Intact Recognition Memory and Altered Hippocampal Glucocorticoid Receptor Signaling in Fkbp5-deficient Mice Following Acute Uncontrollable Stress

The FK506 binding protein 5 (FKBP5) is a co-chaperone that regulates the activity of the glucocorticoid receptor (GR) and has been reported to mediate stress resilience. This study aimed to determine the effects of Fkbp5 deletion on acute stress-induced recognition memory impairment and hippocampal GR signaling. Wild-type and Fkbp5-knockout mice were subjected to acute uncontrollable stress induced by restraint and electrical tail shock. First, we assessed the cognitive status of mice using a novel object recognition task. Next, we measured plasma corticosterone, GR levels, and the levels of GR phosphorylation at serine 211 in the hippocampus. Wild-type mice exhibited stress-induced memory impairments, whereas Fkbp5-knockout mice did not. Plasma corticosterone and GR levels did not differ between the non-stressed wild-type and Fkbp5-knockout mice, but the levels of phosphorylated GR were lower in Fkbp5-knockout mice than in wild-type mice. Wild-type and Fkbp5-knockout mice showed increased nuclear GR levels following stress, indicating GR translocation. However, cytosolic phosphorylated GR levels were lower in the hippocampi of Fkbp5-knockout mice following stress than in those of wild-type mice. These results suggest that FKBP5 deficiency increases resilience to acute stress by altering GR signaling.

Aberrant Resting-state Functional Connectivity in Complex Regional Pain Syndrome: A Network-based Statistics Analysis

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder. Pain catastrophizing, characterized by magnification, rumination, and helplessness, increases perceived pain intensity and mental distress in CRPS patients. As functional connectivity patterns in CRPS remain largely unknown, we aimed to investigate functional connectivity alterations in CRPS patients and their association with pain catastrophizing using a whole-brain analysis approach. Twenty-one patients with CRPS and 49 healthy controls were included in the study for clinical assessment and resting-state functional magnetic resonance imaging. Between-group differences in whole-brain functional connectivity were examined through a Network-based Statistics analysis. Associations between altered functional connectivity and the extent of pain catastrophizing were also assessed in CRPS patients. Relative to healthy controls, CRPS patients showed higher levels of functional connectivity in the bilateral somatosensory subnetworks (components 1~2), but lower functional connectivity within the prefronto-posterior cingulate (component 3), prefrontal (component 4), prefronto-parietal (component 5), and thalamo-anterior cingulate (component 6) subnetworks (p<0.05, family-wise error corrected). Higher levels of functional connectivity in components 1~2 (β=0.45, p=0.04) and lower levels of functional connectivity in components 3~6 (β=-0.49, p=0.047) were significantly correlated with higher levels of pain catastrophizing in CRPS patients. Higher functional connectivity in the somatosensory subnetworks implicating exaggerated pain perception and lower functional connectivity in the prefronto-parieto-cingulo-thalamic subnetworks indicating impaired cognitive-affective pain processing may underlie pain catastrophizing in CRPS.

Efficacy of Computerized Cognitive Behavioral Therapy in Individuals with Non-Cardiac Chest Discomfort : Review and Suggestions for a New Protocol

Since non-cardiac chest discomfort (NCCD) can result in substantial healthcare burden and lower quality of life, interventions such as cognitive behavioral therapy (CBT) have been investigated for the relief of NCCD. In this review, we aimed to summarize the evidence on the efficacy of the CBT for the treatment of NCCD while introducing a newly-developed computerized CBT program for NCCD. Studies applying CBT to individuals with NCCD were searched for from both English and Korean electronic databases. Among 37 studies, 11 randomized controlled trials, 4 case-control studies, 1 case series, and 2 review articles were eligible for this review. Efficacy of conventional CBT for NCCD was shown in a series of studies as most of them reported improved symptom severity of NCCD or NCCD-related anxiety. However, a substantial variability existed among these studies in participants, treatment procedures and durations. High attrition rates were also reported in these studies on conventional CBT. Computerized CBT could be an alternative to the conventional CBT as it can be standardized and more easily accessible, but it was only reported in one previous study. In addition to the literature review, we presented a newly-developed computerized CBT program for NCCD which may overcome some of the limitations of conventional CBT. A computerized CBT could be an alternative treatment of NCCD, however, need further studies on its usefulness.

