Sub-regional volumes changes of the corpus callosum in the drug naive patients with late-onset depression.

Although sub-regional analysis methods of the corpus callosum (CC) have been developed, there has been no in vivo magnetic resonance imaging (MRI) study on a sub-regional volume analysis of the CC of late-onset depression (LOD). The aim of this study was to investigate the CC volume differences between LOD subjects and healthy elderly controls using a sub-regional analysis technique. Forty subjects with LOD and thirty nine group-matched healthy control subjects underwent 3T MRI scanning, and sub-regional volumes of the CC were measured and compared between the groups. The volumes of total (F=5.8, p=0.001), the anterior (F=5.2, p=0.001) and the posterior CC (F=5.1, p=0.001) were significantly reduced in the LOD group as compared to the control group. We measured cognitive functions in several different domains (language functions, verbal learning, visuospatial functions, delayed recall, memory consolidation, recognition memory, and executive functions) through the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease. The anterior CC volume in the LOD group showed significant positive correlation with the Verbal Fluency scores. The posterior CC volume in the LOD group was positively correlated significantly with the Word List Memory, the Word List Recall and the Constructional Praxis scores. This study is the first to elaborate the sub-regional volume differences of the CC between controls and LOD patients. These structural changes in the CC might be at the core of the underlying neurobiological mechanisms in LOD.

Genetic Association of CHRNB3 and CHRNA6 Gene Polymorphisms with Nicotine Dependence Syndrome Scale in Korean Population.

OBJECTIVE: Cholinergic nicotinic receptor (CHRN) gene family has been known to mediate the highly additive effects of nicotine in the body, and implicated nicotine dependence (ND) and related phenotypes. Previous studies have found that CHRNA6-CHRNB3 cluster polymorphisms were significantly associated with the risk of ND and various tobacco behaviors. The aim of study was to evaluate the genetic association of CHRNB3 and CHRNA6 polymorphisms with the risk of ND based on the Fagerstrom Test for Nicotine Dependence (FTND) score and five subscales of nicotine dependence syndrome scale (NDSS) in Korean population. METHODS: Six SNPs in CHRNA6-CHRNB3 cluster were analyzed in 576 Korean subjects. Association analysis using logistic models and regression analysis with NDSS were performed. RESULTS: There was no association in the case-control analysis, whereas all six SNPs were significantly associated with drive factor among NDSS in subgroup based on the FTND score. CHRNB3 rs4954 and CHRNA6 rs16891604 showed significant associations with NDSSF1 (drive) in dominant models among moderate to severe ND among smokers after correction (p(corr) =0.02 and 0.001, respectively), whereas other four SNPs showed significant associations among mild ND after correction (p(corr) =0.03-0.02 in dominant model). CONCLUSION: This study showed that the genetic influence of CHRNB3-CHRNA6 cluster polymorphisms are found in a ND endophenotype (drive) using NDSS subscales, rather than the risk of ND in Korean population. Our findings might be the first report for the association of CHRNB3-CHRNA6 cluster with ND-related phenotypes in Korean and might offer an approach to elucidating the molecular mechanisms of ND and ND-related phenotypes.

Changes of plasma adiponectin levels after smoking cessation.

