Long-Term Culture of Organotypic Hippocampal Slice from Old 3xTg-AD Mouse: An ex vivo Model of Alzheimer's Disease

OBJECTIVE: Conventional methods for organotypic hippocampal tissue slice culture (OHSC) have shown several disadvantages or limitations regarding age of animals used, duration of culture and difficulty using neurodegenerative models. Therefore, we tried to establish OHSC from old 3xTg-Alzheimer’s disease (AD) mice for longer period (over 4 weeks) and to validate utility of this system as a valid platform for translational neuroscience of AD. METHODS: OHSC was performed with old 3xTg-AD mice (12–14 months), old wild type mice (12–14 months) and young 3xTg-AD mice (2–4 months) using serum-free medium for 4 weeks. Hippocampal structure was evaluated by 4’, 6-diamidino-2-phenylindole (DAPI) intensity and neuronal metabolism was measured by Alamarblue assay. Pathologic characteristics of AD were also investigated; β-amyloid levels by ELISA, amyloid plaque deposition by Thioflavin-S staining, and glial activation by immunohistochemistry. RESULTS: Following 4-week culture in serum-free media, hippocampal cells and layers were well preserved in cultured slices from old AD mice as was in those from young AD and old wild type mice. On the contrary, excessive regression of total visible cells was observed in conventional serum-containing medium regardless of genotype of mice. In parallel with this well preserved structure, major pathologic characteristics of AD were also well manifested in hippocampal slices from old AD mice. CONCLUSION: Our findings suggest that long-term OHSC from old 3xTg-AD mouse can serve as a promising ex vivo system for studies on pathophysiology of AD, especially with the minimum number of sacrifice of experimental animals.

Cognitive Behavioral Therapy for Insomnia Reduces Hypnotic Prescriptions

OBJECTIVE: This study determined whether cognitive behavioral therapy for insomnia (CBT-i) decreased the need for sleep medications and produced better treatment outcomes than pharmacotherapy alone. METHODS: We reviewed data from patients with insomnia in the outpatient clinic of a general hospital between 2009 and 2015. We compared 41 patients who received five sessions of CBT-i with 100 age- and sex-matched patients who received pharmacotherapy only. We evaluated the change in prescription for sleep (i.e., antidepressants, hypnotics, and others) between the first and last visits using repeated measures analysis of variance (ANOVA). Clinical global impressions and completion status at the last visit were assessed using the chisquare test. RESULTS: We found a significant decrease in the prescription rate and the dosage of hypnotics among patients who received CBT-i when compared with control patients. There was no significant change in the dosage of antidepressants between the two groups. Achievement of case closure was better in the CBT-i group at the trend level. Clinical global impression at the last visit was not significantly different. CONCLUSION: These results show that CBT-i reduces the need for hypnotics among insomnia patients. Our results indicate that CBT-i offers additional benefits beyond improving sleep characteristics and thus provides another reason for recommending CBT-i as a first-line treatment for insomnia.

Snoring as a Risk Factor of Fall in the Community Elderly

OBJECTIVE: Fall is one of major causes of morbidity and mortality in the elderly. It is known that sleep is associated with quality of life in the elderly. Snoring is one of the factors affecting sleep quality. The aim of the study was to examine whether snoring affect fall in the community elderly. METHODS: This survey was performed as a part of the Korean Social Life, Health, and Aging Project, which studied the elderly living in Ganghwa-gun. Fall was defined as any history of fall in the last year through face-to-face interview. We examined the following variables: age, sex, snoring, insomnia, hypertension, diabetes, stroke, bone disease, vision problems, depression, alcohol intake, mini-mental state examination, and body mass index. The data was analyzed by multiple logistic regression to determine the association of fall with the risk factors. RESULTS: In the multivariate analysis of 516 participants, the adjusted odd ratios (95% confidence interval) of simple snoring affecting fall was 1.70 (1.10–2.63). In addition, sex (female), age, and diabetes were significantly predicted the fall. CONCLUSION: Our result suggested that snoring could be a risk factor of fall. A more comprehensive study of the relationship between snoring and fall is needed to improve the quality of life of the community elderly.