Animal Models of Demyelination and ¹H-Magnetic Resonance Spectroscopy

The proton magnetic resonance spectroscopy (¹H-MRS) is a tool used to detect concentrations of brain metabolites such as N-acetyl aspartate, choline, creatine, glutamate, and gamma-amino butyric acid (GABA). It has been widely used because it does not require additional devices other than the conventional magnetic resonance scanner and coils. Demyelination, or the neuronal damage due to loss of myelin sheath, is one of the common pathologic processes in many diseases including multiple sclerosis, leukodystrophy, encephalomyelitis, and other forms of autoimmune diseases. Rodent models mimicking human demyelinating diseases have been induced by using virus (e.g., Theiler's murine encephalomyelitis virus) or toxins (e.g., cuprizon or lysophosphatidyl choline). This review is an overview of the MRS findings on brain metabolites in demyelination with a specific focus on rodent models.

Immunohistochemical Localization of Translationally Controlled Tumor Protein in Axon Terminals of Mouse Hippocampal Neurons

Translationally controlled tumor protein (TCTP) is a cytosolic protein with microtubule stabilization and calcium-binding activities. TCTP is expressed in most organs including the nervous system. However, detailed distribution and functional significance of TCTP in the brain remain unexplored. In this study, we investigated the global and subcellular distributions of TCTP in the mouse brain. Immunohistochemical analyses with anti-TCTP revealed that TCTP was widely distributed in almost all regions of the brain including the cerebral cortex, thalamus, hypothalamus, hippocampus, and amygdala, wherein it was localized in axon tracts and axon terminals. In the hippocampus, TCTP was prominently localized to axon terminals of the perforant path in the dentate gyrus, the mossy fibers in the cornu ammonis (CA)3 region, and the Schaffer collaterals in the CA1 field, but not in cell bodies of granule cells and pyramidal neurons, and in their dendritic processes. Widespread distribution of TCTP in axon tracts and axon terminals throughout the brain suggests that TCTP is likely involved in neurotransmitter release and/or maintaining synaptic structures in the brain, and that it might have a role in maintaining synaptic functions and synaptic configurations important for normal cognitive, stress and emotional functions.

Reliability and Validity of the Korean Version of the Post-Traumatic Stress Disorder Checklist in Public Firefighters and Rescue Workers

OBJECTIVES: Firefighters and rescue workers are likely to be exposed to a variety of traumatic events; as such, they are vulnerable to the risk of post-traumatic stress disorder (PTSD). The psychometric properties of the Korean version of the PTSD Checklist (PCL), a widely used self-report screening tool for PTSD, were assessed in South Korean firefighters and rescue workers. METHODS: Data were collected via self-report questionnaires and semi-structured clinical interviews administered to 221 firefighters. Internal consistency, item-total correlation, one-week test-retest reliability, convergent validity, and divergent validity were examined. Content validity of the PCL was evaluated using factor analysis and receiver operating characteristic (ROC) analyses were used to estimate the optimal cutoff point and area under the curve. RESULTS: The PCL demonstrated excellent internal consistency (alpha = 0.97), item-total correlation (r = 0.72-0.88), test-retest reliability (r = 0.95), and convergent and divergent validity. The total score of PCL was positively correlated with the number of traumatic events experienced (p < 0.001). Factor analysis revealed two theoretically congruent factors: re-experience/avoidance and numbing/hyperarousal. The optimal cutoff was 45 and the area under the ROC curve was 0.97. CONCLUSIONS: The Korean version of the PCL may be a useful PTSD screening instrument for firefighters and rescue workers, further maximizing opportunities for accurate PTSD diagnosis and treatment.

