Ihn Geun Choi

Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder

Mood abnormalities related to major depressive disorder (MDD) seem to result from disturbances in pathways connecting the fronto-limbic and subcortical, both regions known to be involved in the processing of emotional information. Using functional magnetic resonance imaging (fMRI), we measured neural responses to viewing images of sad, angry and neutral faces in 21 patients with MDD and 15 healthy controls. When shown pictures of sad faces, patients with MDD relative controls showed decreased activations bilaterally in the dorsolateral prefrontal cortex, inferior orbitofrontal cortex (OFC), medial OFC, caudate, and hippocampus. We also found significant group differences under the angry face condition, bilaterally, in the inferior OFC and medial OFC areas. Our findings indicate that decreased activations in the fronto-limbic and subcortical regions in response to affectively negative stimuli may be associated with pathophysiology of MDD.

Decreased N-acetyl-aspartate levels in anterior cingulate and hippocampus in subjects with post-traumatic stress disorder: a proton magnetic resonance spectroscopy study

The purpose of this study was to investigate the concentration of N‐acetyl‐aspartate (NAA) in the brain and its relationship with clinical characteristics in patients with post‐traumatic stress disorder (PTSD). Proton magnetic resonance spectroscopy was performed in order to measure NAA concentrations in the anterior cingulate cortex (ACC) and bilateral hippocampus in 26 subjects with fire‐related PTSD, who were survivors of a subway fire in South Korea, and 25 age‐ and sex‐matched healthy comparison subjects. There were decreased NAA levels in the ACC (tu2003=u2003−3.88, d.f.u2003=u200349, Pu2003<u20030.001) and bilateral hippocampus (right, tu2003=u2003−3.88, d.f.u2003=u200349, Pu2003<u20030.001; left, tu2003=u2003−3.62, d.f.u2003=u200349, Pu2003<u20030.001) in the PTSD group relative to the healthy comparison group. Also, NAA levels of the ACC (ru2003=u2003–0.43, nu2003=u200326, Pu2003=u20030.027) and bilateral hippocampus (right, ru2003=u2003–0.48, nu2003=u200326, Pu2003=u20030.013; left, ru2003=u2003−0.40, nu2003=u200326, Pu2003=u20030.04) were negatively correlated with re‐experience symptom scores in subjects with PTSD. In conclusion, our findings suggest that subjects with PTSD had decreased neuronal viabilities in the ACC and bilateral hippocampus, and that these deficits may play an important role in the pathophysiology of PTSD, especially regarding the re‐experiencing of traumatic events.

Relation between plasma brain-derived neurotrophic factor and nerve growth factor in the male patients with alcohol dependence

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are thought to be related to neuroprotection in cell culture and animal studies. Our aim was to verify the changes in human plasma BDNF and NGF concentrations induced by chronic alcohol use. Forty-one male patients with alcohol dependence were sampled the next morning of admission and compared with 41 healthy male subjects. Plasma BDNF and NGF were assayed using an enzyme-linked immunosorbent assay (ELISA). Mean plasma BDNF level was significantly higher in the patients with alcohol dependence (3502.21+/-1726.9 pg/mL) compared with the healthy subjects (861.75+/-478.9 pg/mL) (P=.000). Mean plasma NGF level was also significantly higher in patients with alcohol dependence (137.64+/-32.7 pg/mL) than in healthy subjects (112.61+/-90.2 pg/mL) (P=.012). Plasma BDNF and NGF levels showed significant negative correlation in alcohol dependence group (r=-0.388, P=.012). Increased plasma BDNF and NGF with negative correlation in alcohol-dependent patients may have some role in the regeneration of damage done by chronic alcohol use.

Ethanol-induced small heat shock protein genes in the differentiation of mouse embryonic neural stem cells.

