Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome.

Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).

Effects of TGF-ß1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells.

We investigated the effectiveness of the transforming growth factor beta-1 (TGF-ß) receptor inhibitor GW788388 on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal fibrosis mouse model. HPMCs were treated with TGF-ß with or without GW788388. Animal experiments were conducted on male C57/BL6 mice. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. GW788388 was administered by once-daily oral gavage. The morphological change, cell migration, and invasion resulted from TGF-ß treatment, but these changes were attenuated by cotreatment with GW788388. TGF-ß-treated HPMCs decreased the level of the epithelial cell marker and increased the levels of the mesenchymal cell markers. Cotreatment with GW788388 reversed these changes. Phosphorylated Smad2 and Smad3 protein levels were stimulated with TGF-ß and the change was attenuated by cotreatment with GW788388. For the peritoneal fibrosis mice, thickness and collagen deposition of parietal peritoneum was increased, but this change was attenuated by cotreatment with GW788388. GW788388, an orally available potent TGF-ß receptor type 1 inhibitor, effectively attenuated TGF-ß-induced EMT in HPMCs. Cotreatment with GW788388 improved peritoneal thickness and fibrosis, and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.

Internet Game Addiction, Depression, and Escape From Negative Emotions in Adulthood: A Nationwide Community Sample of Korea.

The aim of this study was to investigate the association between adult Internet game addiction (IGA) and mental disorders. A total of 1401 adults aged between 18 and 74 years participated in this study. The IGA group had significantly younger patients, and it showed a higher proportion of unmarried and unemployed adults, and higher rates of suicidal ideation, plan, and attempt than the non-IGA group. Multivariate logistic regression indicated that IGA was significantly associated with major depressive disorder, dysthymia, and depressive disorders adjusting for all variables. The Patient Health Questionnaire-9 score was significantly higher in the IGA group than in the non-IGA group for both young adults and middle groups. "Escape from negative emotions like nervousness, sadness, and anger" was the only significant item associated with depression among symptoms of IGA. This study suggests that adults with IGA and depression may use Internet games to escape from negative emotions.

Improvement in subjective and objective neurocognitive functions in patients with major depressive disorder: a 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study.

Although many patients with major depressive disorder (MDD) complain of neurocognitive impairment, the effects of antidepressant medications on neurocognitive functions remain unclear. This study compares neurocognitive effects of tianeptine and escitalopram in MDD. Patients with MDD (N = 164) were randomly assigned in a 1:1 ratio to either tianeptine (37.5 mg/d) or escitalopram (10 mg/d) for 12 weeks. Outcome measures included clinical improvement, subjective cognitive impairment on memory and concentration, the Mini-Mental State Examination, the Continuous Performance Test, the Verbal Learning Test, and the Raven Progressive Matrices, assessed every 4 weeks. After 12 weeks, the tianeptine group showed significant improvement in commission errors (P = 0.002), verbal immediate memory (P < 0.0001), Mini-Mental State Examination (P < 0.0001), delayed memory (P < 0.0001), and reasoning ability (P = 0.0010), whereas the escitalopram group improved in delayed memory and reasoning ability but not in the other measures. Both groups significantly improved in subjective cognitive impairment in memory (P < 0.0001) and concentration (P < 0.0001). Mixed effects model repeated measures analyses revealed that the tianeptine group had a significant improvement in scores of commission errors (F = 6.64, P = 0.011) and verbal immediate memory (F = 4.39, P = 0.038) from baseline to 12 weeks, compared with the escitalopram group, after controlling for age, sex, education years, baseline scores, and changes of depression severity. The treatment of MDD with tianeptine led to more improvements in neurocognitive functions, especially in commission errors and verbal immediate memory, compared with escitalopram, after controlling for changes in depression severity. Both drugs improved subjective cognitive impairment of memory and concentration.

Childhood trauma, parental death, and their co-occurrence in relation to current suicidality risk in adults: a nationwide community sample of Korea.

