Worsening of Migraine Associated with Hyperprolactinemia

A 45-year-old woman presented with worsening of migraine without aura. Laboratory test revealed hyperprolactinemia, but brain magnetic resonance imaging was normal. She had no known etiologies of hyperprolactinemia. Headache improved together with normalization of serum prolactin level after administration of bromocriptine. However, withdrawal of bromocriptine caused elevation of serum prolactin level and worsening of migraine headache. She repeated similar pattern of improvement and aggravation two times more. We suggest that hyperprolactinemia may cause aggravation of migraine headache.

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.

PBT-6, a Novel PI3KC2γ Inhibitor in Rheumatoid Arthritis

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

Effect of 3% Diquafosol Tetrasodium on Tear Film Stability after Laser-assisted in situ Keratomileusis

PURPOSE: To evaluate the efficacy of 3% diquafosol tetrasodium (DQ) after laser-assisted in-situ keratomileusis (LASIK). METHODS: This prospective randomized study included 150 eyes in 75 patients who were scheduled for LASIK. The patients in the 3% diquafosol tetrasodium (DQ) group (37 patients, 74 eyes) were instructed to apply one drop of DQ, six times daily post-op, while the patients in the 0.3% sodium hyaluronate (HA) group (38 patients, 76 eyes) were instructed to apply one drop of HA, six times daily post-op. A Schirmer test, tear film break-up time (BUT), corneal and conjunctival fluorescein staining score (FLSS), and ocular surface disease index (OSDI) were evaluated pre-op and at 1, 4, and 12 weeks post-op while the tear osmolarity was evaluated pre-op and at 4 and 12 weeks post-op. RESULTS: There was no significant difference between the two groups regarding Schirmer test results or tear osmolarity and conjunctival FLSS. The BUT was significantly higher in the DQ group at 1 week and 12 weeks post-op. The corneal FLSS was significantly lower in the DQ group at 1 week, 4 weeks and 12 weeks post-op. The OSDI was significantly lower in the DQ group at 1 week post-op. CONCLUSIONS: Use of 3% diquafosol tetrasodium after surgery improved ocular dryness and increased the tear film stability.

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.

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.

Hyponatremia-induced Seizures in Schizophrenic Patient Treated with Olanzapine

Severe hyponatremia (serum sodium concentration <120 mEq/L) is a well-known etiology of acute symptomatic seizure. Severe hyponatremia may occur as a rare but clinically important adverse reaction of psychotrophic drugs. Among them, patients with psychogenic polydipsia have especially higher risk of severe hyponatremia. We present a schizophrenic patient with polydipsia who developed severe hyponatremia and symptomatic seizures while receiving olanzapine treatment.

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.

Negative myoclonus associated with pregabalin / 영남의대학술지

Negative myoclonus (NM) is a jerky, shock-like involuntary movement caused by a sudden, brief interruption of muscle contraction. An 80-year-old man presented with multifocal NM and confusion. Two days before the onset of NM, he commenced the intake of pregabalin at a dose of 150 mg/day for neuropathic pain. His NM resolved completely and mental status improved gradually after the administration of lorazepam intravenously and the discontinuation of pregabalin. Our study suggests that pregabalin can cause NM even in patients without a history of seizures.

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.

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.

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.

Negative myoclonus associated with pregabalin / 영남의대학술지

Negative myoclonus (NM) is a jerky, shock-like involuntary movement caused by a sudden, brief interruption of muscle contraction. An 80-year-old man presented with multifocal NM and confusion. Two days before the onset of NM, he commenced the intake of pregabalin at a dose of 150 mg/day for neuropathic pain. His NM resolved completely and mental status improved gradually after the administration of lorazepam intravenously and the discontinuation of pregabalin. Our study suggests that pregabalin can cause NM even in patients without a history of seizures.