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Objective: The pathology of post-traumatic stress disorder (PTSD) is associated with changes in brain structure and function, especially in the amygdala, medial prefrontal cortex, hippocampus, and insula. Survivors of tragic accidents often experience psychological stress and develop post-traumatic stress symptoms (PTSS), regardless of the diagnosis of PTSD. This study aimed to evaluate electroencephalographic changes according to PTSS in victims of a single traumatic event. Methods: This study enrolled 60 survivors of the Sewol ferry disaster that occurred in 2014 from Danwon High School and collected electroencephalographic data through 19 channels twice for each person in 2014 and 2015 (mean 451.88 [standard deviation 25.77] days of follow-up). PTSS was assessed using the PTSD Checklist-Civilian Version (PCL-C) and the participants were divided into two groups according to the differences in PCL-C scores between 2014 and 2015. Electroencephalographic data were converted to three-dimensional data to perform low-resolution electrical tomographic analysis. Results: Significant electroencephalographic changes over time were observed. The group of participants with worsened PCL-C score showed an increased change of delta slow waves in Brodmann areas 13 and 44, with the largest difference in the insula region, compared to those with improved PCL-C scores. Conclusion: Our findings suggests that the electrophysiological changes in the insula are associated with PTSS changes. [ABSTRACT FROM AUTHOR]

Objective: There are animal models associating dopamine dysfunction with behavioral impairments that model attention deficit hyperactivity disorder (ADHD). Erythropoietin (EPO) has trophic effects on dopaminergic neurons. The aim of this study was to examine the EPO plasma levels and determine whether there was any correlation between plasma EPO levels and clinical characteristics of ADHD. Methods: Plasma EPO levels were measured in 78 drug-naïve children with ADHD and in 81 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in ADHD children and healthy controls. Results: The difference between median plasma EPO levels in ADHD children and in healthy controls was not statistically significant. Adjusting for age and sex, a linear regression analysis showed that inattention score was significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile. Hyperactivity-impulsivity score was significantly higher in the highest tertile of plasma EPO compared to those in the lowest tertile. Moreover, total K-ARS scores were significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile. Conclusion: These findings suggest that plasma EPO levels were related to some ADHD symptoms, which could be used in the monitoring of the disorder. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the degree of occupational stress and the clinical mental state of dentists. In addition, we investigated the correlation of occupational stress with depression, anxiety, and sleep among dentists in Korea. Methods: A cross-sectional survey on 231 dentists was conducted using the Doctor Job Stress Scale, Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Index (STAI), and Pittsburgh Sleep Quality Index (PSQI). Correlation of occupational stress with mental health was investigated by adjusted multiple regression analysis. Results: The scores of CES-D, STAI, and PSQI revealed a significant correlation with the Doctor Job Stress Scale (t = 3.93, P < 0.0001; t = 4.05, P < 0.0001; t = 4.18, P < 0.0001, respectively). In particular, patient factors and clinical responsibility/judgment factors were significantly associated with depression (t = 2.80, P = 0.0056; t = 4.93, P < 0.0001, respectively), anxiety (t = 2.35, P = 0.0195; t = 5.11, P < 0.0001, respectively), and sleep (t = 3.78, P = 0.0002; t = 4.30, P < 0.0001, respectively), whereas work factors were not associated with any mental health state. Conclusions: This study confirms that dentists as professions experience more severe mental states. For successful mental health care among dentists, stress management focusing on interpersonal relationship with patients and responsibility as an expert rather than the intensity of work should be considered. [ABSTRACT FROM AUTHOR]

Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines have recommended lithium to be the treatment of choice for acute manic, mixed and depressive episodes of BD, along with long-term prophylaxis. Lithium's specific mechanism of action in mood regulation is progressively being clarified, such as the direct inhibition on glycogen synthase kinase 3, and its various effects on neurotrophic factors, neurotransmitters, oxidative metabolism, apoptosis, second messenger systems, and biological systems are also being revealed. Furthermore, lithium has been proposed to exert its treatment effects through mechanisms associated with neuronal plasticity. In this review, we have overviewed the clinical aspects of lithium use for BD, and have focused on the neuroprotective and neurotrophic effects of lithium. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the therapeutic effects of eye movement desensitization and reprocessing (EMDR) on post-traumatic growth (PTG). Methods: This study was conducted using a sample of ten survivors of a large-scale maritime disaster that occurred in the Yellow Sea, South Korea, in April 2014. A total of eight EMDR sessions were administered by a psychiatrist at two-week intervals over a period of five months, starting two or three months after the accident. Post-Traumatic Growth Inventory (PTGI), Stress-Related Growth Scale (SRGS), Clinician-Administered PTSD Scale (CAPS), and Connor-Davidson Resilience Scale (CD-RISC) were measured before treatment, after sessions 4 and 8, and at three months after treatment completion. Results: After three months from treatment completion, significant increases were observed in PTG (PTGI: Z(8)=-2.380, p=0.017; SRGS: Z(8)=-2.380, p=0.017) and resilience (CD-RISC: Z(8)=-2.386, p=0.017). A decrease in post-traumatic stress disorder (PTSD) level was also significant (CAPS: Z(8)=-2.176, p=0.030). The reduction of CAPS scores was correlated with increases of PTGI (rho=0.78, p=0.023) and SRGS (rho=0.79, p=0.020) scores. The changes in CAPS, PTGI, and SRGS scores between time point of end 8-session and three months follow-up was not significant (all p>0.05). Subjects with higher pre-treatment CD-RISC scores showed more significant improvements in PTGI (rho=0.88, p=0.004) and SRGS (rho=0.83, p=0.010) scores after treatment than did those with lower pre-treatment CD-RISC scores. Conclusion: EMDR therapy using standard protocol for trauma processing helped facilitating PTG in disaster survivors. To generalize these findings, further controlled studies comparing with other treatment modalities for PTSD are needed. [ABSTRACT FROM AUTHOR]

Atypical antipsychotics (AAP) are the prevailing form of schizophrenia treatment today due to their low side effects and superior efficacy. Nevertheless, some issues still need to be addressed. First, there are still a large number of patients with treatment-resistant schizophrenia (TRS), which has led to a growing trend to resort to AAP polypharmacy with few side effects. Most clinical treatment guidelines recommend clozapine monotherapy in TRS, but around one third of schizophrenic patients fail to respond to clozapine. For these patients, with clozapine-resistant schizophrenia AAP polypharmacy is a common strategy with a continually growing evidence base. Second, AAP generally have great risks for developing metabolic syndrome, such as weight gain, abnormality in glucose, and lipid metabolism. These metabolic side effects have become huge stumbling blocks in today's schizophrenia treatment that aims to improve patients' quality of life as well as symptoms. The exact reasons why this particular syndrome occurs in patients treated with AAP is as yet unclear though factors such as interaction of AAP with neurotransmitter receptors, genetic pholymorphisms, type of AAPs, length of AAP use, and life style of schizophrenic patients that may contribute to its development. The present article aimed to review the evidence underlying these key issues and provide the most reasonable interpretations to expand the overall scope of antipsychotics usage. [ABSTRACT FROM AUTHOR]

Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and -aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well. The balance of excitation and inhibition has been associated with epigenetic modifications and thus can be analyzed in terms of a neurodevelopmental and neural circuitry perspective. Hence, a novel bio-psychosocial-behavioral model for the treatment of schizophrenia is needed to account for the non-dopaminergic systems involved in schizophrenia, rather than dopaminergic mechanisms. This model can be understood from the viewpoint of neurodevelopment and neural circuitry and should include the staging care, personalized care, preventive care, reducing the cognitive deficits, and reducing stigma. Thomas R. Insel proposed this as a goal for schizophrenia treatment to be achieved by 2030. [ABSTRACT FROM AUTHOR]

Serotonin has been implicated in the pathophysiology of several psychiatric disorders including schizophrenia. Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. We aimed to investigate the associations of HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T variants with schizophrenia. A total of 202 patients with schizophrenia and 165 normal controls were genotyped for HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T single nucleotide polymorphisms (SNPs). In order to assess the severity of a patient's psychiatric symptoms, the brief psychiatric rating scale (BPRS), the positive and negative symptom scale (PANSS), and the Calgary depression scale for Schizophrenia (CDSS) were administered. Genotype and allele frequencies were compared between groups via χ statistics. Associations between the genotypes of candidate SNPs with the severity of symptoms were examined with ANOVA by comparing the mean scores of BPRS, PANSS, and CDSS according to genotype. No significant differences in the genotype distributions and allele frequencies of four SNPs were found between patients with schizophrenia and normal controls. There was a trend towards association of HTR1A C-1019G polymorphism with negative symptom. Negative symptom score of PANSS was lower in the patients with CC genotype than in the G allele carriers. These results suggested that C allele might be associated with lesser negative symptom. More studies are needed to confirm these findings. In the future, we plan to study the associations between schizophrenia and other genetic polymorphisms. [ABSTRACT FROM AUTHOR]

