Added Value of Chemical Exchange-Dependent Saturation Transfer MRI for the Diagnosis of Dementia

Objective@#Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. @*Materials and Methods@#Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTR asym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. @*Results@#Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTR asym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTR asym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. @*Conclusion@#CEST MRI potentially allows noninvasive image alterations in the Alzheimer’s disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

Added Value of Chemical Exchange-Dependent Saturation Transfer MRI for the Diagnosis of Dementia

Objective@#Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. @*Materials and Methods@#Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTR asym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. @*Results@#Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTR asym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTR asym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. @*Conclusion@#CEST MRI potentially allows noninvasive image alterations in the Alzheimer’s disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

Association between endotoxin levels in dust from indoor swine housing environments and the immune responses of pigs

Indoor animal husbandry environments are inevitably contaminated with endotoxins. Endotoxin exposure is associated with various inflammatory illnesses in animals. This cross-sectional study evaluated the relationship between the degree of endotoxin exposure and the cellular and humoral immune profiles of fattening pigs. Blood samples were taken from the jugular vein of 47 pigs from ten pig farms in Korea. Whole blood cell counts and plasma immunoglobulin (Ig) classes were determined. Peripheral-blood mononuclear cells were stimulated in vitro with concanavalin A for 48 h, and cytokines released into culture supernatants were measured. The barns in which the pigs lived were assessed for endotoxin levels in the total and respirable dust by using the limulus amebocyte lysate kinetic QCL method. Low and high endotoxin exposures were defined as ≤ 30 and > 30 EU/m³, respectively. Compared to pigs with low endotoxin exposure (n = 19), highly exposed pigs (n = 28) had higher circulating neutrophil and lymphocyte (particularly B cells) counts, IgG and IgE levels, interferon-gamma (IFNγ) and interleukin (IL)-4 productions, and lower IgA levels and tumor necrosis factor-alpha (TNFα) production. The IL-4, IFNγ, and TNFα levels significantly correlated with endotoxin level and/or pig age. Constant exposure of pigs to high levels of airborne endotoxins can lead to aberrant immune profiles.

A Preliminary Study for the Rating of Pharmacological Effect with Aberrant Behavior Checklist in Children with Autistic Disorder

OBJECTIVES: We assessed the availability of Aberrant Behavior Checklist (ABC) for the evaluation of the pharmacological effect in autistic disorder. METHODS: A retrospective review of the medical records of 27 children with autistic disorder, who visited the department of child and adolescent psychiatry of Kyungpook National University Hospital, from October 2011 to February 2013, was conducted. After treatment with risperidone, changes in the severity and improvement of symptoms were measured using ABC at the baseline, 2nd visit and 3rd visit, respectively. RESULTS: The mean daily dose of risperidone increased from 0.66+/-0.27mg (baseline, initial dose) to 1.02+/-0.50mg, 2nd visit, and 1.19+/-0.50mg, 3rd visit. According to ABC, irritability, lethargy, hyperactivity, and inappropriate speech subscale scores decreased significantly from the baseline to 2nd visit. Irritability and Hyperactivity subscale scores decreased significantly from the 2nd to 3rd visit. All subscales and total scores of ABC decreased significantly from the baseline to 3rd visit. CONCLUSION: The results of this study suggest that ABC can be used as an efficient tool to measure the symptoms of autistic disorder and to evaluate the medication effect on continuous treatment.

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.

A Polymorphism of Fibrinogen Beta Chain (FGB) Gene is Not Associated with Autistic Spectrum Disorder in Korean Population

Evidences has been accumulated the difference of cardiovascular phenotypes in autistic spectrum disorder (ASD). To determine the genetic association between fibrinogen beta chain (FGB) gene and ASD in Korean population, we genotyped single nucleotide polymorphism (SNP) (rs4220, Arg478Lys, exon 8) in the FGB gene by using direct sequencing. Among nonsynonymous SNPs in the coding region of FGB, only one SNP's heterozygosity (rs4220) is more than 0.05. Therefore, we analyzed the association between rs4220 and ASD. Three hundred six control and 196 ASD subjects were evaluated. For the analysis of genetic data, SNPStats, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis (codominant, dominant, and recessive models) was also used. The result showed that a SNP (rs4220) in the FGB gene was not significantly difference between ASD and controls in three alternative models. This result suggests that the FGB gene may have no relation to the development of ASD.

Association Study between 2 Single Nucleotide Polymorphisms in Estrogen Receptor 1 Gene and Korean Female Schizophrenic Patient

OBJECTIVES: Schizophrenia is equally distributed in both sexes. However, later-onset, milder psychopathology, and better outcome are associated with the females. This reason is thought to be partly due to the estrogen system. Recently, it was suggested that estrogen receptor 1(ESR1) gene polymorphisms might affect the expression of ESR1 and were associated with several psychiatric disorders. Thus, we investigated the association between two single nucleotide polymorphisms(SNPs) in the ESR1 gene and Korean schizophrenic patients in this study. METHODS: Genotype, allele, and haplotype frequencies of the two SNPs(rs 2234693 and rs 2228480) were analyzed between 218 Korean controls and 158 Korean schizophrenic patients. Also, age of onset and negative symptom scale scores according to genotypes were analyzed in the patients with schizophrenia. RESULTS: There was a significant difference in allele frequencies of rs 2234693 between the schizophrenic patients and the controls(p=0.03). Genotype distributions(p=0.03) and allele frequencies(p=0.01) of rs 2234693 were significantly different between the female schizophrenic patients and the female controls. The frequency of TC-CC genotypes compared with TT genotype in the female schizophrenic patients was significantly higher than that in the female controls(OR=2.36). The mean age of onset in the schizophrenic patients with TC-CC genotypes was significantly lower than that in the patients with TT genotype. The frequency of rs 2234693C-rs 2228480G haplotype in the female schizophrenic patients was relatively higher than that in the female controls. CONCLUSIONS: These results of our study support the possibility that the ESR1 gene polymorphisms might be involved in the susceptibility of females to schizophrenia and play a role in sex difference of schizophrenia.