Neural stem cells (NSCs) of the neuroepithelium differentiate into one of three central nervous system (CNS) cell lineages: neurons, astrocytes, or oligodendrocytes. In this study, the differentiation potential of NSCs from the forebrain of embryonic day 15 (E15) mouse embryos was analyzed using immunocytochemistry. NSCs were differentiated early in the presence or absence of ethanol (50xa0mM), and gene expression patterns among NSCs, differentiated cells and ethanol-treated differentiated cells were assessed by microarray and real-time PCR analysis. Genes that were up-regulated in differentiated cells both in the presence and in the absence of ethanol when compared to NSCs were related to the Wnt signaling pathway, including Ctnna1, Wnt5a, Wnt5b, Wnt7a, Fzd3, and Fzd2; genes related to cell adhesion, including Cadm1, Ncam1, and Ncam2; and genes encoding small heat shock proteins, including HspB2, HspB7, and HspB8. In particular, the expression levels of HspB2 and HspB7 were elevated in ethanol-treated differentiated cells compared to non-treated differentiated cells. The gene expression patterns of various heat shock transcription factors (HSFs), proteins that regulate the transcription of heat shock genes, were also analyzed. The expression levels of HSF2 and HSF5 increased in differentiated cells in the presence and absence of ethanol when compared to NSCs. Of these two genes, HSF5 demonstrated an enhanced up-regulation, particularly in ethanol-treated differentiated cells compared to cells that were differentiated in the absence of ethanol. These results imply that HspB2 and HspB7, which are small heat shock proteins with tissue-restricted expression profiles, might be up-regulated by ethanol during the short-term differentiation of NSCs.

Genetic polymorphisms of alcohol and aldehyde dehydrogenase, dopamine and serotonin transporters in familial and non-familial alcoholism

One hundred and eleven male patients with alcohol dependence and 123 nonalcoholic healthy men were tested for the genetic polymorphisms of alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2 (ALDH2), serotonin transporter (5-HTT) and dopamine transporter (DAT1). There were significant differences in genotype frequencies of ADH2 C992G and A13543G SNPs between alcoholic patients with family history of alcohol dependence (familial) and alcoholic patients without family history (non-familial). Genotype and allele frequencies of ALDH2 G1951A SNP in familial or non-familial alcoholic patients differ from normal controls. Neither 5-HTTLPR L/S nor DAT1 G2319A SNP genotypes nor alleles discriminated alcoholic patients from normal controls. These findings suggest that the genetic characteristics of alcohol metabolism in non-familial alcoholics fall between non-alcoholism and familial alcoholics.

Efficacy of naltrexone in the treatment of chronic refractory itching in burn patients: preliminary report of an open trial.

Pruritis (itching) constitutes a source of severe distress for burn patients. The authors administered naltrexone to burn patients suffering from itching that was refractory to treatment with antihistamine and anticonvulsant medications to examine the efficacy of this medication as a treatment for pruritis in burn patients. Nineteen burn patients admitted to the Hallym Burn Center at Hangang Sacred Heart Hospital in Seoul, Korea, with burns over 40.32% (±18.3) of their total body surface were recruited for this study. The mean number of postburn days before naltrexone treatment was 157.3 days (±114.7). The authors observed a significant decrease in itching sensations after 2 weeks of treatment with naltrexone (z = −3.32, P = .001). Scratching activity was also decreased in 44.5% (±20.5) of subjects. The authors propose that naltrexone constitutes a potential antipruritic medication for burn patients suffering from treatment-refractory itching.

Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs).

This study used human embryonic carcinoma (NCCIT) cells to evaluate genotoxicity and other effects of ethanol in earlier stages of cellular development. This undifferentiated pluripotent cell line has unlimited self-renewal capacity and has been shown to differentiate in vitro. We analyzed proteome expression profile of ethanol-treated NCCIT cells and NCCIT cell-derived embryoid bodies (EBs) by MALDI-TOF MS. To test the role of ethanol as an embryotoxic and/or teratogenic factor, MetaCore pathway analysis software (GeneGO) was used to evaluate the process of normal growth and differentiation of NCCIT cells and EBs. We compared the different protein expression profiles of ethanol-treated versus untreated NCCIT cells and NCCIT cell-derived EBs. The ethanol-treated NCCIT cells demonstrate significant up regulation of SMAP1, dual specificity phosphatase 1 and pro isomerase domain-containing 1, cytokeratin 18, triosephosphate isomerase and beta-tubulin. However, ethanol-treated NCCIT cell-derived EBs exhibited upregulated signatures of different proteins, including CDC25B phosphatase, alpha-enolase, 3-phosphoglycerate dehydrogenase and tumor suppressor patched L isoform, which suggests that ethanol may play a different role in EBs. These proteins exert their function on transcriptional and translational processes. Moreover, the functional proteomic analysis confirms the relationship between ethanol and ethanol-regulated genes and various signaling pathways and networks. The data presented in this study contribute toward the understanding of the molecular mechanisms of ethanol in NCCIT cells and NCCIT cell-derived EBs.