Genetic factors and catecholaminergic dysfunction have been suggested as the etiology of suicide. The catechol-O-methyltransferase (COMT) 158Val/Met polymorphism affects COMT activity; that is, the alleles encoding Val and Met are associated with relatively high and relatively low COMT activity, respectively. We aimed to identify the role of the COMT Val158Met polymorphism in suicidal attempt behavior. The COMT 158Val/Met polymorphisms were analyzed in 197 suicide attempters (male/female: 70/127), 170 control subjects (male/female: 85/85). All subjects were ethnic Korean. The Lethality Suicide Attempt Rating Scale (LSARS) and risk-rescue rating (RRR) system were explored. For the male subjects, there was a significant difference in genotype distributions and allele frequencies between control subjects and suicide attempters. That is, Val/Val genotype and Val carriers were more frequent in suicide attempters than in control subjects. For the female subjects, however, no significant difference was shown in genotype distributions and allele frequencies between control subjects and suicide attempters. There were no significant differences in LSARS and RRR according to the genotypes. The distribution of the COMT 158Val/Met polymorphism showed a biologically meaningful difference between control subjects and suicide attempters among the male subjects although selection bias should be considered. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Lee H-Y, Kim Y-K. Effect of TGF- β1 polymorphism on the susceptibility to schizophrenia and treatment response to atypical antipsychotic agent. Objective: Several studies have suggested that cytokine alterations could be related to the pathophysiology of schizophrenia. Transforming growth factor-beta1 (TGF- β1) is believed to be an important factor in regulation of inflammatory responses and to have anti-inflammatory effects. TGF- β1 also has trophic effects on dopaminergic neurons. We tested the hypothesis TGF- β1 is associated with the pathophysiology of schizophrenia. Methods: The polymorphisms at codon 10 (T869C) and codon 25 (G915C) of TGF- β1 were analysed in 99 schizophrenia patients and 130 normal controls. At baseline and after 8 weeks of treatment, clinical symptoms were evaluated on Positive and Negative Syndrome Scale (PANSS). Results: None of the subjects were polymorphic at codon 25. However, the C allele at codon 10 was more frequent in schizophrenia ( p = 0.05). Although schizophrenia group showed a higher tendency of allele frequency in the subjects with C allele ( p = 0.05), the allelic difference did not reach statistical significance after correction for multiple comparisons ( p = 0.1). PANSS scores showed no significant correlation with genotypes. The genotype distribution was not significantly different between responders and non-responders. However, the C allele was more frequent among responders ( p = 0.03). Conclusion: These results suggest that the TGF- β1 polymorphism is associated with therapeutic response to antipsychotics. However, further studies with larger numbers of subjects are needed to confirm the effect of TGF- β1 in schizophrenia. [ABSTRACT FROM AUTHOR]

