The Relationship between Plasma Erythropoietin Levels and Symptoms of Attention Deficit Hyperactivity Disorder

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.

Changes in Brain Electrical Activity According to Post-traumatic Stress Symptoms in Survivors of the Sewol Ferry Disaster: A 1-year Longitudinal Study

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.

The Relationship between Plasma Erythropoietin Levels and Symptoms of Attention Deficit Hyperactivity Disorder

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.

Changes in Brain Electrical Activity According to Post-traumatic Stress Symptoms in Survivors of the Sewol Ferry Disaster: A 1-year Longitudinal Study

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.

Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives

Major depressive disorder (MDD) is a serious psychiatric illness that causes functional impairment in many people. While monoaminergic antidepressants have been used to effectively treat MDD, these antidepressants have limitations in that they have delayed onset of action and many patients remain treatment-resistant. Therefore, there is a need to develop antidepressants with a novel target, and researchers have directed their attention to the glutamatergic system. Ketamine, although developed as an anesthetic, has been found to produce an antidepressant effect at sub-anesthetic doses via N-Methyl-D-aspartic acid (NMDA) receptor blockade as well as NMDA receptor- independent pathways. A single infusion of ketamine produced rapid improvement in clinical symptoms to a considerable level and led to the resolution of serious depressive symptoms, including imminent suicidal ideation, in patients with MDD. A series of recent randomized controlled trials have provided a high level of evidence for the therapeutic efficacy of ketamine treatment in MDD and presented new insights on the dose, usage, and route of administration of ketamine as an antidepressant. With this knowledge, it is expected that ketamine treatment protocols for MDD will be established as a treatment option available in clinical practice. However, long-term safety must be taken into consideration as ketamine has abuse potential and it is associated with psychological side effects such as dissociative or psychotomimetic effects.

Panic Disorder: Current Research and Management Approaches

No abstract available.

A Novel Bio-Psychosocial-Behavioral Treatment Model of Panic Disorder

To conceptualize a novel bio-psychosocial-behavioral treatment model of panic disorder (PD), it is necessary to completely integrate behavioral, psychophysiological, neurobiological, and genetic data. Molecular genetic research on PD is specifically focused on neurotransmitters, including serotonin, neuropeptides, glucocorticoids, and neurotrophins. Although pharmacological interventions for PD are currently available, the need for more effective, faster-acting, and more tolerable pharmacological interventions is unmet. Thus, glutamatergic receptor modulators, orexin receptor antagonists, corticotrophin-releasing factor 1 receptor antagonists, and other novel mechanism-based anti-panic therapeutics have been proposed. Research on the neural correlates of PD is focused on the dysfunctional “cross-talk” between emotional drive (limbic structure) and cognitive inhibition (prefrontal cortex) and the fear circuit, which includes the amygdala-hippocampus-prefrontal axis. The neural perspective regarding PD supports the idea that cognitive-behavioral therapy normalizes alterations in top-down cognitive processing, including increased threat expectancy and attention to threat. Consistent with the concept of “personalized medicine,” it is speculated that Research Domain Criteria can enlighten further treatments targeting dysfunctions underlying PD more precisely and provide us with better definitions of moderators used to identify subgroups according to different responses to treatment. Structuring of the “negative valence systems” domain, which includes fear/anxiety, is required to define PD. Therefore, targeting glutamate- and orexin-related molecular mechanisms associated with the fear circuit, which includes the amygdala-hippocampus-prefrontal cortex axis, is required to define a novel bio-psychosocial-behavioral treatment model of PD.

Contemporary Issues in Depressive Disorders

No abstract available.

Diagnostic Issues of Depressive Disorders from Kraepelinian Dualism to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

