Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence.

This study aimed to compare brain structural connectivity using graph theory between patients with alcohol dependence and social drinkers. The participants were divided into two groups; the alcohol group (N=23) consisting of patients who had been hospitalized and had abstained from alcohol for at least three months and the control group (N=22) recruited through advertisements and were social drinkers. All participants were evaluated using 3T magnetic resonance imaging. A total of 1000 repeated whole-brain tractographies with random parameters were performed using DSI Studio. Four hundred functionally defined cortical regions of interest (ROIs) were parcellated using FreeSurfer based on the Schaefer Atlas. The ROIs were overlaid on the tractography results to generate 1000 structural connectivity matrices per person, and 1000 matrices were averaged into a single matrix per subject. Graph analysis was performed through igraph R package. Graph measures were compared between the two groups using analysis of covariance, considering the effects of age and smoking pack years. The alcohol group showed lower local efficiency than the control group in the whole-brain (F=5.824, p=0.020), somato-motor (F=5.963, p=0.019), and default mode networks (F=4.422, p=0.042). The alcohol group showed a lower global efficiency (F=5.736, p=0.021) in the control network. The transitivity of the alcohol group in the dorsal attention network was higher than that of the control (F=4.257, p=0.046). Our results imply that structural stability of the whole-brain network is affected in patients with alcohol dependence, which can lead to ineffective information processing in cases of local node failure.

Hippocampal Subfields and White Matter Connectivity in Patients with Subclinical Geriatric Depression.

Despite an abundance of research related to the functional and structural changes of the brain in patients with geriatric depression, knowledge related to early alterations such as decreased white matter connectivity and their association with cognitive decline remains lacking. We aimed to investigate early alterations in hippocampal microstructure and identify their associations with memory function in geriatric patients with subclinical depression. Nineteen participants with subclinical geriatric depression and 19 healthy controls aged ≥65 years exhibiting general cognitive function within the normal range were included in the study and underwent assessments of verbal memory. Hippocampal subfield volumes were determined based on T1-weighted magnetization-prepared rapid gradient echo (T1-MPRAGE) images, while group tractography and connectometry analyses were conducted using diffusion tensor images. Our findings indicated that the volumes of whole bilateral hippocampus, cornus ammonis (CA) 1, molecular layer, left subiculum, CA3, hippocampal tail, right CA4, and granule cell/molecular layers of the dentate gyrus (GC-ML-DG) were significantly smaller in the subclinical depression group than in the control group. In the subclinical depression group, verbal learning was positively correlated with the volumes of the CA1, GC-ML-DG, molecular layer, and whole hippocampus in the right hemisphere. The fractional anisotropy of the bilateral fornix was also significantly lower in the subclinical depression group and exhibited a positive correlation with verbal learning and recall in both groups. Our results suggest that hippocampal microstructure is disrupted and associated with memory in patients with subclinical depression.

Disrupted Association Between Empathy and Brain Structure in Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: To investigate the relationship between brain structure and empathy in early adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: Nineteen early adolescents with ADHD and 20 healthy controls underwent 3T MRI. All the participants were assessed for different aspects of empathy using measures including the Interpersonal Reactivity Index and Empathy Quotient. Cortical thickness and subcortical structural volume based on T1-weighted scans were analyzed using FreeSurfer. RESULTS: Cognitive empathy (t=-2.52, p=0.016) and perspective taking (t=-2.10, p=0.043) were impaired in the ADHD group compared with the control group. The cluster encompassing the left posterior insular, supramarginal, and transverse temporal cortices [cluster-wise p-value (CWP)=0.001], which are associated with emotional empathy, was significantly smaller in the ADHD group, and the volume of the left nucleus accumbens was greater than that of the control group (F=10.12, p=0.003, effect size=0.22). In the control group, the left superior temporal (CWP=0.002) and lingual cortical (CWP=0.035) thicknesses were positively associated with cognitive empathy, while the right amygdala volume was positively associated with empathic concern (Coef=14.26, t=3.92, p=0.001). However, there was no significant correlation between empathy and brain structure in the ADHD group. CONCLUSION: The ADHD group had a smaller volume of the cortical area associated with emotional empathy than the control group, and there was no brain region showing significant correlation with empathy, unlike in the control group.