Objective This study aimed to investigate whether the monoamine oxidase (MAO) A and B genes are associated with antipsychotic-induced restless legs syndrome (RLS) in schizophrenia. Methods We assessed antipsychotic-induced RLS symptoms in 190 Korean schizophrenic patients and divided the subjects into two groups: those with RLS symptoms (n = 96) and those without RLS symptoms (n = 94). Genotyping was performed for the variable number of tandem repeat (VNTR) polymorphism of the MAOA gene and A644G polymorphism of the MAOB gene. Results There was no significant difference in the genotype and allele frequencies of all polymorphisms investigated between these two groups. However, the result of global haplotype analysis showed a significant difference in haplotype frequencies between male subjects with and without RLS symptoms (p = 0.013). The interaction between two polymorphisms had a significant effect on the RLS scores of both male (p = 0.047) and female (p = 0.028) patients. Conclusions These data do not suggest that the MAOA gene VNTR and MAOB gene A644G polymorphisms are associated with antipsychotic-induced RLS symptoms in schizophrenia. However, we found that the haplotype frequencies differed between the male schizophrenic patients with and without RLS symptom and the interaction between the two polymorphisms had a significant influence on the RLS scores of patients with schizophrenia. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Panic disorder (PD) is a complex and heterogeneous psychiatric condition. Dysfunction within the serotonergic system has been hypothesized to play an important role in PD. The novel brain-specific serotonin synthesizing enzyme, tryptophan hydroxylase 2 (TPH2), which represents the rate-limiting enzyme of serotonin production in the brain, may therefore be of particular importance in PD. We investigated the TPH2 703G/T SNP for association with PD. Patients with PD ( n = 108), and control subjects ( n = 247), were genotyped for rs4570625 (TPH2 703G/T). Male and female subjects were analyzed separately. The severity of their symptoms was measured using the Spielberger state-trait anxiety inventory (STAI), panic disorder severity scale (PDSS), anxiety sensitivity index (ASI), acute panic inventory (API), and Hamilton’s rating scale for depression (HAMD). The genotype and allele frequencies of the PD patients and controls were analyzed using χ2 statistics. There was a significant difference in the allele frequency in rs4570625 between the PD patients and normal controls. The T allele was significantly less frequent in the PD patients. We also found a significant association with rs4570625 in the female subgroup. There was no difference in symptom severity among the genotypes of this polymorphism. This result suggests that rs4570625 polymorphism may play a significant role in the pathogenesis of PD. Moreover, rs4570625 may have a gender-dependent effect on susceptibility to PD. Further studies are needed to replicate the association that we observed. [ABSTRACT FROM AUTHOR]

Cytokine imbalances especially between T helper type (Th) 1 and Th2 and tryptophan breakdown were reported to be involved in the pathophysiology of schizophrenia. The hyperactive inflammatory response system could induce enhanced tryptophan breakdown. This study aimed to investigate the relationship between cytokine changes, tryptophan breakdown parameter changes and clinical parameters in patients with schizophrenia in comparison with normal controls. In the plasma of schizophrenic patients, Th1-specific interferon-γ was significantly higher (F = 7.485, p = 0.007) and Th2-specific interleukin (IL)-4 was significantly lower (F = 126.327, p < 0.0001). The Th1-related cytokine IL-2 was lower (F = 5.409, p = 0.021) but tumor necrosis factor-α (TNF-α) and Th2-related IL-6 were higher (F = 95.004, p < 0.0001 and F = 408.176, p < 0.0001, respectively) in the plasma of schizophrenic patients. After 6 weeks of treatment, IL-6 and TNF-α were significantly reduced (t = –3.762, p < 0.0001 and z = –2.668, p = 0.008). At the time of admission, plasma tryptophan concentrations were lower (F = 6.339, p = 0.012) in schizophrenic patients and were negatively correlated with the total positive symptoms score (r2 = -0.343, p = 0.004). After 6 weeks of medication, both plasma tryptophan and kynurenine concentrations were increased (t = –2.937, p = 0.005 and t = –3.214, p = 0.002, respectively). The findings of this study indicate a hyperactive pro-inflammatory response inducing a change in tryptophan metabolism that might be related to the development of positive symptoms in schizophrenia. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Some neurotropins, including brain-derived neurotropic factor (BDNF) or nerve growth factor-β (β-NGF), play important roles in neurodevelopment and neuroprotection. We examined the plasma levels of these 2 factors in schizophrenia patients at the time of admission and after 6 weeks of treatment with risperidone. Methods: Plasma BDNF and β-NGF levels were measured in 36 schizophrenia patients and 36 healthy controls. All the patients underwent 6 weeks of treatment with risperidone. The severity of schizophrenia and response to treatment were assessed with the positive and negative syndrome scale (PANSS). We compared plasma BDNF and β-NGF levels among much-improved (n = 13, 36.1%, ≥50% PANSS score reduction), minimal-improved (n = 15, 41.7%, ≥25% and <50% PANSS score reduction) and nonresponse patients (n = 8, 22.2%, <25% PANSS score reduction). Results: At baseline, plasma BDNF had no significant difference between schizophrenia patients and controls, but β-NGF levels were significantly lower in schizophrenia patients than controls (p = 0.037). Plasma BDNF and β-NGF in all schizophrenia patients had no significant changes between pre- and posttreatment. Baseline BDNF levels were significantly lower in nonresponse patients than others (p = 0.038). After treatment, much-improved patients had significantly higher plasma BDNF than nonresponse patients (p = 0.023). However, β-NGF levels had no significant differences between them. Conclusions: Our data suggest that higher plasma BDNF levels might be associated with better response to risperidone treatment, while plasma β-NGF levels might have no effect on the clinical response in schizophrenia patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Almost all reported studies have investigated the pharmacokinetics of aripiprazole in healthy volunteers. • The pharmacokinetics of dehydroaripiprazole have not been identified in a combined model with aripiprazole. WHAT THIS STUDY ADDS • The data on aripiprazole and dehydroaripiprazole in psychiatric patients were modelled jointly using a population approach. • The apparent clearance of aripiprazole in cytochrome P450 (CYP) 2D6 intermediate metabolizers (IM) was approximately 60% of that in CYP2D6 extensive metabolizers (EM) having two functional alleles, but the exposure to dehydroaripiprazole in CYP2D6 IM was similar to that in EM. AIMS The aims of this study were to develop a combined population pharmacokinetic model for both aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients and to identify to what extent the genetic polymorphisms of cytochrome P450 (CYP) enzymes contribute to the variability in pharmacokinetics (PK). METHODS A population pharmacokinetic analysis was performed using NONMEM software based on 141 plasma concentrations at steady state from 80 patients receiving multiple oral doses of aripiprazole (10–30 mg day−1). RESULTS A one-compartment model with first-order kinetics for aripiprazole and dehydroaripiprazole each was developed to describe simultaneously the concentration data. The absorption rate constant was fixed to 1.06 h−1. The typical value of apparent distribution volume of aripiprazole was estimated to be 192 l. Covariate analysis showed that CYP2D6 genetic polymorphisms significantly influenced the apparent clearance of aripiprazole (CL/ F), reducing the interindividual variability on CL/ F from 37.8% CV (coefficient of variation) to 30.5%. The CL/ F in the CYP2D6 IMs was approximately 60% of that in CYP2D6 EMs having two functional alleles. Based on the CYP2D6 genotype, the metabolic ratios were calculated at 0.20–0.34. However, the plasma concentration : dose ratios of dehydroaripiprazole were not different across the CYP2D6 genotype. CONCLUSIONS This population pharmacokinetic model provided an adequate fit to the data for both aripiprazole and dehydroaripiprazole in psychiatric patients. The usefulness of CYP genotyping as an aid to select the starting dose should be further investigated. [ABSTRACT FROM AUTHOR]