OBJECTIVE: Cigarette smoking is associated with a variety of health problems including cardiovascular, pulmonary, neoplasms, endocrinopathies including diabetes, the metabolic syndrome, and chronic inflammation. Adiponectin is an adipocyte-derived plasma protein that is closely associated with insulin sensitivity and the metabolic syndrome. The aim of this study was to evaluate the changes of plasma adiponectin levels after smoking cessation. METHODS: Thirty seven smokers that wanted to stop smoking without any nicotine replacement therapy or medication were recruited for this study. Fifteen smokers succeeded in stopping smoking (validated by urine cotinine levels ≤50 ng/mL) and 22 smokers failed. Therefore, only the 15 that succeeded were included in the analysis. The plasma adiponectin levels were determined using a commercially available enzyme-linked immunosorbent assay. RESULTS: The mean age of the successful 15 was 35±9.3 years old. They were all males. The daily smoking habit was a mean of 13.5±5.4 cigarettes per day. The mean Nicotine Dependence Syndrome Scale (NDSS) and Fagerstrom Test for Nicotine Dependence (FTND) scores were 55.6±9.6 and 2.9±1.9. During the study period of three months, the mean body mass index (BMI), body fat mass (BFM), waist-hip ratio (WHR) and body weight increased by 1.1 kg/m(2), 3.0%, 0.02%, and 2.9 kg, respectively. The baseline mean adiponectin level in the subjects was 11.9±5.2 mg/L. The mean adiponectin levels measured at one and three months were 16.0±5.1 mg/L and 14.7±4.5 mg/L respectively. The mean plasma adiponectin levels of the successful group was significantly increased after four weeks when compared to the baseline (z=-2.401, p=0.016). However, the decrease in plasma adiponectin levels at one and three months was not statistically significant. CONCLUSION: Even though the decrease over the next two months was not significant, these findings, the increase of plasma level of adiponectin after smoking cessation, provide preliminary data for future research on the possible mechanisms associated with smoking cessation and changes in body metabolism.

Nicotine dependence syndrome scale and craving: comparing nicotine-dependent individuals with and without comorbid alcohol dependence.

INTRODUCTION: Although several studies have explored craving for certain drugs, there is limited data describing the relationship between alcohol and nicotine craving from a multidimensional perspective among individuals with comorbid nicotine dependence (ND) and alcohol dependence (AD). METHODS: We compared a group of male patients diagnosed with ND and AD (n = 160) to a group of male patients diagnosed with ND only (n = 235). Smoking- and drinking-related clinical features were measured, including craving levels and the Nicotine Dependence Syndrome Scale (NDSS), which is a multidimensional questionnaire measuring ND. Subsequently, we studied factors that influenced smoking and alcohol craving in the ND and AD group. RESULTS: Regarding the NDSS, the sum, priority and tolerance scores were significantly higher in the ND and AD group compared with the ND only group (P < 0.000, P < 0.000 and P = 0.001, respectively). In the comorbid group, regression analyses revealed that alcohol craving and Fagerstrom Test for Nicotine Dependence (FTND) scores contributed to nicotine craving (beta coefficient = 0.37, P = 0.005 and beta coefficient = 0.35, P = 0.026, respectively) and these two factors explained 36% of the variance). Nicotine craving appeared to be the only factor that contributed to alcohol craving (beta coefficient = 0.35, P = 0.002), and nicotine craving explained 16% of the variance. DISCUSSION: This study may help clarify the clinical relationship between comorbid alcohol and nicotine dependence and help guide the development of effective treatment strategies for ND and AD patients.

Development and validation of a smartphone addiction scale (SAS).

OBJECTIVE: The aim of this study was to develop a self-diagnostic scale that could distinguish smartphone addicts based on the Korean self-diagnostic program for Internet addiction (K-scale) and the smartphone's own features. In addition, the reliability and validity of the smartphone addiction scale (SAS) was demonstrated. METHODS: A total of 197 participants were selected from Nov. 2011 to Jan. 2012 to accomplish a set of questionnaires, including SAS, K-scale, modified Kimberly Young Internet addiction test (Y-scale), visual analogue scale (VAS), and substance dependence and abuse diagnosis of DSM-IV. There were 64 males and 133 females, with ages ranging from 18 to 53 years (M = 26.06; SD = 5.96). Factor analysis, internal-consistency test, t-test, ANOVA, and correlation analysis were conducted to verify the reliability and validity of SAS. RESULTS: Based on the factor analysis results, the subscale "disturbance of reality testing" was removed, and six factors were left. The internal consistency and concurrent validity of SAS were verified (Cronbach's alpha = 0.967). SAS and its subscales were significantly correlated with K-scale and Y-scale. The VAS of each factor also showed a significant correlation with each subscale. In addition, differences were found in the job (p<0.05), education (p<0.05), and self-reported smartphone addiction scores (p<0.001) in SAS. CONCLUSIONS: This study developed the first scale of the smartphone addiction aspect of the diagnostic manual. This scale was proven to be relatively reliable and valid.

