Testing the efficacy of real-time fMRI neurofeedback for training people who smoke daily to upregulate neural responses to nondrug rewards.

Although the use of nondrug rewards (e.g., money) to facilitate smoking cessation is widespread, recent research has found that such rewards may be least effective when people who smoke cigarettes are tempted to do so. Specifically, among people who smoke, the neural response to nondrug rewards appears blunted when access to cigarettes is anticipated, and this blunting is linked to a decrease in willingness to refrain from smoking to earn a monetary incentive. Accordingly, methods to enhance the value of nondrug rewards may be theoretically and clinically important. The current proof-of-concept study tested if real-time fMRI neurofeedback training augments the ability to upregulate responses in reward-related brain areas relative to a no-feedback control condition in people who smoke. Adults (n = 44, age range = 20-44) who reported smoking >5 cigarettes per day completed the study. Those in the intervention group (n = 22, 5 females) were trained to upregulate brain responses using feedback of ongoing striatal activity (i.e., a dynamic "thermometer" that reflected ongoing changes of fMRI signal intensity in the striatum) in a single neurofeedback session with three training runs. The control group (n = 22, 5 females) underwent a nearly identical procedure but received no neurofeedback. Those who received neurofeedback training demonstrated significantly greater increases in striatal BOLD activation while attempting to think about something rewarding compared to controls, but this effect was present only during the first training run. Future neurofeedback research with those who smoke should explore how to make neurofeedback training more effective for the self-regulation of reward-related brain activities.

The Role of Decreased Cortical Thickness and Volume of Medial Temporal Lobe Structures in Predicting Incident Psychosis in Patients With Alzheimer's Disease: A Prospective Longitudinal MRI Study.

OBJECTIVE: To investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based prospective longitudinal study enrolled 109 patients with AD. All patients with AD were evaluated at 3-month intervals to investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. OUTCOME MEASURE: The main outcome measure was time-to-progression from AD to incident psychosis. The thickness or volume of medial temporal lobe structures (i.e., the hippocampus, entorhinal cortex, and parahippocampus) were measured using magnetic resonance imaging and the Freesurfer automated segmentation pipeline at baseline. RESULTS: Multivariate Cox proportional hazards regression analysis revealed that a decreased cortical thickness or volume of medial temporal region was associated with a higher risk of incident psychosis in patients with AD. The hazard ratios for decreased cortical thickness of the left entorhinal cortex and decreased cortical volume of the right hippocampus were 4.291 (95% confidence interval [CI], 1.196-15.384) and 2.680 [(CI, 1.003-1.196]), respectively. CONCLUSION: Our study revealed that decreased cortical thickness or volume of medial temporal sub-regions is a risk factor for incident psychosis in patients with AD. A careful assessment of the thickness or volume of the medial temporal lobe structures in AD may improve early detection and intervention of psychosis in AD.

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.

Reduced Thickness of the Anterior Cingulate Cortex as a Predictor of Amnestic-Mild Cognitive Impairment Conversion to Alzheimer's Disease with Psychosis.

BACKGROUND: A long-term follow-up study in patients with amnestic mild cognitive impairment (aMCI) is needed to elucidate the association between regional brain volume and psychopathological mechanisms of Alzheimer's disease with psychosis (AD + P). OBJECTIVE: The purpose of this study was to investigate the effect of the thickness of the angular cingulate cortex (ACC) on the risk of AD + P conversion in patients with aMCI. METHODS: This was a hospital-based prospective longitudinal study including 174 patients with aMCI. The main outcome measure was time-to-progression from aMCI to AD + P. Subregions of the ACC (rostral ACC, rACC; caudal ACC, cACC) and hippocampus (HC) were measured as regions of interest with magnetic resonance imaging and the Freesurfer analysis at baseline. Survival analysis with time to incident AD + P as an event variable was calculated with Cox proportional hazards models using the subregions of the ACC and HC as a continuous variable. RESULTS: Cox proportional hazard analyses showed that the risk of AD + P was associated with sub-regional ACC thickness but not HC volume: reduced cortical thickness of the left cACC (HR [95%CI], 0.224 [0.087-0.575], p = 0.002), right cACC (HR [95%CI], 0.318 [0.132-0.768], p = 0.011). This association of the cACC with the risk of AD also remained significant when adjusted for HC volume. CONCLUSION: We found that reduced cortical thickness of the cACC is a predictor of aMCI conversion to AD + P, independent of HC, suggesting that the ACC plays a vital role in the underlying pathogenesis of AD + P.

