Predicting Autism Spectrum Disorder Using Blood-based Gene Expression Signatures and Machine Learning

OBJECTIVE: The aim of this study was to identify a transcriptomic signature that could be used to classify subjects with autism spectrum disorder (ASD) compared to controls on the basis of blood gene expression profiles. The gene expression profiles could ultimately be used as diagnostic biomarkers for ASD. METHODS: We used the published microarray data (GSE26415) from the Gene Expression Omnibus database, which included 21 young adults with ASD and 21 age- and sex-matched unaffected controls. Nineteen differentially expressed probes were identified from a training dataset (n=26, 13 ASD cases and 13 controls) using the limma package in R language (adjusted p value <0.05) and were further analyzed in a test dataset (n=16, 8 ASD cases and 8 controls) using machine learning algorithms. RESULTS: Hierarchical cluster analysis showed that subjects with ASD were relatively well-discriminated from controls. Based on the support vector machine and K-nearest neighbors analysis, validation of 19-DE probes with a test dataset resulted in an overall class prediction accuracy of 93.8% as well as a sensitivity and specificity of 100% and 87.5%, respectively. CONCLUSION: The results of our exploratory study suggest that the gene expression profiles identified from the peripheral blood samples of young adults with ASD can be used to identify a biological signature for ASD. Further study using a larger cohort and more homogeneous datasets is required to improve the diagnostic accuracy.

The Clinical Association between the Prevalence of Insomnia and Physical and Psychiatric Disorders in Two Areas of Gyeonggi Province of South Korea / 신경정신의학

OBJECTIVES: The purposes of this study are to examine the sociodemographic factors that increase the prevalence of insomnia, as well as to identify the relationship between the prevalence of insomnia and health conditions by navigating through the prevalence rates of insomnia in two different geographical regions with different socioeconomic structures. METHODS: A survey was conducted targeting 937 residents of Guri-si and Yangpyeong-gun in Gyeonggi Province, Korea. The Insomnia Severity Index was used to verify whether a respondent was experiencing insomnia. The Abbreviated Self-Rated Korean version of the Mini-International Neuropsychiatric Interview was used in diagnosis of mental diseases. Chi-square test was performed to determine the unique relationship between sociodemographic characteristics and the prevalence of insomnia. Multivariate logistic regression analysis was performed to examine the association of prevalence of insomnia with categorized relevant factors. RESULTS: The overall prevalence rate of insomnia for all respondents was 9.26%. The prevalence rate for Yangpyeong-gun was 11.75%, marking a significantly higher figure compared with the prevalence rate for Guri-si, which was 6.87%. Advanced age, female, other marital statuses than married, lower education, lower income, non-existence of private health insurance, and unemployment were risk factors for insomnia. The prevalence of insomnia showed strong association with physical and mental conditions, particularly with mental disorders, urologic diseases, and risk of injury from fall. CONCLUSION: The prevalence rates of insomnia in those two surveyed regions showed a meaningful difference even after controlling for sociodemographic characteristics. These findings suggest that such regional differences merits further attention and additional nationwide epidemiologic studies are needed.

Stressful Life Events and Depression in 60 Year Old Population of Gyeonggi Province : Social Support Can Act as Moderators?

OBJECTIVE: 60-year old Korean population has particular life experiences such as Korean War. With this life experience, we aimed to examine the moderating role of social support on the relationship between adverse life events and depressive symptoms in later life. METHODS: The total respondents were 639 people who were 60-year old dwelling in Yangpyung, Gyeonggi Province, South Korea. One to one interviews were conducted by experienced research assistants. RESULTS: Examining depression, 14.7% of total population showed 15 or higher geriatric depression scale-shortform-Korea score. 70% did report stressful life events as many as 13. Also, 31.6% of total participants were isolated or at high risk of isolation. Using hierarchical multiple regression models, the results showed that social support moderated the influence of the exposure to stressful life events on depression (R2=0.124, beta=-0.118, p<0.01). The moderating effect was greater in male (R2=0.118, beta=-1.36, p<0.01) than that of female (R2=0.113, beta=-0.115, p<0.01), which is apposite to our hypothesis. CONCLUSION: This finding suggests that social support play critical roles in the stress-outcome relationship among 60-years old population like it was suggested. Since most stressful events are inevitable, it is important to build sufficient social support networks.