Age-specific influences of emotional distress on performance status in cancer patients.

OBJECTIVE: Improving and maintaining performance status is an important part of cancer treatment because it may predict patients' survival. Several cancer-related medical conditions have been known to influence the functional performance of cancer patients. We here examined whether emotional distress would also contribute to performance decline of cancer patients. METHODS: With consecutive sampling, a total of 880 patients diagnosed as having cancer were recruited and evaluated on cancer-related variables, emotional distress, and performance status using the standardized instruments. RESULTS: Approximately 8.9% of participants showed compromised performance rated 2 or more on the Eastern Cooperative Oncology Group performance status scale. Emotional distress was strongly associated with compromised performance after controlling for demographic and cancer-related external risk factors. The effects of emotional distress on performance decline were likely to be remarkably greater in the younger age group (<45 years) than in old-aged cancer patients (≥65 years). CONCLUSIONS: Our results provide support for the independent effects of emotional distress on having a higher risk for performance decline in cancer patients. These effects seem to be age-dependent suggesting that special clinical attention to emotional distress may be required in younger patients with cancer.

Reliability and validity of the korean version of the cornell scale for depression in dementia.

OBJECTIVE: The aim of this study was to explore the reliability and validity of the Korean version of the Cornell Scale for Depression in Dementia (CSDD-K), a scale for assessment of depression in dementia. METHODS: The original CSDD was translated into Korean and the content was verified through back-translation procedures. This study included 59 depressive patients with Alzheimer's disease (AD), 62 non-depressive patients with AD and 36 healthy elderly controls. The subjects were assessed using CSDD-K, the 17-item Hamilton Depression Rating Scale (HAM-D(17)), the 15-item Korean version of Geriatric Depression Scale (GDS(15)) and the Korean version of Mini-mental Status Examination (MMSE-K). RESULTS: In the reliability test, Cronbach's α coefficient and test-retest reliabilities were 0.92 and 0.91, respectively, indicating that the CSDD-K has good internal consistency. There were significant differences in CSDD-K total scores between AD patients with depression and AD patients without depression (p<0.001). In the analysis of the concurrent validity of the CSDD-K, there were significant correlations between the CSDD-K and HAM-D(17) (r=0.91, p<0.001) and between the CSDD-K and GDS(15) (r=0.75, p<0.001). ROC curve analysis identified a cut-off score of 7 for the CSDD-K, where the sensitivity was 87.5% and the specificity was 100%. Factor analysis resulted in a four-factor solution accounting for 63.8% of the common variance. CONCLUSION: The CSDD-K showed good reliability and validity for the assessment of depressive symptom severity in AD patients. The CSDD-K is a useful instrument for assessing AD patients with depressive symptoms in Korean ethnic population.

Automated hippocampal subfields segmentation in late life depression.

Although a few automated hippocampal subfields segmentation methods have been developed, there has been no in vivo Magnetic Resonance Imaging (MRI) study on the hippocampal subfields volumes of Late Life Depression (LLD). The aim of this study was to investigate the hippocampal subfields volume differences between LLD subjects and healthy elderly controls using an automated hippocampal subfields segmentation technique. Thirty subjects with LLD and 30 group-matched healthy control subjects underwent 3T MRI scanning, and hippocampal subfields volumes were measured and compared between the groups. Subjects with LLD exhibited significant hippocampal volume reductions in the total hippocampus, subiculum, and Cornu Ammonis (CA) 2-3 areas compared with healthy subjects (uncorrected, p<0.001). This study is the first to elaborate the subfields volume differences of both hippocampi between controls and LLD patients. These structural changes in the hippocampal presubiculum, subiculum, and CA2-3 areas might be at the core of the underlying neurobiological mechanisms of hippocampal dysfunction in LLD.