The Effects of a Brief Intervention for Insomnia on Community Dwelling Older Adults / 수면정신생리

OBJECTIVES: Insomnia is one of the major concerns in the elderly population. Cognitive behavioral treatment for insomnia is the first line treatment option, but there are some limitations including time and cost burdens and the requirement for sufficient cognitive resources to obtain a proper treatment effect. The Brief intervention for insomnia (BII) is a treatment that focuses on behavioral aspects of insomnia in primary care practices. The purpose of this study was to evaluate the effects of BII in community-dwelling older adults. METHODS: A total of 47 older adults with insomnia were enrolled from community centers between May 2016 and January 2018. They participated in the BII program for three weeks. We gathered sleep-related participant information with using the Pittsburgh sleep quality index (PSQI), the Sleep hygiene index, and a sleep diary. Clinical efficacy was evaluated by comparing total sleep time (TST), sleep latency (SL), waking after sleep onset (WASO), and sleep efficiency (SE) before and after the treatment. RESULTS: There was significant improvement in sleep-related features after BII. Global score and sleep quality from the PSQI, freshness, and WASO from the sleep diary showed statistically significant improvement. CONCLUSION: We found BII showed positive clinical efficacy in community dwelling older adults, especially from the perspective of subjective sleep quality and WASO. This finding implies that BII can be effectively applied for the managment of elderly insomnia patients in a community setting.

Prediction of Sleep Disturbances in Korean Rural Elderly through Longitudinal Follow Up / 수면정신생리

OBJECTIVES: Sleep disturbance is a very rapidly growing disease with aging. The purpose of this study was to investigate the prevalence of sleep disturbances and its predictive factors in a three-year cohort study of people aged 60 years and over in Korea. METHODS: In 2012 and 2014, we obtained data from a survey of the Korean Social Life, Health, and Aging Project. We asked participants if they had been diagnosed with stroke, myocardial infarction, angina pectoris, arthritis, pulmonary tuberculosis, asthma, cataract, glaucoma, hepatitis B, urinary incontinence, prostate hypertrophy, cancer, osteoporosis, hypertension, diabetes, hyperlipidemia, or metabolic syndrome. Cognitive function was assessed using the Mini-Mental State Examination for dementia screening in 2012, and depression was assessed using the Center for Epidemiologic Studies Depression Scale in 2012 and 2014. In 2015, a structured clinical interview for Axis I psychiatric disorders was administered to 235 people, and sleep disturbance was assessed using the Pittsburgh Sleep Quality Index. The perceived stress scale and the State-trait Anger Expression Inventory were also administered. Logistic regression analysis was used to predict sleep disturbance by gender, age, education, depression score, number of coexisting diseases in 2012 and 2014, current anger score, and perceived stress score. RESULTS: Twenty-seven percent of the participants had sleep disturbances. Logistic regression analysis showed that the number of medical diseases three years ago, the depression score one year ago, and the current perceived stress significantly predicted sleep disturbances. CONCLUSION: Comorbid medical disease three years previous and depressive symptoms evaluated one year previous were predictive of current sleep disturbances. Further studies are needed to determine whether treatment of medical disease and depressive symptoms can improve sleep disturbances.

Factors Associated with Insomnia among the Elderly in a Korean Rural Community

OBJECTIVE: Sleep disturbance is common in the elderly, which is result from multi-factorial causes encompassing socio-demographic, behavioral, and clinical factors. We aimed to identify factors associated with insomnia among the elderly in a rural community in South Korea, a country with a rapidly growing aged population. METHODS: This cross-sectional study used the data from the second wave of the Korean Social life, Health and Ageing Project, which is a cohort study of individuals living in a typical rural community in South Korea. Socio-demographic, behavioral, and clinical characteristics were obtained through face-to-face interviews. Various factors suspected to be associated with insomnia were compared between elderly participants with and without insomnia, and multiple logistic regression analyses were conducted to identify independent risk factors for insomnia. RESULTS: We found that 32.4% of 509 participants (72.8±7.7 years old) had insomnia. Female sex [odds ratio (OR)=2.19], low education level (OR=2.44), current smoking (OR=2.26), number of chronic diseases (OR=2.21 for 2–3 chronic diseases; OR=2.06 for 4 or more chronic diseases), and depression (OR=2.53) were independently associated with insomnia. CONCLUSION: We found that sex, education, chronic disease, and depression independently increase the risk of insomnia of the elderly in a Korean rural community. To overcome the elderly's insomnia, interventions should target modifiable factors such as depression. To promote active aging, longitudinal studies of factors associated with insomnia among the elderly should be performed in different regions and communities.

