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1.
Polymers (Basel) ; 15(10)2023 May 19.
Article in English | MEDLINE | ID: mdl-37242958

ABSTRACT

Polyimide-bearing retainer has been successfully used in space environment. However, the structural damage of polyimide induced by space irradiation limits its wide use. In order to further improve the atomic oxygen resistance of polyimide and comprehensively investigate the tribological mechanism of polyimide composites exposed in simulate space environment, 3-amino-polyhedral oligomeric silsesquioxane (NH2-POSS) was incorporated into a polyimide molecular chain and silica (SiO2) nanoparticles were in situ added into polyimide matrix and the combined effect of vacuum environment, and atomic oxygen (AO) on the tribological performance of polyimide was studied using bearing steel as the counterpart by a ball on disk tribometer. XPS analysis demonstrated the formation of protective layer induced by AO. The wear resistance of polyimide after modification was enhanced under AO attack. FIB-TEM confirmed that the inert protective layer of Si was formed on the counterpart during the sliding process. Mechanisms behind this are discussed based on the systematic characterization of worn surfaces of the samples and the tribofilms formed on the counterbody.

2.
Medicine (Baltimore) ; 99(31): e21490, 2020 Jul 31.
Article in English | MEDLINE | ID: mdl-32756179

ABSTRACT

BACKGROUND: Whether the combination of gefitinib and chemotherapy is beneficial for advanced non-small cell lung cancer (NSCLC) remains controversial. This study aimed to summarize the currently available evidence and compare the efficacy and safety of gefitinib combined with chemotherapy versus chemotherapy alone for treating advanced NSCLC. METHODS: Literature on comparing the effects of gefitinib combined with chemotherapy and chemotherapy alone in treating NSCLC was retrieved from the PubMed, EMBASE and Cochrane Database. The primary outcome measures included progression-free survival (PFS) and overall survival (OS). Revman 5.3 was used for data processing. RESULTS: Seven randomized controlled trials were included, involving a total of 1418 patients. There appeared a significant improvement in PFS (hazard ratio (HR) = 0.60 [95% CI 0.43, 0.82], P = .001) after treatment with gefitinib combined with chemotherapy when compared with chemotherapy alone. The subgroup analysis showed a significant advantage of sequential administration (HR = 0.67 [95% CI 0.57, 0.79], P < .00001). There was no significant improvement in OS (HR = 0.92 [95% CI 0.71, 1.20], P = .54), and no significant improvement in overall response rate (ORR) (HR = 0.98 [95% CI 0.67, 1.44], P = .93). The risks of rash and diarrhea (odds ratios) were higher in gefitinib combined with chemotherapy group when compared with chemotherapy alone, and there were significant differences on grade 3/4 rash and thrombocytopenia between 2 groups. CONCLUSION: Gefitinib combined with chemotherapy is superior to chemotherapy alone in PFS, sequential administration prolongs the patients' PFS, however, a survival advantage is not shown in OS or ORR. Gefitinib combined with chemotherapy aggravates rash, diarrhea and thrombocytopenia.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Gefitinib/administration & dosage , Lung Neoplasms/drug therapy , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Diarrhea/chemically induced , Disease-Free Survival , Exanthema/chemically induced , Female , Gefitinib/adverse effects , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Progression-Free Survival , Thrombocytopenia/chemically induced , Treatment Outcome
3.
Neuroscience ; 343: 21-29, 2017 02 20.
Article in English | MEDLINE | ID: mdl-27916731

ABSTRACT

The CNTNAP2 (contactin-associated protein-like 2) gene, highly expressed in the human prefrontal cortex, has been linked with autism and language impairment. Potential relationships between CNTNAP2, dorsolateral prefrontal cortex (DLPFC), and cognition have been suggested by previous clinical studies, but have not been directly examined in the same study. The current study collected structural MRI, genetic, and behavioral data in 317 healthy Chinese adults, and examined associations between CNTNAP2 variants, DLPFC, and cognitive performance (measured by the Stroop task). After controlling for intracranial volume, sex, and age, the CNTNAP2 genetic polymorphism at SNP rs7809486 had the strongest association with bilateral DLPFC volume (p=0.00015 and 0.00014 for left and right DLPFC volumes, respectively), with GG homozygotes having greater bilateral DLPFC volumes and surface areas than the other genotypes. Furthermore, TT homozygotes of CNTNAP2 rs4726946 (a nearby SNP that had moderate linkage disequilibrium with rs7809486) had greater left DLPFC volume and surface area, and better cognitive performance than the other genotypes. Subjects with greater left DLPFC surface area had better cognitive performance. Importantly, the left DLPFC surface area mediated the association between the CNTNAP2 rs4726946 genotype and cognitive performance. This study provides the first evidence for associations among the CNTNAP2 gene, left DLPFC structure, and cognitive control.


