The relationship between the Met allele of the BDNF Val66Met polymorphism and impairments in decision making under ambiguity in patients with obsessive-compulsive disorder

Brain-derived neurotrophic factor (BDNF) gene has an important link to neurotransmitter systems, including serotonin, and seems to play a major role in emotional decision making. Impairment of decision making is an important feature of psychiatric disorders such as obsessive-compulsive disorder (OCD). We explore the link between decision making and the BDNF Val66Met polymorphism, which results in a reduction of BDNF activity, in a sample of Caucasian OCD patients. We used the Iowa Gambling Task (IGT) to measure decision making in 122 OCD patients. All patients were assessed using the Yale-Brown Obsessive-Compulsive Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Raven Progressive Matrices. Patients also performed the Continuous Performance Task (CPT-II) and the Trail Making Test (TMT). We grouped Met-allele carriers because these act in a dominant way. Met-allele carries exhibited low performance on both halves of the IGT (first half -F = -2.51, df = 120, P = 0.01; second half -F = -2.32, df = 120, P = 0.02). However, logistic regression analyses showed that the influence of the Met allele seemed to be restricted to the first half of the IGT [first half -β = 0.55, df = 1, P < 0.01, odds ratio (OR) = 5.62; second half -β = 0.32, df = 1, P = 0.15, OR = 2.30]. No differences were observed in tests used to evaluate executive functions associated with the dorsolateral prefrontal cortices (TMT and CPT-II, df = 120, P > 0.05 for both). Met-allele impairment may only be related to decisions made under ambiguous conditions. The null results involving TMT and CPT-II are possibly related to the dysfunction of the orbitofrontal cortices that is associated with OCD.     

创伤后应激障碍（PTSD）的生物学研究概述

创伤后应激障碍（posttraumatic stress disorder,PTSD）是灾害后精神及行为障碍的一种重要表现形式,具有发病率及患病率高、病程长、疗效差等特点,严重影响了临床救治。对于创伤后应激障碍发病机制及其防治的研究日益受到关注。致力于PTSD研究的研究者,从行为学、神经内分泌等宏观研究,到形态学、细胞分子生物学等功能研究,再到临床实验研究,做了大量的工作,得到了许多具有实际指导意义的结果。本文针对国内外研究者近年来在这方面的研究现状进行综述,从宏观上为PTSD后续的研究提供一些循证的证据。     

注意缺陷多动障碍低觉醒模型的新证据

注意缺陷多动障碍（Attention Deficit Hyperactivity Disorder,ADHD）是儿童期常见的一种发展性的异常,其病因及发生机理至今未明。低觉醒模型是ADHD成因的一种假设。本文从睡眠障碍导致的低觉醒探讨ADHD发生机理。通过对ADHD儿童的睡眠障碍进行分析以及将ADHD外在表现与睡眠剥夺后的表现进行对比分析,得出ADHD儿童存在的低觉醒是由于外显的或内隐的睡眠障碍引起的,一方面间接证明了低觉醒模型,另一方面为ADHD的成因研究开拓了新的思路。     

Are atypical depression,borderline personality disorder and bipolar II disorder overlapping manifestations of a common cyclothymic diathesis?

The constructs of atypical depression, bipolar II disorder and borderline personality disorder (BPD) overlap. We explored the relationships between these constructs and their temperamental underpinnings. We examined 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features. Those who also met the DSM-IV criteria for BPD (BPD+), compared with those who did not (BPD-), had a significantly higher lifetime comorbidity for body dysmorphic disorder, bulimia nervosa, narcissistic, dependent and avoidant personality disorders, and cyclothymia. BPD+ also scored higher on the Atypical Depression Diagnostic Scale items of mood reactivity, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the Hopkins Symptoms Check List obsessive-compulsive, interpersonal sensitivity, anxiety, anger-hostility, paranoid ideation and psychoticism factors. Logistic regression revealed that cyclothymic temperament accounted for much of the relationship between atypical depression and BPD, predicting 6 of 9 of the defining DSM-IV attributes of the latter. Trait mood lability (among BPD patients) and interpersonal sensitivity (among atypical depressive patients) appear to be related as part of an underlying cyclothymic temperamental matrix.     

Genetic evaluation of ovulatory disorders in Austrian Fleckvieh cows: a comparison between linear models and survival analysis

The objective of this study was to compare linear models and survival analysis for genetic evaluation of ovulatory disorders, which included veterinary treatments of silent heat/anestrus and cystic ovaries. Data of 23 450 daughters of 274 Austrian Fleckvieh sires were analyzed. For linear model analyses, ovulatory disorders were defined as a binary response (presence or absence) in the time periods from calving to 150 days after calving and from calving to 300 days after calving. For survival analysis, ovulatory disorders were defined either as the number of days from calving to the day of the first treatment for an ovulatory disorder (uncensored record) or from calving to the day of culling, or the last day of the period under investigation (until 150 or 300 days after calving; censored record). Estimates of heritability were very similar (0.016 to 0.020) across methods and periods. Correlations between sire estimated breeding value from linear model and survival analysis were 0.98, whereas correlations between different time periods were somewhat lower (0.95 and 0.96). The results showed that the length of time period had a larger effect on genetic evaluation than methodology.     