Although previous studies have suggested that childhood trauma and parental death are strongly associated with suicidality in adulthood, it is still unclear how these factors interact within the same population. A total of 1396 adults were recruited through nationwide multistage probability sampling in South Korea. Subjects were evaluated through face-to-face interviews using the Suicidality Module of the Mini-International Neuropsychiatric Interview and the Early Trauma Inventory Self Report-Short Form. Among the 1396 adults, the group that experienced both childhood trauma and parental death had the highest current suicidality risks (F = 12.16, p < 0.0001) and lifetime suicide attempt (χ2 = 35.81, p < 0.0001) compared with the other groups, which were only childhood trauma, only parental death, and neither. Multivariate logistic regression analyses revealed that middle-to-high current suicidality risk and lifetime suicide attempt were significantly associated with concurrent childhood trauma and parental death (odds ratio, 3.64; 95% confidence interval, 1.99-6.65) as well as with only childhood trauma (odds ratio, 1.95; 95% confidence interval, 1.33-2.87), after adjusting for age, sex, education, marital status, household monthly income, and living area. Emotional abuse was the only type of childhood trauma significantly associated with higher current suicidality scores in those who experienced childhood parental death than in those who did not (F = 3.26, p = 0.041). Current suicidality risk and lifetime suicide attempt are associated with experiencing both parental death and trauma, especially emotional abuse, in childhood, whereas experiencing only childhood parental death is associated with neither.

TGF-ß1 Receptor Inhibitor SB525334 Attenuates the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells via the TGF-ß1 Signaling Pathway.

We investigated the effect of SB525334 (TGF-ß receptor type 1 (TßRI) inhibitor) on the epithelial to mesenchymal transition (EMT) signaling pathway in human peritoneal mesothelial cells (HPMCs) and a peritoneal fibrosis mouse model. In vitro experiments were performed using HPMCs. HPMCs were treated with TGF-ß1 and/or SB525334. In vivo experiments were conducted with male C57/BL6 mice. The 0.1% chlorhexidine gluconate (CG) was intraperitoneally injected with or without SB52534 administration by oral gavage. Mice were euthanized after 28 days. EMT using TGF-ß1-treated HPMCs included morphological changes, cell migration and invasion, EMT markers and collagen synthesis. These pathological changes were reversed by co-treatment with SB525334. CG injection was associated with an increase in peritoneal fibrosis and thickness, which functionally resulted in an increase in the glucose absorption via peritoneum. Co-treatment with SB525334 attenuated these changes. The levels of EMT protein markers and immunohistochemical staining for fibrosis showed similar trends. Immunofluorescence staining for EMT markers showed induction of transformed cells with both epithelial and mesenchymal cell markers, which decreased upon co-treatment with SB525334. SB525334 effectively attenuated the TGF-ß1-induced EMT in HPMCs. Cotreatment with SB525334 improved peritoneal thickness and fibrosis and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.

Effect of Korean Red Ginseng in individuals exposed to high stress levels: a 6-week, double-blind, randomized, placebo-controlled trial.

BACKGROUND: To investigate the neurobiological evidence supporting the adaptogenic effects of Korean Red Ginseng in reducing the harmful consequences of stress using a double-blind, placebo-controlled trial. METHOD: Sixty-three subjects with high stress levels were randomized to receive an orally administered, double-blind, 6-week treatment with Korean Red Ginseng (n = 32) or placebo (n = 31). All participants underwent a comprehensive psychological evaluation using Beck Depression Inventory and Stress Response Inventory, cognitive evaluation using the continuous performance test, biological evaluation by measuring blood levels of lipids, catecholamines, inflammation markers, and heart rate variability at baseline and after 6 weeks. RESULTS: At baseline, both groups showed no significant differences in age, sex, years of education, Beck Depression Inventory, and Stress Response Inventory. After 6 weeks, triglyceride levels were significantly increased within the normal limit in theKorean Red Ginseng group (F = 4.11, p = 0.048), and the epinephrine level was decreased in this group (F = 4,35, p = 0.043). The triglyceride increase was significantly associated with epinephrine decrease (B = -0.087, p = 0.041), suggesting that Korean Red Ginseng may stabilize the sympathetic nervous system. In addition, we detected a significant group by time effect in the visually controlled continuous performance test, suggesting positive effects of Korean Red Ginseng on cognition. CONCLUSION: Korean Red Ginseng might help to stabilize the sympathetic nervous system and improve cognition in individuals with high stress.

Clusterin deficiency induces lipid accumulation and tissue damage in kidney.