Objective: The incidence of restless legs syndrome (RLS) is presumed to be higher among people with schizophrenia who take antipsychotic medication, most of which blocks the dopamine D2 receptor. The purpose of this study was to determine whether the G-protein β3 subunit ( GNB3) C825T polymorphism is associated with antipsychotic-induced RLS in schizophrenia. Methods: We examined 178 Korean patients with schizophrenia. All of the subjects were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group and the International Restless Legs Scale. Genotyping was performed for the C825T polymorphism in the GNB3 gene. Results: The genotype distribution did not differ significantly between antipsychotic-induced RLS patients and patients who had no-RLS symptoms ( χ2 = 4.30, p = 0.116). The genotypes of the C825T single-nucleotide polymorphism (SNP) were classified into two groups: C+ (CC and CT genotypes) and C– (TT genotype). The presence of the C allele (C+) was associated with an increased likelihood of RLS ( χ2 = 4.14, p = 0.042; odds ratio = 2.56, 95% confidence interval = 1.02–6.47). Conclusions: These results suggest that the GNB3 C825T SNP is associated with RLS in schizophrenia. However, confirming this association requires future larger scale studies in which the effects of medication are strictly controlled. [ABSTRACT FROM AUTHOR]

Background:  Many reports have suggested possible relationships between brain-derived neurotrophic factor (BDNF) and alcohol dependence. A protective effect of BDNF against ethanol-induced cell damage has been suggested, and this effect may contribute to the development or maintenance of alcohol dependence. This study was carried out in order to verify the significance of BDNF in alcohol dependence. Methods:  Peripheral BDNF levels were measured in alcohol-dependent patients and control subjects using an enzyme-linked immunosorbent assay. A physician’s interview and standardized questionnaire were used to obtain information regarding each patient’s history of alcohol consumption. Results:  The mean BDNF level was lower in the alcohol dependence group (389.5 ± 501.7 pg/ml) than in the normal controls (822.5 ± 420.7 pg/ml) by analysis of covariance (ANCOVA) ( F = 25.79, p < 0.01). The mean BDNF level was lower in the alcohol-dependent patients with a positive family history of alcohol dependence (247.6 ± 289.2 pg/ml) than in those with a negative family history of alcohol dependence (583.9 ± 652.8 pg/ml) by ANCOVA ( F = 6.51, p = 0.01). The BDNF levels did not correlate significantly with any of the variables analyzed in this study, including Beck depression inventory, state and trait anxiety inventory (STAI-S and T), and various drinking behaviors. Conclusions:  Changes in the levels of BDNF might play a role in the pathophysiology and inheritance of alcohol dependence. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests that changes in the serum levels and cellular production of various cytokines are associated with the immunological abnormalities of schizophrenia. Several studies have examined alterations in T helper type 1 (Th1) and T helper type 2 (Th2) cytokines in schizophrenia. We explored monocytic, Th1 and Th2 cytokines in 43 schizophrenia patients and 50 normal controls. The mitogen-induced production of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-4, γ-interferon (IFN-γ) and IL-2 was measured with enzyme-linked immunosorbent assays before and after antipsychotic treatment. IL-6 and TNF-α production by schizophrenic patients was significantly higher than by normal controls, while IL-2, IL-4 and IFN-γ production was significantly lower in schizophrenic patients. After 6 weeks of antipsychotic treatment, IL-6 and TNF-α production was significantly decreased, while IL-4, IFN-γ and IL-2 productions were not significantly changed. Our results suggest that increased monocytic cytokines and decreased Th1 and Th2 cytokines may be associated with the immunopathogenesis of acute psychotic schizophrenia, and that antipsychotics may play an important role in immune response by decreasing elevated monocytic cytokines. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotics. We evaluated whether a candidate functional polymorphism of the dopamine D4 receptor (DRD4) gene is associated with drug-induced TD in 209 Korean schizophrenic patients with TD (n = 83) and without TD (n = 126) who were matched for antipsychotic drug exposure and other relevant variables. There was no significant association of the genotype and allele frequencies determined by the –521 C/T SNP of DRD4 between TD and non-TD patients. In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the 3 genotype groups. Within the limitations imposed by the size of the clinical sample, these findings suggest that the DRD4 –521 C/T SNP does not contribute significantly to the risk for TD. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Recent studies have raised the possibility that nerve growth factor (NGF) is abnormally regulated in the central nervous system (CNS) of animal models of chronic ethanol treatment. The goals of this study were to determine whether prolonged alcohol consumption is associated with the plasma NGF levels and to assess the effect of a positive family history of alcohol dependence on plasma NGF levels in the alcohol-dependent patients. Methods: We used the enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of peripheral NGF in patients with alcohol dependence and in a control group. Results: The plasma NGF concentrations in the alcohol-dependent patients were significantly lower than in the controls (71.9 vs 110.5 pg/mL, respectively). Moreover, the alcohol-dependent patients with positive family histories showed a greater decrease in their NGF levels than those subjects with negative family histories (64.7 vs 83.3 pg/mL, respectively). Conclusions: Our study suggests that the NGF levels may be a trait marker for the development of alcohol dependence. [ABSTRACT FROM AUTHOR]

Background: Borna disease virus (BDV) predominantly infects horses and sheep, causing a broad range of behavioural disorders. It is controversial whether BDV infects humans and causes psychiatric disorders. Objectives: We searched for BDV-derived nucleic acids in blood of race horses and jockeys riding the horses. Methods: We assayed for the BDV genome in RNA extracted from peripheral blood mononuclear cells (PBMC) of 39 race horses and 48 jockeys. Two polymerase chain reaction protocols [one-tube reverse transcription–polymerase chain reaction (RT-PCR) and two-step RT-PCR] were used to assay BDV p24 and p40 transcripts. Results: The p24 and p40 viral nucleic acid sequences were not detected in the PBMC RNAs from any of the race horses or jockeys. Conclusions: These data do not support an epidemiological association between BDV infection, race horses and humans. [ABSTRACT FROM AUTHOR]