White matter integrity in alcohol-dependent patients with long-term abstinence.

ABSTRACT: Based on association studies on amounts of alcohol consumed and cortical and subcortical structural shrinkage, we investigated the effect of chronic alcohol consumption on white matter pathways using probabilistic tractography.Twenty-three alcohol-dependent men (with an average sobriety of 13.1 months) from a mental health hospital and 22 age-matched male healthy social drinkers underwent 3T magnetic resonance imaging. Eighteen major white matter pathways were reconstructed using the TRActs Constrained by UnderLying Anatomy tool (provided by the FreeSurfer). The hippocampal volumes were estimated using an automated procedure. The lifetime drinking history interview, Alcohol Use Disorder Identification Test, Brief Michigan Alcoholism Screening Test, and pack-years of smoking were also evaluated.Analysis of covariance controlling for age, cigarette smoking, total motion index indicated that there was no definite difference of diffusion parameters between the 2 groups after multiple comparison correction. As hippocampal volume decreased, the fractional anisotropy of the right cingulum-angular bundle decreased. Additionally, the axial diffusivity of right cingulum-angular bundle was positively correlated with the alcohol abstinence period.The results imply resilience of white matter in patients with alcohol dependence. Additional longitudinal studies with multimodal methods and neuropsychological tests may improve our findings of the changes in white matter pathways in patients with alcohol dependence.

Cognitive and Emotional Empathy in Young Adolescents: an fMRI Study.

OBJECTIVES: We investigated the differences in cognitive and emotional empathic ability between adolescents and adults, and the differences of the brain activation during cognitive and emotional empathy tasks. METHODS: Adolescents (aged 13-15 years, n=14) and adults (aged 19-29 years, n=17) completed a range of empathic ability questionnaires and were scanned functional magnetic resonance imaging (fMRI) during both cognitive and emotional empathy task. Differences in empathic ability and brain activation between the groups were analyzed. RESULTS: Both cognitive and emotional empathic ability were significantly lower in the adolescent compared to the adult group. Comparing the adolescent to the adult group showed that brain activation was significantly greater in the right transverse temporal gyrus (BA 41), right insula (BA 13), right superior parietal lobule (BA 7), right precentral gyrus (BA 4), and right thalamus whilst performing emotional empathy tasks. No brain regions showed significantly greater activation in the adolescent compared to the adult group while performing cognitive empathy task. In the adolescent group, scores of the Fantasy Subscale in the Interpersonal Reactivity Index, which reflects cognitive empathic ability, negatively correlated with activity of right superior parietal lobule during emotional empathic situations (r=-0.739, p=0.006). CONCLUSION: These results strongly suggest that adolescents possess lower cognitive and emotional empathic abilities than adults do and require compensatory hyperactivation of the brain regions associated with emotional empathy or embodiment in emotional empathic situation. Compensatory hyperactivation in the emotional empathy-related brain areas among adolescents are likely associated with their lower cognitive empathic ability.

Novel Cyclosilazane-Type Silicon Precursor and Two-Step Plasma for Plasma-Enhanced Atomic Layer Deposition of Silicon Nitride.