Because the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) was mainly influenced by the neo-Kraepelinian approach, its categorical approach to defining mental disorders has been criticized from the viewpoint of etiological neutrality. In the context of bridging the gap between “presumed etiologies-based symptomatology” and “identifiable pathophysiological etiologies,” the content in 5th edition, the DSM-5, has been revised to incorporate a combination of categorical and dimensional approaches. The most remarkable change of note regarding the diagnostic classification of depressive disorders in the DSM-5 is the splitting of mood disorders into bipolar disorders and depressive disorders, which is in accordance with the deconstruction of the Kraepelinian dualism for psychoses. The transdiagnostic specifiers “with mixed features,” “with psychotic features,” and “with anxious distress” are introduced to describe the relationships of depressive disorders with bipolar disorders, schizophrenia, and generalized anxiety disorder, respectively, in a dimensional manner. The lowering of the diagnostic threshold for major depressive disorder (MDD) may be caused by the addition of “hopelessness” to the subjective descriptors of depressive mood and the elimination of “bereavement exclusion” from the definition of MDD. Since the heterogeneity of MDD is equivalent to the Wittgensteinian “games” analogy, the different types of MDD are related not by a single essential feature but rather by “family resemblance.” Network analyses of MDD symptoms may therefore need further review to elucidate the connections among interrelated symptoms and other clinical elements.

196G/A of the Brain-Derived Neurotrophic Factor Gene Polymorphisms Predicts Suicidal Behavior in Schizophrenia Patients

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has possible neurobiologic impact on etiology of schizophrenia. We hypothesized that the specific allele or the genotype such as two single nucleotide polymorphisms (SNPs) , 196G/A (rs6265), 11757G/C(rs16917204) is associated with schizophrenia or its clinical features. METHODS: 241 normal controls and 157 schizophrenia patients are included. The differences in allele or genotype distribution for the patients and normal controls were analyzed. We also analyzed clinical variables among patients. RESULTS: We found no significant difference in genotype or allele distributions of two studied SNPs between the patient group and the control group. However, history of suicide attempt was relatively higher in patients with genotype with A allele, compared to patients with genotype G/G for 196G/A (p-value=0.045). CONCLUSION: Our results suggest that it is possible to use BDNF gene allele and genotype as a predictor for suicide attempt in schizophrenia patients. It can help manage the schizophrenia patients regarding suicidal behavior and furthermore, mortality.

Current Update on Transcranial Direct Current Stimulation as Treatment for Major Depressive Disorder

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that delivers 1–2 mA of current to the scalp. Several clinical studies have been conducted to confirm the therapeutic effect of major depressive disorder (MDD) patients with tDCS. Some studies have shown tDCS's antidepressant effect, while the others showed conflicting results in antidepressant effects. Our aim of this review is to understand the biological bases of tDCS's antidepressant effect and review the results of studies on tDCS's antidepressant effect. For the review and search process of MDD treatment using tDCS, the US National Library of Medicine search engine PubMed was used. In this review, we discuss the biological mechanism of tDCS's antidepressant effect and the existing published literature including meta-analysis, systematic review, control trial, open studies, and case reports of antidepressant effects and cognitive function improvement in patients with MDD are reviewed. We also discuss the appropriate tDCS protocol for MDD patients, factors predictive of response to tDCS treatment, the disadvantages of tDCS in MDD treatment, and side effects.

Rapid-Acting Antidepressant Effect of Ketamine and Its Clinical Application / 신경정신의학

Although the biological causes of depression have been well established, the current use of antidepressants are still mostly based on the monoamine hypothesis of depression. However, monoamine antidepressants delay treatment of depression, and there is the problem of depressed patients who are resistant. Ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, is firstly introduced as an anesthetic. The hypothesis on the mechanism of ketamine as an antidepressant has been proposed through direct NMDAR inhibition, inhibition of γ-aminobutyric acid-ergic interneuron NMDARs and the role of ketamine metabolite (2R,6R)-hydroxynorcetamine (HNK). The ketamine also reverses the lack of synaptic connectivity and neurotrophic factors in depressed states by downstream mechanism of action. Through preclinical trials, there is a growing body of evidence indicating that ketamine has the potential for treatment of depression. In recent clinical studies, ketamine exhibits rapid-acting antidepressants effects and improvement of depression and even suicidality. This review examines current researches on molecular and cellular mechanisms of ketamine as an antidepressant, and reviews the current status of clinical studies, problems, and clinical applicability of ketamine.