Objective: To evaluate any correlation between plasma levels of nitric oxide metabolites (NOx) and suicide attempt. Method: Plasma NOx levels were measured in 53 patients who had recently attempted suicide, 58 nonsuicidal psychiatric patients, and 75 normal controls. The severity of suicidal behaviors was evaluated using Weisman and Worden’s Risk-Rescue Rating Scale. Results: Plasma NOx levels were significantly higher in suicidal patients than nonsuicidal psychiatric patients or normal control subjects (F = 11.029, d.f. = 2, 183, p < 0.001). Among the patients with a diagnosis of major depression, suicidal depressive patients had significantly higher plasma NOx levels than nonsuicidal depressive patients (t = –3.090, d.f. = 84, p = 0.003). Conclusion: Our study suggests that increased NO production in plasma is associated with suicide attempt, especially in depressive patients. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This study investigated the relationship between G-protein β3 subunit (GNB3) C825T polymorphism and seasonal variation in 189 young male college students. The subjects were genotyped for C825T and were evaluated by the Seasonality Pattern Assessment Questionnaire. The Global Seasonality Score (GSS) between the three genotypes revealed a marginal difference. The heterozygotes showed significantly higher seasonal variations in GSS than the homozygotes. The prevalence of heterozygotes tended to be higher in seasonals compared with normal subjects, although it was not statistically significant. These results suggest that GNB3 C825T polymorphism tends to be related to seasonal variation in mood and behavior in the normal population. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder marked by behavioral, physiologic, and hormonal alterations. The etiology of PTSD is unknown, although exposure to a traumatic event constitutes a necessary, but not sufficient, factor. Serotonergic dysfunction has been implicated in PTSD. The present study examined the possible association between the serotonin-transporter-linked polymorphic region (SERTPR) and PTSD. The genotype and allele frequencies of the SERTPR were analyzed in 100 PTSD patients and 197 unrelated healthy controls using a case–control design. The frequency of the s/s genotype was significantly higher in PTSD patients than in normal controls. These findings suggest that the SERTPR s/s genotype is one of the genetic factors for the susceptibility to PTSD. Further investigations are required into the influence of gene polymorphisms on the biological mechanisms of PTSD, its clinical expression, and its response to treatment. Depression and Anxiety 00:1–5, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objective To find the optimal changes needed for resolution of amenorrhoea associated with risperidone. Method Between November 2001 and May 2002, 16 female outpatients who had taken risperidone for more than 3 months voluntarily reported amenorrhoea. Following each report of amenorrhoea, serum prolactin level was measured and treatment changes were undertaken. The menstrual cycles and clinical mental status of each patient were followed for the next 6 months. For nine of the 16 patients, the dose of risperidone was reduced. For the other seven patients, risperidone was switched to olanzapine or quetiapine. Results Fourteen of 16 patients had hyperprolactinemia. Two patients who had discontinuation of risperidone recovered from amenorrhoea and three of the risperidone-reduction patients resumed their periods. All subjects in the drug-switch patients recovered. The patients who recovered from amenorrhoea at a reduced dosage of risperidone took ≤3 mg/day. Two patients in the risperidone-reduction group dropped out. Conclusion Stopping risperidone (without starting any other antipsychotic) or switching to a prolactin-sparing antipsychotic is an effective strategy for resolution of amenorrhoea on risperidone, but that dose reduction is rarely effective either because amenorrhoea continues despite lower dose or because relapse of psychosis appears. [ABSTRACT FROM AUTHOR]

Aims: Ghrelin is a peptide hormone that antagonizes the action of leptin and is thereby thought to regulate feeding behaviour. The actions of ghrelin and leptin appear to be mediated by the neuropeptide Y (NPY) and Agouti-related protein (AGRP) system. Recent studies have suggested that leptin and NPY play significant roles in the pathophysiology of alcoholism. The aim of this study was to determine whether ghrelin is associated with the state and duration of abstinence in individuals with alcohol dependence. Methods: Fasting plasma ghrelin levels were compared between 47 individuals with chronic alcoholism during a period of abstinence and 50 control subjects. Results: Fasting plasma ghrelin levels were higher in alcohol abstainers than those in controls. Furthermore, a positive correlation was observed between ghrelin levels and the duration of abstinence. In addition, daily alcohol intake prior to abstinence was inversely related to ghrelin levels. Conclusions: These findings suggest that ghrelin plays a role in the pathogenesis of alcohol dependence, particularly during the abstinence period, in individuals with chronic alcoholism. [ABSTRACT FROM AUTHOR]

