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Vitamin D deficiency is considered a major public health problem worldwide and has been reported as having an association with depression. However, studies on the association between vitamin D deficiency and depressive symptoms in secondary amenorrhea (SA) patients are still scarce. This study examined the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and depressive symptoms among Korean women with SA. In this cross-sectional observational study, 78 patients with SA were initially recruited. Clinical and biochemical parameters, including serum 25(OH)D level, were measured. Data from 63 SA patients who met the study inclusion criteria and completed psychiatric assessments were finally analyzed. We analyzed their association with depression using a hierarchical regression model. The average serum 25(OH)D level was 34.40 ± 24.02 ng/mL, and 41.3% of the women with SA were vitamin D-deficient (

Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called 'symptomics' and is concurrently applied to various areas of symptomatology.Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia.Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability.An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clusters - extrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism.Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.

Background The suicide rate of the youth in South Korea has been increasing, and suicide of the youth still has been the most common cause of death since 2007. We aimed to determine the trends and the regional risk factors of youth suicide in South Korea from 2001 to 2010. Subjects and methods We used the data from the National Statistical Office to calculate the standardized suicide rates and various regional data including population census, employment, and labor. To calculate the effect of individual risk factors, we used the data from the fourth Korean Youth Risk Behavior Web-based Survey (KYRBWS-VI). Conditional autoregressive model for regional standardized mortality ratio (SMR) using inter-regional spatial information was fitted. Results Suicide rates of adolescents aged 12 to 18 was from 3.5 per 100,000 people in 2001 and 5.3 per 100,000 in 2010. There were no significant gender difference in suicide rates, however, the number of suicides among adolescents aged 15-18 accounted for four times than those of adolescents ages 12-14. High proportion of late adolescents, higher number of recipients of national basic livelihood, and higher number of adolescents who treated with depression were related to elevated suicide rate of adolescent. Total sleep time of adolescents and regional unemployment rate were negatively associated with the suicide risk of respective regions. Conclusions Age distribution, economic status, total sleep time, and the number of adolescent patients with depression were different between those in low and in high adolescent suicidal regions in Korea. Our findings suggest that preferential appliance of adolescent suicide prevention program for regions by considering those factors may be important steps to reduce adolescent suicide in Korea.

Glucocorticoid receptor (GR) promoter I7 is susceptible to epigenetic changes induced by environmental influences. Early life stress (ELS) has a persistent impact on GR expression, as well as behavior, in adult rodents via epigenetic changes of GR promoter I7. Moreover, various stressors can induce histone modifications in this region during adulthood. Thus, the present study aimed to investigate whether maternally separated (MS) rats exposed to chronic restraint stress (RS) would exhibit histone modifications of GR promoter I7 in the hippocampus. Rats were subjected to MS (3h per day) on postnatal days (PND) 1-21. Then, during adulthood (PND 56-77), the rats were exposed to RS (2h per day) followed by treatment with escitalopram (10mg/kg). The MS and RS groups exhibited significant decreases in total and exon I7 GR mRNA levels and the combination of MS and RS exerted a greater effect on these mRNA levels than either MS or RS alone. Additionally, both the MS and RS groups showed significant reductions in histone H3 acetylation at GR promoter I7 and the combination of MS and RS had a greater effect than did either MS or RS alone. Chronic escitalopram treatment ameliorated these changes. The present results indicate that postnatal MS and adult RS influence GR expression through histone modification at GR promoter I7, and that the combination of the two stressors potentiates these changes. Furthermore, epigenetic mechanisms are involved in escitalopram action.

OBJECTIVE To investigate whether serum 25-hydroxyvitamin D [25(OH)D] level is associated with ovarian reserve markers in secondary amenorrhea (SA) patients. METHODS Sixty-three women diagnosed with SA were recruited during 12 months from the initiation of this prospective observational study. Serum 25(OH)D levels, serum anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) were estimated in study participants and ovarian reserve markers were compared between participants with vitamin D deficiency and those with normal vitamin D levels. RESULTS Of the 63 participants, 27 (42.9%) were vitamin D deficient (

