Relationship between Stress-Coping and Personality in Patients with Bipolar and Depressive Disorders / 우울ㆍ조울병

Background@#Personality might be one of the important factors related to stress-coping in mood disorders. This study aimed to investigate the relationship between personality and stress-coping strategies in patients with bipolar and depressive disorders. @*Methods@#A total of 195 patients diagnosed with bipolar and depressive disorders according to the criteria mentioned in Diagnostic and Statistical Manual of Mental disorders’ 5th edition were included. Pearson’s correlation and multiple regression analyses were used to analyze the relationship between personality, measured by Temperament and Character Inventory and NEO-Five Factor Inventory, and coping strategies, measured by Coping Inventory for Stressful Situations. @*Results@#Self-directedness was reported to be positively associated with task-oriented coping in bipolar disorders, and harm avoidance was negatively associated with task-oriented coping in depressive disorders. Beck Depression Inventory score, neuroticism, and extroversion were found to be positively associated with emotion-oriented coping in bipolar disorders, and neuroticism was positively associated with emotion-oriented coping in depressive disorders. Extroversion was reported to be positively associated with avoidance-oriented coping in bipolar disorders, and extroversion, novelty seeking, and reward dependence were positively associated with avoidance-oriented coping in depressive disorders. @*Conclusion@#This study concluded that the relationship between personality and stress-coping strategies may vary based on the type of mood disorder that is diagnosed. The interaction between personality and stress-coping might be considered for the modification of coping strategies in mood disorders.

Emotional Distress of the COVID-19 Cluster Infection on Health Care Workers Working at a National Hospital in Korea

Background@#Frontline healthcare workers responding to coronavirus disease 2019 (COVID-19) inevitably face tremendous psychological burden. Thus, the present study aimed to identify the psychological impact and the factors contributing to the likely increase in emotional distress of healthcare workers. @*Methods@#The participants include a total of 99 healthcare workers at Bugok National Hospital. Psychometric scales were used to assess emotional distress (12-item General Health Questionnaire; GHQ-12), depression symptoms (Patient Health Questionnaire-9; PHQ-9), and post-traumatic stress disorder-related symptoms (Impact of Events Scale-Revised; IES-R). A supplementary questionnaire was administered to investigate the experience of healthcare workers exposed to COVID-19-infected patients. Based on the results of GHQ-12 survey, participants were categorized into two groups: distress and non-distress. All the assessed scores were compared between the two groups. A logistic regression model was constructed to identify factors associated with emotional distress. @*Results@#Emotional distress was reported by 45.3% (n = 45) of all participants. The emotionally distressed group was more likely to be female, manage close contacts, have higher scores on PHQ-9 and IES-R, feel increased professional risk, and report that proper infection control training was not provided. Female gender, managing close contacts, higher scores on PHQ-9, and a feeling that proper infection control training was not provided were associated with emotional distress in logistic regression. @*Conclusion@#Frontline healthcare workers face tremendous psychological burden during the COVID-19 pandemic. Therefore, appropriate psychological interventions should be provided to the HCWs engaged in the management of COVID-19-infected patients.

Effect of Fetal Sex Hormone on the Development of Alzheimer’s Disease in Woman:A Cross-Sectional Study Using 2D/4D Digit Length Ratio

Objective@#The purpose of this study is to investigate an association between sex-hormone exposure during fetal period and the development of Alzheimer’s disease (AD). @*Methods@#Twenty four AD patients and 25 normal controls were included from Memory Impairment Clinic of Pusan National University Hospital in Korea. Subjects are measured the ratio of the length of the second to the fourth digit (2D/4D) to estimate fetal sex-hormone exposure. Analysis of covariance was used to investigate an association between fetal sex-hormone exposure and the development of AD after adjusting age, education level, Korean Mini-Mental Status Examination and head circumference. @*Results@#We found that the females with AD had significantly lower 2D/4D ratios than the female controls. In the females withAD, the 2D/4D ratios in the left hand was 0.021 and 0.017 in the right hand compared with the controls. @*Conclusion@#Our findings suggest that the development of AD in female may be related with higher testosterone and lower es-trogen exposure during fetal period.