Profiling of Proteins Regulated by Venlafaxine during Neural Differentiation of Human Cells

OBJECTIVE: Antidepressants are known to positively influence several factors in patients with depressive disorders, resulting in increased neurogenesis and subsequent relief of depressive disorders. To study the effects of venlafaxine during neural differentiation at the cellular level, we looked at its effect on protein expression and regulation mechanisms during neural differentiation. METHODS: After exposing NCCIT cell-derived EBs to venlafaxine during differentiation (1 day and 7 days), changes in protein expression were analyzed by 2-DE and MALDI-TOF MS analysis. Gene levels of proteins regulated by venlafaxine were analyzed by real-time RT-PCR. RESULTS: Treatment with venlafaxine decreased expression of prolyl 4-hydroxylase (P4HB), ubiquitin-conjugating enzyme E2K (HIP2) and plastin 3 (T-plastin), and up-regulated expression of growth factor beta-3 (TGF-beta3), dihydropyrimidinase-like 3 (DPYSL3), and pyruvate kinase (PKM) after differentiation for 1 and 7 days. In cells exposed to venlafaxine, the mRNA expression patterns of HIP2 and PKM, which function as negative and positive regulators of differentiation and neuronal survival, respectively, were consistent with the observed changes in protein expression. CONCLUSION: Our findings may contribute to improve understanding of molecular mechanism of venlafaxine.

NCAM140 and pCREB Expression after Tianeptine Treatment of SH-SY5Y Cells

OBJECTIVE: Antidepressants Modulate Neuronal Plasticity. Tianeptine, An Atypical Antidepressant, Might Be Involved In The Restoration Of Neuronal Plasticity; It Primarily Enhances The Synaptic Reuptake Of Serotonin. Ncam140 Is Involved In Neuronal Development Processes, Synaptogenesis And Synaptic Plasticity. We Investigated The Effect Of Tianeptine On The Expression Of Ncam140 And Its Downstream Signaling Molecule In The Human Neuroblastoma Cell Line Sh-sy5y. METHODS: NCAM protein expression was measured in human neuroblastoma SH-SY5Y cells that were cultivated in serum-free media and treated with 0, 10, or 20 microM tianeptine for 6, 24, or 72 hours. NCAM140 expression in the tianeptine treatment group was confirmed by Western blot, and quantified through measurement of band intensity by absorbance. CREB and pCREB expression was identified after treatment with 20 microM tianeptine for 6, 24, and 72 hours by Western blot. RESULTS: Compared to cells treated for 6 hours, cells treated with 0 or 10 microM tianeptine for 72 hours showed a significant increase in NCAM140 expression and cells treated with 20 microM tianeptine showed a significant increase after 24 and 72 hours. The pCREB level in cells treated with 20 microM tianeptine increased in time-dependent manner. CONCLUSION: Our findings indicated that the tianeptine antidepressant effect may occur by induction of NCAM140 expression and CREB phosphorylation.

Evidence-Based, Non-Pharmacological Treatment Guideline for Depression in Korea

Although pharmacological treatment constitutes the main therapeutic approach for depression, non-pharmacological treatments (self-care or psychotherapeutic approach) are usually regarded as more essential therapeutic approaches in clinical practice. However, there have been few clinical practice guidelines concerning self-care or psychotherapy in the management of depression. This study introduces the 'Evidence-Based, Non-Pharmacological Treatment Guideline for Depression in Korea.' For the first time, a guideline was developed for non-pharmacological treatments for Korean adults with mild-to-moderate depression. The guideline development process consisted of establishing several key questions related to non-pharmacologic treatments of depression, searching the literature for studies which answer these questions, assessing the evidence level of each selected study, drawing up draft recommendation, and peer review. The Scottish Intercollegiate Guidelines Network grading system was used to evaluate the quality of evidence. As a result of this process, the guideline recommends exercise therapy, bibliotherapy, cognitive behavior therapy, short-term psychodynamic supportive psychotherapy, and interpersonal psychotherapy as the non-pharmacological treatments for adult patients with mild-to-moderate depression in Korea. Hence, it is necessary to develop specific methodologies for several non-pharmacological treatment for Korean adults with depression.