The Status Quo and Problems of Private Health Insurances for Psychiatric Illnesses in Korea / 신경정신의학

OBJECTIVES: Recently, Korean psychiatrists have noticed the complaints from probands and family members that private health insurance companies do not pay for most psychiatric disorders. Furthermore, probands cannot even apply for insurance because of their medical record of psychiatric disorders. Authors investigated and reviewed contracts of Korean private insurance companies to find reasons for banning psychiatric disorders from insurance policies. METHODS: Authors reviewed more than 800 contracts from 48 insurance companies. RESULTS: Among all the psychiatric diagnoses, few of them-dementia and some other organic mental disorders-are guaranteed to be paid from insurance companies. Less then 10 contracts say they pay for psychiatric illnesses. Most insurance companies have contracts prohibiting F codes ; however, there are not enough reasons in these contracts. CONCLUSIONS: In the private health insurance system, psychiatric illnesses have almost no rooms. It is very urgent to add space for patients with psychiatric illnesses and psychiatrists in the insurance policies.

-1438A/G Polymorphism of the 5-HT2A Receptor Gene in Korean and Han Chinese Patients with Schizophrenia / 신경정신의학

OBJECTIVES: The purpose of the present study was to investigate the association between -1438A/G polymorphism of 5-HT2A receptor gene and schizophrenia in Korean and Han Chinese population. METHODS: A sample of 184 Korean patients with schizophrenia and 96 Korean healthy normal controls and 96 Han Chinese patients with schizophrenia and 96 Han-Chinese healthy normal controls were genotyped for a single nucleotide polymorphism with in 5-HT2A receptor gene (promoter region, A-1438G) by Msp I Restriction Fragment Length Polymorphism (RFLP). RESULTS: There was no difference in allelic frequencies and genotype frequencies of -1438A/G polymorphism between Korean schizophrenics and controls (p=0.13) and Han Chinese schizophrenics and controls (p=0.40). Also, -1438A/G polymorphism did not show ethnical difference between Korean and Han Chinese controls. The Scale for the Assessment of Negative Symptoms (SANS) scores showed no significant differences between genotypes of -1438A/G polymorphism in both of Korean and Han Chinese schizophrenics. CONCLUSION: These results suggest that -1438A/G polymorphism of the 5-HT2A receptor gene is not causally related to the development of schizophrenia in Korean and Han Chinese population, and there no ethnic difference between Korean and Han Chinese population.

-1438A/G Polymorphism of the 5-HT2A Receptor Gene in Korean and Han Chinese Patients with Schizophrenia / 신경정신의학

OBJECTIVES: The purpose of the present study was to investigate the association between -1438A/G polymorphism of 5-HT2A receptor gene and schizophrenia in Korean and Han Chinese population. METHODS: A sample of 184 Korean patients with schizophrenia and 96 Korean healthy normal controls and 96 Han Chinese patients with schizophrenia and 96 Han-Chinese healthy normal controls were genotyped for a single nucleotide polymorphism with in 5-HT2A receptor gene (promoter region, A-1438G) by Msp I Restriction Fragment Length Polymorphism (RFLP). RESULTS: There was no difference in allelic frequencies and genotype frequencies of -1438A/G polymorphism between Korean schizophrenics and controls (p=0.13) and Han Chinese schizophrenics and controls (p=0.40). Also, -1438A/G polymorphism did not show ethnical difference between Korean and Han Chinese controls. The Scale for the Assessment of Negative Symptoms (SANS) scores showed no significant differences between genotypes of -1438A/G polymorphism in both of Korean and Han Chinese schizophrenics. CONCLUSION: These results suggest that -1438A/G polymorphism of the 5-HT2A receptor gene is not causally related to the development of schizophrenia in Korean and Han Chinese population, and there no ethnic difference between Korean and Han Chinese population.

The Association between Korean Schizophrenics and GDNF Gene Polymorphism / 대한정신약물학회지

OBJECTIVE: The association of neurotrophic factors with the etiology of schizophrenia has been widely studied. Among them, glial cell line-derived neurotrophic factor (GDNF) is known to promote the survival and differentiation of dopaminergic neurons. Considering dopamine hypothesis and neurodevelopmental theory, GDNF gene may be related with schizophrenia. In this study, we tried to clarify the association between schizophrenia and GDNF gene polymorphism. METHODS: Genotype and allele frequencies in the promoter and intron regions of GDNF gene were studied by using restriction fragment length polymorphism to compare 180 Korean schizophrenics with 105 Korean controls. RESULTS: We found significant differences between the schizophrenics and the controls in genotype and allele frequencies of BsaI polymorphism in the promoter region of GDNF gene (x2=18.208, df=2, p=0.0001/x2=11.264, df=1, p=0.0008). But no significant differences were found in intron region (p=0.06, p=0.984). CONCLUSION: These results suggest that polymorphism of GDNF gene might be related to the pathogenesis of schizophrenia.

Aspiration Pneumonia during Clozapine Therapy / 대한정신약물학회지

Authors experienced aspiration pneumonia during clozapine therapy in a 31 year-old woman patient with treatment-resistant schizophrenia. Development of aspiration pneumonia appeared to be related with side effects of clozapine including sedation, sialorrhea, and esophageal dysfunction. Each side effect seems to be mild, however it can cause fatal problems such as aspiration pneumonia if they appear simultaneously.