We designed cyclosilazane-type silicon precursors and proposed a three-step plasma-enhanced atomic layer deposition (PEALD) process to prepare silicon nitride films with high quality and excellent step coverage. The cyclosilazane-type precursor, 1,3-di-isopropylamino-2,4-dimethylcyclosilazane (CSN-2), has a closed ring structure for good thermal stability and high reactivity. CSN-2 showed thermal stability up to 450 °C and a sufficient vapor pressure of 4 Torr at 60 °C. The energy for the chemisorption of CSN-2 on the undercoordinated silicon nitride surface as calculated by density functional theory method was -7.38 eV. The PEALD process window was between 200 and 500 °C, with a growth rate of 0.43 Å/cycle. The best film quality was obtained at 500 °C, with hydrogen impurity of ∼7 atom %, oxygen impurity less than 2 atom %, low wet etching rate, and excellent step coverage of ∼95%. At 300 °C and lower temperatures, the wet etching rate was high especially at the lower sidewall of the trench pattern. We introduced the three-step PEALD process to improve the film quality and the step coverage on the lower sidewall. The sequence of the three-step PEALD process consists of the CSN-2 feeding step, the NH3/N2 plasma step, and the N2 plasma step. The H radicals in NH3/N2 plasma efficiently remove the ligands from the precursor, and the N2 plasma after the NH3 plasma removes the surface hydrogen atoms to activate the adsorption of the precursor. The films deposited at 300 °C using the novel precursor and the three-step PEALD process showed a significantly improved step coverage of ∼95% and an excellent wet etching resistance at the lower sidewall, which is only twice as high as that of the blanket film prepared by low-pressure chemical vapor deposition.

Autism and Beauty: Neural Correlates of Aesthetic Experiences in Autism Spectrum Disorder.

OBJECTIVES: The purpose of this study was to investigate whether the neural activity of autism spectrum disorder (ASD) patients is different from that of normal individuals when performing aesthetic judgments. METHODS: We recruited typical ASD patients without savant skills (ASD group, n=17) and healthy controls (HC group, n=19) for an functional magnetic resonance imaging study. All subjects were scanned while performing aesthetic judgment tasks on two kinds of artwork (magnificent landscape images and fractal images). Differences in brain activation between the two groups were assessed by contrasting neural activity during the tasks. RESULTS: The aesthetic judgment score for all images was significantly lower in the ASD group than in the HC group. During the aesthetic judgment tasks, the ASD group showed less activation than the HC group in the anterior region of the superior frontal gyrus, and more activation in the temporoparietal area and insula, regardless of the type of images being judged. In addition, during the aesthetic judgment task for the fractal images, the ASD group exhibited greater neural activity in the amygdala and the posterior region of the middle/inferior temporal gyrus (Brodmann area 37) than the HC group. CONCLUSION: The results of this study suggest that the brain activation patterns associated with aesthetic experiences in ASD patients may differ from those of normal individuals.

Large-scale synthesis of uniform hexagonal boron nitride films by plasma-enhanced atomic layer deposition.

Hexagonal boron nitride (h-BN) has been previously manufactured using mechanical exfoliation and chemical vapor deposition methods, which make the large-scale synthesis of uniform h-BN very challenging. In this study, we produced highly uniform and scalable h-BN films by plasma-enhanced atomic layer deposition, which were characterized by various techniques including atomic force microscopy, transmission electron microscopy, Raman spectroscopy, and X-ray diffraction. The film composition studied by X-ray photoelectron spectroscopy and Auger electron spectroscopy corresponded to a B:N stoichiometric ratio close to 1:1, and the band-gap value (5.65 eV) obtained by electron energy loss spectroscopy was consistent with the dielectric properties. The h-BN-containing capacitors were characterized by highly uniform properties, a reasonable dielectric constant (3), and low leakage current density, while graphene on h-BN substrates exhibited enhanced electrical performance such as the high carrier mobility and neutral Dirac voltage, which resulted from the low density of charged impurities on the h-BN surface.

Volume of hippocampal subfields in patients with alcohol dependence.

