Hee Jeong

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.

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).

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.

A case of acute psychosis in a patient following exposure to a single high dose of styrene

We report a case of acute psychotic symptoms following exposure to a single high dose of styrene monomer. The 24‐year‐old male patient showed psychotic and cognitive symptoms immediately after exposure. His psychotic symptoms included auditory hallucinations and delusions of reference. Brain magnetic resonance imaging, electroencephalography, and laboratory examinations were performed to evaluate any other causes. The clinical, neuroimaging, and laboratory review in this case suggested that the suddenly developed psychotic symptoms that led to chronic deterioration were caused by the single exposure to styrene monomer. This is the first recent report in which acute psychotic symptoms developed from a single high dose of styrene suffocation compared with previous findings showing symptoms because of long‐term low‐dose exposure.

Case of psychotic patient with suspected Shprintzen–Goldberg syndrome

COTARD’S SYNDROME, CHARACTERIZED by nihilistic delusions, mostly occurs in presenile women and is accompanied by depression. The French physician Jules Cotard first presented a case of this syndrome in 1880. Its cause, however, still remains unclear. ‘I have no brain, heart, stomach or entrails. My body has entirely fallen into decay and only spirit exists. I can’t even die and would live forever.’ These are the words of a 62-year-old woman diagnosed with Cotard’s syndrome at our hospital. We consider this case significant because of the marked biochemical changes that occurred in her body, or ‘the dead body,’ according to her. The patient commenced treatment for depression in 2007, and was admitted to our hospital in April 2010 because of nihilistic delusions, appetite loss, and furious excitement. Before admission, her adherence to medication was poor, and she took only paroxetine (10 mg/day) irregularly. On admission, she had neither fever nor consciousness-related disorders. The results of various tests revealed only minor changes, for example, slight dehydration and undernourishment. No laboratory finding indicated renal failure, inflammation, or endocrine abnormality. The brain magnetic resonance imaging scan showed slight cortical atrophy compatible with her age. However, considerable changes were observed in the plasma monoamine metabolite levels on admission; the homovanillic acid (HVA, dopamine metabolite) level was 154.8 ng/mL (normal range for 50–60-year-old subjects, 4–15 ng/mL); the total 3-methoxy-4-hydroxyphenylglycol (MHPG, noradrenaline metabolite) level was 202.1 ng/mL (normal range, 16–26 ng/mL); and the free MHPG level was 57.9 ng/mL (normal range, 4–7 ng/mL). The patient was diagnosed with Cotard’s syndrome that developed during the course of psychotic depression. After admission, she was treated with an antidepressant (amoxapine, 50–90 mg/day) and antipsychotics (mainly olanzapine, 2.5–10 mg/day). The varied psychotic symptoms gradually improved, and the monoamine levels returned to approximately normal. At the time of discharge in June, the patient said ‘My spirit comes back to my body.’ Recently, researchers have tried to formulate a neuropsychological theory to explain this syndrome and to identify the structural changes associated with this syndrome. However, these approaches have failed to adequately explain the severe and enigmatic symptoms of this syndrome, even though previous studies have demonstrated high dopaminergic activities in psychotic depression. In this case, we focused on the plasma monoamine metabolite levels, which had drastically increased, and then normalized, on improvement of clinical symptoms. The high levels of HVA and total and free MHPG were not thought to be due to medication before admission, taking into account that her adherence to medication was poor. In addition, laboratory findings did not suggest any physical condition that could be responsible for the increased plasma monoamine metabolite levels. We attribute the symptoms of this patient to the broad disruption of the neurotransmission systems, including the dopamine and noradrenaline systems. In conclusion, we introduce a new standpoint: some patients develop Cotard’s syndrome in the presence of other neurochemical disorders.