Decreased Hippocampal Metabolism in Amnestic Mild Cognitive Impairment: Positron Emission Tomography Study

Objective@#Little is known about factors influencing of hippocampal metabolism (HM) in mild cognitive impairment (MCI). Our objective was to determine whether HM in patients with amnestic MCI (aMCI) is decreased than non-amnestic MCI (naMCI). @*Methods@#Overall, 32 MCI patients underwent 18F-fluorodeoxyglucose-positron emission tomography. They were characterized as aMCI (n=18) or naMCI (n=14) according to comprehensive neuropsychological criteria. Analysis of variances were used to assess differences on HM between aMCI and naMCI after controlling age, sex, education and Korean version of Mini Mental Status Examination. @*Results@#We found that HM was more decreased in aMCI than naMCI. This result was not changed after controlling hippocampal volume. @*Conclusion@#Our findings suggest that aMCI is associated with decreased HM in MCI.

Learning and Oxytocin / 생물치료정신의학

Neuropeptide oxytocin serves as a neuromodulator in the brain and as a hormone in the body. Oxytocin as a hypothalamic hormone causes contractions during the second and third stages of labor and lets milk come out during breast feeding. As a neuromodulator, oxytocin that influences social affiliative behavior plays an important role in social cognition and emotional learning. Recent studies showed that oxytocin affects basic fear learning and fear extinction precess in a social context. Furthermore, oxytocin has anxiolytic and stress-dampening effects when combined with social support, i.e. a safety stimuli. Also, oxytocin enhances basic emotional learning precesses of both acquisition and extinction of an emotional content while simultaneously decreasing pain experiences. Oxytocin has involvement in attachment, and is shown to improve positive affective behavior in romantic relations. Social buffering effects that social touch and emotional and physical intimacy play crucial roles in coping with negative effects are assumed to be mediated through brain oxytocin mechanisms. Researches indicate that oxytocin significantly inhibits hypothalamic-pituitary-adrenal axis activity in response to stress, and consequently reduces cortisol levels. Conversely, exposure to stress triggers the release of intrahypothalamic and plasma oxytocin. These results suggest that oxytocin may be a new pavement in treating post-traumatic stress disorder and depression.

Effect of Amyloid Deposition in PET on Hippocampal Metabolism in Amnestic-Mild Cognitive Impairment : Pilot Study / 생물치료정신의학

OBJECTIVES: Most studies of hippocampal metabolism(HM) in amnestic mild cognitive impairment(aMCI) gave inconsistent results. Our objective was to evaluate the effect of amyloid-beta(Aβ) status on hippocampal metabolism in aMCI.METHODS: Overall, 23 aMCI underwent three-dimensional magnetic resonance imaging(MRI), ¹⁸F-fluorodeoxyglucose-positron emission tomography(¹⁸FDG-PET) and ¹⁸F-Fluorbetaben amyloid positron emission tomography (amyloid-PET). According to Aβ status on amyloid PET, 23 aMCI were classified as either Aβ+aMCI(N=13) or Aβ−aMCI(N=10). The primary outcome was HM using ¹⁸FDG-PET and we investigate the difference on HM between Aβ+aMCI and Aβ−aMCI using analysis of variance(ANOVA) model, after controlling hippocampal volume.RESULTS: We found that HM was more decreased in Aβ+aMCI than Aβ−aMCI. This result was not changed after controlling hippocampal volume.CONCLUSION: Our findings suggest that Aβ+ is associated with decreased HM, regardless of hippocampal volume, in aMCI.