Altered Functional Connectivity of the Default Mode Network in Low-Empathy Subjects

Empathy is the ability to identify with or make a vicariously experience of another person's feelings or thoughts based on memory and/or self-referential mental simulation. The default mode network in particular is related to self-referential empathy. In order to elucidate the possible neural mechanisms underlying empathy, we investigated the functional connectivity of the default mode network in subjects from a general population. Resting state functional magnetic resonance imaging data were acquired from 19 low-empathy subjects and 18 medium-empathy subjects. An independent component analysis was used to identify the default mode network, and differences in functional connectivity strength were compared between the two groups. The low-empathy group showed lower functional connectivity of the medial prefrontal cortex and anterior cingulate cortex (Brodmann areas 9 and 32) within the default mode network, compared to the medium-empathy group. The results of the present study suggest that empathy is related to functional connectivity of the medial prefrontal cortex/anterior cingulate cortex within the default mode network. Functional decreases in connectivity among low-empathy subjects may reflect an impairment of self-referential mental simulation.

Association between the Catechol-O-Methyltransferase (COMT) Val(158)Met Polymorphism and Alexithymia in Patients with Obsessive-Compulsive Disorder

PURPOSE: Alexithymia, defined as a deficit in the ability to recognize and describe one's own feelings, may be related to the development and maintenance of obsessive-compulsive symptoms. The aim of this study was to evaluate the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and alexithymia in patients with obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: We recruited 244 patients with OCD (169 males, 75 females). Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20), and genotyping of the COMT Val(158)Met polymorphism was evaluated. RESULTS: Patients with the COMT Val/Val genotype had significantly higher total and "difficulty identifying feelings" (DIF) subdimension scores than those with the Val/Met or Met/Met genotypes. Patients with the COMT Val/Val genotype had significantly higher "difficulty describing feelings" (DDF) subdimension scores than those with the COMT Val/Met genotype. However, there were no differences in the scores for the "externally oriented thinking" (EOT) subdimension among the three genotypes. CONCLUSION: These results indicate that the high-activity Val allele of the COMT Val(158)Met polymorphism is associated with increased alexithymic traits in patients with OCD. The present finding suggests that alexithymia is an endophenotype of OCD that is mediated by the COMT Val(158)Met polymorphism.

Factors Affecting Stigma Resistance in Patients with Bipolar Disorder / 신경정신의학

OBJECTIVES: Stigma resistance is an individual capacity to fight the stigma of mental illness and is an issue of ongoing research regarding the stigma. The aim of this study was to evaluate predictors of stigma resistance in patients with bipolar disorder. METHODS: Demographic, clinical, and psychosocial data were collected from 102 bipolar patients in a university mental hospital. Stigma resistance was measured using a subscale of the Internalized Stigma of Mental Illness Scale. Patients completed self-reported questionnaires including items on self-esteem, hopelessness, social support, and social conflict. RESULTS: Stigma resistance showed positive association with functioning, self-esteem, and social support, and showed negative association with depressive symptoms, hopelessness, and social conflict. In multivariate analysis, stigma resistance was predicted by sex, education, and self-esteem. Self-esteem was the strongest predictive factor of stigma resistance. CONCLUSION: In accordance with previous studies, self-esteem was a central role of predicting stigma resistance. A program for improving self-esteem and its related psychosocial factors will be helpful to enhancing stigma resistance in bipolar patients.

