Development of a Guideline for Antipsychotic-induced Hyperprolactinemia in Korea Using the ADAPTE Process

Objective@#To develop an evidence-based guideline for the diagnosis and treatment of antipsychotic-induced hyperprolactinemia by adapting existing high-quality clinical guidelines with a view to improve the clinical symptoms and long-term quality of life of patients by providing appropriate management. @*Methods@#This guideline was developed according to the ADAPTE methodology. The adaptation process included determining key health questions, systematically searching and screening guidelines, evaluating the quality and contents of these guidelines, deriving recommendations for key questions, and performing a peer review. The selection criteria for the guideline search were (1) evidence-based guidelines, (2) published within the last 5 years, and (3) written in English or Korean. @*Results@#After evaluating the quality and content, we finally selected three guidelines for adaptation. The final output of the development process was 25 recommendations for 10 key questions. We adopted the Agency for Health Research Quality methodology and presented the level of evidence from levels I to IV. In addition, we defined the recommendation grades from grade A (strongly recommended) to D (no recommendation) based on the level of evidence and clinical significance of the recommendation. @*Conclusion@#The development and dissemination of the adapted guideline is expected to increase the certainty of medical decision making and improve the quality of medical care. Further studies on the effectiveness and applicability of the developed guideline are necessary.

Changes in Human Gene Expression After Sleep Deprivation

Objectives@#Sleep is fundamental to maintaining homeostatic control and has behavioral and psychological effects on humans. To better understand the function and pathophysiology of sleep, specific gene expressions in reference to sleep deprivation have been studied. In this study, we investigated the gene expression of peripheral blood mononuclear cells after sleep deprivation to better understand the functional consequence of sleep. @*Methods@#In eight healthy men, 24 h sleep deprivation was induced. Blood was sampled at 14:00, before and after sleep deprivation.mRNA was isolated and analyzed via microarrays. cDNAs before and after sleep deprivation were coupled to Cy3 or Cy5, respectively, and normalized cDNAs were selected with a ratio greater than two as a significant gene. Results are expressed as mean. @*Results@#Among 41174 transcripts, 38852 genes were selected as reliable, and only a small minority (< 1%) of the genes were up-or down-regulated. Total six and eleven genes were selected as significant upregulated and downregulated genes, respectively. Protein tyrosine phosphatase receptor type O was most upregulated (6.9-fold), and low-density lipoprotein receptor-related protein 5-like protein showed the most substantial inhibition (0.06-fold). @*Conclusions@#This study showed significant associations between sleep deprivation and the immune system. Acute sleep deprivation affects pathways in proinflammatory cytokines as well as metabolic pathways of glutamate and purine, neurotransmitters related to sleep and wake cycle.

The Effect of Structured Music Therapy Program on Emotional Function in the Dementia Patients

Objective@#The effectiveness of music therapy programs for the elderly with dementia has been verified through several studies, but there is a limitation in that most of them are compared with a single group, no treatment group or waiting group. In this study, to overcome this problem, the two groups that performed similar interventions were selected and compared retrospectively. @*Methods@#For 37 people who participated in the treatment programs for the elderly with dementia at Dongdaemun Center for De-mentia and its branch center, we retrospectively analyzed the changes in Korean version of Geriatric Depression Scale and GeriatricQuality of Life Scale-Dementia scores measured before and after treatment. @*Results@#Prior to treatment, there is no significant difference between the groups in the demographic variables and the depression and quality of life scores. The difference between pre- and post-scores was not significant in the group at the branch center without a music therapy, but depression was significantly reduced and quality of life had improved in the group at Dongdaemun center with the music therapy program. @*Conclusion@#It was confirmed that participation in the structured music therapy program had a positive effect on the improve-ment of depression and quality of life in the elderly with dementia compared to other similar interventions.