Prefrontal Cortical Thickness Deficit in Detoxified Alcohol-dependent Patients

Alcohol dependence is a serious disorder that can be related with a number of potential health-related and social consequences. Cortical thickness measurements would provide important information on the cortical structural alterations in patients with alcohol dependence. Twenty-one patients with alcohol dependence and 22 healthy comparison subjects have been recruited and underwent high-resolution brain magnetic resonance (MR) imaging and clinical assessments. T1-weighted MR images were analyzed using the cortical thickness analysis program. Significantly thinner cortical thickness in patients with alcohol dependence than healthy comparison subjects was noted in the left superior frontal cortical region, correcting for multiple comparisons and adjusting with age and hemispheric average cortical thickness. There was a significant association between thickness in the cluster of the left superior frontal cortex and the duration of alcohol use. The prefrontal cortical region may particularly be vulnerable to chronic alcohol exposure. It is also possible that the pre-existing deficit in this region may have rendered individuals more susceptible to alcohol dependence.

Advances in Functional Connectomics in Neuroscience : A Focus on Post-Traumatic Stress Disorder

Recent breakthroughs in functional neuroimaging techniques have launched the quest of mapping the connections of the human brain, otherwise known as the human connectome. Imaging connectomics is an umbrella term that refers to the neuroimaging techniques used to generate these maps, which recently has enabled comprehensive brain mapping of network connectivity combined with graph theoretic methods. In this review, we present an overview of the key concepts in functional connectomics. Furthermore, we discuss articles that applied task-based and/or resting-state functional magnetic resonance imaging to examine network deficits in post-traumatic stress disorder (PTSD). These studies have provided important insights regarding the etiology of PTSD, as well as the overall organization of the brain network. Advances in functional connectomics are expected to provide insight into the pathophysiology and the development of biomarkers for diagnosis and treatment of PTSD.

Peripheral Biomarker Candidates of Posttraumatic Stress Disorder

There is high variability in the manifestation of physical and mental health problems following exposure to trauma and disaster. Although most people may show a range of acute symptoms in the aftermath of traumatic events, chronic and persistent mental disorders may not be developed in all individuals who were exposed to traumatic events. The most common long-term pathological consequence after trauma exposure is posttraumatic stress disorder (PTSD). However, comorbid conditions including depression, anxiety disorder, substance use-related problems, and a variety of other symptoms may frequently be observed in individuals with trauma exposure. Post-traumatic syndrome (PTS) is defined collectively as vast psychosocial problems that could be experienced in response to traumatic events. It is important to predict who will continue to suffer from physical and mental health problems and who will recover following trauma exposure. However, given the heterogeneity and variability in symptom manifestations, it is difficult to find identify biomarkers which predict the development of PTSD. In this review, we will summarize the results of recent studies with regard to putative biomarkers of PTSD and suggest future research directions for biomarker discovery for PTSD.

Neurocognitive Changes and Their Neural Correlates in Patients with Type 2 Diabetes Mellitus

As the prevalence and life expectancy of type 2 diabetes mellitus (T2DM) continue to increase, the importance of effective detection and intervention for the complications of T2DM, especially neurocognitive complications including cognitive dysfunction and dementia, is receiving greater attention. T2DM is thought to influence cognitive function through an as yet unclear mechanism that involves multiple factors such as hyperglycemia, hypoglycemia, and vascular disease. Recent developments in neuroimaging methods have led to the identification of potential neural correlates of T2DM-related neurocognitive changes, which extend from structural to functional and metabolite alterations in the brain. The evidence indicates various changes in the T2DM brain, including global and regional atrophy, white matter hyperintensity, altered functional connectivity, and changes in neurometabolite levels. Continued neuroimaging research is expected to further elucidate the underpinnings of cognitive decline in T2DM and allow better diagnosis and treatment of the condition.

Disturbance of the Glutamatergic System in Mood Disorders

The role of glutamatergic system in the neurobiology of mood disorders draws increasing attention, as disturbance of this system is consistently implicated in mood disorders including major depressive disorder and bipolar disorder. Thus, the glutamate hypothesis of mood disorders is expected to complement and improve the prevailing monoamine hypothesis, and may indicate novel therapeutic targets. Since the contribution of astrocytes is found to be crucial not only in the modulation of the glutamatergic system but also in the maintenance of brain energy metabolism, alterations in the astrocytic function and neuroenergetic environment are suggested as the potential neurobiological underpinnings of mood disorders. In the present review, the evidence of glutamatergic abnormalities in mood disorders based on postmortem and magnetic resonance spectroscopy (MRS) studies is presented, and disrupted energy metabolism involving astrocytic dysfunction is proposed as the underlying mechanism linking altered energy metabolism, perturbations in the glutamatergic system, and pathogenesis of mood disorders.