Parental Behavior Influence on the Onset and Severity of Anorexia Nervosa and Bulimia Nervosa / 정신신체의학

OBJECTIVES: To determine the influence of parental behaviors on the onset and severity of eating disorders, this study compared aspects of perceived parental styles, according to eating disorder subtypes and age at onset in Korean women with eating disorders. METHODS: One hundred and sixty-seven patients with eating disorders[Anorexia Nervosa (AN), N=49; Bulimia Nervosa(BN), N=118] were recruited for this study. Perceived parent behaviors were assessed with Parental Behavior Inventory(PBI) self-rating scale. The study subjects also completed the Eating Disorder Inventory -2 (EDI-2) to assess the severity of eating disorder symptoms. RESULTS: In anorexia nervosa, early onset group(<16 years) reported low paternal affection and high paternal rational expression, low maternal interference than group with age at onset over 16 years. The severity of eating disorder symptoms was negatively associated with mother affection and rational expression in two subtypes of eating disorder(AN and BN). On stepwise regression analysis, paternal affection and maternal over-protection were associated with age of onset only in AN group and maternal affection was associated with the severity of symptoms in both groups of eating disorder. CONCLUSIONS: Considering the role of family function and perceived parental styles could help improve the management of eating disorders. These results emphasize the importance of fathers' role in the eating disorder on the age of onset, a relatively unexplored area of eating disorder research. Also, we investigated the importance of mothers' affection on the severity of symptoms.

The Relationship between Risk Taking, Impulsivity and Intolerance of Uncertainty

OBJECTIVES: Risk taking has been implicated in the development of various psychiatric disorders. Previous studies have indicated that risk taking behavior is associated with high levels of impulsiveness. Risk taking entail uncertain situation that outcome probability is unknown. This study tested impulsivity, intolerance of uncertainty and risk taking behavior. METHODS: A total of 73 participants completed a test battery comprised of the UPPS-P scale as a psychometric measurement of five dimensions of impulsivity, Intolerance of Uncertainty Scale, and Balloon Analog Risk Task (BART) as a behavioral measure of risk taking. The Pearson correlation analysis was used. RESULTS: The sensation seeking factor was positively correlated with BART measure (r = 0.27, p = 0.02). Specifically, the relationship between sensation seeking and BART was significant in females. CONCLUSIONS: Among the five factors of UPPS-P, only the sensation seeking factor predicts risk taking propensity.

Relationships between Chronotypes and Temperament and Character Dimensions in Healthy Young Adults

OBJECTIVES: Circadian rhythms have been known to have associations with psychiatric disorders and personality traits. The present study investigated the relationships between circadian typology and temperaments/characters in a non-clinical Korean population. METHODS: Two hundred six healthy Korean college students (male 109, female 97) participated in this study. The subjects completed the Composite Scale of Morningness for circadian typology and 140-item Temperament and Character Inventory-Revised-Short version (TCI-RS). RESULTS: Multivariate analyses of covariance showed a significant association between chronotypes and temperamental dimensions of the TCI-RS. Morning types were significantly associated with lower harm avoidance and higher persistence and self-directedness dimensions, compared to evening types and intermediate types. No interaction effects between sex and chronotypes were shown for temperamental dimensions. CONCLUSIONS: The present findings suggest that high persistence and self-directedness characters are related to morning types and high harm avoidance temperament is more related to evening types.

Disruption of Orbitofronto-Striatal Functional Connectivity Underlies Maladaptive Persistent Behaviors in Alcohol-Dependent Patients

OBJECTIVE: Alcohol dependence is characterized by persistent alcohol-seeking despite negative consequences. Previous studies suggest that maladaptive persistent behaviors reflect alcohol-induced brain changes that cause alterations in the cortico-striatal-limbic circuit. METHODS: Twenty one alcohol dependent patients and 24 age-matched healthy controls performed a decision-making task during functional MRI. We defined the medial orbitofrontal cortex (mOFC) as a region-of-interest and performed seed-based functional connectivity analysis. RESULTS: Healthy controls were more flexible in adapting an alternative behavioral strategy, which correlated with stronger mOFC-dorsal striatum functional connectivity. In contrast, alcohol dependent patients persisted to the first established behavioral strategy. The mOFC-dorsal striatum functional connectivity was impaired in the alcohol-dependent patients, but increased in correlation with the duration of abstinence. CONCLUSION: Our findings support that the disruption of the mOFC-striatal circuitry contribute to the maldaptive persistent behaviors in alcohol dependent patients.