Questionnaires for Assessing Stress and Mental Health / 한양의대학술지

Psychological factors can influence physical health. The relationship between psychological stress and physical disease is evident in everyday clinical practice and therefore, assessing stress and mental health has been an important issue in clinical practice and research. This review discusses the assessment of stress and mental health by examining the psychometric parameters and other qualities of some of the best-known instruments used to assess stress and mental health. At present, the questionnaire method is the most popular for measuring stress and mental health status. There are many different kinds of questionnaires for assessing mental stress; each questionnaire has its own advantages and disadvantages. The authors' intend to evaluate and summarize useful questionnaires for assessing stress and mental health in order to aid in choosing the appropriate questionnaire according to the clinical purpose of the examination.

The Psychological Characteristics and Functional Magnetic Resonance Imaging Findings in Firefighters with Partial Posttraumatic Stress Disorder and the Effect of Treatment by Using Eye Movement Desensitization and Reprocessing / 신경정신의학

OBJECTIVES: This study investigated the clinical characteristics and functional magnetic resonance imaging (fMRI) findings of firefighters suffering from partial posttraumatic stress disorder (partial PTSD). They were treated by eye movement desensitization and reprocessing (EMDR) and the treatment effect was evaluated. METHODS: A total of 116 firefighters were screened and 15 of them were diagnosed as partial PTSD. 1) We compared sociodemographic and psychological characteristics between the firefighter partial PTSD group and the firefighter control group. 2) Subjects in the firefighter partial PTSD group (n=10), firefighter control group (n=8), and general control group (n=12) underwent fMRI with traumatic, negative, positive, and neutral picture stimuli. We compared clinical characteristics and fMRI findings among these three groups. 3) Seven firefighters in the partial PTSD group were treated by EMDR and the treatment effect was evaluated according to psychological scales. RESULTS: In fMRI analysis, there was a left middle temporal/occipital activation in the order of the general control group, firefighter control group, than the firefighter partial PTSD group for the Traumatic-Baseline contrast. For the Negative-Baseline contrast, there was an increased left middle temporal/occipital activation in the general control group versus decreased activation in the firefighter control group and the firefighter partial PTSD group. All firefighters in the partial PTSD group treated by EMDR showed significant improvement of Clinician-Administered PTSD Scale scores. CONCLUSION: These results show high incidence rate of partial PTSD in firefighters. In addition, partial PTSD firefighters exhibited distinct clinical characteristics and fMRI findings and showed significant improvement by EMDR treatment.

Prevalence and Correlates of Depressive Symptoms in Korean Adults: Results of a 2009 Korean Community Health Survey

The aim of this study was to investigate the prevalence and correlates of depressive symptoms in the largest number of Korean individuals examined to date. We analyzed cross-sectional data collected from 229,595 Korean adults aged 19 yr and above who participated in a Korean Community Health Survey conducted in 2009. The Center for Epidemiologic Studies Depression Scale (CES-D) was used as the measurement tool for depressive symptoms (CES-D score over 16) and definite depression (CES-D score over 25). Multivariate logistic regression analysis was performed to identify associations between sociodemographic factors and depressive symptoms. The percentages of depressive symptoms and definite depression in the total study population were 11% (7.8% for men, 14.0% for women) and 3.7%, (2.4% for men, 5.0% for women), respectively. Female gender, older age, disrupted marital status, low education and income level, multigenerational household composition and metropolitan residence were associated with greater risk of depressive symptoms. The present study provides a valid prevalence and correlates of depressive symptoms, using the largest representative sample of the Korean general population to date. Various sociodemographic factors contribute to the prevalence and effects of depressive symptoms in Korea.