Reliability and Validity of the Fatigue Severity Scale among University Student in South Korea

OBJECTIVES: There are only a limited number of studies on instruments assessing fatigue in university students, although fatigue exerts negative influences on their health and academic performances and fatigue-related complaints are more frequently reported in young adults than middle-aged adults. The aim of this study was to validate the 9-item Fatigue Severity Scale (FSS) among university students including both undergraduate and graduate students in South Korea. METHODS: A total of 176 university students completed a battery of self-report questionnaires, including the FSS, the Brief Fatigue Inventory (BFI), the Beck Depression Inventory-II (BDI-II), the Beck Anxiety Inventory (BAI), the Medical Outcomes Study Short Form 36 version 2 (MOS-SF36v2), and the Inclusion of Community in the Self Scale (ICS). The data were collected from February of 2012 to June of 2012. The reliability, convergent validity, divergent validity, and exploratory factor analyses were conducted to assess psychometric properties of the FSS. RESULTS: The mean FSS score was 3.20 (standard deviation = 1.43). The FSS demonstrated an excellent internal consistency (Cronbach's alpha = 0.93) and item-total correlations ranged from 0.56 to 0.90. Correlations of the FSS with the BFI (r = 0.71, p < 0.01), BDI-II (r = 0.54, p < 0.01), BAI (r = 0.46, p < 0.01), MOS-SF36v2 physical component summary (r = -0.28, p < 0.01), MOS-SF36v2 mental component summary (r = -0.55, p < 0.01), and ICS (Spearman's rho = -0.07, p = 0.33) showed acceptable convergent and divergent validity. Exploratory factor analysis defined one underlying factor (eigenvalue = 5.67) that explained 93.50% of the total variance. CONCLUSIONS: To the best of our knowledge, this is the first study to investigate reliability and validity of the FSS in university students. The FSS exhibits good psychometric properties for evaluation of fatigue among university students in South Korea. Since the FSS is easy to administer, score, and interpret, it could be a useful tool in research and practice for assessing fatigue among university students.

The Role Transition and Development Direction of the Psychiatric Day Hospital in General Hospital : Introduction of Day Intensive Care Center / 신경정신의학

The role of the day hospital as a mediator between psychiatric ward admission and return to the community has been weakening in general hospitals. The purpose of this paper is to suggest new developmental directions for the day hospital in general hospitals. The history and the operation model of day hospitals were investigated through a bibliographic search. The national mental health care system and the operational realities of the day hospital were also reviewed. The Seoul National University Hospital (SNUH) Day intensive care center (DICC) was introduced ; we then observed several indexes of the SNUH day hospital before and after the institution of DICC. The number of national community mental health care centers is increasing, and the role of this center is similar to the role of the day hospital. The SNUH day hospital invented a short-term intensive care program named DICC for patients with obsessive compulsive disorder, panic and mood disorders and showed marked increment of the number of patients and income after introduction of the DICC. There might be some benefits in introduction of the DICC to psychiatric day hospitals. The role of the DICC will be highlighted in general hospitals, not only for improvement of day hospital management, but also to help patients through early intervention.

Effects of Temperament and Character on the Specialty Interests of Medical Students

OBJECTIVES: In the previous studies, it has been suggested that temperament and character may affect specialty choice in medical students. The aim of this study is to investigate the effects of temperament and character on specialty interests in medical students. METHODS: A total 132 third-year medical students initially participated in this study. Among these participants, 128 students had filled out both demographic and Temperament and Character Inventory (TCI) questionnaires. Socio-demographic data, specialty interests and Cloninger's TCI scores were obtained. The specialty interests were categorized into surgical, medical and other departments. RESULTS: Among 128 students, 88 (68.7%), 29 (22.7%) and 22 (8.6%) students chose medical, surgical and other departments, respectively. Students choosing surgery departments showed lower Harm Avoidance scores (F = 4.39, df = 1, p = 0.04) and higher Self-Directedness scores (F = 4.30, df = 1, p = 0.04) than those who chose medical departments. There was no significant differences in Novelty Seeking, Reward dependence, Persistence, Cooperativeness, Self-Transcendence scores between groups. CONCLUSIONS: To the best of our knowledge, this is the first study that has demonstrated the relationship between TCI scores and specialty interests of medical students in Korea. The current study suggests that temperament and character influence specialty interests in medical students. These findings could have implications for medical education research and career counseling.