Investigation of Maternal Effects, Maternal-Fetal Interactions, and Parent-of-Origin Effects (Imprinting) for Candidate Genes Positioned on Chromosome 18q21, in Probands with Schizophrenia and their First-Degree Relatives

OBJECTIVE: A popular design for the investigation of such effects, including effects of parent-of-origin (imprinting), maternal genotype, and maternal-fetal genotype interactions, is to collect deoxyribonucleic acid (DNA) from affected offspring and their mothers and to compare with an appropriate control sample. We investigate the effects of estimation of maternal, imprinting and interaction effects using multimodal modeling using parents and their offspring with schizophrenia in Korean population. METHODS: We have recruited 27 probands (with schizophrenia) with their parents and siblings whenever possible. We analyzed 20 SNPs of 7 neuronal genes in chromosome 18. We used EMIM analysis program for the estimation of maternal, imprinting and interaction effects using multimodal modeling. RESULTS: Of analyzed 20 single nucleotide polymorphisms (SNPs), significant SNP (rs 2276186) was suggested in EMIM analysis for child genetics effects (p=0.0225438044) and child genetic effects allowing for maternal genetic effects (p=0.0209453210) with very stringent multiple comparison Bonferroni correction. CONCLUSION: Our results are the pilot study for epigenetic study in mental disorder and help to understanding and use of EMIM statistical genetics analysis program with many limitations including small pedigree numbers.

Hippocampal Atrophy and Psychotic Symptoms in Patients with Alzheimer's Disease / 신경정신의학

OBJECTIVES: This study examined the difference in the volume or thickness of the medial temporal lobe between Alzheimer's disease patients with psychosis (AD+P) and those without psychosis (AD−P). METHODS: Overall, 31 AD+P patients and 29 AD−P patients were included from the Memory impairment clinics of Pusan National University Hospital in Korea. AD+P was diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of Alzheimer's disease. AD−P included AD patients with no psychotic symptoms during a 5-year follow-up period. Medial temporal volume or thickness was measured by 3-tesla MRI and freesufer analysis. Analysis of variance was used to examine the difference in the volume or thickness of medial temporal lobe between AP+P and AD−P after controlling for age, gender, education years, Clinical Dementia Rating scale-Sum of Box, and total intracranial volume. RESULTS: The hippocampal volume in AD+P was smaller than that in AD−P. CONCLUSION: These findings suggest that AD+P is associated with a reduced hippocampal volume.

Protein Kinase C Activity and Delayed Recovery of Sleep-Wake Cycle in Mouse Model of Bipolar Disorder

OBJECTIVE: Previous studies reported the delayed recovery group after circadian rhythm disruption in mice showed higher quinpiroleinduced locomotor activity. This study aimed to compare not only Protein Kinase C (PKC) activities in frontal, striatal, hippocampus and cerebellum, but also relative PKC activity ratios among brain regions according to recovery of circadian rhythm. METHODS: The circadian rhythm disruption protocol was applied to eight-week-old twenty male Institute Cancer Research mice. The circadian rhythm recovery patterns were collected through motor activities measured by Mlog system. Depressive and manic proneness were examined by forced swim test and quinpirole-induced open field test respectively. Enzyme-linked immunosorbent assay was employed to measure PKC activities. RESULTS: The delayed recovery group presented greater locomotor activities than the early recovery group (p=0.033). The delayed recovery group had significantly lower frontal PKC activity than the other (p=0.041). The former showed lower frontal/cerebellar PKC activity ratio (p=0.047) but higher striatal/frontal (p=0.038) and hippocampal/frontal (p=0.007) PKC activities ratios than the latter. CONCLUSION: These findings support potential mechanism of delayed recovery after circadian disruption in bipolar animal model could be an alteration of relative PKC activities among mood regulation related brain regions. It is required to investigate the PKC downstream signaling related to the delayed recovery pattern.