Risk Factors Associated with the Development and the Course of Alcohol Withdrawal Delirium / 신경정신의학

OBJECTIVES: The aim of this study was to analyze the clinical variables associated with the occurrence, duration, and severity of alcohol withdrawal delirium (AWD) in patients with alcohol dependence. METHODS: We conducted a retrospective case-control study in alcohol dependent inpatients admitted to the psychiatric department, between 2006 and 2012 (n=863). Multivariable logistic and linear regression models were used for analysis of risk factors associated with development of AWD and the duration of illness, respectively. And multivariable logistic regression models were applied for assessment of risk factors associated with seclusions or physical restraints, which reflect the severity of AWD. RESULTS: Significant predictors for the occurrence of AWD included higher body temperature, lower platelet count, lower serum potassium, higher drinking amount, history of AWD, and history of head trauma or structural brain lesion. Variables associated with prolongation of delirium included higher body temperature, higher drinking amount, and less use of benzodiazepine during the AWD episode. Significant predictors for severe AWD included higher systolic blood pressure, longer duration of harmful alcohol use, and higher drinking amount. CONCLUSION: Easily determinable parameters, such as vital signs and past history related to drinking are significantly associated with not only development of AWD, but also its severity and duration. Therefore, when initially assessing alcohol dependent patients, clinicians should keep these parameters in mind in order to prevent occurrence of risky withdrawal delirium and behavioral problems.

Screening and Treating Wernicke's Encephalopathy among Alcoholic Patients in a University Hospital / 신경정신의학

OBJECTIVES: The purpose of this study was to investigate the prevalence and clinical characteristics of Wernicke's encephalopathy (WE) patients in alcoholics and to evaluate the utility of Caine's criteria as a screening test. METHODS: We made an admission note including Caine's criteria and applied it to patients who were admitted to an alcohol treatment unit. Demographic, clinical, and laboratory data were collected on 204 alcoholics. Our alcoholics who met more than one of Caine's criteria were considered at risk for WE and were given high-dose thiamine IV therapy. RESULTS: We was diagnosed in 15.2% of the alcoholic patients. Age and head trauma history were risk factors of WE. The sensitivity of Caine's criteria was 97% and specificity was 54%. High-dose thiamine IV therapy appeared to be a safe and cost-effective method to prevent the serious complications of WE. CONCLUSION: Caine's criteria is useful as a screening test for WE among alcoholic patients. High-dose thiamine IV therapy is cost-effective for alcoholic patients who are considered to be at risk for WE.

Psychotic Features as the First Manifestation of 22q11.2 Deletion Syndrome

The 22q11.2 deletion is a genetic disorder which is characterized by abnormalities in cardiac functioning, facial structure, neurobehavioral development, T cell functioning, and velopharyngeal insufficiencies. In the presented case study, 22q11.2 deletion was found in a patient who has psychotic symptoms only. A 25-year-old woman with a history of hypoparathyroidism and hypothyroidism presented with auditory hallucinations and persecutory delusions. After three months of treatment with antipsychotic medications, the patient was readmitted with generalized tonic-clonic seizures. The following week, the patient went into sepsis. A fluorescent in situ hybridization (FISH) analysis revealed the presence of a 22q11.2 microdeletion. This case study suggests that psychotic symptoms can develop prior to the typical symptoms of a 22q11.2 deletion. As such, psychiatrists should test for genetic abnormalities in patients with schizophrenia when these patients present with seizures and immunodeficiencies.

Social Pressure-Induced Craving in Patients with Alcohol Dependence: Application of Virtual Reality to Coping Skill Training

OBJECTIVE: This study was conducted to assess the interaction between alcohol cues and social pressure in the induction of alcohol craving. METHODS: Fourteen male patients with alcohol dependence and 14 age-matched social drinkers completed a virtual reality coping skill training program composed of four blocks according to the presence of alcohol cues (x2) and social pressure (x2). Before and after each block, the craving levels were measured using a visual analogue scale. RESULTS: Patients with alcohol dependence reported extremely high levels of craving immediately upon exposure to a virtual environment with alcohol cues, regardless of social pressure. In contrast, the craving levels of social drinkers were influenced by social pressure from virtual avatars. CONCLUSION: Our findings imply that an alcohol cue-laden environment should interfere with the ability to use coping skills against social pressure in real-life situations.