Prevalence and Associated Risk Factors of Psychological Distress in Patients with Gastric Cancer / 정신신체의학

OBJECTIVES: Though gastric cancer is one of the most common cancer in Korea, there have been few studies to explore psychological distress in gastric cancer. The purpose of this study was to investigate the prevalence and associated risk factors of psychological distress among patients with gastric cancer. METHODS: With consecutive sampling, a total of 274 patients with gastric cancer who admitted to a cancer center in a general hospital were recruited and assessed on psychological distress using the Hospital Anxiety and Depression Scale(HADS). Sociodemographic and cancer-related clinical variables were also evaluated. RESULTS: One hundred fifty-three(55.8%) patients with gastric cancer showed psychological distress. Logistic regression models revealed that having alcohol drinking experience[odds ratio(OR)=2.10, p=0,034] and low performance status(OR=2.40 p=0.002) were significantly associated with psychological distress in patients with gastric cancer. CONCLUSIONS: These findings indicate that approximately half of patients with gastric cancer suffered from psychological distress and having alcohol drinking experience and low performance status would be associated risk factors, suggesting the need for distress screening and psychosocial supportive care in patients with gastric cancer.

Contribution of Genetic and Neuroimaging Studies towards a Better Understanding of Post-Traumatic Stress Disorder

significant advances have been made in understanding the biological underpinnings of post-traumatic stress disorder(PTSD), particularly in the field of genetics and neuroimaging. Association studies in candidate genes related with hypothalamic-pituitary-adrenal axis, monoamines including serotonin, dopamine and noradrenaline, and proteins including FK506-binding protein 5 and brain-derived neurotrophic factor have provided important insights with regard to the vulnerability factors in PTSD. Genome-wide association studies and epigenetic studies may provide further information for the role of genes in the pathophysiology of PTSD. Hippocampus, medial prefrontal cortex, anterior cingulated cortex and amygdala have been considered as key structures that underlie PTSD pathophysiology. Future research that combines genetic and neuroimaging information may provide an opportunity for a more comprehensive understanding of PTSD.

The Standardization of the Korean Version of Brief Edinburgh Depression Scale as a Screening Tool for Depression in Cancer Patients

Objectives : Depression is a common psychiatric disorder in cancer patients. The Brief Edinburgh Depression Scale(BEDS), which is an abbreviated version of the Edinburgh Depression Scale, may serve as a useful tool in screening for the depression in patients with the medical illnesses. This report investigated the reliability and validity of the Korean Version of the BEDS(K-BEDS) for the depression in cancer patients. METHODS : One-hundred cancer patients were enrolled in this study. All subjects completed the K-BEDS, the Hospital Anxiety Depression Scale(HADS), and the Karnofsky Performance Status Scale(KPSS). Reliability, validity and Receiver Operating Characteristic(ROC) curve analysis measures were assessed. RESULTS : The K-BEDS showed good internal consistency(Cronbach alpha=0.77) and test-retest reliability(0.94, p<0.001). All item-total correlations were above 0.3. Also, it revealed moderate correlation with the depression subscale of the HADS(r=0.617), but no correlation with the KPSS. Exploratory factor analysis produced only one factor, accounting for 47.1% of the total variance. The most valid cutoff value to screen for depression was a total score of 5 on the K-BEDS, which showed sensitivity of 62.5% and specificity of 86.4% with a positive predictive value of 4.60 and a negative predictive value of 0.43. CONCLUSION : The present findings suggested that the K-BEDS would have good psychometric properties to screen for the depression in cancer patients.