Heritability and Familiality of MMPI Personality Dimensions in the Korean Families with Schizophrenia

OBJECTIVE: Categorical syndrome such as schizophrenia could be the complex of many continuous mental structure phenotypes including several personality development/degeneration dimensions. This is the study to search heritability and familiality of MMPI personality dimensions in the Korean schizophrenic LD (Linkage Disequilibrium) families. METHODS: We have recruited 204 probands (with schizophrenia) with their parents and siblings whenever possible. We have used MMPI questionnaires for measuring personality and symptomatic dimensions. Heritabilities of personality dimensions in total 543 family members were estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Personality dimensions in total family members were compared with those in 307 healthy unrelated controls for measuring the familialities using ANOVA analysis. RESULTS: Seven of the 10 MMPI variables were significantly heritable and were included in the subsequent analyses. The three groups (control, unaffected 1st degree relative, case) were found to be significantly different with the expected order of average group scores for all heritable dimensions. CONCLUSION: Our results show that the aberrations in several personality dimensions could form the complexity of schizophrenic syndrome as a result of genetic-environment coactions or interactions in spite of some limitations (recruited family, phenotyping).

Psychometric Properties of the Coping Inventory for Stressful Situations in Korean Adults

OBJECTIVE: The Coping Inventory for Stressful Situations (CISS) is a globally recognized measure of stress coping methods. However, research into the applicability of the CISS in a Korean context is still in its infancy. The aim of this study is to assess and report the validity of the CISS in Korean adults for the first time. METHODS: Three hundred and two Korean adults who currently have no distressing problems requiring psychiatric treatment completed the Korean version of the CISS. Principal component analysis was used to extract factors in the process of exploratory factor analysis. RESULTS: The result displayed a clear pattern matrix, and a high level of internal consistency was shown by Chronbach's alpha. The items classified under task-oriented and emotion-oriented coping presented adequate factorial validity, and only three items grouped under avoidance-oriented coping loaded poorly or loaded onto factors differing from the original. CONCLUSION: These results seem to indicate that the CISS may indeed be both applicable and useful in gauging the coping styles of Korean adults. However, the ambiguous meanings of certain items under avoidance-oriented coping would require adjustment for the purposes of future study.

Association of Temporal Lobe Atrophy and Psychosis in Patients with Alzheimer's Disease

OBJECTIVE: The purpose of this study is to investigate the difference on regional volume in temporal lobe between Alzheimer's disease patients with psychosis (AD+P) and Alzheimer's disease patients without psychosis (AD-P). METHODS: Altogether, 24 AD+P and 25 AD-P matched age, gender, and clinical dementia rating sum of box (CDR-SOB) were include from a Memory impairment clinics of Pusan National University Hospital in Korea. AD+P were diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of Alzheimer's disease. Grey matter volume of temporal lobe was measured with 3-tesla magnetic resonance imaging and freesufer analysis. Analysis of variance was used to investigate the association between temporal lobe and AD+P after controlling age, gender, education years, CDR-SOB and total intracranial volume. RESULTS: We found an association between AD+P and reduced grey matter volume in total temporal lobe as well as in specific temporal regions such as left middle temporal lobe, left inferior temporal lobe, both hippocampus and both fusiform. CONCLUSION: Our findings suggest that AD+P are associated with reduced grey matter volume of temporal lobe.

Heritability and Familiality of Temperament and Character Dimensions in Korean Families with Schizophrenic Linkage Disequilibrium

OBJECTIVE: Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD). METHODS: We recruited 179 probands (with schizophrenia) as well as, whenever possible, their parents and siblings. We used the Temperament and Character Inventory (TCI) to measure personality and symptomatic dimensions. The heritability of personality dimensions in a total of 472 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). To measure familiality, we compared the personality dimensions of family members with those of 336 healthy unrelated controls using analysis of variance (ANOVA) analysis. RESULTS: Three of the seven TCI variables were significantly heritable and were included in subsequent analyses. The three groups (control, unaffected first-degree relative, case) were found to significantly differ from one another, with the expected order of average group scores, for all heritable dimensions. CONCLUSION: Despite several study limitations with respect to family recruitment and phenotyping, our results show that aberrations in several personality dimensions related to genetic-environment coactions or interactions may underlie the complexity of the schizophrenic syndrome.

