Young In Chung

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 Combination of the Korean Version of the Mini-Mental State Examination and Korean Dementia Screening Questionnaire Is a Good Screening Tool for Dementia in the Elderly

Objective The aim of this study is to investigate whether a combination of the Korean version of the mini-mental state examination (K-MMSE) and the Korean dementia screening questionnaire (KDSQ) is better than the use of test alone when differentiating patients with dementia from those without dementia in Korea. Methods The subjects (patients without dementia, 1120; patients with dementia, 908) were recruited from the Clinical Research Center for Dementia of South Korea. K-MMSE and KDSQ were used. Diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, fourth Edition. The weighted sum rule derived from logistic regression analysis was used for the combination of K-MMSE and KDSQ. Results On comparing the Area Under the Curve for each test using the method of Hanley and McNeil, the weighted sum was significantly greater than KDSQ or K-MMSE, and K-MMSE was significantly greater than KDSQ. Conclusion This study shows that when differentiating patients with dementia from those without dementia in Korea, a combination of K-MMSE and KDSQ achieved using the weighted sum method is better than either test performed alone. Further epidemiological studies in community-based settings are required before our results can be generalized to nonclinical samples.

Amnestic multiple cognitive domains impairment and periventricular white matter hyperintensities are independently predictive factors progression to dementia in mild cognitive impairment.

Mild cognitive impairment (MCI) usually represents a transitional phase between normal cognitive function and dementia, but not all people with MCI develop dementia because MCI is a clinically and etiologically heterogeneous grouping. The aim of this study was to determine whether clinical subtypes of MCI and severity of white matter hyperintensities (WMH) were associated with progression of MCI to dementia.

Association of the Neuronal Cell Adhesion Molecule (NrCAM) Gene Variants with Personality Traits and Addictive Symptoms in Methamphetamine Use Disorder

Objective 1) To investigate the relationship between NrCAM polymorphisms and methamphetamine abuse in an ethnically homogenous Korean population. 2) To further support our findings by investigating the association among NrCAM gene variants, certain personality traits, and addictive symptoms of methamphetamine abusers. Methods Thirty-seven male methamphetamine abusers (age=43.3±7.8) and30 non-users (16 men, 14 women; age=59.8±10.4) were recruited. Ten single nucleotide polymorphisms (SNPs) in the NrCAM gene were assayed to compare genotype distributions between the 2 groups. Personality characteristics were measured using the Temperament and Character Inventory (TCI) and the NEO Personality Inventory, Revised (NEO PI-R). Addictive symptoms were assessed using the Diagnostic Interview for Genetic Studies (DIGS) and reviews of the subjects medical records. Results Among the 10 SNPs in the NrCAM gene, the frequency of the TA genotype at rs1990162 was significantly lower in methamphetamine abusers compared to non-users (p=0.042). In the 3 NrCAM gene SNPs (rs381318, rs2072546, and rs6954366), the distribution of genotypes and alleles were significantly associated with some traits in the TCI and NEO PI-R. Genotypes and alleles at 5 gene SNPs (rs2142325, rs381318, rs1269621, rs1269634, and rs1990162) were associated with certain addictive symptom dimensions in the patients. Conclusion These findings support the idea that NrCAM is associated with genetic susceptibility of methamphetamine abuse and is also associated with certain personality characteristics that may increase disturbed addictive behavior.

Cortical atrophy, reduced integrity of white matter and cognitive impairment in subcortical vascular dementia of Binswanger type.

An association between white matter hyperintensities (WMH) and cognitive dysfunction has long been recognized. However, subjects with identically appearing WMH on magnetic resonance imaging present with a wide variance in cognitive function ranging from normal cognition to dementia. The aim of this study was to compare cortical atrophy and integrity of white matter of patients with subcortical vascular dementia of Binswanger type (SVaD‐BT) with those of the normal cognition group with WMH (ncWMH).

Memory impairment, in mild cognitive impairment without significant cerebrovascular disease, predicts progression to Alzheimer's disease.

Aims: Mild cognitive impairment (MCI) usually represents a transitional phase between normal cognitive function and dementia, but not all people with MCI develop dementia because MCI is a clinically and etiologically heterogeneous grouping. The aim of this study was to compare progression rates to Alzheimer’s disease (AD) among various MCI subtypes which show minimal white matter ischemia. Methods: Our study cohort consisted of 504 patients aged 55 years or older who had a diagnosis of MCI at their baseline visit, and had at least 1 follow-up contact after baseline. Results: Subjects with multiple-domain MCI with amnesia (mdMCI+a) were found to be significantly more likely to progress to AD in comparison to patients with nonamnesic MCI. There was no difference in the progression rate to AD between amnesic MCI and mdMCI+a during the follow-up period. The results of the multivariable Cox proportional hazards model analysis showed the same pattern of results as described above. Conclusion: Subjects with mdMCI+a had a statistically significant association with progression to AD. Especially, in cases of degenerative etiologies, impairment of the memory domain is more important than impairment of multiple domains in predicting the progression to dementia.

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 Chronbachs 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.

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.

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 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.