Clusterin is a secretory glycoprotein that is involved in multiple physiopathological processes, including lipid metabolism. Previous studies have shown that clusterin prevents hepatic lipid accumulation via suppression of sterol regulatory element-binding protein (SREBP) 1. In this study, we examined the role of clusterin in renal lipid accumulation in clusterin-knockout mice and NRK52e tubular epithelial cells. Clusterin deficiency increased the expression of SREBP1 and its target genes and decreased malonyl-CoA decarboxylase protein levels in the kidney. Expression of the endocytic receptor, megalin, and scavenger receptor class A was increased in clusterin-deficient mice. Functional analysis of lipid metabolism also revealed that lipid uptake and triglyceride synthesis were increased and fatty acid oxidation was reduced, leading to increased lipid accumulation in clusterin-deficient mice. These phenomena were accompanied by mesangial expansion, fibrosis and increased urinary protein-to-creatinine ratio. High-fat feeding aggravated these clusterin deficiency-induced pathological changes. Clusterin knockdown in NRK52e cells increased lipogenic gene expression and lipid levels, whereas overexpression of clusterin by treatment with adenovirus or recombinant clusterin protein suppressed lipogenic gene expression and lipid levels. Transforming growth factor-beta 1 (TGFB1) expression increased in the kidney of clusterin-deficient mice and suppression of TGFB1 in NRK52e cells suppressed lipid accumulation. These results suggest that clusterin deficiency induces renal lipid accumulation by dysregulating the expression of lipid metabolism-related factors and TGFB1, thereby leading to chronic kidney disease. Hence, clusterin may serve as a therapeutic target for lipid-induced chronic kidney disease.

Agoraphobia and Follicle-Stimulating Hormone Levels between Tamoxifen and Goserelin versus Tamoxifen Alone in Premenopausal Hormone Receptor-Positive Breast Cancer: A 12-Month Prospective Randomized Study.

OBJECTIVE: Tamoxifen is an estrogen receptor antagonist used to prevent recurrence of breast cancer, which may provoke depression and anxiety and increase follicle-stimulating hormone (FSH) to patients. We compared anxiety and depression symptoms and FSH levels who received conventional tamoxifen alone and combination treatment of goserelin, a gonadotropin-releasing hormone (GnRH) analogue, with tamoxifen. METHODS: Sixty-four premenopausal women with hormone receptor-positive early-stage breast cancer were included and were assigned randomly to receive either tamoxifen and goserelin combination or tamoxifen alone for 12 months. The participants were evaluated blindly using the Hamilton Depression and Anxiety Rating Scale, the Beck Depression Rating Scale, and the Albany Panic and Phobia Questionnaire (APPQ). Blood FSH levels were assessed at baseline, 6 and 12 months. RESULTS: A significant time×group difference was detected in the agoraphobia trends subscale of the APPQ and in FSH levels. The combination group showed significantly less increases in agoraphobia subscale of APPQ and greater decreases in FSH level than those in the tamoxifen-alone group from baseline to 12 months of treatment. No significant differences for age, tumor grade, body mass index, or family history were found at baseline between the two groups. CONCLUSION: Our results suggest that the combination treatment of tamoxifen and goserelin resulted in less agoraphobia than tamoxifen alone in premenopausal women with breast cancer, which may associated with FSH suppression of goserelin.

Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

Methionine-S-sulfoxide reductase (MsrA) protects against high-fat diet-induced insulin resistance due to its antioxidant effects. To determine whether its counterpart, methionine-R-sulfoxide reductase (MsrB) has similar effects, we compared MsrB1 knockout and wild-type mice using a hyperinsulinemic-euglycemic clamp technique. High-fat feeding for eight weeks increased body weights, fat masses, and plasma levels of glucose, insulin, and triglycerides to similar extents in wild-type and MsrB1 knockout mice. Intraperitoneal glucose tolerance test showed no difference in blood glucose levels between the two genotypes after eight weeks on the high-fat diet. The hyperglycemic-euglycemic clamp study showed that glucose infusion rates and whole body glucose uptakes were decreased to similar extents by the high-fat diet in both wild-type and MsrB1 knockout mice. Hepatic glucose production and glucose uptake of skeletal muscle were unaffected by MsrB1 deficiency. The high-fat diet-induced oxidative stress in skeletal muscle and liver was not aggravated in MsrB1-deficient mice. Interestingly, whereas MsrB1 deficiency reduced JNK protein levels to a great extent in skeletal muscle and liver, it markedly elevated phosphorylation of JNK, suggesting the involvement of MsrB1 in JNK protein activation. However, this JNK phosphorylation based on a p-JNK/JNK level did not positively correlate with insulin resistance in MsrB1-deficient mice. Taken together, our results show that, in contrast to MsrA deficiency, MsrB1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

Effects of smartphone use with and without blue light at night in healthy adults: A randomized, double-blind, cross-over, placebo-controlled comparison.