Subject(s)
Cognition , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , Prefrontal Cortex/diagnostic imaging , Adolescent , Analysis of Variance , Asian People/genetics , Asian People/psychology , China , Executive Function , Female , Functional Laterality , Genotyping Techniques , Haplotypes , Humans , Magnetic Resonance Imaging , Male , Organ Size , Polymorphism, Single Nucleotide , Reaction Time , Stroop Test , Young Adult
4.
Front Comput Neurosci ; 10: 100, 2016.
Article in English | MEDLINE | ID: mdl-27721750

ABSTRACT

The striatum is an important subcortical structure with extensive connections to other regions of the brain. These connections are believed to play important roles in behaviors such as reward-related processes and impulse control, which show significant sex differences. However, little is known about sex differences in the striatum-projected fiber connectivity. The current study examined sex differences between 50 Chinese males and 79 Chinese females in their fiber connections between the striatum and nine selected cortical and subcortical regions. Despite overall similarities, males showed stronger fiber connections between the left caudate and rostral cingulate cortex, between the right putamen and the lateral orbitofrontal cortex, between the bilateral putamen and the ventro-lateral prefrontal cortex, and between the right caudate and the ventro-lateral prefrontal cortex, whereas females showed stronger fiber connections between the right putamen and the dorsolateral prefrontal cortex, between bilateral caudate and hippocampus, and between the left putamen and hippocampus. These findings help us to understand sex differences in the striatum-projected fiber connections and their implications for sex differences in behaviors.

5.
PLoS One ; 11(10): e0162160, 2016.
Article in English | MEDLINE | ID: mdl-27755551

ABSTRACT

Cooperativeness is an essential behavioral trait evolved to facilitate group living. Social and cognitive mechanisms involved in cooperation (e.g., motivation, reward encoding, action evaluation, and executive functions) are sub-served by the striatal-projected circuits, whose physical existence has been confirmed by animal studies, human postmortem studies, and in vivo human brain studies. The current study investigated the associations between Cooperativeness and fiber connectivities from the striatum to nine subcortical and cortical regions, including the amygdala, hippocampus, medial orbitofrontal cortex, lateral orbitofrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate cortex/retrosplenial cortex, dorsal cingulate cortex, and rostral cingulate cortex. Results showed that Cooperativeness was negatively correlated with fiber connectivity for the cognitive control system (from the dorsal caudate to the rostral cingulate cortex and ventrolateral prefrontal cortex), but not with fiber connectivity for the social cognitive system (e.g., connectivity with the medial prefrontal cortex and amygdala). These results partially supported Declerck et al.'s (2013) cognitive neural model of the role of cognitive control and social cognition in cooperation.


Subject(s)
Cooperative Behavior , Corpus Striatum/physiology , Neural Pathways/physiology , Personality , Amygdala/physiology , Brain/diagnostic imaging , Female , Gyrus Cinguli/physiology , Hippocampus/physiology , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Prefrontal Cortex/physiology , Young Adult
6.
Brain Struct Funct ; 221(8): 4045-4057, 2016 11.
Article in English | MEDLINE | ID: mdl-26586602

ABSTRACT

There is a keen interest in identifying specific brain regions that are related to individual differences in true and false memories. Previous functional neuroimaging studies showed that activities in the hippocampus, right fusiform gyrus, and parahippocampal gyrus were associated with true and false memories, but no study thus far has examined whether the structures of these brain regions are associated with short-term and long-term true and false memories. To address that question, the current study analyzed data from 205 healthy young adults, who had valid data from both structural brain imaging and a misinformation task. In the misinformation task, subjects saw the crime scenarios, received misinformation, and took memory tests about the crimes an hour later and again after 1.5 years. Results showed that bilateral hippocampal volume was associated with short-term true and false memories, whereas right fusiform gyrus volume and surface area were associated with long-term true and false memories. This study provides the first evidence for the structural neural bases of individual differences in short-term and long-term true and false memories.