Automated hippocampal subfield segmentation in amnestic mild cognitive impairments.

Although a few automated hippocampal subfield segmentation methods have been developed, the effects of amnestic mild cognitive impairment (aMCI) on the hippocampal subfield volumes on magnetic resonance imaging (MRI) are not clear. The aim of this study was to investigate the hippocampal subfield volume changes and their relationships with various neuropsychological tests in aMCI using an automated hippocampal subfield segmentation technique. Forty-five subjects with aMCI and 49 group-matched healthy control subjects underwent 3-tesla MRI scanning, and hippocampal subfield volumes were measured and compared. Additionally, we explored the correlation pattern between hippocampal subfield volumes and the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) neuropsychological test scores in aMCI subjects. Subjects with aMCI exhibited significant hippocampal volume reductions in the presubiculum, subiculum and cornu ammonis 2-3 areas compared with healthy subjects. In addition, we also found significant positive correlations between presubiculum and subicular area volumes and the CERAD-K verbal and visuospatial delayed recall scores in aMCI. This study was the first to explore the relationships between hippocampal subfield volumes and various types of cognitive performances in aMCI. These structural changes might be at the core of the underlying neurobiological mechanisms of hippocampal dysfunction in aMCI.

Relationships between hippocampal shape and cognitive performances in drug-naïve patients with Alzheimer's disease.

Previous studies provided hippocampal shape analysis of Alzheimer's disease (AD) patients using automated segmentation techniques. However, the relationships between the hippocampal deformations and various cognitive impairments were not clear. The aim of this study was to investigate hippocampal shape changes and their relationship to cognitive impairments. Fifty-one drug-naïve patients with AD and 50 group-matched healthy control subjects underwent 3T MRI scanning, and the hippocampal volumes and deformations were compared between the groups. Additionally, we explored the correlation pattern between the hippocampal deformations and the cognitive dysfunctions in AD using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K). AD subjects exhibited significant hippocampal deformations in the cornu ammnonis (CA1) and subiculum areas compared to those in healthy subjects (p<0.05, false discovery rate (FDR) corrected). Significant correlations were observed between hippocampal deformations in CA1 and subiculum areas and verbal immediate recall, verbal delayed recall, verbal recognition memory, and constructional recall scores (p<0.05, FDR corrected). This study was the first to explore the relationships between hippocampal deformations and various cognitive impairments of drug-naïve patients with AD. These structural changes in hippocampal CA1 and subiculum areas might be the core of the underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to the various cognitive dysfunctions in AD.

Hippocampal shape and cognitive performance in amnestic mild cognitive impairment.

Previous studies have carried out hippocampal shape analysis of amnestic mild cognitive impairment (aMCI) patients using automated segmentation techniques. However, the relationships between hippocampal deformations and various episodic memory impairments were not clear. The aim of this study was to investigate hippocampal shape changes and their relationships with various episodic memory impairments in aMCI. Hippocampal volumes and deformations were compared between the aMCI and the controls. In addition, we explored the correlation pattern between hippocampal deformations and cognitive dysfunctions in aMCI using a comprehensive neuropsychological battery. Patients with aMCI exhibited significant hippocampal deformations in the right cornu ammonis 1 (CA1) and subiculum areas compared with healthy individuals. Significant correlations were observed between constructional recall scores and the right CA1 and subiculum areas in aMCI. Verbal delayed recall scores were also significantly correlated with the left CA1 and subiculum areas in aMCI. This study was the first to explore the relationships between hippocampal deformations and various types of cognitive performances in aMCI. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to verbal and visuospatial delayed recall in aMCI.

Regional cortical thickness and subcortical volume changes are associated with cognitive impairments in the drug-naive patients with late-onset depression.