The Association of DRD2 −141C and ANKK1 TaqIA Polymorphisms with Alcohol Dependence in Korean Population Classified by the Lesch Typology

AIMSnDopamine receptors are associated with reward and dependence towards alcohol. The polymorphisms of dopamine D2 receptor (DRD2) genes have been reported to be involved in susceptibility to alcoholism. Therefore, we investigated the association of three single-nucleotide polymorphisms (SNPs) in DRD2 and ankyrin repeat and kinase domain containing one (ANKK1) genes with alcohol dependence in Korean subjects, who were classified by the criteria of the Lesch typology.nnnMETHODSnThe DRD2 -141C (Insertion (Ins)/Deletion (Del)), exon8 (A/G) and the ANKK1 TaqIA (A1/A2) polymorphisms were genotyped in a case-control sample consisting of 245 alcohol-dependent (AD) patients and 110 healthy controls. AD patients were classified into four subtypes by the Lesch typology. The majority of them (77.1%) were Lesch type 1. Differences in genotype and allele frequencies were examined between the AD patients and the controls. Also those analyses were done between the Lesch type 1 group and the controls.nnnRESULTSnThere were significant differences in the genotype and allele frequencies of -141C Ins/Del and TaqIA A1/A2 between the AD patients and the controls. However, there were no significant differences in genotype or allele frequencies of exon8 A/G between the AD patients and the controls. The -141C Ins/Ins and TaqIA A1+ variants were associated with Lesch type 1 AD patients. When analysing haplotypes of three SNPs, the odds ratio of -141C Ins-A-A1 was 2.286, while the odds ratio of -141C Del-G-A2 was 0.323.nnnCONCLUSIONnThe present study showed a significant difference in DRD2 -141C and ANKK1 TaqIA polymorphisms between the AD patients and the controls. Our findings suggest that -141C Ins and TaqIA A1 alleles can be a predisposing factor for alcohol dependence in the Korean population.

Naltrexone influences protein kinase Cε and integrin α7 activity in SH-SY5Y neuroblastoma cells

Alcohol influences the neuroadaptation of brain cells where receptors and enzymes like protein kinase C (PKC) exist. Naltrexone acts on opioid receptors. However, other mechanisms of action remain unknown. We prepared SH-SY5Y neuroblastoma cells, and fed them with 150 mM ethanol for 72 h followed by treatment with naltrexone for 24 h. We performed microarray analysis and reverse transcriptase-polymerase chain reaction. Our results showed that PKCε increased 1.90 times and showed an overall decreasing pattern as time increased. Phosphorylated ERK also increased 2.0 times according to the change of PKCε. Integrin α7 increased 2.32 times and showed an increasing pattern as time increased. In conclusion, naltrexone influences PKCε neuronal signaling system and endothelial adhesion molecule integrin α7 in addition to the well-known opioid system.

Increased Transforming Growth Factor-beta1 in Alcohol Dependence

Ethanol and its metabolite acetaldehyde increase transforming growth factor beta1 (TGF-β1) expression in animal studies. TGF-β1 is related with the hepatic stellate cell (the key element of hepatic fibrogenesis) and the radial glia (the key element of neuronal migration). Blood samples were collected from 41 patients with alcohol dependence, TGF-β1 levels measured by ELISA were compared with 41 normal subjects. Plasma TGF-β1 levels in the patients with alcohol dependence (1,653.11±532.45 pg/mL) were significantly higher than those of healthy subjects (669.87±366.53 pg/mL) (P=0.000). Patients with or without liver pathology showed no difference in TGF-β1 (P=0.36). Increased TGF-β1 may mediate deleterious effect of alcohol such as hepatic fibrosis and suppressed neuronal developments in alcohol dependence patients.