The Effect of Structured Music Therapy Program on Emotional Function in the Dementia Patients

Objective@#The effectiveness of music therapy programs for the elderly with dementia has been verified through several studies, but there is a limitation in that most of them are compared with a single group, no treatment group or waiting group. In this study, to overcome this problem, the two groups that performed similar interventions were selected and compared retrospectively. @*Methods@#For 37 people who participated in the treatment programs for the elderly with dementia at Dongdaemun Center for De-mentia and its branch center, we retrospectively analyzed the changes in Korean version of Geriatric Depression Scale and GeriatricQuality of Life Scale-Dementia scores measured before and after treatment. @*Results@#Prior to treatment, there is no significant difference between the groups in the demographic variables and the depression and quality of life scores. The difference between pre- and post-scores was not significant in the group at the branch center without a music therapy, but depression was significantly reduced and quality of life had improved in the group at Dongdaemun center with the music therapy program. @*Conclusion@#It was confirmed that participation in the structured music therapy program had a positive effect on the improve-ment of depression and quality of life in the elderly with dementia compared to other similar interventions.

Depression, Anxiety, Related Risk Factors and Cognitive Distortion in Korean Patients with Inflammatory Bowel Disease

Objective@#To evaluate the severity of depression, anxiety, associated risk factors, and cognitive distortion in Korean patients with ulcerative colitis (UC) and Crohn’s disease (CD). @*Methods@#This study included 369 patients with inflammatory bowel disease. The severity of depression and anxiety was examined using Patient Health Questionnaire-9 and Hospital Anxiety and Depression Scale. The Anxious Thoughts and Tendencies scale was used to measure catastrophizing tendency. Multivariate regression analyses were performed. @*Results@#The predictors of depression were marital status, anti-tumor necrosis factor-α (TNF-α) agent use, age, and body mass index in UC patients and marital status, disease activity, alcohol use, and employment status in CD patients. For anxiety, sex and marital status were the associated factors in UC patients, whereas steroid use was the only significant predictor in CD patients. Comparing the cognitive distortion level, there were no significant differences between UC and CD patients although there was an increasing tendency according to the severity of depression or anxiety. @*Conclusion@#If patients are accompanied by high levels of depression or anxiety and their associated risk factors including TNF-α agent or steroid use, it is recommended that not only symptoms are treated but also cognitive approach and evaluation be performed.

Association of the Promoter Haplotype of IFN-γ-Inducible Protein 16 Gene with Schizophrenia in a Korean Population

Objective@#Viral infections play an important role in the development of schizophrenia, inducing the faulty immunological responses and aberrant inflammation. IFN-γ-inducible protein 16 (IFI16) is an immunological DNA sensor against viral infections, triggering the inflammatory responses. In this study, we investigated an association between putative promoter single nucleotide polymorphisms (SNPs) and haplotypes of IFI16 and schizophrenia. @*Methods@#A total of 280 schizophrenia patients and 427 control subjects were recruited in this study. We genotyped three promoter SNPs (rs1465175, rs3754464, rs1417806) using direct sequencing. Associations of SNPs and haplotypes of IFI16 with schizophrenia were analyzed. The promoter activities on the haplotypes of IFI16 were measured. @*Results@#The T allele of rs1465175 and the C allele of rs1417806 were protectively associated with schizophrenia (p=0.021 on rs1465175; p=0.016 on rs1417806), whereas the G allele of rs3754464 was associated with an increased risk of schizophrenia (p=0.019). In haplotype analysis, a significant association between the GGA haplotype and schizophrenia was shown (p=0.013). Moreover, we found that the GGA haplotype elevated the promoter activity compared to the GAA haplotype, whereas the TAC haplotype reduced that. @*Conclusion@#The promoter SNPs and haplotypes of IFI16 may contribute to the susceptibility of schizophrenia, affecting the promoter activity of IFI16.

NR3C1 Polymorphisms for Genetic Susceptibility to Schizophrenia

OBJECTIVES: Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia.METHODS: Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models).RESULTS: The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16–2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11–2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13–2.10, p = 0.0067).CONCLUSIONS: This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.