Previous studies have shown an association between late-onset depression (LOD) and cognitive impairment in older adults. However, the neural correlates of this relationship are not yet clear. The aim of this study was to investigate the differences in both cortical thickness and subcortical volumes between drug-naive LOD patients and healthy controls and explore the relationship between LOD and cognitive impairments. A total of 48 elderly, drug-naive patients with LOD and 47 group-matched healthy control subjects underwent 3T MRI scanning, and the cortical thickness was compared between the groups in multiple locations, across the continuous cortical surface. The subcortical volumes were also compared on a structure-by-structure basis. Subjects with LOD exhibited significantly decreased cortical thickness in the rostral anterior cingulate cortex, the medial orbitofrontal cortex, dorsolateral prefrontal cortex, the superior and middle temporal cortex, and the posterior cingulate cortex when compared with healthy subjects (all p<0.05, false discovery rate corrected). Reduced volumes of the right hippocampus was also observed in LOD patients when compared with healthy controls (p<0.001). There were significant correlations between memory functions and cortical thickness of medial temporal, isthmus cingulate, and precuneus (p<0.001). This study was the first study to explore the relationships between the cortical thickness/subcortical volumes and cognitive impairments of drug-naive patients with LOD. These structural changes might explain the neurobiological mechanism of LOD as a risk factor of dementia.

The changes of blood glucose control and lipid profiles after short-term smoking cessation in healthy males.

OBJECTIVE: Our aim was to evaluate the changes in blood glucose control and lipid profiles after 2-months of smoking cessation in healthy males. METHODS: Smoking abstinence was evaluated through self-report and urine cotinine levels. 12 individuals who succeeded in quitting smoking were analyzed. Fasting values of glucose and insulin were used to estimate the ß-cell activity and insulin resistance was evaluated using the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: The data showed that the subjects had a significant increase in weight, body mass index and fasting plasma glucose levels after smoking cessation. The HOMA-Insulin Resistance and the HOMA ß-cell function increased significantly (p=0.005, p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In addition, the low-density lipoprotein cholesterol levels decreased significantly (p=0.028); however, changes in the high-density lipoprotein cholesterol, the triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445 respectively). CONCLUSION: During the initial stage of smoking abstinence, insulin resistance increased and insulin sensitivity decreased due to elevated body weight and fat composition. Therefore, it is important to educate individuals that stop smoking about the necessity of weight control during smoking cessation programs.

The change of plasma ghrelin and leptin levels by the development of type 2 diabetes mellitus in patients with alcohol dependence.

BACKGROUND: There have been lots of studies about the relationship between chronic use of alcohol and the development of type 2 diabetes mellitus (T2DM). Chronic use of alcohol can be affected by the altered level of ghrelin and leptin which regulate food-seeking behavior having similar mechanism of controlling alcohol-craving behavior. Those peptides are known to be correlated with T2DM. Ghrelin and leptin also have been regarded as possible regulators of glucose metabolism and insulin function. Hence, there is the possibility that ghrelin and leptin can be related with deteriorated pathophysiology of T2DM in alcoholic patients. METHODS: Patients with alcohol dependence diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) underwent an 75 g oral glucose-tolerance test (OGTT), to classify them to normal glucose tolerance (NGT, n = 52), pre-diabetes including impaired glucose tolerance (IGT), impaired fasting glucose level (IFG) and combination of IGT and IFG (Pre-DM, n = 26) and T2DM (n = 24) groups. Fasting plasma ghrelin and leptin levels were compared among groups. RESULTS: There was no difference of ghrelin concentration among the groups but the leptin concentration was significantly different between NGT and T2DM group (p < 0.05). Increased leptin levels were significantly correlated with body mass index (BMI), insulin level, and insulin resistance. CONCLUSIONS: Chronic alcohol drinking might produce leptin resistance which makes leptin significantly correlated with fasting insulin concentration and insulin resistance. Therefore, we suppose that increased level of leptin by chronic alcohol use could be one of the main mechanisms that develop insulin resistance in alcoholic patients.