Cognitive Behavioral Therapy of Insomnia / 한양의대학술지

Cognitive behavioral therapy for insomnia (CBT-I) is a group of strategies which includes sleep restriction, stimulus control therapy, relaxation training, cognitive therapy, and various combinations of those methods. Growing evidence from controlled clinical trials indicates that the majority of patients (70 to 80%) with persistent insomnia respond to CBT, and approximately half of them achieve clinical remission. CBT-I produces significant improvements of sleep-onset latency, wake after sleep onset, sleep efficiency, and sleep quality. These benefits are paralleled by reductions of daytime fatigue, improvement in psychological symptoms, and decreased usage of hypnotics. Changes in sleep patterns are well maintained after completing therapy. Treatment outcomes have been documented primarily with prospective sleep diaries; studies using polysomnography and actigraphy have also supported these results. Considering the results of current peer-reviewed research, CBT-I should be the first-line therapy for persistent insomnia. Despite strong evidence supporting its efficacy and effectiveness, CBT-I remains under utilized by health care practitioners. Increased application of evidence-based CBT-I therapies and their extension into primary medical practices should be highly effective and should be recommended in the future for better clinical management of insomnia-related disorders.

Comparison of Neurite Outgrowth Induced by Erythropoietin (EPO) and Carbamylated Erythropoietin (CEPO) in Hippocampal Neural Progenitor Cells

A previous animal study has shown the effects of erythropoietin (EPO) and its non-erythropoietic carbamylated derivative (CEPO) on neurogenesis in the dentate gyrus. In the present study, we sought to investigate the effect of EPO on adult hippocampal neurogenesis, and to compare the ability of EPO and CEPO promoting dendrite elongation in cultured hippocampal neural progenitor cells. Two-month-old male BALB/c mice were given daily injections of EPO (5 U/g) for seven days and were sacrificed 12 hours after the final injection. Proliferation assays demonstrated that EPO treatment increased the density of bromodeoxyuridine (BrdU)-labeled cells in the subgranular zone (SGZ) compared to that in vehicle-treated controls. Functional differentiation studies using dissociated hippocampal cultures revealed that EPO treatment also increased the number of double-labeled BrdU/microtubule-associated protein 2 (MAP2) neurons compared to those in vehicle-treated controls. Both EPO and CEPO treatment significantly increased the length of neurites and spine density in MAP2(+) cells. In summary, these results provide evidences that EPO and CEPO promote adult hippocampal neurogenesis and neuronal differentiation. These suggest that EPO and CEPO could be a good candidate for treating neuropsychiatric disorders such as depression and anxiety associated with neuronal atrophy and reduced hippocampal neurogenesis.

Difference of the Heart Rate Variability According to the Social Support Level in a County / 정신신체의학

OBJECTIVES: The present study takes part of the agricultural district cohort study of a certain county located in Gyeonggido and aims to investigate the difference of the heart rate variability(HRV) according to the social support level. METHODS: We used data from 1727 participants of a health promotion program who are older than 40 years old. A physical examination, as well as a one-to-one interview to obtain sociodemographic characteristics, was performed with each participant. In addition, the participants completed the Medical Outcomes Study-Social Support Survey(MOS-SSS) for their the social support level to be assessed, and their HRV were measured to evaluate their autonomic function. The entire group was divided in two groups according to its MOS-SSS points to facilitate the research. Those who were evaluated as the high 25%(432 persons) were denominated as high social support (HSS) group and those who were evaluated as the low 25%(425 persons) were denominated as poor social support(PSS) group. RESULTS: The two groups showed significant differences on the sociodemographic factor such as mean age and gender composition(p<0.05). Comparing the indices related to the HRV, the HSS group had the following values higher than the PSS group : SDNN(F=4.938, p=0.027), TP(F=8.088, p=0.005), VLF(F=6.220, p=0.013) LF (F=3.873, p=0.049). CONCLUSION: According to the research, the PSS group showed dysfunction on their autonomic nervous system comparing to the HSS group. The social support helps an individual overcome difficulties, helps the adaptation during the changes of circumstances and in stressful situations it serves like a buffer. Based on that, it's possible to define that a low social support level gave an impact on the autonomic function. Also, using the fact that the HRV can evaluate the autonomic function in an objective view, it was possible to visualize that it has a potential to be used as an assistant factor to evaluate the social support.