Alcohol-induced hippocampal atrophy has been well documented in many studies and is known to affect various subfields. Given the functional heterogeneity of these subfields, we investigated the precise effects of alcohol-induced damage in these areas. Twenty-six male patients with alcohol dependence (alcohol group) and twenty-six age-matched male healthy social drinkers were recruited from a mental health hospital and the community respectively, with the aim of comparing the hippocampal subfields between groups. Each participant underwent a 3T MRI scan. Hippocampal subfield volumes were estimated using an automated procedure and drinking history recorded using Lifetime Drinking History, Alcohol Use Disorder Identification Test, and the Brief Michigan Alcoholism Screening Test. The alcohol group showed a lower total hippocampus volume, specifically in the left presubiculum, fimbria, and bilateral subiculum. Regression analysis assessing the influence of age and group showed that group was a more significant factor than age in most subfields. Our findings suggest that alcohol dependence alters hippocampal subfield volumes. Further longitudinal studies on the interaction of structural and neurocognitive changes would improve our understanding of brain structural changes resulting from long-term alcohol consumption.

Surface-Based Parameters of Brain Imaging in Male Patients with Alcohol Use Disorder.

OBJECTIVE: The structural alteration of brain shown in patients with alcohol use disorder (AUD) can originate from both alcohol effects and genetic or developmental processes. We compared surface-based parameters of patients with AUD with healthy controls to prove the applicability of surface-based morphometry with head size correction and to determine the areas that were sensitive to brain alteration related to AUD. METHODS: Twenty-six abstinent male patients with AUD (alcohol group, mean abstinence=13.2 months) and twenty-eight age-matched healthy participants (control group) were recruited from an inpatient mental hospital and community. All participants underwent a 3T MRI scan. Surface-based parameters were determined by using FreeSurfer. RESULTS: Every surface-based parameter of the alcohol group was lower than the corresponding control group parameter. There were large group differences in the whole brain, grey and white matter volume, and the differences were more prominent after head size correction. Significant group differences were shown in cortical thicknesses in entire brain regions, especially in parietal, temporal and frontal areas. There were no significant group differences in surface areas, but group difference trends in surface areas of the frontal and parietal cortices were shown after head size correction. CONCLUSION: Most of the surface-based parameters in alcohol group were altered because of incomplete recovery from chronic alcohol exposure and possibly genetic or developmental factors underlying the risk of AUD. Surface-based morphometry with controlling for head size is useful in comparing the volumetric parameters and the surface area to a lesser extent in alcohol-related brain alteration.

Plasma-Enhanced Atomic Layer Deposition of Silicon Nitride Using a Novel Silylamine Precursor.

We report the plasma-enhanced atomic layer deposition (PEALD) of silicon nitride thin film using a silylamine compound as the silicon precursor. A series of silylamine compounds were designed by replacing SiH3 groups in trisilylamine by dimethylaminomethylsilyl or trimethylsilyl groups to obtain sufficient thermal stability. The silylamine compounds were synthesized through redistribution, amino-substitution, lithiation, and silylation reactions. Among them, bis(dimethylaminomethylsilyl)trimethylsilyl amine (C9H29N3Si3, DTDN2-H2) was selected as the silicon precursor because of the lowest bond dissociation energy and sufficient vapor pressures. The energies for adsorption and reaction of DTDN2-H2 with the silicon nitride surface were also calculated by density functional theory. PEALD silicon nitride thin films were prepared using DTDN2-H2 and N2 plasma. The PEALD process window was between 250 and 400 °C with a growth rate of 0.36 Å/cycle. The best film quality was obtained at 400 °C with a RF power of 100 W. The PEALD film prepared showed good bottom and sidewall coverages of ∼80% and ∼73%, respectively, on a trench-patterned wafer with an aspect ratio of 5.5.

Atomic Layer Deposition of Zirconium-Based High-k Metal Gate Oxide: Effect of Si Containing Zr Precursor.