Differences in Personality, Defense Styles, and Coping Strategies in Individuals with Depressive Disorder According to Age Groups Across the Lifespan

OBJECTIVE: This study aimed to examine the differences in personality, defense style, and coping styles among patients with depression according to age groups.METHODS: A total of 211 participants ranging from 19 to 81 years old were recruited for the study. To assess participants’ five dimensions of personality, the Neuroticism-Extraversion-Openness Personality Inventory-Revised (NEO-PI-R) was administered. In addition, the Korean-Defense Style Questionnaire and the Korean version of the coping checklist were administered to examine the defense and coping style.RESULTS: In the analysis of NEO-PI-R, the mean value of Agreeableness, Conscientiousness, and Neuroticism showed significant differences between the young adult age group (20–34 years) and the late middle age group (50–64 years) (p<0.05). The young age group used more immature defense styles and made less use of problem-focused coping strategy than the old age patients (65 years and older) (p<0.05).CONCLUSION: In the young age group associations with lower Agreeableness and Conscientiousness, as well as higher Neuroticism than the late middle age group were observed. Moreover, the young age group had a higher usage of immature defense style, and restricted use of problem-focused coping style than other age groups.

The Development of Evidence-Based Guideline for Diagnosis and Management of Headache in Korea

OBJECTIVE: We aimed to develop the clinical guideline for headache by the systematic review and synthesis of existing evidence-based guidelines. The purpose of developing the guideline was to improve the appropriateness of diagnosis and treatment of headache disorder, and consequently, to improve patients’ pain control and quality of life. The guideline broadly covers the differential diagnosis and treatment of tension-type headache, migraine, cluster headache, and medication-overuse headache. METHODS: This is a methodological study based on the ADAPTE methodology, including a systematic review of the literature, quality assessment of the guidelines using the Appraisal of Clinical Guidelines for REsearch & Evaluation II (AGREE II) Instrument, as well as an external review using a Delphi technique. The inclusion criteria for systematic search were as follows: topic-relevant, up-to-date guidelines including evidence from within 5 years, evidence-based guidelines, guidelines written in English or Korean, and guidelines issued by academic institutions or government agencies. RESULTS: We selected five guidelines and conducted their quality assessment using the AGREE II Instrument. As a result, one guideline was found to be eligible for adaptation. For 13 key questions, a total of 39 recommendations were proposed with the grading system and revised using the nominal group technique. CONCLUSION: Recommendations should be applied to actual clinical sites to achieve the ultimate goal of this guideline; therefore, follow-up activities, such as monitoring of guideline usage and assessment of applicability of the recommendations, should be performed in the future. Further assessment of the effectiveness of the guideline in Korea is needed.

Differences of Personality Characteristics According to the Suicide Symptoms in Patients with Depression / 정신신체의학

OBJECTIVES@#The purpose of this study was to examine personality traits associated with suicidal symptoms (with history of suicide attempt or suicidal idea) in depressed patients.@*METHODS@#A sample 186 patients diagnosed with major depressive disorder was divided into two groups : suicidal group (with history of suicide attempt or suicidal idea, n=70) and non-suicidal group (without history of suicide attempt or suicidal idea, n=116). NEO Personality Assessment System were used to evaluate personality trait.@*RESULTS@#Neuroticism was high in suicidal group (p=0.041). In multivariate logistic regression, Neuroticism was also a significant influence on suicidal symptoms (Odds Ratio=1.04, 95% Confidence Interval 1.01–1.07, p=0.0145).@*CONCLUSIONS@#High Neuroticism is a useful information to identify individuals at high risk of suicide in depressive patients.

Gray Matter Volume Reductions Were Associated with TPH1 Polymorphisms in Depressive Disorder Patients with Suicidal Attempts

OBJECTIVE: Structural changes of brain areas have been reported in depressive disorder and suicidal behavior (SB), in which TPH1 also has been known as a promising candidate gene. We investigated gray matter volume (GMV) differences, TPH1 rs1800532 and rs1799913 polymorphisms previously found to be associated with depressive disorder and SB, and the relationship between the two markers. METHODS: Thirteen depressive disorder patients with suicidal attempts (SA) and twenty healthy controls were included. We examined GMV differences using a voxel-based morphometry and regions of interest analysis. Direct sequencing was used for genotyping. RESULTS: The patients showed significant GMV reduction in left cerebral region including middle frontal gyrus, inferior frontal gyrus, and anterior cingulate cortex; in right middle temporal gyrus; in left cerebellar tonsil; and in right cerebral region including precentral gyrus and postcentral gyrus (corrected p < 0.005). The right precentral and postcentral gyri GMV values of AA and CA genotypes patients were significantly decreased compared to those of CC genotype subjects (corrected p=0.040). CONCLUSION: These findings show the possibility that both GMV reductions and TPH1 rs1800532/rs1799913 A allele may be involved in the pathogenesis of depressive disorder patients with SA.