Fluoxetine Increases the Expression of NCAM140 and pCREB in Rat C6 Glioma Cells

OBJECTIVE: Dysfunction of neural plasticity in the brain is known to alter neural networks, resulting in depression. To understand how fluoxetine regulates molecules involved in neural plasticity, the expression levels of NCAM, NCAM140, CREB and pCREB, in rat C6 glioma cells after fluoxetine treatment were examined. METHODS: C6 cells were cultured after 20 min or after 6, 24 or 72 h treatments with 10 microM fluoxetine. Immunocytochemistry was used to determine the effect of fluoxetine on the expression of NCAM. Western blot analysis was used to measure the expression levels of NCAM140 and CREB and the induction of pCREB after fluoxetine treatment. RESULTS: NCAM expression following 72-h fluoxetine treatment was significantly increased around cell membranes compared to control cells. Cells treated with fluoxetine for 6 and 72 h showed a significant increase in NCAM140 expression compared to cells treated for 20 min. The level of pCREB in the cells treated with fluoxetine for 72 h not only increased more than 60%, but was also significantly different when compared with the other treatment times. The 72-h fluoxetine treatment led to the increase of NCAM140 and the phosphorylation of CREB in C6 cells. CONCLUSION: Our findings indicate that fluoxetine treatment regulates neuronal plasticity and neurite outgrowth by phosphorylating and activating CREB via the NCAM140 homophilic interaction-induced activation of the Ras-MAPK pathway.

Fluoxetine Up-Regulates Bcl-xL Expression in Rat C6 Glioma Cells

OBJECTIVE: To analyze both differentially expressed genes and the Bcl-xL protein expression after acute and chronic treatment with fluoxetine in rat C6 glioma cells. METHODS: C6 glioma cells were cultured for 24 h or 72 h after treatment with 10 microM fluoxetine, and gene expression patterns were observed using microarray and qRT-PCR. Then, cells were cultured for 6 h, 24 h, 72 h or 96 h after treatment with 10 microM fluoxetine, and the expression of Bcl-xL protein was measured using western blot. RESULTS: As determined by microarray, treatment with fluoxetine for 24 h up-regulated 33 genes (including Bcl-xL and NCAM140) and down-regulated 7 genes (including cyclin G-associated kinase). Treatment with fluoxetine for 72 h up-regulated 53 genes (including Gsalpha and Bcl-xL) and down-regulated 77 genes (including Galphai2 and annexin V). Based on the qRT-PCR results, there was an increase in Gsalpha mRNA and a decrease in Galphai2 mRNA at 72 h in fluoxetine-treated cells as compared to control, a result that was consistent with microarray. We also observed an increase in Bcl-xL mRNA (both at 24 h and at 72 h) in fluoxetine-treated cells as compared to control, demonstrating a tendency to increase gradually. Bcl-xL protein expression increased as the duration of fluoxetine treatment increased. CONCLUSION: These results suggest that chronic treatment with fluoxetine not only initiates the cAMP pathway through inducing Gsalpha expression but also induces Bcl-xL expression, thus inhibiting apoptosis.