Synaptic connections of cone bipolar cells that express the neurokinin 1 receptor in the rabbit retina

We have investigated and further characterized, in the rabbit retina, the synaptic connectivity of the ON-type cone bipolar cells that are immunoreactive for an antibody against the neurokinin-1 receptor (NK1R). NK1R-immunoreactive bipolar cell axons terminate in stratum 4 of the inner plexiform layer. The axons of NK1R-positive bipolar cells receive synaptic inputs from amacrine cells through conventional synapses and from putative AII amacrine cells via gap junctions. The major outputs from NK1R-positive bipolar cells make contacts with amacrine cell processes. The most frequent postsynaptic dyads comprise two amacrine cell processes. Double-labeling experiments with antibodies against NK1R and either calretinin or glycine have demonstrated that NK1R-immunoreactive bipolar cells form gap junctions with AII amacrine cells. Thus, NK1R-positive cone bipolar cells, together with calbindin-positive cone bipolar cells, may play an important role in transferring rod signals to the ON-type ganglion cells of the cone pathway in the rabbit retina.I.-B. Kim and M.R. Park contributed equally to this work.This work was supported by the Ministry of Science and Technology of Korea (grant no. M1-0108-00-0059; Neurobiology Support Grant).     

Structure of a full length psychrophilic cellulase from Pseudoalteromonas haloplanktis revealed by X-ray diffraction and small angle X-ray scattering

Pseudoalteromonas haloplanktis is a psychrophilic Gram-negative bacterium isolated in Antarctica, that lives on organic remains of algae. This bacterium converts the cellulose, highly constitutive of algae, into an immediate nutritive form by biodegrading this biopolymer. To understand the mechanisms of cold adaptation of its enzymatic components, we studied the structural properties of an endoglucanase, Cel5G, by complementary methods, X-ray crystallography and small angle X-ray scattering. Using X-ray crystallography, we determined the structure of the catalytic core module of this family 5 endoglucanase, at 1.4A resolution in its native form and at 1.6A in the cellobiose-bound form. The catalytic module of Cel5G presents the (beta/alpha)(8)-barrel structure typical of clan GH-A of glycoside hydrolase families. The structural comparison of the catalytic core of Cel5G with the mesophilic catalytic core of Cel5A from Erwinia chrysanthemi revealed modifications at the atomic level leading to higher flexibility and thermolability, which might account for the higher activity of Cel5G at low temperatures. Using small angle X-ray scattering we further explored the structure at the entire enzyme level. We analyzed the dimensions, shape, and conformation of Cel5G full length in solution and especially of the linker between the catalytic module and the cellulose-binding module. The results showed that the linker is unstructured, and unusually long and flexible, a peculiarity that distinguishes it from its mesophilic counterpart. Loops formed at the base by disulfide bridges presumably add constraints to stabilize the most extended conformations. These results suggest that the linker plays a major role in cold adaptation of this psychrophilic enzyme, allowing steric optimization of substrate accessibility.     

Addressing the intrinsic disorder bottleneck in structural proteomics

The Center for Eukaryotic Structural Genomics (CESG), as part of the Protein Structure Initiative (PSI), has established a high-throughput structure determination pipeline focused on eukaryotic proteins. NMR spectroscopy is an integral part of this pipeline, both as a method for structure determinations and as a means for screening proteins for stable structure. Because computational approaches have estimated that many eukaryotic proteins are highly disordered, about 1 year into the project, CESG began to use an algorithm (the Predictor of Naturally Disordered Regions, PONDR to avoid proteins that were likely to be disordered. We report a retrospective analysis of the effect of this filtering on the yield of viable structure determination candidates. In addition, we have used our current database of results on 70 protein targets from Arabidopsis thaliana and 1 from Caenorhabditis elegans, which were labeled uniformly with nitrogen-15 and screened for disorder by NMR spectroscopy, to compare the original algorithm with 13 other approaches for predicting disorder from sequence. Our study indicates that the efficiency of structural proteomics of eukaryotes can be improved significantly by removing targets predicted to be disordered by an algorithm chosen to provide optimal performance.     

Functional polymorphisms of HSPA5: possible association with bipolar disorder

Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder.     

Serotonin transporter polymorphisms affect human blood glucose control

We measured the effect of nutritional intervention on clinical data, including fasting blood glucose (FBG), and their association with polymorphisms of the serotonin transporter-linked polymorphic region (5-HTTLPR) which might affect adherence. Enrolled in the intervention program were 264 Japanese women not on medication for diabetes, hypercholesterolemia or hypertension. The 5-HTTLPR allele (S and L) frequencies among the subjects differed markedly from those of Caucasians: SS (n = 183), LS (n = 69), and LL (n = 12). The decrease in FBG (DeltaFBG) from the beginning to the end of the program (11 weeks; short-term study), and DeltaFBG from the beginning to a follow-up check performed between 2002 and 2004 (average of 23 years later; long-term study) was calculated. The SS homozygotes of 5-HTTLPR showed larger DeltaFBG (P = 0.01 and P < 0.0001 in the short- and long-term studies, respectively) than DeltaFBG with other genotypes.