Chang Uk Lee

Identification of antibodies to heat shock proteins 90 kDa and 70 kDa in patients with schizophrenia.

OBJECTIVESnRecent reports of antibodies to heat shock proteins 60kDa (HSP60) and HSP70 suggested that antibodies to the heat shock protein that plays a protective role against environmental stresses in a cell might be related to the pathogenesis of schizophrenia, although the antibody to HSP90 had not yet been identified in patients with schizophrenia. In this study, we tried to elucidate the specific involvement of the autoimmunity to HSPs in the pathogenesis and development of schizophrenia.nnnMETHODSnAntibodies to HSP90 and HSP70 in 90 patients with schizophrenia and in 83 normal controls were measured by enzyme-linked immunosorbent assay (ELISA) coupled with the avidin-biotin system. In the patients, the association between antibody levels and clinical variables were sought. In addition, changes in antibody levels after treatment with antipsychotic medication were investigated.nnnRESULTSnEighteen (20.0%) of the 90 patients showed high levels of antibody to HSP90 above a cutoff value, and 28 (31.1%) of those showed high antibody levels to HSP70. On the other hand, only four (4.8%) of the normal controls showed high HSP90 antibody levels, and one (1.2%) of these showed high antibody level to HSP70. The distribution of elevated HSP90 antibody was significantly associated with that of elevated HSP70 antibody in the patients with schizophrenia. The patients with high levels of antibody to HSP70 showed higher initial Brief Psychiatric Rating Scale (BPRS) scores and showed greater clinical improvement than those with low levels, while the patients with high levels of antibody to HSP90 did not. The frequency of patients with high levels of antibody to HSP70 was decreased significantly after 6 weeks of antipsychotic treatment, while the frequency of patients with high levels of antibody to HSP90 was not.nnnCONCLUSIONSnOur results presented the presence of abnormal immune reactivity involving antibody to HSP90 and antibody to HSP70 in a subset of patients with schizophrenia. Differential patterns of distribution, of the association with clinical symptom severity, and of the changes of levels with treatment suggested the possibility that these two antibodies might be involved specifically in the pathogenesis of schizophrenia.

Apathy and white matter integrity in Alzheimer's disease: a whole brain analysis with tract-based spatial statistics.

The aim of this study was to investigate the microstructural alterations of white matter (WM) in Alzheimer’s disease (AD) patients with apathy and to observe the relationships with the severity of apathy. Sixty drug-naïve subjects took part in this study (30 apathetic and 30 nonapathetic subjects with AD). The loss of integrity in WM was compared in AD patients with and without apathy through measurement of fractional anisotropy (FA) using by tract-based spatial statistics (TBSS). In addition, we explored the correlation pattern between FA values and the severity of apathy in AD patients with apathy. The apathy group had significantly reduced FA values (pcorrected<0.05) in the genu of the corpus callosum compared to the nonapathy group. The severity of apathy was negatively correlated with FA values of the left anterior and posterior cingulum, right superior longitudinal fasciculus, splenium, body and genu of the corpus callosum and bilateral uncinate fasciculusin the apathy group (pcorrected<0.05). This study was the first to explore FA values in whole brain WM in AD patients with apathy. The findings of these microstructural alterations of WM may be the key to the understanding of underlying neurobiological mechanism and clinical significances of apathy in AD.

Effect of 5-haplotype of dysbindin gene (DTNBP1) polymorphisms for the susceptibility to bipolar I disorder

We investigated a possible association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). Five SNPs within DTNBP1 (rs3213207, rs1011313, rs2005976, rs760761, and rs2619522) were genotyped for 151 patients with BID and 478 controls. We observed a significant protective association of the haplotype A‐C‐G‐T‐A (all SNPs, Pu2009=u20090.00016) and particularly G‐T‐A (the last three SNP, Pu2009=u20090.00007) within DTNBP1 variants investigated. Single marker and subgroup (e.g., psychotic features, age at onset, family history, etc.) analyses showed no significant association. Although the association was due to a small number of subjects, specific DTNBP1 haplotypes, previously associated with schizophrenia, may be also associated with BID. Adequately powered studies from different ethnicities will be necessary to confirm our findings.

Comparison of risperidone orodispersible tablet and intramuscular haloperidol in the treatment of acute psychotic agitation: a randomized open, prospective study.