Smartphones deliver light to users through Light Emitting Diode (LED) displays. Blue light is the most potent wavelength for sleep and mood. This study investigated the immediate effects of smartphone blue light LED on humans at night. We investigated changes in serum melatonin levels, cortisol levels, body temperature, and psychiatric measures with a randomized, double-blind, cross-over, placebo-controlled design of two 3-day admissions. Each subject played smartphone games with either conventional LED or suppressed blue light from 7:30 to 10:00PM (150 min). Then, they were readmitted and conducted the same procedure with the other type of smartphone. Serum melatonin levels were measured in 60-min intervals before, during and after use of the smartphones. Serum cortisol levels and body temperature were monitored every 120 min. The Profile of Mood States (POMS), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and auditory and visual Continuous Performance Tests (CPTs) were administered. Among the 22 participants who were each admitted twice, use of blue light smartphones was associated with significantly decreased sleepiness (Cohen's d = 0.49, Z = 43.50, p = 0.04) and confusion-bewilderment (Cohen's d = 0.53, Z = 39.00, p = 0.02), and increased commission error (Cohen's d = -0.59, t = -2.64, p = 0.02). Also, users of blue light smartphones experienced a longer time to reach dim light melatonin onset 50% (2.94 vs. 2.70 h) and had increases in body temperature, serum melatonin levels, and cortisol levels, although these changes were not statistically significant. Use of blue light LED smartphones at night may negatively influence sleep and commission errors, while it may not be enough to lead to significant changes in serum melatonin and cortisol levels.

Reduced Venous Blood Basophil Count and Anxious Depression in Patients with Major Depressive Disorder.

OBJECTIVE: Anxious depression has a distinct neurobiology, clinical course and treatment response from non-anxious depression. Role of inflammation in anxious depression has not been examined. As an exploratory study to characterize the role of inflammation on a development of anxious depression, we aimed to determine the relationship between white blood cell (WBC) subset counts and anxiety in individuals with major depressive disorder (MDD). METHODS: A total of 709 patients who were newly diagnosed with MDD were recruited. Anxiety levels of participants were evaluated using the Anxiety/ Somatization subitem of the Hamilton Depression Rating Scale. The association between WBC subset fraction and anxiety was evaluated. RESULTS: Basophil and eosinophil sub-fractions showed significant negative correlations with HAM-D anxiety/somatization factor scores (basophils: r=-0.092, p=0.014 and eosinophils: r=-0.075, p=0.046). When an anxiety score (a sum of somatic and psychic anxiety) was entered as a dependent variable, only basophils showed significant negative association with the anxiety scores after adjusting for all other WBC subset counts and demographic factors (t=-2.57, p=0.010). CONCLUSION: This study showed that anxious depression had a decreased basophil subfraction, which might be associated with involvement of inflammation in development of anxious depression.

Lifetime suicidal ideation and attempt in adults with full major depressive disorder versus sustained depressed mood.

BACKGROUND: Major depressive disorder (MDD) is a well-known risk factor for suicidality, but depressed mood has been used non-specifically to describe the emotional state. We sought to compare influence of MDD versus sustained depressed mood on suicidality. METHODS: A total of 12,532 adults, randomly selected through the one-person-per-household method, completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) and a questionnaire for lifetime suicidal ideation (LSI) and lifetime suicidal attempt (LSA). RESULTS: Of 12,361 adults, 565 were assessed as 'sustained depressed mood group' having depressed mood for more than two weeks without MDD (4.6%), and 810 adults were assessed as having full MDD (6.55%) which consisted of 'MDD with depressed mood group' (6.0%) and 'MDD without depressed mood group' (0.5%). The MDD with depressed mood group showed higher odds ratios for LSI and LSA than the sustained depressed mood group. Contrarily, no significant differences were found in LSI and LSA between the MDD group with and without depressed mood. MDD showed significant associations with LSI (AOR=2.83, 95%CI 2.12-3.78) and LSA (AOR=2.17, 95%CI 1.34-3.52), whereas sustained depressed mood showed significant associations with neither LSI nor LSA after adjusting for MDD and other psychiatric comorbidities. Interaction effect of sustained depressed mood with MDD was significant for LSI but not for LSA. CONCLUSIONS: Sustained depressed mood was not related to LSI and LSA after adjusting for psychiatric comorbidities, whereas MDD was significantly associated with both LSI and LSA regardless of the presence of sustained depressed mood.