Zirconium based thin film have been deposited by atomic layer deposition (ALD) process using Zr and Si containing Zr precursor with ozone as oxidant. We have pursued a means to control composition by varying Zr and Si containing precursor by cycle frequency. The molar ratio of Si to Zr in the Zr based films was 0.2, 0.25, 0.33, and 0.5. Addition of Si containing Zr precursor on Zirconium based thin films was effective for the decrease of the roughness, while an increase of density. XPS analysis indicated that the addition of Si containing Zr precursors in the Zr based film formed the silicate structure. The XRD analysis of the all ZrO2-SiO2 mixed films annealed at 600 degrees C for 5 min indicated the presence of amorphous. However, the ZrO2 film showed diffraction peaks at 2θ = 30.6 degrees due to the presence of the Tetragonal ZrO2. The incorporation of Si into ZrO2 films helps stabilize an amorphous structure during deposition and annealing. The Zr based thin film (Si/Zr = 0.25) exhibited that the leakage current density was 6.2 x 10(-7) A/cm2 at a bias of - 1.5 V.

Satisfaction of immediate or delayed switch to paliperidone palmitate in patients unsatisfied with current oral atypical antipsychotics.

Patient satisfaction with treatment is an important clinical index associated with the efficacy and adherence of treatment in schizophrenia. Although switching from oral antipsychotics to the long-acting injectable formulation may improve convenience, patient satisfaction has not been studied extensively. We carried out a 21-week, multicenter, randomized, open-label comparative study. A total of 154 patients with schizophrenia unsatisfied with current oral atypical antipsychotics were assigned randomly to either immediate or delayed switching to paliperidone palmitate, the long-acting injectable formulation of paliperidone. The Medication Satisfaction Questionnaire (MSQ) and the Treatment Satisfaction Questionnaire for Medication (TSQM) were used to evaluate patient satisfaction with treatment, whereas the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance (PSP) scale were used to evaluate efficacy. From baseline to the final assessment, the MSQ score increased significantly in both groups, and the increase was greatest after the first administration of paliperidone palmitate in the immediate switch group. The scores of TSQM effectiveness, convenience, and global satisfaction as well as the PSP total score increased significantly, whereas the PANSS total score decreased significantly in both groups. The immediate switch group showed a significant improvement in the TSQM convenience score compared with the delayed switch group on oral antipsychotics during the comparison period. Most adverse events were minor and tolerable. In short, switching from oral atypical antipsychotics to paliperidone palmitate because of poor satisfaction significantly improved patient satisfaction, with comparable efficacy and tolerability.

Preparation of ansa-metallocenes for production of poly(α-olefin) lubricants.

An ansa-zirconocene bearing methyl substituents at all positions adjacent to the bridgehead [(-C(Ph)HC(Ph)H-)(η(5)-2,5-Me2C5H2)2ZrCl2] (4) was prepared in high yields (78%) through the reductive dimerization of 1,4-dimethyl-6-phenylfulvene utilizing ZrCl2·DME generated in situ. The structure of 4 was subsequently confirmed using X-ray crystallography. 4 exhibited excellent catalytic performance with regard to 1-decene oligomerization, which was carried out with the intention of preparing lubricant base stocks. High activities (21 × 10(6) g mol(-1) Zr h(-1) activity; TON = 150 000; TOF = 42 s(-1)) were observed at temperatures as high as 120 °C and the oligomer distribution was appropriate for lubricant application. The simulated distillation (SIMDIS) data confirmed that a wide range of oligomers were formed, ranging from the dimer (2-mer) to 20-mer. A minimal amount of the dimer and oligomers larger than the 10-mer was formed (13 and 25 wt%, respectively). Alternatively, a typical unbridged complex such as (η(5)-nBuC5H4)2ZrCl2 primarily produced dimers (54 wt%), whereas the ansa-zirconocene (EBI)ZrCl2 primarily produced oligomers larger than 10-mer (62 wt%). The methyl substituents at the positions adjacent to the bridgehead in 4 played a significant role in the catalytic performance.

An FMRI study investigating adolescent brain activation by rewards and feedback.