Association Study of Dopamine D2, D4 Receptor Gene, GABA(A) Receptor beta Subunit Gene, and Serotonin Transporter Gene Polymorphism with Children of Alcoholics in Korea: Preliminary Study / 신경정신의학

OBJECTIVES: The studies on the genetic risk factors of the children of alcoholics (COAs) are still in an early stage. The A 1 allele of the dopamine receptor 2 gene (DRD2) may be associated with the negative affect and positive alcohol expectancy of the COAs. In addition, several researchers reported that COAs might be associated with the GABAA receptor beta subunit gene (GABRB3) and serotonin transporter gene (5-HTTLPR). In this study, we investigated the association of polymorphism of the DRD2, Dopamine D4 receptor gene (DRD4), GABRB3, 5-HTTLPR with COAs to examine the genetic risk factors of COAs. METHODS: Twenty-two COAs and 23 control children (children of non-Alcoholics ; Non-COAs) were included for the genetic study. All COAs aged 6 to 18 were recruited and selected from families of alcoholic patients in alcohol clinics of three university and mental hospital. Alcoholism of parents was classified as type I (non-antisocial, late onset) and type II (antisocial, early onset) by Cloninger's classification. The genotyping of the DRD2, DRD4, GABRB3, 5-HTTLPR was carried out. Chi-square method was used for evaluating the associations between genetic polymorphism and the COAs. RESULTS: The frequency of A1+ allele of DRD2 in COAs were significantly higher than Non-COAs (Chi-square=4.45, df=1, p=0.035). Significant association between the genotype of DRD4 and COAs was found (Chi-square=8.32, df=1, p=0.004). G1- alleles of GABRB3 in COAs were significantly higher than in Non-COAs (Chi-square=6.622, df=1, p=0.022). We found no association of the polymorphic alleles of 5-HTTLPR with the COAs (Chi-square=0.021, df=1, p=0.884). There were significant associations between the type of parental alcoholism and depression of COAs. CONCLUSION: We found that the children of alcoholics had significantly increased genetic risk of alcohol drinking expectancy. This study provides some preliminary information on the risk and protective factors associated with the COAs, which can be used as a foundation for prevention and intervention of future psychopathology.

Psychosocial Aspects and Mental Health in Cancer Patients / 신경정신의학

Cancer patients suffer from significant psychological distress and considerable psychological morbidity throughout the course of their disease. The diagnosis of cancer, active treatment, palliative care and aftermath of cancer involve a long process of adaptation to multiple threats and stressful events. This review focused on psychosocial aspects of cancer, psychological reaction and adaptation of patients to cancer, psychological issues and psychiatric disorders in patients with cancer, and the need for screening of psychological distress at all stages of illness.

Cortical Information Transmission during Tic Suppression in Boys with Tourette's Disorder / 신경정신의학

OBJECTIVES: Tourette's Disorder (TD) is a chronic neuropsychiatric disorder characterized by multiple motor and vocal tics with onset in childhood. The aim of this study was to ascertain the increased cortical information transmission in frontal area during tic suppression in drug naive boys with TD using new nonlinear analysis of EEGs, be called Transfer Entropy (TE) which can detect the directed exchange of information between two systems. METHODS: Subjects were 11 drug naive boys with DSM-IV diagnosis of TD and 10 control boys. Clinical assessments were performed, and EEGs were recorded from 19 scalp loci of the international 10-20 systems. TE was estimated by EEG timeseries data after noise reduction. TE difference between TD and control during resting state and between tic suppression and resting state in TD were investigated. RESULTS: Elevated TE was found in extensive channels, including frontal, central and temporal channels (F7, Fz, F8,Cz, C3, P3, T3, and T4) in resting state of Tourette's disorder compared to normal controls. During tic suppression elevated TE was found in more extensive and asymmetrical channels especially prefrontal area (Fp1, Fp2, F3, Fz, F7, F8, Cz, C4, C5, T3, and T4). CONCLUSION: These findings suggest that pathogenesis of Tourette's disorder involve impaired cortical neuronal modulation in subcortical neural circuits. EEG analysis of TE may be a useful tool to investigation of cortical mechanism of psychiatric illness.