Cross-national differences in hypochondriasis symptoms between Korean and American outpatients with major depressive disorder.

Hypochondriasis is defined as the tendency to worry excessively about having a serious illness. This study aimed to investigate cross-national differences in hypochondriasis symptoms between Korean and American patients with major depressive disorder (MDD). This study examined 1592 Korean and 3744 American MDD outpatients of age ≥18 years using the Hamilton Rating Scale for Depression (HAM-D) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). Korean MDD patients exhibited significantly higher scores for hypochondriasis than Americans after controlling for total HAM-D scores and demographic variables (p<0.0001), even though Americans had significantly higher total HAM-D scores (p<0.0001). Multivariate logistic regression analyses revealed that hypochondriasis was significantly associated with somatic and psychic anxiety, insomnia-middle, and suicide for both Korean and American MDD patients after adjusting for demographic covariates. Among all factors, somatic anxiety was the most strongly associated with hypochondriasis in both Korean (AOR=2.14, 95% CI 1.31-3.52) and American (AOR=1.98, 95% CI 1.69-2.31) MDD outpatients. Hypochondriasis symptoms are more prevalent among Korean than American MDD patients but appear to be associated with high levels of somatic anxiety regardless of culture. This suggests that cultural and personal factors play a shared role in the presentation of hypochondriasis symptoms.

Loss of sexual interest and premenstrual mood change in women with postpartum versus non-postpartum depression: A nationwide community sample of Korean adults.

BACKGROUND: Postpartum depression (PPD) is a type of clinical depression that can affect women after childbirth. Few previous studies have explored the association of depressive and physical symptoms among women with PPD in a nationwide community study. METHOD: A total of 18,807 adults, randomly selected, completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) (response rate 80.2%). PPD was defined as a major depressive episode that began within 4 weeks after delivery. RESULTS: Of 679 female subjects with major depressive disorder (MDD), 14.0% (n=95) experienced PPD. Subjects with PPD were significantly more likely to have higher income, education, and reside in an urban area, compared to those with non-PPD. No significant differences were found in number of children. Multiple logistic regression revealed that the loss of sexual interest was the only symptom among 23 depressive symptoms that was significantly associated with depressive episodes among individuals with PPD (AOR=1.91, 95% CI 1.01-3.60) when compared with non-PPD. Loss of sexual interest was also significantly associated with the subjects with lifetime PPD regardless of depressive episode (AOR=1.93, 95% CI 1.12-3.31). Conversely, loss of confidence and loss of pleasure were less frequent in subjects with PPD. Premenstrual mood change (χ(2)=5.57, p=0.0036) and comorbid alcohol use disorder (χ(2)=5.11, p=0.031) showed a valid association with PPD. CONCLUSIONS: Loss of sexual interest and premenstrual mood change were associated with women with PPD, whereas those with non-PPD were not, thereby suggesting the possible link between sexual hormones and PPD.

Interleukin-10 deficiency aggravates angiotensin II-induced cardiac remodeling in mice.