Smaller hippocampal volume in APOE ε4 carriers independent of amyloid-ß (Aß) burden.

OBJECTIVE: To investigate the association of the APOE ε4 genotype with hippocampal volume, independent of Aß burden. METHOD: This cross-sectional study included 71 participants with mild cognitive impairment or mild AD. All participants were divided into carriers or non-carriers of the ε4 allele. The main outcome was hippocampal volume measured using structural magnetic resonance imaging; 18F-florbetaben positron emission tomography was additionally performed to investigate the association of APOE ε4 genotype with hippocampal volumes, independently of Aß burden. Analysis of covariance was conducted to compare the differences in hippocampal volumes between carriers and non-carriers of the ε4 allele after controlling for global Aß burden or local hippocampal Aß burden. RESULTS: The APOE ε4 genotype was associated with a smaller right and total hippocampal volume (right: 3160.16 ± 365.71 vs. 3365.24 ± 434.88, p < 0.05; total: 6257.48 ± 790.60 vs. 6599.52 ± 840.58, p < 0.05), independent of Aß burden. CONCLUSION: Our findings on the association of APOEε4 genotype with hippocampal volume independent of Aß burden suggest that the APOEε4 genotype may contribute to hippocampal neurodegeneration through an Aß-independent mechanism.

Association of Temporolimbic Volumes with Treatment Response to Antipsychotic Medication for Delusion in Patients with Alzheimer's Disease.

Objective: This study investigated the association between gray matter volume and the treatment response to antipsychotic medication in patients with Alzheimer's disease (AD). Methods: We included 26 AD patients with delusions from the Memory Impairment Center of the Pusan National University Hospital in South Korea. All participants underwent baseline brain magnetic resonance imaging and took risperidone as an antipsychotic medication for 6 weeks. Gray matter volumes were measured using voxel-based morphometry at baseline. Treatment response with respect to delusional symptoms was defined as the change in delusion item scores in the Korean version of the Neuropsychiatry Inventory (K-NPI), from baseline to 6 weeks later. A voxel-based multiple linear regression model integrated with statistical parametric mapping was used to investigate the association between gray matter volume and treatment response after controlling for covariates. Results: The treatment response was significantly positively correlated with gray matter volume in the temporal lobe (both the fusiform gyri and the left superior and inferior temporal gyri) and the limbic system (the left parahippocampal gyrus and left amygdala) after controlling for age, sex, education level, total intracranial volume, risperidone dosage, baseline Korean version of the Mini-Mental Status Examination scores, and baseline K-NPI scores for the delusion and non-delusion domains (P < .001, uncorrected, KE > 100 voxels). Conclusion: Our findings suggest that specific gray matter volumes, including those of the temporal region and the limbic system, may affect treatment response to antipsychotic medication in terms of delusional symptoms in patients with AD.

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.

Heritability and familiality of psychopathologic dimensions in Korean families with schizophrenia.

AIM: Categorical syndromes such as schizophrenia could be a combination of many continuous mental structure phenotypes including several personality development/degeneration dimensions. This study investigated the heritability and familiality of symptom check list (SCL) psychopathologic dimensions in Korean schizophrenia linkage disequilibrium families. METHOD: We recruited 204 probands (with schizophrenia) with their parents and siblings whenever possible. We used the SCL questionnaire to measure psychopathologic dimensions. The heritability of symptomatic dimensions in 543 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Psychopathologic dimensions in the 543 family members were compared with those in 307 healthy unrelated controls to measure familiality on using analysis of variance (ANOVA) analysis. RESULTS: Five of the nine SCL variables were significantly heritable and were included in the subsequent analyses. The three groups (control, unaffected first-degree relative, schizophrenia patient) were found to be significantly different with regard to the expected order of average group scores for all heritable dimensions. CONCLUSION: Aberrations in several symptomatic dimensions could contribute to the complexity of schizophrenia syndrome as a result of genetic-environment coaction or interaction in spite of some limitations (recruited family, phenotyping).

Right hippocampus atrophy is independently associated with Alzheimer's disease with psychosis.