Neurobiological Mechanism of Memory

Memory is one of the most important mental mechanisms which is crucial for us to adapt to environmental surroundings and to maintain our identity. The neurobiological mechanisms for memory are based upon the synaptic plasticity that involve both functional and structural changes at the synapses in the neural circuits participating in learning and memory. Memory is not a single process but has two forms of short-term and long-term memory that are two independent but overlapping processes that blend into one another. The short-term memory depends upon the functional change of synaptic strength but the long-term memory requires anatomic changes of synapses in the neural circuit. Memory storage seems to use elements of a common genetic switch, involving cyclic adenosine monophospate (cAMP)-dependent protein kinase, mitogen activated protein kinase, and cAMP response element-binding protein, to convert short-term memory into long-term memory.

Impact of Metabolic Syndrome on the White Matter Integrity in Alzheimer's Disease Patients : Tract-Based Spatial Statistics Study under 3-Tesla MRI

OBJECTIVE: The aim of this study is to determine whether there is any difference in white matter (WM) integrity between Alzheimer's disease (AD) with metabolic syndrome (MetS) and without MetS. METHODS: Altogether, 30 subjects were finally recruited from the Memory Impairment Clinics of Pusan National University Hospital in Korea. All subjects (AD with MetS : n=15, matched AD without MetS for age, gender and year of education : n=15) were underwent 3-tesla magnetic resonance imaging scans of diffusion tensor imaging. RESULTS: The mean fractional anisotropy of the AD with MetS was lower (p<0.05) in right posterior corona radiate, right corticospinal tract and right superior longitudinal fasciculus than that of the AD without MetS. CONCLUSION: Our findings suggest that WM integrity damage.

A Study on Factors Related to Long-term Hospitalization in Patients with Chronic Schizophrenia / 신경정신의학

OBJECTIVES: The purpose of this study is to investigate the factors related to long-term hospitalization of schizophrenia. METHODS: The subjects were inpatients with schizophrenia who were constantly hospitalized for more than 12 months and their caregivers. They were compared with schizophrenia with no previous experience of sustained hospitalization for more than 12 months and their caregivers. Demographic and clinical data, Korea version of the Positive and Negative Symptom Scale, functional disability and family burden scale were analyzed. RESULTS: In this study long-term hospitalization of schizophrenia was influenced by the following measures. First, primary caregivers variables such as parents/non-parents and cohabitation with patients, second, negative symptom severity of passive/apathetic social withdrawal and lack of spontaneity and flow of conversation, and third, functional disability of go to hospital/take a dose regularly and using public transportation/facilities were associated with long-term hospitalization. And they were significant in logistic regression analysis. CONCLUSION: The above results suggest that long-term hospitalization of schizophrenic patients in Korea might be affected by caregiver's factor, negative symptoms, and functional disability.

Reduced Cortical Thickness in Patients with Late Life Depression without Cerebral Vascular Disease

OBJECTIVES: The aim of this study is to compare cortical thickness in late life major depression patients without cerebral vascular disease (CVD) with that of non-depressed normal comparison subjects using magnetic resonance imaging (MRI). METHODS: Altogether, 47 subjects were finally recruited from the Memory impairment clinics of Pusan National University Hospital in Korea. All subjects (late life major depression patients without CVD : n=21, matched non-depressed normal comparison subjects : n=26) underwent 3-tesla MRI. RESULTS: Late life major depression patients without CVD showed reduced cortical thickness in left precuneus, left inferior temporal gyrus, and left cuneus compared with non-depressed normal comparison subjects. CONCLUSION: Our findings suggest that late life major depression without CVD is associated with reduced cortical thickness.

Delay in the Recovery of Normal Sleep-Wake Cycle after Disruption of the Light-Dark Cycle in Mice: A Bipolar Disorder-Prone Animal Model?