Application of Assessment Tools to Examine Mental Health in Workplaces: Job Stress and Depression

Despite the fact that the lifetime and yearly prevalence rates of mental illness continue rising, such diseases have only been acknowledged as involved in workplace health issue since the 2000s. Additionally, while the number of recognized cases of mental illnesses is rather low compared to their prevalence, they have a high likelihood of causing significant problems, including fatalities. Many workers are terrified of losing their jobs due to mental illness and therefore attempt to hide their mental health problems. For this reason, clinicians involved in occupational and environmental medicine should focus on interviews or screenings to identify such hidden mental health problems. More specifically, it would be helpful to evaluate job stress and depression in workplaces to ensure appropriate preventive actions and thereby reduce the prevalence of mental illness. Job stress not only causes mental illness and dissatisfaction with work, but also can increase the prevalence and morbidity of medical diseases, as well as other physical health problems. Depression is a major contributor to work loss and absence with effects surpassing almost all of the chronic medical disorder. These facts show why measure of job stress and depression should be highlighted in the occupational settings. This article introduces a variety of assessment tools to examine mental health, particularly stress and depression, in workplaces. These tools can be used by clinicians or professionals involved in the mental health, occupational safety, or health service fields for running diagnostics or screening tests.

Natural Course of Posttraumatic Symptoms in Late-Adolescent Maritime Disaster Survivors: Results of A 12-Month Follow-Up Study

OBJECTIVE: This study is a prospective observational study on 75 late-adolescent survivors of a large passenger ship accident from immediately after the accident to one year later. METHODS: Assessments of student survivors were conducted on day 2 and at months 1, 6, and 12. The PTSD Checklist (PCL), Patient Health Questionnaire-9 (PHQ-9), State subscale of the State and Trait Anxiety Inventory (STAI-S), Athens Insomnia Scale (AIS), and Brief Resilience Scale (BRS) were administered. RESULTS: When the assessments for day 2 and month 12 were compared, all the scales, except the PCL-avoidance subscale, showed a significant improvement in symptoms among males. However, among females, all the scales, except the PCL-re-experience subscale and the STAI-S, failed to show a significant improvement. All the symptoms for both males and females showed a pattern that decreased to the lowest level at month 1 (camp-based controlled intervention period), then increased at months 6 and 12 (voluntary individual treatment after returning to school). CONCLUSION: The rapid deterioration of psychological symptoms was found during the chronic phase, when students returned to their daily routines and received voluntary individual therapy. There is a need to screen high-risk adolescents and be more attentive to them during this period.

Neuroprotection in Schizophrenia and Its Therapeutic Implications

Schizophrenia is a chronic and debilitating mental disorder. The persisting negative and cognitive symptoms that are unresponsive to pharmacotherapy reveal the impairment of neuroprotective aspects of schizophrenia. In this review, of the several neuroprotective factors, we mainly focused on neuroinflammation, neurogenesis, and oxidative stress. We conducted a narrative and selective review. Neuroinflammation is mainly mediated by pro-inflammatory cytokines and microglia. Unlike peripheral inflammatory responses, neuroinflammation has a role in various neuronal activities such as neurotransmission neurogenesis. The cross-talk between neuroinflammation and neurogenesis usually has beneficial effects in the CNS under physiological conditions. However, uncontrolled and chronic neuroinflammation exert detrimental effects such as neuronal loss, inhibited neurogenesis, and excessive oxidative stress. Neurogenesis is also a major component of neuroprotection. Adult neurogenesis mainly occurs in the hippocampal region, which has an important role in memory formation and processing. Impaired neurogenesis and an ineffective response to antipsychotics may be thought to indicate a deteriorating course of schizophrenia. Oxidative stress and excessive dopaminergic neurotransmission may create a vicious cycle and consequently disturb NMDA receptor-mediated glutamatergic neurotransmission. Based on the current evidences, several neuroprotective therapeutic approaches have been reported to be efficacious for improving psychopathology, but further longitudinal and large-sample based studies are needed.

Eye Movement Desensitization and Reprocessing to Facilitate Posttraumatic Growth: A Prospective Clinical Pilot Study on Ferry Disaster Survivors

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.

Prevalence and Associated Factors of Depression in General Population of Korea: Results from the Korea National Health and Nutrition Examination Survey, 2014

Depressive disorder is a common mental illness and remains a major cause of morbidity worldwide. The present study, a cross-sectional, nationwide, population-based survey assessed the prevalence of depression in the general population of Korea through a random sampling of the non-institutionalized population for the Korea National Health and Nutrition Examination Survey (KNHANES) VI. The Patient Health Questionnaire (PHQ)-9 was first introduced into the KNHANES to detect depression. The point prevalence of depression (PHQ score of 10 or higher) was 6.7% (95% confidence interval [CI], 5.7–7.6) in 4,949 subjects. Based on the analysis using the diagnostic algorithm of the PHQ-9, the prevalence of major depressive disorder was 2.7% (95% CI, 2.2–3.3). Multiple logistic regression analysis, after adjusting the sociodemographic variables, also showed that the factors associated with depression were perceived stress and health status. This study reported for the first time that the point prevalence of depression screened using the PHQ-9 in this nationwide survey of the Korean population was similar to that of the western countries. As the KNHANES to detect depression is conducted biennially, further studies on the accumulated data are expected in the future.