Background: The suicide rate of the youth in South Korea has been increasing, and suicide of the youth still has been the most common cause of death since 2007. We aimed to determine the trends and the regional risk factors of youth suicide in South Korea from 2001 to 2010. Subjects and Methods: We used the data from the National Statistical Office to calculate the standardized suicide rates and various regional data including population census, employment, and labor. To calculate the effect of individual risk factors, we used the data from the fourth Korean Youth Risk Behavior Web-based Survey (KYRBWS-VI). Conditional autoregressive model for regional standardized mortality ratio (SMR) using inter-regional spatial information was fitted. Results: Suicide rates of adolescents aged 12 to 18 was from 3.5 per 100,000 people in 2001 and 5.3 per 100,000 in 2010. There were no significant gender difference in suicide rates, however, the number of suicides among adolescents aged 15-18 accounted for four times than those of adolescents ages 12-14. High proportion of late adolescents, higher number of recipients of national basic livelihood, and higher number of adolescents who treated with depression were related to elevated suicide rate of adolescent. Total sleep time of adolescents and regional unemployment rate were negatively associated with the suicide risk of respective regions. Conclusions: Age distribution, economic status, total sleep time, and the number of adolescent patients with depression were different between those in low and in high adolescent suicidal regions in Korea. Our findings suggest that preferential appliance of adolescent suicide prevention program for regions by considering those factors may be important steps to reduce adolescent suicide in Korea.

Early life stress (ELS) exerts long-lasting epigenetic influences on the brain and makes an individual susceptible to later depression. It is poorly understood whether ELS and subsequent adult chronic stress modulate epigenetic mechanisms. We examined the epigenetic mechanisms of the BDNF gene in the hippocampus, which may underlie stress vulnerability to postnatal maternal separation (MS) and adult restraint stress (RS). Rat pups were separated from their dams (3 h/day from P1-P21). When the pups reached adulthood (8 weeks old), we introduced RS (2 h/day for 3 weeks) followed by escitalopram treatment. We showed that both the MS and RS groups expressed reduced levels of total and exon IV BDNF mRNA. Furthermore, RS potentiated MS-induced decreases in these expression levels. Similarly, both the MS and RS groups showed decreased levels of acetylated histone H3 and H4 at BDNF promoter IV, and RS exacerbated MS-induced decreases of H3 and H4 acetylation. Both the MS and RS groups had increased MeCP2 levels at BDNF promoter IV, as well as increased HDAC5 mRNA, and the combination of MS and RS exerted a greater effect on these parameters than did RS alone. In the forced swimming test, the immobility time of the MS + RS group was significantly higher than that of the RS group. Additionally, chronic escitalopram treatment recovered these alterations. Our results suggest that postnatal MS and subsequent adult RS modulate epigenetic changes in the BDNF gene, and that these changes may be related to behavioral phenotype. These epigenetic mechanisms are involved in escitalopram action.

Recent studies have shown that antipsychotic drugs have epigenetic effects. However, the effects of antipsychotic drugs on histone modification remain unclear. Therefore, we investigated the effects of antipsychotic drugs on the epigenetic modification of the BDNF gene in the rat hippocampus. Rats were subjected to chronic restraint stress (6 h/d for 21 d) and then were administered with either olanzapine (2 mg/kg) or haloperidol (1 mg/kg). The levels of histone H3 acetylation and MeCP2 binding at BDNF promoter IV were assessed with chromatin immunoprecipitation assays. The mRNA levels of total BDNF with exon IV, HDAC5, DNMT1, and DNMT3a were assessed with a quantitative RT-PCR procedure. Chronic restraint stress resulted in the downregulation of total and exon IV BDNF mRNA levels and a decrease in histone H3 acetylation and an increase in MeCP2 binding at BDNF promoter IV. Furthermore, there were robust increases in the expression of HDAC5 and DNMTs. Olanzapine administration largely prevented these changes. The administration of haloperidol had no effect. These findings suggest that the antipsychotic drug olanzapine induced histone modification of BDNF gene expression in the hippocampus and that these epigenetic alterations may represent one of the mechanisms underlying the actions of antipsychotic drugs.

Background Mood disturbance has been described in women with menstrual abnormalities. Aims To access the prevalence of depression in patients with secondary amenorrhea (SA), and investigate the relationship between depressive scores and serum anti-Müllerian hormone (AMH) levels among these women. Methods Sixty-six women with SA completed the Centre for Epidemiological Studies-Depression Rating Scales (CES-D) and Hamilton-Depression Rating Scales (HAM-D) in a university hospital. Clinical and biochemical parameters were measured in all individuals, and their associations with depressive scores were analysed. Results Among the 66 patients with SA, 42 (63.6 per cent) were diagnosed with polycystic ovarian syndrome, followed by 14 patients (21.2 per cent) with unexplained chronic anovulation, and the remaining 10 (15.2 per cent) were identified as primary ovarian insufficiency or low ovarian reserve. In the analysis of CES-D Scales, 21 (31.8 per cent) women had scores indicative of depression. Serum AMH levels and antral follicle counts were lower in patients with depressive symptoms than those in patients without depressive symptoms. (4.76±4.77ng/ml vs. 10.49±7.52ng/ml (P=0.003), 10.67±6.20 vs. 14.78±7.35 (P=0.030), respectively). The CES-D and HAM-D scores also correlated negatively with serum AMH levels after adjusting age, body mass index and androgen level (γ=-0.429, P=0.001 and γ=-0.428, P=0.001). Conclusion This cross-sectional study showed that the prevalence of depression in SA patients was high and higher depressive scores were associated with lower serum AMH levels. This observation suggests that decreased AMH level may possibly be linked to a particular spectrum of depression in patients with SA.