Chronic ethanol ingestion, type 2 diabetes mellitus, and brain-derived neurotrophic factor (BDNF) in rats.

Chronic alcohol consumption contributes to the development of type 2 diabetes mellitus (T2DM) while decreasing the level of brain-derived neurotrophic factor (BDNF). BDNF may be an important regulator of glucose metabolism, so it may be associated with an increased risk for T2DM in alcoholism. We evaluated the association of chronic heavy alcohol exposure, T2DM and BDNF level. Ten week-old type 2 diabetic OLETF rats and non-diabetic LETO rats of similar weight were used. The rats were randomized by weight into four treatment groups: (1) OLETF-Ethanol (O-E, n=13), (2) OLETF-Control (O-C, n=15), (3) LETO-Ethanol (L-E, n=11), and (4) LETO-Control (L-C, n=14). The ethanol groups were fed an isocaloric liquid diet containing ethanol while the control groups were fed with the same diet containing maltose-dextran over a 6-week period using a pair-feeding control model in order to regulate different caloric ingestion. After 6 weeks of feeding, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and BDNF levels were analyzed. Prior to IP-GTT, the mean glucose levels in the O-E, O-C, L-E, and L-C groups were 90.38±12.84, 102.13±5.04, 95.18±6.43, and 102.36±4.43mg/dL, respectively. Thirty minutes after intraperitoneal injection, the mean glucose levels were 262.62±63.77, 229.07±51.30, 163.45±26.63, and 156.64±34.42mg/dL, respectively; the increased amount of the mean glucose level in the O-E group was significantly higher than that in the O-C group (p<0.05). One hundred twenty minutes after intraperitoneal injection, the mean glucose levels were 167.38±45.37, 121.20±18.54, 106.73±6.94, and 104.57±9.49mg/dL, respectively; the increased amount of the mean glucose level in the O-E group was significantly higher than that in the O-C group (p<0.01). The difference in mean glucose levels between the O-E group and O-C group was still significant even after adjusting for time (p<0.05). Mean BDNF levels were 405.95±326.16, 618.23±462.15, 749.18±599.93, and 1172.00±839.17pg/mL, respectively; mean BDNF level in the O-E group was significantly lower than the L-C group (p<0.05). In conclusion, the results of the present study suggest that chronic heavy alcohol ingestion may aggravate T2DM and may possibly lower BDNF level.

Paroxetine in the treatment of depressed patients with haematological malignancy: an open-label study.

OBJECTIVE: The efficacy and tolerability of paroxetine in the treatment of depressive disorders is well known, however, its efficacy and safety for the treatment of depression in patients with cancer has been poorly studied. Therefore this study was aimed at evaluating the efficacy and tolerability of paroxetine in the treatment of depressed patients with haematological malignancy (HM). METHOD: Fifty-two patients with major depressive disorder (MDD) based on DSM-IV criteria along with comorbid HM were allotted to an 8 week trial with a flexible-dose regime of paroxetine in combination with their chemotherapy or supportive pharmacotherapy. The treatment response was assessed at baseline, week 2, week 4 and week 8 with the 17-item Hamilton rating scale for depression (HAM-D17), the Montgomery Asberg depression rating scale (MADRS) and the clinical global impression-severity (CGI-S). Side effects were collected with reported adverse events and laboratory tests throughout the study period. RESULTS: 44.2% of 52 patients completed the 8 week trial. Scores on the HAM-D17, MADRS and CGI-s (last observation carried forward, LOCF) at baseline were significantly reduced with a mean reduction of 30.5%, 32.8% and 39.1%, respectively, after 8 weeks treatment with paroxetine. CONCLUSION: In this preliminary study, paroxetine was found to be effective and moderately tolerated in the treatment of depressed patients with HM, and the present study calls for a controlled study in this field to extend and form a framework on the psychopharmacological data in this field.