AIM: The purpose of this study was to determine whether regionally distributed medial temporal cortex thickness (or hippocampal volume) and frontal lobe volume are independently associated with the onset of Alzheimer's disease (AD) with psychosis. METHODS: We identified 26 AD patients with psychosis (AD+P) and 48 AD patients without psychosis (AD-P) from the Memory Impairment Clinic at Pusan National University Hospital in South Korea. They were matched for age, gender, duration of AD, and Clinical Dementia Rating sum of box score. All participants met the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for probable AD. Psychosis was diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of AD. All participants underwent 3-T magnetic resonance imaging, and 3-D magnetization-prepared rapid gradient echo sequence was acquired for each. The FreeSurfer version 5.1 software package was used to analyze cortical thickness and volume on 3-D T1 -weighted images. anova was used to investigate the differences in cortical thickness and the volume of the total frontal cortex, total temporal cortex, and subregions of the medial temporal cortex between groups after age, gender, years of education, Clinical Dementia Rating sum of box score, duration of AD, and total intracranial volume were controlled for. Furthermore, we added the total frontal volume as an additional variable to investigate whether the association between the medial temporal cortex and AD+P is independent of the frontal cortex. RESULTS: We found that both left and right hippocampal volume were smaller in AD+P than in AD-P. In particular, there was a significant difference in right hippocampal volume between the AD+P and AD-P groups after total frontal volume was added as an additional variable. CONCLUSION: We found that more severe hippocampal atrophy is associated with AD+P than with AD-P. In addition, atrophy of the right hippocampus remained significant among AD+P after adjustment for frontal volume. These findings suggest that right hippocampal atrophy is independently associated with AD+P.

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.

Transmissibility and familiality of NEO personality dimensions in a sample of Korean families with schizophrenia.

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 Neuroticism-Extraversion-Openness to experience (NEO) personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD).We have recruited 204 probands (with schizophrenia) with their parents and siblings whenever possible. We have used NEO 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.Four of the 5 NEO variables were significantly heritable and were included in the subsequent analyses. The 3 groups (control, unaffected first-degree relative, case) were found to be significantly different and with the expected order of average group scores for all heritable dimensions.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).

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.

Onset of dieting in childhood and adolescence: implications for personality, psychopathology, eating attitudes and behaviors of women with eating disorder.

PURPOSE: This study examined the MMPI-2 and EDI-2 scores of 205 Korean women with eating disorders to identify difference between early and adulthood onset of dieting groups. METHODS: 101 women had started dieting in their childhood to adolescence (EARLYdieting group) and 104 had started dieting in their adulthood (ADULTdieting group). RESULTS: Both of the MMPI-2 and EDI-2 scores were significantly different between the two groups before and after adjusting for the duration since the onset of eating disorder. EARLYdieting group scored higher in the MMPI-2 clinical scales 1, 3, 0 and the EDI-2 bulimia scale. EARLYdieting group tended to use a more varied dieting strategy. CONCLUSIONS: The findings suggested that starting to diet early in life may be related to more severe psychopathology and dieting behaviors in adulthood.

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.

Decreased gray matter volume is associated with the subtypes of psychotic symptoms in patients with antipsychotic-naïve mild or moderate Alzheimer's disease: A voxel-based morphometry study.

The purpose of this study was to investigate the association between brain regional gray matter volume and two subtypes of psychotic symptoms, namely paranoid and misidentification subtypes, in antipsychotic-naïve mild or moderate Alzheimer's disease (AD) patients. Forty AD patients with psychotic symptoms and 25 AD patients without psychotic symptoms were assessed for cognitive and functional impairment. Presence and subtype of psychotic symptoms were assessed by using the delusion and hallucination subscale of the Korean Neuropsychiatric Inventory (K-NPI). Structural MRI images were acquired on a 3 T scanner, and were analyzed using voxel-based morphometry (VBM) for automated analysis. The misidentification subtype is associated with more severe gray matter atrophy, and paranoid subtype is associated with less severe gray matter atrophy compared to non-psychosis group. These results suggest that the misidentification, the paranoid subtype and the non-psychosis group have a distinct neural correlation.

Gray matter volumes and treatment response of psychotic symptoms to risperidone in antipsychotic-naïve Alzheimer's disease patients.