OBJECTIVE This study aimed to assess the efficacy of aripiprazole for the management of cognitive impairments and hyperprolactinemia in patients with schizophrenia on a stable dose of risperidone. METHODS Thirty-five subjects stabilized on risperidone (3-6 mg/day) for a minimum of 3 months were enrolled in a double-blind, placebo-controlled phase for 12 weeks and an open-label phase for another 12 weeks. Subjects were randomly assigned to receive 10 mg/day aripiprazole (n=17) or placebo (n=18). Over the following 12 weeks, the the aripiprazole group received a flexible dose of aripiprazole while tapering risperidone. At baseline, week 12, and week 24, subjects were evaluated using the Positive and Negative Syndrome Scale (PANSS), Extrapyramidal Syndrome Rating Scale (ESRS), and standardized neuropsychological assessments. Serum prolactin levels were checked at baseline, week 1, week 2, and week 24. RESULTS The mean change in total PANSS and cognitive function test scores between baseline and endpoint were similar in the aripiprazole and placebo groups. Scores on the ESRS and negative subscale of PANSS differed significantly between groups in both phases of the study (p

Glucocorticoid receptor (GR) promoter I

ObjectiveaaTo investigate the effects of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, on cognitive impairments in patients with chronic schizophrenia. MethodsaaA 12-week, placebo-controlled trial was conducted to determine the effectiveness of memantine as an adjunctive treatment with conventional antipsychotic medications in 26 patients with chronic schizophrenia. The subjects were evaluated with the Korean version of the Mini-Mental State Examination (K-MMSE), the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), and a standard neuropsychological screening test. ResultsaaMemantine treatment was not associated with significantly improved cognitive test scores compared with the placebo control treatment. An improvement in the scores on the PANSS negative subscale was noted with memantine, but it was not significant. ConclusionaaAdjunctive memantine treatment did not improve cognitive functioning or affect psychopathology in patients with chronic schizophrenia in the present study. Memantine, however, was tolerated well and did not exacerbate positive symptoms in patients with chronic schizophrenia. Psychiatry Investig 2012;9:166-173 Key Wordsaa Memantine, Cognition, Antipsychotic drugs, Schizophrenia, Tolerability.

Recent studies have demonstrated that mTORC1 activation may be related to antidepressant action. However, the relationship between mTORC1 signaling activation and currently prescribed antidepressants remains unclear. The aim of the present study was to determine whether alterations in mTORC1 signaling are observable following treatment with tianeptine under toxic conditions induced by B27 deprivation. Additionally, we investigated whether this drug affects synaptic proteins, neurite outgrowth, and spine density via mTORC1 signaling. Using Western blotting, we measured the phosphorylation levels of mTORC1, 4E-BP-1, p70S6K, Akt, and ERK in rat primary hippocampal neurons. Changes in BDNF, dendritic outgrowth, spine density, and synaptic proteins (PSD-95, synaptophysin, and GluR1) were measured. Tianeptine significantly increased the phosphorylation of mTORC1, 4E-BP-1, p70S6K, Akt, and ERK. The increase in mTOR phosphorylation was blocked by the PI3K, MEK, and mTORC1 inhibitors. Tianeptine increased BDNF, dendritic outgrowth, spine density, and synaptic proteins; all of these effects were blocked by the mTORC1 inhibitor. In this study, we demonstrated that tianeptine activates the mTORC1 signaling pathway and increases dendritic outgrowth, spine density, and synaptic proteins through mTORC1 signaling under toxic conditions in rat primary hippocampal neurons.