Association of Therapeutic Response and Change of Mismatch Negativity in Schizophrenia Patients

OBJECTIVES: Schizophrenia is characterized by disturbances in perception and cognition. Attenuated mismatch negativity (MMN) reflects central auditory dysfunction in schizophrenia. The aim of this study is to compare MMN changes before and after treatment in schizophrenia patients and to assess their association with treatment response. METHODS: Twenty-three schizophrenia patients underwent an oddball paradigm. MMN was calculated by the difference waveforms of the event-related potentials (ERPs) elicited by subtracting standard from deviant stimulus. The clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS), the Psychotic Symptom Rating Scale (PSYRATS). Follow-up evaluation was conducted when the PANSS total score decreased by 30% or more (treatment response group) or before discharge (non-response group). RESULTS: The treatment response group showed significantly larger MMN amplitude improvement and latency reduction than the non-response group after treatment (Fz ; mean amplitude p = 0.035, FCz ; p = 0.041). The auditory hallucination group showed shorter latency than that of the group without hallucinations. Additionally, auditory hallucination was associated with prolonged MMN latency and shortened after treatment in the auditory hallucination response group (Fz ; p = 0.048). CONCLUSIONS: These results suggest that the attenuated MMN amplitude reflects the progression of the disease. The increment of MMN amplitude and shortening of latency after treatment may reflect cognitive functional recovery of central auditory sensory processing.

Association between Mitofusin 2 Gene Polymorphisms and Late-Onset Alzheimer's Disease in the Korean Population

OBJECTIVE: Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. METHODS: One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72.3±4.41) and 186 healthy control subjects (82 men and 104 women, mean age 76.5±5.98). RESULTS: Among these three SNPs, rs1042837 showed statistically significant differences in allele frequency, and genotype frequency in the co-dominant 1 model and in the dominant model. CONCLUSION: These results suggest that the rs1042837 polymorphism in MFN2 may be involved in the pathogenesis of AD.

Factors Related to Noncompliance in Screening and Tracking Mild Cognitive Impairment Patients in a Single Community

OBJECTIVE: We assessed the cumulative conversion rates (CCR) from minor cognitive impairment (MCI) to dementia among individuals who failed to participate in annual screening for dementia. Additionally, we analyzed the reasons for failing to receive follow-up screening in order to develop better strategies for improving follow-up screening rates. METHODS: We contacted MCI patients who had not visited the Dongdaemun-gu Center for Dementia for annual screening during the year following their registration. We compared the CCR from MCI to dementia in the following two groups: subjects registered as having MCI in the Dongdaemun-gu Center for Dementia database and subjects who failed to revisit the center, but who participated in a screening test for dementia after being contacted. The latter participants completed a questionnaire asking reasons for not previously visiting for follow-up screening. RESULTS: The final diagnoses of the 188 subjects who revisited the center only after contact were 19.1% normal, 64.9% MCI and 16.0% dementia. The final diagnoses of the 449 subjects in the Dongdaemun-gu Center for Dementia database were 25.6% normal, 46.1% MCI and 28.3% dementia. The CCR of the revisit-after-contact group was much lower than anticipated. The leading cause for noncompliance was “no need for tests” at 28.2%, followed by “other reasons” at 23.9%, and “I forgot the appointment date” at 19.7%. CONCLUSION: Considering the low dementia detection rate of the group who revisited only after contact and the reasons they gave for noncompliance, there appears to be a need for ongoing outreach and education regarding the course and prognosis of MCI.