OBJECTIVE: The purpose of this study was to determine whether gray matter volumes are associated with treatment response of psychotic symptoms in Alzheimer's disease (AD) patients. METHOD: Risperidone, which is commonly used as an atypical antipsychotic drug, was administered in a clinical setting for 6 weeks from April 2012 to February 2013 to 25 antipsychotic-naïve AD patients with psychosis, diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of Alzheimer's disease. Psychotic symptoms were rated with the Korean version of the Neuropsychiatric Inventory (K-NPI) at baseline and at 6 weeks, and treatment response was defined as the change in K-NPI score from baseline to 6 weeks. Gray matter volumes were measured with magnetic resonance imaging and voxel-based morphometry at baseline. Age, gender, years of education, total intracranial volume, apolipoprotein E genotype, dosage of risperidone, the baseline scores on the Korean version of the Mini-Mental State Examination, and the baseline psychotic and nonpsychotic symptoms scores on the K-NPI were measured as covariates of no interest. RESULTS: We found that treatment response of psychotic symptoms to risperidone in antipsychotic-naïve AD patients was positively associated with both left and right putamina, left parahippocampal gyrus, and left amygdala volume after controlling covariates of no interest (uncorrected P < .001, KE > 100 voxels). CONCLUSIONS: Therefore, we conclude that gray matter volumes of putamina, left parahippocampal gyrus, and left amygdala are associated with treatment response of psychotic symptoms after 6 weeks of treatment with risperidone in antipsychotic-naïve AD patients with psychosis. These results suggest that the volumes of specific gray matter regions probably contribute to treatment response of psychotic symptoms in AD patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01198093.

Impact of Apolipoprotein E4 Polymorphism on the Gray Matter Volume and the White Matter Integrity in Subjective Memory Impairment without White Matter Hyperintensities: Voxel-Based Morphometry and Tract-Based Spatial Statistics Study under 3-Tesla MRI.

OBJECTIVE: The aim of this study is to compare gray matter (GM) volume and white matter (WM) integrity in Apolipoprotein E4 (ApoE ε4) carriers with that of ApoE ε4 noncarriers using the voxel-based morphometry and diffusion tensor imaging (DTI) to investigate the effect of the ApoE ε4 on brain structures in subjective memory impairment (SMI) without white matter hyperintensities (WMH). METHODS: Altogether, 26 participants with SMI without WMH were finally recruited from the Memory impairment clinics of Pusan National University Hospital in Korea. All participants were ApoE genotyped (ApoE ε4 carriers: n = 13, matched ApoE ε4 noncarriers: n = 13) and underwent 3-tesla magnetic resonance imaging (MRI) including 3-dimensional volumetric images for GM volume and DTI for WM integrity. RESULTS: ApoE ε4 carriers compared with noncarriers in SMI without WMH showed the atrophy of GM in inferior temporal gyrus, inferior parietal lobule, anterior cingulum, middle frontal gyrus, and precentral gyrus and significantly lower fractional anisotropy WM values in the splenium of corpus callosum and anterior corona radiate. CONCLUSION: Our findings suggest that the ApoE ε4 is associated with both atrophy of GM volume and disruption of WM integrity in SMI without WMH.

Apolipoprotein E genotype modulates effects of vitamin B12 and homocysteine on grey matter volume in Alzheimer's disease.

AIMS: The aim of the present study was to investigate whether the effects of vitamin B12 and homocysteine on brain volume are influenced by apolipoprotein E (APOE) genotype. We examined the effects in each subgroup (APOE ε4 carriers and non-carriers) of Alzheimer's disease (AD) patients and healthy normal controls. METHODS: Forty participants with AD and 20 healthy normal controls were recruited from memory impairment clinics at Pusan National University Hospital in Korea. All participants were APOE genotyped and underwent magnetic resonance imaging, including 3-D volumetric images for grey matter (GM) volume. A multiple regression model integrated into statistical parametric mapping was used to see if there was any correlation between vitamin B12 or homocysteine and GM volume in each subgroup (APOE ε4 carriers and non-carriers) of AD patients and healthy normal controls. RESULTS: There was a significant positive correlation between serum concentrations of vitamin B12 and regional GM volume in APOE ε4 carriers with AD but not in non-carriers. We also found that there was a significant negative correlation between serum concentrations of homocysteine and regional GM volume in APOE ε4 non-carriers with AD but not in carriers (P < 0.001, uncorrected for multiple comparisons; extent threshold = 100 voxel). CONCLUSION: The present findings suggest that the effects of vitamin B12 and homocysteine on GM volume might be influenced by APOE genotype.

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.