Subject(s)
Hippocampus/anatomy & histology , Individuality , Memory, Long-Term/physiology , Memory, Short-Term/physiology , Temporal Lobe/anatomy & histology , Adult , Female , Functional Laterality , Humans , Magnetic Resonance Imaging , Male , Parahippocampal Gyrus/anatomy & histology , Young Adult
7.
Child Adolesc Ment Health ; 21(3): 161-168, 2016 Sep.
Article in English | MEDLINE | ID: mdl-32680355

ABSTRACT

BACKGROUND: Parental psychopathological symptoms have been associated with a number of child psychological problems, yet little research has examined the role of parental emotion dysregulation on the intergenerational transmission of psychopathological symptoms. This study aims to examine the relationship between parents' and children's psychopathological symptoms with a focus on the mediating mechanism of parental emotion dysregulation on these relationships. METHODS: Eighty-nine Chinese parents and their school-age children between the ages of 7 and 12 (49 males, M age = 8.79, SD = 1.81) participated in the study. In the initial phase of the study, parents filled out a series of questionnaires reporting their own psychopathological symptoms via SCL-90 and difficulties with emotion regulation via Difficulties in Emotion Regulation Scale. After 9 months, the parents reported their children's internalizing and externalizing problems via Child Behavior Checklist, and the children self-reported anxiety symptoms via Screen for Child Anxiety Related Emotional Disorders in the second phase of the study. RESULTS: The results showed that parental emotion dysregulation played an important role as a mediator of the relationship between parental psychopathological symptoms and child internalizing problems and separation anxiety, which indicates that parents' mental health problems were significantly associated with their difficulties with emotion regulation, which in turn led to more internalizing problems and separation anxiety in their children. However, we did not find a mediating effect of parental emotion dysregulation on the links between parent psychopathology and child externalizing problems or other types of self-reported anxiety symptoms. CONCLUSIONS: Our findings highlighted the importance of implementing more psycho-education programs that specifically target parents' emotion regulation abilities in both community and clinical settings to ameliorate the intergenerational transmission of psychopathological symptoms between generations.

8.
PLoS One ; 10(8): e0133143, 2015.
Article in English | MEDLINE | ID: mdl-26308205

ABSTRACT

Sensory processing sensitivity (SPS) is an intrinsic personality trait whose genetic and neural bases have recently been studied. The current study used a neural mediation model to explore whether resting-state brain functions mediated the effects of dopamine-related genes on SPS. 298 healthy Chinese college students (96 males, mean age = 20.42 years, SD = 0.89) were scanned with magnetic resonance imaging during resting state, genotyped for 98 loci within the dopamine system, and administered the Highly Sensitive Person Scale. We extracted a "gene score" that summarized the genetic variations representing the 10 loci that were significantly linked to SPS, and then used path analysis to search for brain regions whose resting-state data would help explain the gene-behavior association. Mediation analysis revealed that temporal homogeneity of regional spontaneous activity (ReHo) in the precuneus actually suppressed the effect of dopamine-related genes on SPS. The path model explained 16% of the variance of SPS. This study represents the first attempt at using a multi-gene voxel-based neural mediation model to explore the complex relations among genes, brain, and personality.