Objectives: Psychotic agitation of psychiatric patients is a common manifestation that needs emergent management. Traditionally, parenteral or intramuscular injection of antipsychotics was conducted for treatment of psychotic agitation. Considering that the rapidly absorbed form of risperidone (risperidone orodispersible tablet) could be used for the agitated patient, comparison of oral risperidone and intramuscular haloperidol was performed in emergency treatment of psychotic agitation in this study. Methods: 124 patients with psychotic agitation were recruited at the emergency room or inpatient ward. They were randomly assigned to either the group of oral risperidone or intramuscular haloperidol. Efficacy of both treatments was measured and compared using the 5-item acute agitation cluster from the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and the Clinical Global Impression-Severity of Illness Scale (CGI-S). Tolerability and safety were also compared between the two groups. Results: The PANSS-EC and CGI-S scores were significantly decreased over time in both treatment groups without any significant group difference and time by group interaction effect (F = 459.7, p < 0.0001). There were no serious adverse events in both groups. Conclusion: For the emergency treatment of psychotic agitation, risperidone orodispersible tablet was as effective and tolerable as intramuscular administration of haloperidol. Therefore, we might choose oral medication instead of intramuscular injection for treatment of patients with acute psychotic agitation.

Automated hippocampal subfields segmentation in late life depression

Although a few automated hippocampal subfields segmentation methods have been developed, there has been no in vivo Magnetic Resonance Imaging (MRI) study on the hippocampal subfields volumes of Late Life Depression (LLD). The aim of this study was to investigate the hippocampal subfields volume differences between LLD subjects and healthy elderly controls using an automated hippocampal subfields segmentation technique. Thirty subjects with LLD and 30 group-matched healthy control subjects underwent 3T MRI scanning, and hippocampal subfields volumes were measured and compared between the groups. Subjects with LLD exhibited significant hippocampal volume reductions in the total hippocampus, subiculum, and Cornu Ammonis (CA) 2-3 areas compared with healthy subjects (uncorrected, p<0.001). This study is the first to elaborate the subfields volume differences of both hippocampi between controls and LLD patients. These structural changes in the hippocampal presubiculum, subiculum, and CA2-3 areas might be at the core of the underlying neurobiological mechanisms of hippocampal dysfunction in LLD.

Neuroimaging Findings in Late-Onset Schizophrenia and Bipolar Disorder

In recent years, there has been an increasing interest in late-onset mental disorders. Among them, geriatric schizophrenia and bipolar disorder are significant health care risks and major causes of disability. We discussed whether late-onset schizophrenia (LOS) and late-onset bipolar (LOB) disorder can be a separate entity from early-onset schizophrenia (EOS) and early-onset bipolar (EOB) disorder in a subset of late-life schizophrenia or late-life bipolar disorder through neuroimaging studies. A literature search for imaging studies of LOS or LOB was performed in the PubMed database. Search terms used were “(imaging OR MRI OR CT OR SPECT OR DTI OR PET OR fMRI) AND (schizophrenia or bipolar disorder) AND late onset.” Articles that were published in English before October 2013 were included. There were a few neuroimaging studies assessing whether LOS and LOB had different disease-specific neural substrates compared with EOS and EOB. These researches mainly observed volumetric differences in specific brain regions, white matter hyperintensities, diffusion tensor imaging, or functional neuroimaging to explore the differences between LOS and LOB and EOS and EOB. The aim of this review was to highlight the neural substrates involved in LOS and LOB through neuroimaging studies. The exploration of neuroanatomical markers may be the key to the understanding of underlying neurobiology in LOS and LOB.

Relationships between hippocampal shape and cognitive performances in drug-naïve patients with Alzheimer's disease

Previous studies provided hippocampal shape analysis of Alzheimers disease (AD) patients using automated segmentation techniques. However, the relationships between the hippocampal deformations and various cognitive impairments were not clear. The aim of this study was to investigate hippocampal shape changes and their relationship to cognitive impairments. Fifty-one drug-naïve patients with AD and 50 group-matched healthy control subjects underwent 3T MRI scanning, and the hippocampal volumes and deformations were compared between the groups. Additionally, we explored the correlation pattern between the hippocampal deformations and the cognitive dysfunctions in AD using the Korean version of the Consortium to Establish a Registry for Alzheimers Disease (CERAD-K). AD subjects exhibited significant hippocampal deformations in the cornu ammnonis (CA1) and subiculum areas compared to those in healthy subjects (p<0.05, false discovery rate (FDR) corrected). Significant correlations were observed between hippocampal deformations in CA1 and subiculum areas and verbal immediate recall, verbal delayed recall, verbal recognition memory, and constructional recall scores (p<0.05, FDR corrected). This study was the first to explore the relationships between hippocampal deformations and various cognitive impairments of drug-naïve patients with AD. These structural changes in hippocampal CA1 and subiculum areas might be the core of the underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to the various cognitive dysfunctions in AD.