Pharmacological Therapy of Prozac

Fluoxetine (Prozac(R)) has been reported to have equivalent efficacy and less side effects compared to the tricyclic antidepressants. It has become a new trend in the treatment of major depressive disorder since 1980's. Efficacy of fluoxetine has been shown not only in major depressive disorder, but also in obsessive compulsive disorder, panic disorder, bulimia nervosa, premenstrual dysphoric disorder, obesity, premature ejaculation, pain syndrome and other medical/psychiatric diseases. Fluoxetine is known to have more activating or stimulating effect than other selective serotonin reuptake inhibitors, which might be beneficial in treating the atypical feature of depression. It is also effective in diminishing appetite and carbohydrate craving. However, this effect is belived to be transient. Regarding the adverse effects, fluoxetine has the lower risk of discontinuation syndrome in comparison with other antidepressants, due to its long halflife. However, long half-life can be problematic when adverse effects become intolerable. Caution should be made when there is a possibility of drug interaction especially in the elderly. When it is prescribed to children and adolescents, monitoring for suicidal intent should be made.

Characteristics of Sleep Pattern among Korean College Students / 수면정신생리

INTRODUNTION: The objective of the present study was to investigate bedtime, rise time and time-in-bed of Korean college students, separately on weekday and on weekend and to compare them. In addition, this study also aimed to evaluate the influence of gender, age and grade on the above sleep parmeters in Korean college students. METHODS: Information regarding bedtime and rise time, separately on weekday and on weekend, of Korean college students were obtained by self-administered questionnaire. Questionnaires of 1,825 students (1,416 females and 409 males, age 18-30 ; mean age 21.1+/-2.2) were used for statistical analyses. RESULTS: Korean college students retired to bed 50 minutes later (00 : 49 on weekday ; 01 : 40 on weekend ; t=39.67, p<0.001), rose 1 hour 58 minutes later (07 : 52 on weekday ; 09 : 50 on weekend ; t=39.46, p<0.001), and slept 1 hour 8 minutes longer (t=13.33, p<0.001) on weekend. Compared to male students, female students had earlier rise time (t=8.96, p<0.01 ; t=3.89, p<0.01) and earlier bedtime both on weekday and weekend (t=7.10, p<0.01; t=6.04, p<0.01), and shorter time-in-bed on weekday (t=1.99, p<0.01). In addition, rise time delay and time-in-bed increase on weekend were more prominent in female students than in male students (t=3.41, p<0.01 ; t=3.68, p<0.01). Grade was correlated with bedtime and rise time on weekday (beta=0.1022, p<0.01 ; beta=0.1009, p<0.01), bedtime and time-in-bed on weekend (beta=0.1096, p<0.01 ; beta=-0.0990, p<0.01), and differences between weekday and weekend of the rise time and the time-in-bed (beta=-0.0906, p<0.01 ; beta=-0.1115, p=0.02). CONCLUSIONS: In this study, Korean college students had earlier bedtime/rise time and shorter time-in-bed on weekday than on weekend. These findings suggest that weekday sleep-wake schedule of Korean college students may be advanced relative to their biological sleep-wake cycle and that this discrepancy may be associated with weekday sleep deprivation. In addition, differences of sleep patterns between weekday and weekend were more prominent in female students and students with lower grade. Therefore, discrepancy between weekday sleep-wake schedule and biological sleep-wake cycle, as well as weekday sleep deprivation, might be more serious in female or lower-grade students.

The Temperament and Character Pattern of Korean Narcolepsy Patients / 수면정신생리

OBJECTIVES: To compare the biogenetic temperament and character patterns of subjects with narcolepsy and those of healthy control subjects. METHODS: Twenty-two subjects with narcolepsy, diagnosed with the International Classification of Sleep Disorder (ICSD) criteria, and 22 healthy control subjects were recruited. The Korean version of the Temperament and Character Inventory was administered to all subjects. RESULTS: Compared to healthy control subjects, subjects with narcolepsy showed significantly higher Novelty-Seeking (ANCOVA, F=5.42, p=0.025), lower Persistence (F=8.41, p=0.006) and lower Self-Directedness scores (F=4.70, p=0.036). CONCLUSION: Narcoleptic patients have a distinct pattern of biogenetic temperament and character. Our findings suggest that narcoleptic patients are exploratory in response to novelty but give up easily. In addition, our findings show that narcoleptic patients consider themselves ineffective, purposeless, and fragile.