AIMS: This study examined the role of interleukin (IL)-10 in angiotensin II-induced cardiac remodeling. MAIN METHODS: Angiotensin II was infused subcutaneously (1.1mg/kg/day) for one week in IL-10 knockout and wild-type mice, after which cardiac function and hypertrophy were assessed by echocardiogram. KEY FINDINGS: IL-10 gene expression in the heart was increased by angiotensin II infusion. Plasma levels of brain natriuretic peptide (BNP) and gene expression of BNP in the heart were increased by IL-10 deficiency or angiotensin II, and plasma BNP levels were further increased by IL-10 deficiency with angiotensin II. IL-10 deficiency increased the left ventricular dimension, whereas treatment with angiotensin II increased heart weight. Angiotensin II significantly reduced cardiac function in IL-10 knockout mice compared with wild-type mice. Gene expression of tumor necrosis factor-α and interleukin-6 was increased by IL-10 deficiency or angiotensin II infusion, and these increases were further enhanced by IL-10 deficiency with angiotensin II. Gene expression of collagen I/III and collagen III protein levels were increased by angiotensin II but not by IL-10 deficiency. Gene expression of matrix metalloproteinase2/9 was increased by IL-10 deficiency or angiotensin II, and this expression was further increased by IL-10 deficiency with angiotensin II. Akt phosphorylation was increased by IL-10 deficiency or angiotensin II and further increased by IL-10 deficiency with angiotensin II. Phosphorylation of p38 was increased by IL-10 deficiency. SIGNIFICANCE: These results suggest that IL-10 deficiency causes deterioration in cardiac functions in angiotensin II-infused mice, suggesting that IL-10 plays a protective role against angiotensin II-induced cardiac remodeling.

Review of Cohort Studies for Mood Disorders.

This paper aimed to review currently available cohort studies of subjects with mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD). Using the PubMed and KoreaMed databases, we reviewed eight major cohort studies. Most studies recruited participants with MDD and BD separately, so direct comparison of factors associated with diagnostic changes was difficult. Regular and frequent follow-up evaluations utilizing objective mood ratings and standardized evaluation methods in a naturalistic fashion are necessary to determine detailed clinical courses of mood disorders. Further, biological samples should also be collected to incorporate clinical findings in the development of new diagnostic and therapeutic approaches. An innovative cohort study that can serve as a platform for translational research for treatment and prevention of mood disorders is critical in determining clinical, psychosocial, neurobiological and genetic factors associated with long-term courses and consequences of mood disorders in Korean patients.

Gender Differences in Somatic Symptoms and Current Suicidal Risk in Outpatients with Major Depressive Disorder.

OBJECTIVE: Although somatic symptoms are common complaints of patients with major depressive disorder (MDD), their associations with suicide are still unclear. METHODS: A total of 811 MDD outpatients of aged between 18 to 64 years were enrolled nationwide in Korea with the suicidality module of the Mini-International Neuropsychiatric Interview (MINI) and the Depression and Somatic Symptom Scale (DSSS). RESULTS: On stepwise regression analysis, current suicidality scores were most strongly associated with chest pain in men, and neck or shoulder pain in women. Severe chest pain was associated with higher current suicidality scores in men than in women, whereas severe neck or shoulder pain showed no significant differences between the genders. In conclusion, MDD patients of both sexes with suicidal ideation showed significantly more frequent and severe somatic symptoms than those without. Current suicidal risk was associated with chest pain in men, and neck or shoulder pain in women. CONCLUSION: We suggest that clinicians pay attention to patients' somatic symptoms in real world practice.

Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder.

Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18 pg/ml) and dopamine (34.87±3.57 pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72 pg/ml and 20.40±3.53 pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine.

Efficacy of ziprasidone monotherapy in patients with anxious depression: a 12-week, randomized, double-blind, placebo-controlled, sequential-parallel comparison trial.

UNLABELLED: Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus non-anxious depression. One hundred and twenty outpatients were enrolled in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 multi-ratio to receive ziprasidone for 12 weeks, placebo for 6 weeks, followed by ziprasidone for 6 weeks, or placebo for 12 weeks. Efficacy was measured according to the 17-item Hamilton Depression Rating Scale (HRDS-17), Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-SR). Anxious depression was defined as a score of ≥7 on the HDRS-17 anxiety/somatization subscale. In phase I and II, ziprasidone monotherapy led to no significant changes compared with placebo on the HDRS-17 and QIDS-SR scores in patients with both anxious and non-anxious depression. In the pooled analysis, ziprasidone monotherapy also produced no significance on the HDRS-17 (Z = 0.25, P = 0.80) and QIDS-SR (Z = 0.43, P = 0.67) in patients with anxious depression. In conclusion, treatment with ziprasidone monotherapy may produce no significant improvement compared with placebo in patients with in anxious depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00555997.