This study investigated the psychophysiological effects of sleep deprivation on auditory event-related potentials (AERPs) and their relationship with psychological parameters. Twenty-four subjects remained awake for 37 h under continuous surveillance. In the mornings and the evenings of 2 consecutive study days, AERPs were recorded and 4 self-rated scales (sleepiness, fatigue, anxiety, and mood) were quantified. The latencies of P300 and N200 were significantly prolonged (p < 0.001) and their amplitudes decreased (p < 0.05) as a consequence of sleep deprivation. However, the only significant change in N100 and P200 was an increase in the P200 amplitude (p < 0.05). The increase in the latencies of P300 and N200 were correlated with increased sleepiness (p < 0.05), and the increase in P200 amplitude was correlated with negative mood, anxiety, and fatigue (p < 0.05). Although the changes in P300 and N200 induced by sleep deprivation are due to sleepiness, which may slow cognitive processing and decrease the efficiency of mental processing, the increase in P200 may be related with increased anxiety, negative mood, and fatigue. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Lee S-H, Chung Y-C, Yang J-C, Kim Y-K, Suh K-Y. Abnormal speech perception in schizophrenia with auditory hallucinations. The neurobiological mechanism of auditory hallucination (AH) in schizophrenia remains elusive, but AH can be caused by the abnormality in the speech perception system based on the speech perception neural network model. The purpose of this study was to investigate whether schizophrenic patients with AH have the speech processing impairment as compared with schizophrenic patients without AH, and whether the speech perception ability could be improved after AH had subsided. Twenty-four schizophrenic patients with AH were compared with 25 schizophrenic patients without AH. Narrative speech perception was assessed using a masked speech tracking (MST) task with three levels of superimposed phonetic noise. Sentence repetition task (SRT) and auditory continuous performance task (CPT) were used to assess grammar-dependent verbal working memory and non-language attention, respectively. These tests were measured before and after treatment in both groups. Before treatment, schizophrenic patients with AH showed significant impairments in MST compared with those without AH. There were no significant differences in SRT and CPT correct (CPT-C) rates between both groups, but CPT incorrect (CPT-I) rate showed a significant difference. The low-score CPI-I group showed a significant difference in MST performance between the two groups, while the high-score CPI-I group did not. After treatment (after AH subsided), the hallucinating schizophrenic patients still had significant impairment in MST performance compared with non-hallucinating schizophrenic patients. Our results support the claim that schizophrenic patients with AH are likely to have a disturbance of the speech perception system. Moreover, our data suggest that non-language attention might be a key factor influencing speech perception ability and that speech perception dysfunction might be a trait marker in schizophrenia with AH. [ABSTRACT FROM AUTHOR]

Superconducting dc reactor protects power system by limiting the amplitude of fault current with its inductance. Therefore, it is very important to design and simulate the dc reactor precisely for making the power system stable and effective. In this paper, we designed the superconducting dc reactor of inductive superconducting fault current limiter conceptually and acquired the optimal design parameters by using Finite Element Method (FEM). We manufactured the superconducting dc reactor and tested its characteristics at cryocooler-cooled 20 K temperature. Moreover, compared experimental characteristics with simulation results and analyzed them. We introduced the design method of the superconducting dc reactor and the fabrication method of 1.2 kV/80 A class dc reactor for inductive superconducting fault current limiter. Finally, we performed the short circuit test and discussed the results. [ABSTRACT FROM AUTHOR]

The energy method based on the first law of thermodynamics is employed to predict the whole range of stress-strain behavior of twisted hybrid fibrous structures. The model blend yams considered are sheath/core and mixed two-component yarns. Analytical expressions for the load-elongation response including failure are derived as functions of yam geometry and the mechanical properties of component fibers. The mathematical expressions are applicable to the hybrid yam structures made of nonlinear materials with any fractional combination of two components. [ABSTRACT FROM PUBLISHER]

Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an N-methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics. [ABSTRACT FROM AUTHOR]