Subject(s)
Brain/metabolism , Dopamine/metabolism , Personality/genetics , Brain/physiology , Genetic Variation , Healthy Volunteers , Humans , Magnetic Resonance Imaging , Male , Models, Neurological , Personality/physiology , Young Adult
9.
Neuroimage ; 102 Pt 2: 756-63, 2014 Nov 15.
Article in English | MEDLINE | ID: mdl-25192656

ABSTRACT

The GABRB1 gene encodes the beta 1 subunit of the gamma-aminobutyric acid A receptor (GABA A receptor), which is responsible for mediating inhibitory neurotransmission in the thalamus. Potential relationships between the GABRB1 gene, thalamus volume, and intelligence have been suggested by previous clinical studies, but have not been directly examined among nonclinical samples. The current study collected structural MRI, genetic, and behavioral data from 316 healthy Chinese adults (including 187 females and 129 males), and examined associations between GABRB1 variants, thalamus volume, and intelligence (measured by the Wechsler Adult Intelligence Scale Revised). After controlling for intracranial volume, sex, and age, GABRB1 genetic polymorphism at the SNP rs7435958 had the strongest association with thalamus volume (p = 0.002 and 0.00008 for left and right thalamus volumes, respectively), with GG homozygotes having smaller bilateral thalamus volumes than the other genotypes. Furthermore, there were positive correlations between bilateral thalamus volumes and intelligence, especially for GABRB1 rs7435958 GG female homozygotes (r's = 0.31 and 0.29, p < 0.01, for the correlations of intelligence with left and right thalamus volumes, respectively). This study provides the first evidence for the involvement of the GABRB1 gene in the thalamus structure and their interactive effects on intelligence. Future studies of the thalamus-intelligence associations should consider genetic factors as potential moderators.


Subject(s)
Intelligence/genetics , Receptors, GABA-A/genetics , Thalamus/anatomy & histology , Adolescent , Female , Humans , Male , Organ Size/genetics , Young Adult
10.
Neuroimage ; 89: 226-34, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-23618602

ABSTRACT

The seven-factor biopsychosocial model of personality distinguished four biologically based temperaments and three psychosocially based characters. Previous studies have suggested that the four temperaments-novelty seeking (NS), reward dependence (RD), harm avoidance (HA), and persistence (P)-have their respective neurobiological correlates, especially in the striatum-connected subcortical and cortical networks. However, few studies have investigated their neurobiological basis in the form of fiber connectivity between brain regions. This study correlated temperaments with fiber connectivity between the striatum and subcortical and cortical hub regions in a sample of 50 Chinese adult males. Generally consistent with our hypotheses, results showed that: (1) NS was positively correlated with fiber connectivity from the medial and lateral orbitofrontal cortex (mOFC, lOFC) and amygdala to the striatum; (2) RD was positively correlated with fiber connectivity from the mOFC, posterior cingulate cortex/retrosplenial cortex (PCC), hippocampus, and amygdala to the striatum; (3) HA was positively linked to fiber connectivity from the dorsolateral prefrontal cortex (dlPFC) and PCC to the striatum; and (4) P was positively linked to fiber connectivity from the mOFC to the striatum. These results extended the research on the neurobiological basis of temperaments by identifying their anatomical fiber connectivity correlates within the subcortical-cortical neural networks.


Subject(s)
Brain/anatomy & histology , Cerebral Cortex/anatomy & histology , Corpus Striatum/anatomy & histology , Nerve Net/anatomy & histology , Temperament , Adult , Amygdala/anatomy & histology , Asian People , Diffusion Tensor Imaging , Humans , Male , Nerve Fibers, Myelinated , Neural Pathways , Young Adult
11.
Neuroimage ; 88: 181-7, 2014 03.
Article in English | MEDLINE | ID: mdl-24291503

ABSTRACT

The Allen Brain Atlas shows that the semaphorin 5A (SEMA5A) gene, which encodes an important protein for neurogenesis and neuronal apoptosis, is predominantly expressed in the human hippocampus. Structural and functional neuroimaging studies have further shown that the hippocampus plays an important role in the performance on Raven's Progressive Matrices (RPM), a measure of reasoning ability and general fluid intelligence. Thus far, however, no study has examined the relationships between the SEMA5A gene polymorphism, hippocampal volume, and RPM performance. The current study collected both structural MRI, genetic, and behavioral data in 329 healthy Chinese adults, and examined associations between SEMA5A variants, hippocampal volume, and performance on RAPM (the advanced form of RPM). After controlling for intracranial volume (ICV), sex, and age, SEMA5A genetic polymorphism at the SNP rs42352 had the strongest association with hippocampal volume (p=0.00000552 and 0.000103 for right and left hippocampal volumes, respectively), with TT homozygotes having higher hippocampal volume than the other genotypes. Furthermore, there was a high correlation between right hippocampal volume and RAPM performance (r=0.42, p=0.0000509) for SEMA5A rs42352 TT homozygotes. This study provides the first evidence for the involvement of the SEMA5A gene in hippocampal structure and their interaction on RAPM performance. Future studies of the hippocampus-RPM associations should consider genetic factors as potential moderators.