OBJECTIVE: This study aimed to investigate the adolescent brain activation patterns in response to performance feedback (PF), social reward (SR) and monetary reward (MR) and their association with psychological factors. METHODS: Functional magnetic resonance imaging (fMRI) was performed while middle school boys (n=15) performed tests pertained to PF, SR and MR. The brain activation pattern in each condition was investigated, and the extent of brain activation in each of the three conditions was compared at once. RESULTS: The caudate and the dorsal prefrontal area were activated in all three conditions. Furthermore, the cuneus showed significantly greater activation in the PF condition than the SR or MR condition. And the self - related areas, such as the right precentral gyrus and paracenral lobule, were more activated in the SR condition than the PF or MR condition. The left middle frontal gyrus was more activated in the MR condition than the PF or SR condition. CONCLUSION: Not only various reward stimuli but also feedback stimulus might commonly activate dorsal prefrontal and subcortical area in adolescents. Moreover, several different brain activation patterns were also observed in each condition. The results of this study could be applied to planning of learning and teaching strategy for adolescents in various ways.

Abnormal brain activation of adolescent internet addict in a ball-throwing animation task: possible neural correlates of disembodiment revealed by fMRI.

While adolescent internet addicts are immersed in cyberspace, they are easily able to experience 'disembodied state'. The purposes of this study were to investigate the difference of brain activity between adolescent internet addicts and normal adolescents in a state of disembodiment, and to find the correlation between the activities of disembodiment-related areas and the behavioral characteristics related to internet addiction. The fMRI images were taken while the addiction group (N=17) and the control group (N=17) were asked to perform the task composed with ball-throwing animations. The task reflected on either self-agency about ball-throwing or location of a ball. And each block was shown with either different (Changing View) or same animations (Fixed View). The disembodiment-related condition was the interaction between Agency Task and Changing View. Within-group analyses revealed that the addiction group exhibited higher activation in the thalamus, bilateral precentral area, bilateral middle frontal area, and the area around the right temporo-parietal junction. And between-group analyses showed that the addiction group exhibited higher activation in the area near the left temporo-parieto-occipital junction, right parahippocampal area, and other areas than the control group. Finally, the duration of internet use was significantly correlated with the activity of posterior area of left middle temporal gyrus in the addiction group. These results show that the disembodiment-related activation of the brain is easily manifested in adolescent internet addicts. Internet addiction of adolescents could be significantly unfavorable for their brain development related with identity formation.

Dose pattern and effectiveness of paliperidone extended-release tablets in patients with schizophrenia.

OBJECTIVES: The objectives of this 12-week multicenter, open-label, noncomparative study were to evaluate the overall effectiveness of paliperidone extended release (ER), the feasibility of maintaining patients on the initial dose of 6 mg, and the relationship between dose pattern and treatment response in schizophrenic patients with inadequate responses to initial treatment in a natural setting. METHODS: All patients received 6 mg of paliperidone ER during the first 2 weeks, and subsequently, the dose was adjusted at each visit based on the patient response. We examined the response rate and the effectiveness of different dose patterns of paliperidone ER such as "early increase (dose increased to 9 mg at week 2)," "late increase (dose increased to 9 mg at week 4)," and "maintenance group." RESULTS: The response rate based on the Clinical Global Impression of Improvement or Severity response criteria was 33.6% or 61.7%, respectively. The proportion of patients who stayed with the initial dose of 6 mg was 44.5% and the response rate of these patients was 79.8%. When the treatment response to the initial dose of 6 mg is inadequate (Clinical Global Impression of Improvement ≥ 4 at week 2), an early increase in the dose seems to be more effective than maintenance or late increase of the initial dose. CONCLUSIONS: This study suggests that paliperidone ER may be an effective and well-tolerated antipsychotics in the treatment of patients with schizophrenia.

Associations between DRDs and schizophrenia in a Korean population: multi-stage association analyses.