Changing Trends in the Occurrence and Management of Delirium for 5 Years in a University Hospital / 정신신체의학

OBJECTIVES: Delirium is a disorder defined as a sudden disturbance in thinking, speaking, acting and sleep pattern due to altered level of consciousness and cognitive function. The objective of this study is to analyze characteristics and therapeutic methods of the delirious patients during the recent 5 years, and provide basic data for further studies and investigation regarding delirium in the occurrence and treatment. METHODS: We retrospectively reviewed medical records of 475 patients who were consulted for delirium in Kyunghee University Medical Center from January 2007 to December 2011. RESULTS: During the 5 years, among the 475 patients who were diagnosed as delirium, men were more common(61.7%). The most commonly consulted reason and cause were sleep disturbance(80.8%) and post-operational delirium(30.9%), respectively. The medication prescription percentage was 76.6% and was significantly increased year after year. Ratio of using antipsychotics were 76.4% among prescribed medication and the most frequently prescribed antipsychotic drug was quetiapine(46.8%). Other specialists commonly misdiagnosed delirium when the patient was previously diagnosed as dementia(6.8%). CONCLUSIONS: In our study, post-operational delirium was the most commonly referred reason and the percentage of medication prescription tended to increase. Patients with history of dementia were more easily misdiagnosed as diseases other than delirium. Our study suggests that we should evaluate symptoms, causes, reasons of consultation, management tendency of delirium. We should also closely observe changes in sleep patterns and establish the prevention strategies for post-operational delirium and therapeutic bases for pharmacotherapy.

Assessment between Dopamine Receptor D2 (DRD2) Polymorphisms and Schizophrenia in Korean Population

OBJECTIVE: The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of dopamine receptor D2 (DRD2) are associated with schizophrenia in Korean population. METHODS: Four SNPs (rs4648317, rs7131056, rs4936270, and rs1076562) of DRD2 were selected and genotyped by direct sequencing in 197 schizophrenia patients and 370 control subjects. SNPAnalyzer, SNPStats, and Haploview version 4.2 programs were performed to analyze the genetic data. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, overdominant, and log-additive) were used to evaluate the odds ratios (ORs), 95% confidence intervals (CIs), and p values. For multiple testing, p values (pc) were re-evaluated by Bonferroni's correction. RESULTS: The genotype frequency of DRD2 rs4936270 SNP was associated with the development of schizophrenia (p=0.0007, OR=1.71, 95% CI=1.16-2.52 in the codominant1 model; p=0.011, OR=1.63, 95% CI=1.12-2.37 in the dominant model; p=0.035, OR=1.41, 95% CI=1.03-1.95 in the log-additive model). The allele frequency of rs4936270 was also associated with the development of schizophrenia (p=0.024, OR=1.45, 95% CI=1.05-1.98). After Bonferroni's correction, the genotype distribution of rs4936270 was still related to the development of schizophrenia (pc=0.0028 in the codominant1 model; pc=0.044 in the dominant model). A linkage disequilibrium block consisted of rs4648317, rs7131056, and rs4936270. The CAT haplotype frequency was different between schizophrenia and controls (p=0.039). CONCLUSION: These results suggest that DRD2 SNPs may be associated with the development of schizophrenia in Korean population.

Secondary Adrenal Insufficiency Initially Misdiagnosed as Depression: A Case Report / 정신신체의학

The abnormalities in Hypothalamic-pituitary-adrenal(HPA) axis are associated with many psychiatric symptoms including depression. We present a report of a 71 year old man who was admitted to the psychiatric department presenting symptoms of headache, avolition, loss of energy, psychomotor retardation, poor appetite, insomnia, anxiety resulting from adrenal insufficiency and hypopituitarism. Hypothyroidism and electrolyte disturbance were managed and headache, insomnia, anxiety, GI symptoms were improved. But he remained in anergic state. After discharge, he was readmitted to infection department with high fever and drowsy mentality. Adrenal insufficiency was recognized and he was treated with corticosteroid replacement therapy. Finally his diagnosis was made as panhypopituitarism and overall symptoms were resolved. In this case, we showed how the atypical symptoms resulting from hypopituitarism develop and progress. Hypothyroidism, adrenal insufficiency, and growth hormone deficiency resulting secondarily from panhypopituitarism were associated with various nonspecific symptoms such as loss of energy, fatigue, insomnia, weight loss, decreased appetite etc. In clinical situation, differential diagnosis with depression is needed when clinicians were met a patient with these nonspecific symptoms. It is important that laboratory tests and differential diagnosis with endocrine diseases should be conducted, especially in geriatric patients with nonspecific symptoms like anergia, fatigue, poor appetite and so on.