Subject(s)
Hippocampus/anatomy & histology , Intelligence/physiology , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , Thinking/physiology , Adolescent , Adult , Female , Hippocampus/diagnostic imaging , Humans , Intelligence/genetics , Magnetic Resonance Imaging , Male , Semaphorins , Young Adult
12.
PLoS One ; 8(3): e58717, 2013.
Article in English | MEDLINE | ID: mdl-23554917

ABSTRACT

OBJECTIVE: Obesity has become a worldwide health problem in the past decades. Human and animal studies have implicated serotonin in appetite regulation, and behavior genetic studies have shown that body mass index (BMI) has a strong genetic component. However, the roles of genes related to the serotoninergic (5-hydroxytryptamine,5-HT) system in obesity/BMI are not well understood, especially in Chinese subjects. SUBJECTS AND DESIGN: With a sample of 478 healthy Chinese volunteers, this study investigated the relation between BMI and genetic variations of the serotoninergic system as characterized by 136 representative polymorphisms. We used a system-level approach to identify SNPs associated with BMI, then estimated their overall contribution to BMI by multiple regression and verified it by permutation. RESULTS: We identified 12 SNPs that made statistically significant contributions to BMI. After controlling for gender and age, four of these SNPs accounted for 7.7% additional variance of BMI. Permutation analysis showed that the probability of obtaining these findings by chance was low (p = 0.015, permuted for 1000 times). CONCLUSION: These results showed that genetic variations in the serotoninergic system made a moderate contribution to individual differences in BMI among a healthy Chinese sample, suggesting that a similar approach can be used to study obesity.


Subject(s)
Asian People/genetics , Body Mass Index , Genetic Variation , Adolescent , Adult , China , Female , Humans , Male , Polymorphism, Single Nucleotide , Receptors, Serotonin/genetics , Serotonin/metabolism , Vesicular Monoamine Transport Proteins/genetics , Young Adult
13.
Article in English | MEDLINE | ID: mdl-23276884

ABSTRACT

DOPA decarboxylase (DDC) is involved in the synthesis of dopamine, norepinephrine and serotonin. It has been suggested that genes involved in the dopamine, norepinephrine, and cholinergic systems play an essential role in the efficiency of human attention networks. Attention refers to the cognitive process of obtaining and maintaining the alert state, orienting to sensory events, and regulating the conflicts of thoughts and behavior. The present study tested seven single nucleotide polymorphisms (SNPs) within the DDC gene for association with attention, which was assessed by the Attention Network Test to detect three networks of attention, including alerting, orienting, and executive attention, in a healthy Han Chinese sample (N=451). Association analysis for individual SNPs indicated that four of the seven SNPs (rs3887825, rs7786398, rs10499695, and rs6969081) were significantly associated with alerting attention. Haplotype-based association analysis revealed that alerting was associated with the haplotype G-A-T for SNPs rs7786398-rs10499695-rs6969081. These associations remained significant after correcting for multiple testing by max(T) permutation. No association was found for orienting and executive attention. This study provides the first evidence for the involvement of the DDC gene in alerting attention. A better understanding of the genetic basis of distinct attention networks would allow us to develop more effective diagnosis, treatment, and prevention of deficient or underdeveloped alerting attention as well as its related prevalent neuropsychiatric disorders.