Objectives Depression and diabetes are closely biologically and behaviorally intertwined. We examined the impact of comorbid diabetes mellitus on the incidence of serious psychiatric outcomes among patients with depression. Methods We used claims data from the Korean Health Insurance Review & Assessment Service database of patients who were diagnosed with depression within one year of an index prescription for antidepressants between January 2007 and June 2008. We investigated the association between the comorbidity of diabetes mellitus and serious psychiatric outcomes of depression, such as psychiatric hospitalization, psychiatric emergency room visits, and suicide attempts. Results Among 200,936 patients with depression, 74,160 (36.9%) had diabetes mellitus, including 57,418 (28.6%) with complications. The incidence of serious psychiatric outcomes was 3.3% in patients with depression without diabetes and 6.7% in patients with depression and diabetes mellitus. Patients with depression and diabetes mellitus complications showed higher rates of serious outcomes than that did those without diabetes mellitus complications (odds ratio, 1.19; 95% confidence interval, 1.11–1.13). Similarly, depressed patients with micro and macrovascular diabetic complications were more likely to experience serious outcomes than those without diabetes mellitus complications (odds ratio, 2.2; 95% confidence interval, 2.07–2.34). Conclusions Our results showed that comorbid diabetes mellitus can increase the risk of serious outcomes of depression, such as suicide and hospitalization, and thus may alter the antidepressants prescription patterns and healthcare service use among patients with depressive disorders.

Background p11 (S100A10) is a key regulator of depression-like behaviors and antidepressant drug response in rodent models. Recent studies suggest that p11 mediates the behavioral antidepressant action of brain-derived neurotrophic factor (BDNF) in rodents. BDNF improves neural plasticity, which is linked to the cellular actions of antidepressant drugs. In the present study, we investigated whether p11 regulated BDNF action on neural plasticity in vitro . Methods We generated primary hippocampal cultures. p11 expression, total dendritic length, and spine density were investigated under toxic conditions induced by B27 deprivation, which causes hippocampal cell death. Results B27 deprivation significantly decreased p11 expression. Treatment with BDNF significantly prevented the B27 deprivation-induced decrease in p11 levels in a concentration-dependent manner, whereas these concentrations had no effect on control cultures. B27 deprivation significantly reduced the total length of hippocampal dendrites and spine density. BDNF increased the total dendritic length and spine density in conditions with or without B27. Furthermore, p11 knockdown through small interfering RNA (siRNA) transfection blocked these effects. The overexpression of p11 in B27-deprived cells increased the total dendritic length and spine density, and treatment with BDNF potentiated these effects. Limitation This study should be confirmed in animal models of depression. Conclusion Taken together, our data suggest that BDNF-induced improvement in neural plasticity may depend on the regulation of p11 in hippocampal cells with B27 deprivation. These results provide evidence to strengthen the theoretical basis of a role for p11 in BDNF-induced antidepressant action.

Future of Clinical Practice in Psychiatry Jong-Min Woo, MD, MPH, PhD, Myoung Ha Son, MD, Gyung-Mee Kim, MD, PhD, and Kyu-Chang Chae, BA Department of Psychiatry, Seoul Paik Hospital, Inje University School of Medicine, Seoul, Korea Stress Research Institute, Inje University, Seoul, Korea Department of Psychiatry, Haeundae Paik Hospital, Inje University School of Medicine, Busan, Korea Department of Neuropsychiatry, Seife Hospital, Seoul, Korea

uicide has dramatically increased in recent years, and South Korea is the highest rate among the Organization for Economic Cooperation and Development member countries. Noteably, suicide is the leading cause of death in South Korea in youths aged 15-24. Approximately 70-90% of youth suicides are related to a preexisting psychiatric disorder such as depressive disorder, conduct disorder, or substance abuse. Recently, some studies have proposed nation- wide suicide prevention programs, but there have been no systematic studies about suicide and suicide prevention programs particularly for adolescents. In South Korea, to establish an evalua- tion system of mental health screening services and to develop a case management program, a mental health promotion model for adolescents and a few programs for depression and suicide prevention for adolescents are currently being developed. Developmental considerations and a multidisciplinary approach in the treatment and prevention of suicidal adolescents are very impor- tant. In addition it is necessary to conduct a systematized nationwide survey of depression and suicide in adolescents.

Background: Recently, social concern about occupational stress and disputes, which are surrounded with judgements of work relatedness for various psychiatric sequels, is increasing. Objective: We present a case of work-related, illness judgement in which panic disorder and adjustment disorder with conversion symptoms were associated with work stress due to job reallocation. M e t h o d s: We performed psychiatric assessment including mental status examination and neuropsychological test batteries. We also assessed job stress profiles using the Korean version of the Occupational Stress Inventory (K-OSI). Results: The patient showed no specific psychological or physical problems and had previously demonstrated suitable coping skills. However, the patient, who was sensitive to emotional stress, suffered chronic stress symptoms after a role change from a car mechanic to office manager which required continuous interaction with customers and a strong emotional burden. Panic attack and conversion symptoms were judged to be associated with disharmony between individual characteristics and environmental needs. Conclusion: It is noteworthy that this is the first reported case considered as a psychiatric illness related with psychological work stress. A further study will be attempted to assign standards of judgment for similar cases through systematic source collection and tool development.