Reliability and Validity of the Korean Version of the Childhood Trauma Questionnaire-Short Form for Psychiatric Outpatients

OBJECTIVE: The Childhood Trauma Questionnaire (CTQ) is perhaps the most widely used and well-studied retrospective measure of childhood abuse or neglect. This study tested the initial reliability and validity of a Korean translation of the Childhood Trauma Questionnaire (CTQ-K) among non-psychotic psychiatric outpatients. METHODS: The CTQ-K was administered to a total of 163 non-psychotic psychiatric outpatients at a university-affiliated training hospital. Internal consistency, four-week test-retest reliability, and validity were calculated. A portion of the participants (n=65) also completed the Trauma Assessment Questionnaire (TAQ), the Impact of Events Scale-Revised, and the Dissociative Experiences Scale-Taxon. RESULTS: Four-week test-retest reliability was high (r=0.87) and internal consistency was good (Cronbach's alpha=0.88). Each type of childhood trauma was significantly correlated with the corresponding subscale of the TAQ, thus confirming its concurrent validity. In addition, the CTQ-K total score was positively related to post-traumatic symptoms and pathological dissociation, demonstrating the convergent validity of the scale. The CTQ-K was also negatively correlated with the competence and safety subscale of the TAQ, confirming discriminant validity. Additionally, we confirmed the factorial validity by identifying a five-factor structure that explained 64% of the total variance. CONCLUSION: Our study indicates that the CTQ-K is a measure of psychometric soundness that can be used to assess childhood abuse or neglect in Korean patients. It also supports the cross-cultural equivalence of the scale.

Prevalence of Main Psychiatric Disorders in Relation to Urbanization in Gyeonggi Province by Using the Korean Version of the Mini-International Neuropsychiatric Interview / 신경정신의학

OBJECTIVES: Epidemiological studies have supplied growing evidence of an association between the prevalence of psychiatric disorders and the urban/rural division. We investigated the prevalence and risk factors of the main psychiatric disorders in two areas of Gyeonggi Province of South Korean with different levels of urbanization. METHODS: A survey was conducted of the adult population (over 40 years of age) in Yangpyeong-gun (lower level of urbanization ; n=639) and Guri-si (higher level of urbanization ; n=335) in Gyeonggi Province. The Korean version of the Mini-International Neuropsychiatric Interview (K-MINI) was used as a structured psychiatric diagnostic interview instrument. Major depressive disorder (MDD), suicidality, alcohol dependence, alcohol abuse, generalized anxiety disorder (GAD), somatoform disorder, bipolar disorder, and schizophrenia were selected as the 8 main psychiatric problems. RESULTS: The prevalence of the 8 main psychiatric disorders in Guri-si (25.6%) was higher than those of Yangpyeong-gun (15.1%, p<0.05). In particular, the prevalence of MDD, suicidality, and GAD, which are thought to be strongly influenced by psychosocial factors, were significantly higher in Guri-si (p<0.05). CONCLUSION: A greater prevalence of almost all major psychiatric disorders is associated with higher levels of urbanization, exceptions being somatoform disorders and bipolar disorder. This urban.rural difference may be related to environmental risk factors.

A Case of Gastric Low-grade MALT Lymphoma Induced by a Helicobacter heilmannii-like Organism / 대한소화기내시경학회지

Helicobacter heilmannii is a Gram negative, long spiral-shaped organism associated with zoonotic infections acquired from primates including cats and dogs. Infection with H. heilmannii leads to gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We experienced a 54-year-old man with dyspepsia who was diagnosed with primary gastric MALT lymphoma (stage IE1) associated with a H. heilmannii-like organism. Upper gastrointestinal endoscopy revealed only microvascular dilatation and mucosal granularity without elevated or ulcerative lesions at the stomach angle. He was probably infected by a pet dog. The man was treated with eradication therapy for 2 weeks including lansoprazole, amoxicillin, and clarithromycin. Four weeks after eradication of the H. heilmannii-like organism, follow-up endoscopy and pathological biopsy findings showed complete remission of the gastric MALT lymphoma.