OBJECTIVE: Disruption of the circadian rhythm is known as a provoking factor for manic episodes. Individual differences exist in the recovery rate from disruption in the general population. To develop a screening method to detect individuals vulnerable to bipolar disorder, the authors observed the relationship between the recovery of the normal sleep-wake cycle after switching the light-dark (LD) cycle and quinpirole-induced hyperactivity in mice. METHODS: Sixteen male mice (age of 5 weeks, weight 28-29 gm) were subjected to a circadian rhythm disruption protocol. Sleep-wake behaviors were checked every 5 min for a total duration of 15 days, i.e., 2 days of baseline observations, 3 days of LD cycle changes, and 10 days of recovery. During the dark cycle on the 16th experimental day, their general locomotor activities were measured in an open field for 120 minutes after an injection of quinpirole (0.5 mg/kg, s.c.). RESULTS: The individual differences in the recovery rate of the baseline sleep-wake cycle were noted after 3 days of switching the LD cycle. Fifty percent (n=8) of the mice returned to the baseline cycle within 6 days after normalizing the LD cycle (early recovery group). The locomotor activities of mice that failed to recover within 6 days (delayed recovery group) were significantly higher (mean rank=12.25) than those of the early recovery group (mean rank=4.75, u=62.0, p=0.001, Mann-Whitney U test). CONCLUSION: Given that the quinpirole-induced hyperactivity is an animal model of bipolar disorder, our results suggest individuals who have difficulties in recovery from circadian rhythm disruption may be vulnerable to bipolar disorder.

A Pilot Study for Discovering Candidate Genes of Chromosome 18q21 in Methamphetamine Abusers: Case-control Association Study

OBJECTIVE: It was previously suggested that the malic enzyme 2 (ME2) as the candidate gene for psychosis in fine mapping of chromosome 18q21. Chromosome 18q21 is also one of the possible regions that can contribute to addiction. METHODS: We performed a pilot study for discovering candidate gene of chromosome 18q21 in the methamphetamine abusers for elucidating the candidate gene for methamphetamine addiction leading to psychosis. We have selected 30 unrelated controls (16 males, 14 females; age=59.8+/-10.4) and 37 male methamphetamine abusers (age=43.3+/-7.8). We analyzed 20 single nucleotide polymorphisms (SNPs) of 7 neuronal genes in chromosome 18q21 for DNA samples that was checked for the data quality and genotype error. The association between the case-control status and each individual SNP was measured using multiple logistic regression models (adjusting for age and sex as covariates). And we controlled false discovery rate (FDR) to deal with multiple testing problem. RESULTS: We found 3 significant SNPs of 2 genes in chromosome 18q21 (p-value<0.05; adjusting for age as covariate) in methamphetamine abusers compared to controls. We also found 2 significant SNPs of 1 gene (p-value<0.05; adjusting for age and sex as covariates) (rs3794899, rs3794901:MAPK4). Two SNPs in MAPK4 gene were significant in both statistical groups. CONCLUSION: MAPK4, the gene for mitogen-activated protein kinase 4, is one of the final 6 candidate genes including ME2 in 18q12-21 in our previous finemapping for psychosis. Our results suggest that MAPK4 can be a candidate gene that contribute to the methamphetamine addiction leading to psychosis.

Pharmacotherapy for Behavioral and Psychological Symptoms in Dementia

Behavioral and psychological symptoms in dementia (BPSD) are one of the common causes leading to significant impairment in quality of life for both patients and their caregivers, as well as an increased risk of institutionalization. In the treatment of BPSD, the first step is to check medical illness, and environmental status that can cause BPSD. When BPSD are associated with medical illness or environmental status, it is important to correct this condition for treatment of BPSD. However, if BPSD are very severe enough to be dangerous to patients or others and are not treatable by nonpharmacological approaches, pharmacological treatments could be considered. In pharmacological approaches, it is important to select relevant drugs according to the target symptoms, such as psychosis, depression, agitation, sleep disturbance, and so on. Due to the altered pharmacokinetics and pharmacodynamics, drug dosages for the patients with dementia should be started very low and increased slowly.