The dysregulation of the dopaminergic system has been implicated in the pathophysiology of major psychosis, including schizophrenia, with dopamine receptor genes (DRDs) presently targeted as the most promising candidate genes. We investigated DRD1-5 for association with schizophrenia using a multi-stage approach in a Korean sample. One hundred forty-two SNPs in DRD1-5 were selected from the dbSNP, and the associations of each SNP were then screened and typed by MALDI-TOF mass spectrometry using pooled DNA samples from 150 patients with major psychosis and 150 controls. Each of the suggested SNPs was then genotyped and tested for an association within the individual samples comprising each pool. Finally, the positively associated SNPs were genotyped in an extended sample of 270 patients with schizophrenia and 350 controls. Among the 142 SNPs, 88 (62%) SNPs in our Korean population were polymorphic. At the pooling stage, 10 SNPs (DRD1: 2, DRD2: 3, and DRD4: 5) were identified (P<0.05). SNPs rs1799914 of DRD1 (P=0.046) and rs752306 of DRD4 (P=0.017) had significantly different allele frequencies in the individually genotyped samples comprising the pool. In the final stage, with the extended sample, the suggestive association of DRD4 with rs752306 was lost, but the association of DRD1 with rs1799914 gained greater significance (P=0.017). In these large-scale multi-stage analyses, we were able to find a possible association between DRD1 and schizophrenia. These findings suggested the potential contribution of a multi-step strategy for finding genes related to schizophrenia.

Synthesis of [RhCl(CO)(cyclopentadienone)]2 from [RhCl(cod)]2 and a 1,6-diyne under CO: application to Rh(I)-catalyzed tandem [2+2+1] carbonylative cycloaddition of diynes and Claisen rearrangement.

Although Rh(I)Cl(CO)(cpd) (cpd = cyclopentadienone) complexes were identified more than 40 years ago, their exact structures have not been determined because of the polymeric nature of these complexes. We determined the structure of [Rh(I)Cl(CO)(cpd)](2), which was formed by the reaction of [Rh(cod)Cl](2) with a 1,6-diyne under CO. In addition, based on determination of the structure of the [Rh(I)Cl(CO)(cpd)](2) complex, we identified a new catalytic tandem reaction--the Rh-catalyzed [2+2+1] carbonylative cycloaddition of phenoxide-substituted diynes and Claisen rearrangement.

The genetic factors affecting drinking behaviors of korean young adults with variant aldehyde dehydrogenase 2 genotype.

OBJECTIVE: We determined whether aldehyde dehydrogenase 2 (ALDH2) activity alters the way in which drinking behaviors are affected by gene polymorphisms of other alcohol-metabolizing enzymes and serotonin-related proteins. METHODS: Through a follow-up survey with a cohort comprising 551 university freshmen over a period of 6 years, we examined the genetic factors affecting drinking behaviors. In 2000, drinking behaviors were assessed and tryptophan hydroxylase (TPH) and ALDH2 gene polymorphisms were determined. Drinking behaviors were repeated in 2006 (n=150), and the gene polymorphisms of ADH1B, ADH1C, CYP2E1, 5-HTR2A 1438A/G, and 5-HTR2A IVS2 were also determined. RESULTS: In 2000, the variant and wild-type ALDH2 groups exhibited little difference in terms of drinking frequency and problem drinking. Furthermore, some genotypes influenced only the variant group: ADH1B*2/*2 was associated with a lower drinking frequency, and CYP2E1 c2 allele was associated with an increased risk of problem drinking. In 2006, drinking frequency and risk of problem drinking were significantly lower in the variant group than in the wild-type group. However, the TPH AA genotype disturbed that difference, meaning that the subjects in the variant group had developed a similar level of risk of problem drinking to that in the wild-type group. CONCLUSION: Korean university freshmen who were identified as a variant group drank as frequently as those in the wild-type group. For the subsequent 6 years they drank less frequently, thus decreasing the risk of problem drinking. However, that frequency drop was interrupted in those with gene polymorphisms such as ADH1B*1, CYP2E1 c2, and TPH A.