Paradigm Shift in the Study of Treatment Resistant Depression

Treatment-resistant depression (TRD) is a major public health problem. It is estimated that about 30% of patients with major depressive disorder do not show substantial clinical improvement to somatic or psychosocial treatment. Most of studies for TRD have focused on the subjects already known as TRD. Patients with unipolar depressive episodes that do not respond satisfactorily to numerous sequential treatment regimens were included in the TRD studies. Such post hoc experimental design can be regarded only as consequences of having TRD, rather than as causal risk factors for it. Although informative, data derived from such studies often do not allow a distinction to be made between cause and effect. So, we should shift paradigm toward examining the risk for developing TRD in untreated depressed patients. To deal with this problem, untreated depressed patients should be enrolled in the study to identify biological markers for treatment resistance. The peripheral or central biological markers should be explored before starting treatment. Subsequent systematic administration of treatments with appropriate monitoring in the subjects can determine the risk for developing treatment resistance in untreated individuals. Such information could give a cue to improve the initial diagnosis and provide more effective treatment for TRD.

Decreased Plasma BDNF Levels of Patients with Somatization Disorder

OBJECTIVE: Brain-derived neurotrophic factor (BDNF), one of the most abundant and important neurotrophins, is known to be involved in the development, survival, maintenance, and plasticity of neurons in the nervous system. Some studies have suggested that BDNF may play a role in the pathophysiology of several psychiatric illnesses such as depression and schizophrenia. Similarly, it is likely that the alteration of BDNF may be associated with the neuro-modulation that contributes to the development of somatization disorder. METHODS: The purpose of this study was to determine whether there is an abnormality of plasma BDNF levels in patients with somatization disorder, and to analyze the nature of the alteration after pharmacotherapy using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The plasma BDNF levels of the patients with a somatization disorder were significantly lower compared with those of the control volunteers (83.61±89.97 pg/mL vs. 771.36±562.14 pg/mL); moreover, the plasma BDNF levels of those patients who received an antidepressant were significantly increased after the treatment (118.13±91.45 pg/mL vs. 72.92±88.21 pg/mL). CONCLUSION: These results suggest that BDNF may play a role in the pathophysiology of somatization disorder.

Do Somatic Symptoms Predict the Severity of Depression? A Validation Study of the Korean Version of the Depression and Somatic Symptoms Scale

This study aimed at exploring the psychometric characteristics of the Korean Version of the Depression and Somatic Symptoms Scale (DSSS) in a clinical sample, and investigating the impact of somatic symptoms on the severity of depression. Participants were 203 consecutive outpatients with current major depressive disorders (MDD) or lifetime diagnosis of MDD. The DSSS was compared with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-items Hamilton Depression Rating Scale (HAMD). The DSSS showed a two-factor structure that accounted for 56.8% of the variance, as well as excellent internal consistency (Cronbach’s alpha = 0.95), concurrent validity (r = 0.44–0.82), and temporal stability (intraclass correlation coefficient = 0.79). The DSSS had a high ability to identify patients in non-remission (area under receiver operating characteristic [ROC] curve = 0.887). Maximal discrimination between remission and non-full remission was obtained at a cut-off score of 22 (sensitivity = 82.1%, specificity = 81.4%). The number of somatic symptoms (the range of somatic symptoms) and the scores on the somatic subscale (SS, the severity of somatic symptoms) in non-remission patients were greater than those in remission patients. The number of somatic symptoms (slope = 0.148) and the SS score (slope = 0.472) were confirmed as excellent predictors of the depression severity as indicated by the MADRS scores. The findings indicate that the DSSS is a useful tool for simultaneously, rapidly, and accurately measuring depression and somatic symptoms in clinical practice settings and in consultation fields.