A Comparison Study between Visual Interpretation and Statistical Parametric Mapping Analysis of Single Photon Emission Computed Tomography Images in Traumatic Brain Injury Patients / 신경정신의학

OBJECTIVES: The first objective of this study was to examine the extent to which the results of the visual interpretation of brain single photon emission computed tomography (SPECT) images correspond with those of SPM analysis in patients with traumatic brain injury (TBI). The second objective was to explore the possibility of the clinical application of SPM analysis for finding the brain lesions related to the neuropsychiatric symptoms, of which the patients complained. METHODS: SPECT images from 10 TBI patients (all male, mean age: 46.8+/-12.32) and 10 age- and sex-matched control subjects were interpreted by an experienced radiologist. Their SPECT images were also analyzed by SPM2 software for comparing the individual images with the controls. RESULTS: The results of visual interpretation of SPECT images generally corresponded with those of SPM analysis in five of the 10 TBI cases. In the remaining cases, brain lesions not identified from visual interpretation were found through SPM analysis. The location of these lesions included the anterior cingulate gyrus, caudate nucleus, thalamus, and subcallosal gyrus. SPM analysis also made it easy to find brain hypoperfusion areas associated with the TBI patients' neuropsychiatric symptoms. CONCLUSION: This study suggested possible clinical applications of SPM analysis of SPECT data from patients with TBI. Its advantages and limitations were discussed.

The Expression of Corticotropin-Releasing Factor in the Central Nucleus of the Amygdala, Induced by Colorectal Distension, is Attenuated by General Anesthesia

Corticotrophin-releasing factor (CRF), a key regulator of the hypothalamic-pituitary axis, is expressed in the central nucleus of the amygdala (CeA) and its expression is upregulated in stress-related disorders. We investigated here the effect of noxious colorectal distension (CRD) on the expression of CRF in the CeA of conscious and unconscious rats. Adult male rats with or without general anesthesia were exposed to visceral pain induced by CRD for 5 min; this procedure was repeated 3 times with 1 min resting after each distension. The rats were sacrificed and sections of the CeA were immunostained for CRF as an indicator for anxiety response, and for phosphorylated extracellular signal-regulated kinase (p-ERK) as a marker for pain-specific activation of neurons; sections of lumbosacral spinal cord were immunostained for c-Fos as a marker for activation of spinal neurons. CRD elicited a significant increase in the expression of CRF and p-ERK in the CeA and of c-Fos in the spinal cord. General anesthesia attenuated the increase in CRF and p-ERK in the CeA, but did not affect the expression of spinal c-Fos. These results suggest that conscious recognition of pain at higher brain centers is an important determinant of CRF expression in the CeA.

Increased Glycogen Synthase Kinase-3beta mRNA Level in the Hippocampus of Patients with Major Depression: A Study Using the Stanley Neuropathology Consortium Integrative Database

OBJECTIVE: Glycogen synthase kinase-3beta (GSK-3beta) has become recognized as a broadly influential enzyme affecting diverse range of biological functions, including gene expression, cellular architecture, and apoptosis. The results of previous studies suggest that GSK-3beta activity may be increased in the brain of patients with major depressive disorders (MDD). A recent animal study reported increased GSK-3beta messenger ribonucleic acid (mRNA) level in the hippocampus of those with depression. However, few studies have investigated GSK-3beta activity in the brain of patients with MDD. METHODS: In order to test whether patients with MDD have an increase in GSK-3beta activity in the brain compared to normal controls, we explored GSK-3beta expression level in all brain regions by using the Stanley Neuropathology Consortium Integrative Database (SNCID), which is a web-based method of integrating the Stanley Medical Research Institute data sets. RESULTS: The level of GSK-3beta mRNA expression in the hippocampus was significantly increased in the MDD group (n=8) compared with the control group (n=12, p<0.05). Spearman's test also reveals that GSK-3beta mRNA expression levels were significantly correlated with nitric oxide synthase 1 (NOS1)(rho=0.70, p<0.0001) and stathmin-like 3 (STMN3)(rho=0.70, p<0.0001) in the hippocampus. CONCLUSION: Our results correspond with the results of previous animal studies that reported increased GSK-3beta activity in the hippocampus of those with depression. Our findings also suggest that oxidative stress-induced neuronal cell death and abnormal synaptic plasticity in the hippocampus may play important roles in the pathophysiology of major depression.