Subject(s)
Attention/physiology , Dopa Decarboxylase/genetics , Adolescent , Analysis of Variance , Asian People , China/epidemiology , DNA/genetics , Data Interpretation, Statistical , Executive Function/physiology , Female , Gene Frequency , Genotype , Haplotypes , Humans , Male , Nerve Net/physiology , Orientation/physiology , Polymorphism, Single Nucleotide , Psychomotor Performance/physiology , Young Adult
14.
Neuroimage ; 75: 79-86, 2013 Jul 15.
Article in English | MEDLINE | ID: mdl-23110888

ABSTRACT

The genetic and neural basis of working memory (WM) has been extensively studied. Many dopamine (DA) related genes, including the NTSR1 gene (a DA modulator gene), have been reported to be associated with WM performance. The NTSR1 protein is predominantly expressed in the cerebral cortex and the hippocampus, the latter of which is closely involved in WM processing based on both lesion and fMRI studies. Thus far, however, no study has examined the joint effects of NTSR1 gene polymorphism and hippocampal morphology on WM performance. Participants of the current study were 330 healthy Chinese college students. WM performance was measured with a 2-back WM paradigm. Structural MRI data were acquired and then analyzed using an automated procedure with atlas-based FreeSurfer segmentation software (v 4.5.0) package. Linear regression analyses were conducted with a NTSR1 C/T polymorphism which was previously reported to be associated with WM (rs4334545), hippocampal volume, and their interaction as predictors of WM performance, with gender and intracranial volume (ICV) as covariates. Results showed a significant interaction between NTSR1 genotype and hippocampal volume (p<.05 for both the left and right hippocampi). Further analysis showed that the correlation between hippocampal volume and WM scores was significant for carriers of the NTSR1 T-allele (p<.05 for both hippocampi), but not for CC homozygotes. These results indicate that the association between hippocampal structure and WM performance was modulated by variation in the NTSR1 gene, and suggest that further studies of brain-behavior associations should take genetic background information into account.


Subject(s)
Hippocampus/anatomy & histology , Memory, Short-Term/physiology , Receptors, Neurotensin/genetics , Adolescent , Female , Genotype , Hippocampus/physiology , Humans , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging , Male , Polymorphism, Single Nucleotide , Young Adult
15.
PLoS One ; 7(10): e47019, 2012.
Article in English | MEDLINE | ID: mdl-23071701

ABSTRACT

Humans demonstrate an inherent bias towards making maladaptive decisions, as shown by a phenomenon known as the gambler's fallacy (GF). The GF has been traditionally considered as a heuristic bias supported by the fast and automatic intuition system, which can be overcome by the reasoning system. The present study examined an intriguing hypothesis, based on emerging evidence from neuroscience research, that the GF might be attributed to a weak affective but strong cognitive decision making mechanism. With data from a large sample of college students, we found that individuals' use of the GF strategy was positively correlated with their general intelligence and executive function, such as working memory and conflict resolution, but negatively correlated with their affective decision making capacities, as measured by the Iowa Gambling Task. Our result provides a novel insight into the mechanisms underlying the GF, which highlights the significant role of affective mechanisms in adaptive decision-making.


Subject(s)
Cognition , Decision Making , Gambling/psychology , Executive Function , Female , Humans , Intelligence Tests , Intuition , Male , Nontherapeutic Human Experimentation , Young Adult
16.
Sci Rep ; 2: 677, 2012.
Article in English | MEDLINE | ID: mdl-22997551

ABSTRACT

Both genetic and environmental factors have been shown to influence decision making, but their relative contributions and interactions are not well understood. The present study aimed to reveal possible gene-environment interactions on decision making in a large healthy sample. Specifically, we examined how the frequently studied COMT Val(158)Met polymorphism interacted with an environmental risk factor (i.e., stressful life events) and a protective factor (i.e., parental warmth) to influence affective decision making as measured by the Iowa Gambling Task. We found that stressful life events acted as a risk factor for poor IGT performance (i.e., high reward sensitivity) among Met carriers, whereas parental warmth acted as a protective factor for good IGT performance (i.e., higher IGT score) among Val/Val homozygotes. These results shed some new light on gene-environment interactions in decision making, which could potentially help us understand the underlying etiology of several psychiatric disorders associated with decision making impairment.


Subject(s)
Catechol O-Methyltransferase/genetics , Decision Making , Gene-Environment Interaction , Life Change Events , Parent-Child Relations , Polymorphism, Single Nucleotide , Adolescent , Adult , Amino Acid Substitution , Analysis of Variance , Female , Gambling , Games, Experimental , Genetic Association Studies , