gastrointestinal endoscopy and colonoscopy. Genomic DNA was extracted for GNB3 genotyping. After 5 years, the subjects were reevaluated using the same questionnaires. RESULTS: GNB3 825T carrier status was significantly related to FD in Koreans (p=0.04). After 5 years, 61.0% of the initial FD patients and 12.2% of the initial normal subjects were diagnosed with FD (odds ratio [OR], 11.7; 95% confidence interval [CI], 4.3 to 31.1; p<0.001). Regardless of the GNB3 genotype (p=0.798), female sex was strongly correlated with FD after 5 years (OR, 3.3; 95% CI, 1.2 to 9.1; p=0.017). CONCLUSIONS: The T allele of GNB3 is linked to FD in Koreans but does not predict long-term prognosis. Female sex is related to a higher prevalence of FD after 5 years.

Plasma Levels of IL-23 and IL-17 before and after Antidepressant Treatment in Patients with Major Depressive Disorder.

OBJECTIVE: Cytokines are believed to have a role in the pathophysiology of major depression. The alteration in levels of pro-inflammatory cytokines [interleukin 1ß (IL-1ß), IL-2, IL-6, IL-12, interferon γ, and tumor necrosis factor α] in major depression supports the cytokine hypothesis of this illness. IL-23 and IL-17 are also pro-inflammatory cytokines, but few studies have focused on their role in major depression. This study investigated the potential role of the IL-23 and IL-17 axis in major depression. METHODS: Plasma IL-23 and IL-17 levels were measured in 26 major depressive disorder (MDD) patients before and after 6-week treatment with antidepressants; these levels were measured in 28 age- and sex-matched normal controls. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). IL-23 and IL-17 plasma levels were estimated using quantitative enzyme-linked immunosorbent assay. RESULTS: Pre-treatment plasma levels of IL-23 and IL-17 in MDD patients were not significantly different from those of normal controls. In MDD patients, IL-23 and IL-17 levels after 6 weeks of antidepressant treatment were not different from the baseline levels. There was no significant correlation between changes in the cytokine levels and changes in the HDRS scores representing the severity of depression. CONCLUSION: The present study does not support a potential involvement of IL-23 and IL-17 axis in major depression. Replication and extension using a larger sample are required.

TNF-alpha -308G>A polymorphism is associated with suicide attempts in major depressive disorder.

BACKGROUND: Despite the substantial role of the cytokine network in depression and suicide, few studies have investigated the role of genetic polymorphisms of pro- and anti-inflammatory cytokines in suicide in major depressive disorder (MDD). The aim of this study was to investigate whether tumor necrosis factor-alpha (TNF-alpha) -308G>A, interferon-gamma (IFN-gamma) +874A>T, and interleukin-10 (IL-10) -1082A>G are associated with increased risk for suicide attempts in MDD. METHODS: Among patients with MDD, 204 patients who had attempted suicide and 97 control patients who had not attempted suicide were recruited. A chi-square test was used to identify a possible risk genotype or allele type for suicide. A subsequent multivariate logistic regression analysis was conducted to investigate the influence of a risk genotype or allele type adjusted for other environmental factors. The lethality of the suicide attempt was also tested between genotype and allele types among suicidal patients with MDD. RESULTS: The GG genotype of the TNF-alpha -308G>A polymorphism was found to significantly increase risk for suicide attempt (adjusted OR=2.630, 95% CI=1.206 to 5.734). IFN-gamma +874A>T and IL-10 -1082A>G were not associated with risk for suicide. Lethality of the suicide attempt was not associated with any of the three cytokine genotypes or allele types. LIMITATIONS: Limitations include a relatively small sample size and a cross-sectional design. CONCLUSIONS: TNF-alpha -308G>A polymorphism is an independent risk factor for suicide attempts in MDD. Future studies should clarify the neural mechanisms by which the GG genotype of TNF-alpha -308G>A influences suicide in MDD.

Oxidative stress and tardive dyskinesia: pharmacogenetic evidence.

Tardive dyskinesia (TD) is a serious adverse effect of long-term antipsychotic use. Because of genetic susceptibility for developing TD and because it is difficult to predict and prevent its development prior to or during the early stages of medication, pharmacogenetic research of TD is important. Additionally, these studies enhance our knowledge of the genetic mechanisms underlying abnormal dyskinetic movements, such as Parkinson's disease. However, the pathophysiology of TD remains unclear. The oxidative stress hypothesis of TD is one of the possible pathophysiologic models for TD. Preclinical and clinical studies of the oxidative stress hypothesis of TD indicate that neurotoxic free radical production is likely a consequence of antipsychotic medication and is related to the occurrence of TD. Several studies on TD have focused on examining the genes involved in oxidative stress. Among them, manganese superoxide dismutase gene Ala-9Val polymorphisms show a relatively consistent association with TD susceptibility, although not all studies support this. Numerous pharmacogenetic studies have found a positive relationship between TD and oxidative stress based on genes involved in the antioxidant defense mechanism, dopamine turnover and metabolism, and other antioxidants such as estrogen and melatonin. However, many of the positive findings have not been replicated. We expect that more research will be needed to address these issues.

Role of cytokines in atypical depression.

BACKGROUND: Atypical depression (AD) is considered a biologically and psychologically distinct subtype of depression. AD, contrary to melancholic depression (MD), may have different alteration in cytokine activity. AIMS: We aimed to investigate the differences of cytokine activity between AD patients and MD patients. Among psychiatric patients visited to the Psychiatry Department, Korea University Medical Center, 105 patients with major depression who met the Diagnostic and Statistical Manual (DSM-IV) criteria based on clinical interviews using a Structured Clinical Interview for DSM-IV were recruited. Among 105 patients, 35 patients had atypical feature. We measured in vitro cytokines (interleukins) IL-2, IL-4, IL-6 and tumor necrosis factor-α (TNF-α). RESULTS: Decreased IL-4 and increased IL-2 was observed in AD patients. IL-6 and TNF-α level of AD patients showed no difference from the controls. CONCLUSIONS: Contrary to MD, AD has reversed vegetative symptoms, i.e. hypersomnia and hyperphagia. It is assumed that the phenotype difference between AD and MD might be related to Th1 cytokines (IL-2) and Th2 cytokines (IL-4) and not related to monocytic cytokines (IL-6, and TNF-α).

Atypical antipsychotic drugs perturb AMPK-dependent regulation of hepatic lipid metabolism.

Dysregulation of lipid metabolism is a key feature of metabolic disorder related to side effects of antipsychotic drugs. Here, we investigated the molecular mechanism by which second-generation atypical antipsychotic drugs (AAPDs) affect hepatic lipid metabolism in liver. AAPDs augmented hepatic lipid accumulation by activating expression of sterol regulatory element-binding protein (SREBP) transcription factors, with subsequent induction of downstream target genes involved in lipid and cholesterol synthesis in hepatocytes. We confirmed the direct involvement of SREBPs on AAPD-induced expression of lipogenic and cholesterogenic genes by utilization of adenovirus for dominant negative SREBP (Ad-SREBP-DN). Interestingly, AAPDs significantly decreased phosphorylation of AMPKα and expression of fatty acid oxidation genes. Treatment of constitutive active AMPK restored AAPD-mediated dysregulation of genes involved in both lipid synthesis and fatty acid oxidation. Moreover, AAPDs decreased transcriptional activity of PPARα, a critical transcriptional regulator for controlling hepatic fatty acid oxidation, via an AMPK-dependent manner. Close investigations revealed that mutations at the known p38 MAPK phosphorylation sites (S6/12/21A), but not mutations at the putative AMPKα phosphorylation sites (S167/373/453A), block AAPD-dependent reduction of PPARα transcriptional activity, suggesting that p38 MAPK might be also involved in the regulatory pathway as a downstream effector of AAPDs/AMPK. Taken together, these data suggest that AAPD-stimulated hepatic dysregulation of lipid metabolism could result from the inhibition of AMPK activity, and pharmaceutical means to potentiate AMPK activity would contribute to restore hepatic lipid homeostasis that occurs during AAPD treatment.

Depressive mood and quality of life in functional gastrointestinal disorders: differences between functional dyspepsia, irritable bowel syndrome and overlap syndrome.