Changes of Plasma Adiponectin Levels after Smoking Cessation

Objective Cigarette smoking is associated with a variety of health problems including cardiovascular, pulmonary, neoplasms, endocrinopathies including diabetes, the metabolic syndrome, and chronic inflammation. Adiponectin is an adipocyte-derived plasma protein that is closely associated with insulin sensitivity and the metabolic syndrome. The aim of this study was to evaluate the changes of plasma adiponectin levels after smoking cessation. Methods Thirty seven smokers that wanted to stop smoking without any nicotine replacement therapy or medication were recruited for this study. Fifteen smokers succeeded in stopping smoking (validated by urine cotinine levels ≤50 ng/mL) and 22 smokers failed. Therefore, only the 15 that succeeded were included in the analysis. The plasma adiponectin levels were determined using a commercially available enzyme-linked immunosorbent assay. Results The mean age of the successful 15 was 35±9.3 years old. They were all males. The daily smoking habit was a mean of 13.5±5.4 cigarettes per day. The mean Nicotine Dependence Syndrome Scale (NDSS) and Fagerstrom Test for Nicotine Dependence (FTND) scores were 55.6±9.6 and 2.9±1.9. During the study period of three months, the mean body mass index (BMI), body fat mass (BFM), waist-hip ratio (WHR) and body weight increased by 1.1 kg/m2, 3.0%, 0.02%, and 2.9 kg, respectively. The baseline mean adiponectin level in the subjects was 11.9±5.2 mg/L. The mean adiponectin levels measured at one and three months were 16.0±5.1 mg/L and 14.7±4.5 mg/L respectively. The mean plasma adiponectin levels of the successful group was significantly increased after four weeks when compared to the baseline (z=-2.401, p=0.016). However, the decrease in plasma adiponectin levels at one and three months was not statistically significant. Conclusion Even though the decrease over the next two months was not significant, these findings, the increase of plasma level of adiponectin after smoking cessation, provide preliminary data for future research on the possible mechanisms associated with smoking cessation and changes in body metabolism.

Association between Estrogen Receptor Gene Polymorphisms and Depression in Post-Menopausal Women: A Preliminary Study

Post-menopausal women experience variable biological and psychological changes. The effect of reduced levels of estrogen can effect on post-menopausal depression. Estrogen triggers physiological responses by binding to the estrogen receptor (ER). Two subtypes of ER, ERa and ERb are now known. We investigated the significance of ERa and ERb polymorphisms and post-menopasal depression in this study. Forty three women with post-menopausal depression and 63 post-menopausal women without depression as normal controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate genotypes of ERa and ERb polymorphisms. Genotypes of PvuII and XbaI polymorphism of ERa receptor were significantly different in patients with post-menopausal depression comparing with controls. Genotypes of ERb did not show association with post-menopausal depression. Our study showed that ERa receptor polymorphism had an association with depression in post-menopausal women. It suggests that investigation of ER genes and their functions might be important for understanding pathophysilogical mechanism of post-menopausal depression.

Three Large-Scale Functional Brain Networks from Resting-State Functional MRI in Subjects with Different Levels of Cognitive Impairment

Normal aging and to a greater degree degenerative brain diseases such as Alzheimers disease (AD), cause changes in the brains structure and function. Degenerative changes in brain structure and decline in its function are associated with declines in cognitive ability. Early detection of AD is a key priority in dementia services and research. However, depending on the disease progression, neurodegenerative manifestations, such as cerebral atrophy, are detected late in course of AD. Functional changes in the brain may be an indirect indicator of trans-synaptic activity and they usually appear prior to structural changes in AD. Resting-state functional magnetic resonance imaging (RS-fMRI) has recently been highlighted as a new technique for interrogating intrinsic functional connectivity networks. Among the majority of RS-fMRI studies, the default mode network (DMN), salience network (SN), and central executive network (CEN) gained particular focus because alterations to their functional connectivity were observed in subjects who had AD, who had mild cognitive impairment (MCI), or who were at high risk for AD. Herein, we present a review of the current research on changes in functional connectivity, as measured by RS-fMRI. We focus on the DMN, SN, and CEN to describe RS-fMRI results from three groups: normal healthy aging, MCI and AD.