OBJECTIVE: To investigate the differences in depressive mood and quality of life in patients with between functional dyspepsia (FD), irritable bowel syndrome (IBS), and FD-IBS overlap as diagnosed based on Rome III criteria. METHODS: The subjects completed a questionnaire based on Rome III criteria, the Beck Depressive Inventory (BDI) including Cognitive Depression Index (CDI) for depressive mood evaluation and the 36-item Short Form general health survey (SF-36) for quality of life assessment. Upper gastrointestinal endoscopy and colonoscopy were performed to exclude organic disease. RESULTS: Of 279 subjects, 70 and 124 subjects were diagnosed as FD and IBS, respectively. FD-IBS overlap patients (n=42) and FD alone patients (n=28) showed higher BDI scores than normal subjects (n=127) (P<.001 and P=.02, respectively), whereas that of IBS alone patients (n=82) did not show difference (P=.17). All the SF-36 subscores of the FD-IBS overlap patients were significantly lower than normal subjects (P<.05). CONCLUSIONS: Depressive mood was significantly related to FD and FD-IBS overlap but not to IBS based on Rome III criteria. FD-IBS overlap patients have worse quality of life than FD-alone and IBS-alone patients.

Association between norepinephrine transporter gene polymorphism and major depression.

Noradrenergic and serotonergic abnormalities have long been implicated in patients with major depression. The novel selective norepinephrine reuptake inhibitor reboxetine has been shown to be at least as effective as imipramine, desipramine and fluoxetine in the treatment of major depression. It is suggested that the dysfunction of the norepinephrine transporter (NET) may be related to major depression. Although the transcriptional activity related to the NET gene expression is little known, it may be a good candidate gene for major depression. Therefore, we investigated whether the T-182C polymorphism of the NET gene is associated with major depression in a Korean sample of 112 major depression patients compared with 136 healthy controls. We found a significantly lower frequency in TT genotype in patients with major depression than in normal controls when the genotypes of T-182C polymorphism were classified into two groups: TT group versus TC + CC group (p = 0.019). This result suggests that the T-182C polymorphism in the NET gene might be associated with major depression.

Effects of season and climate on the first manic episode of bipolar affective disorder in Korea.

The purpose of this study was to determine if a seasonal pattern existed for the first manic episodes in Korea. The first manic episodes out of 152 bipolar disorder patients were investigated, in subjects who were admitted in two hospitals in Seoul between 1996 and 1999. Correlations between the monthly climate variables and the first monthly manic episodes indicated that the first manic episodes peaked in 25 cases during March. The mean monthly hours of sunshine and sunlight radiation correlated significantly with manic episodes. Separating the patients into two groups, namely, with and without major depressive episode, only the occurrence of manic episodes with major depressive episode was significantly correlated with mean monthly hours of sunshine. Separating the subjects by gender, the monthly first manic episodes was significantly correlated with the intensity of sunlight radiation in female patients only. These findings suggested that increasing the duration and intensity of sunlight could facilitate breakdown into the manic episodes.

Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for smoking in schizophrenia.

We examined the genetic effect of DRD2 A1 allele in 167 Korean schizophrenics in relation to their smoking habit. Although there was no apparent difference in the genotype distributions of DRD2 gene among the female schizophrenics (n = 66), the male counterpart (n = 101) showed significant differences in their genotype distributions. The comparison between male smoking and non-smoking patients showed the difference in genotype distribution (P = 0.010) with a higher prevalence of A1 allele (P = 0.020) and frequency of heterozygotes (P = 0.005), but not frequency of the A1 allele. The A1A2 heterozygotes male showed significantly higher smoking rate compared to the A1A1 or A2A2 homozygotes male, and non-smokers were deficient in heterozygotes. By contrast, among female schizophrenics, the heterozygotes showed a lower smoking rate than homozygotes and there were more heterozygotes in non-smokers. The deviation from Hardy-Weinberg expectations was observed in male and female non-smokers showing quite opposite profiles. Highly significant differences were seen between male and female non-smokers in A1 prevalence (P = 0.001), genotype distribution (P = 0.00011), and frequency of heterozygotes (P = 0.00003), but not in A1 frequency. The analyses from both male and female as one group showing no significant difference in the genotype distributions between smokers and non-smokers could be explained by the gender difference in the genetic effect of DRD2 A1 allele. Our findings present the gender-specific molecular heterosis of DRD2 gene in relation specifically to the smoking status of schizophrenic patients. They indicate the importance of heterosis and gender effects that should be taken into consideration for the association studies.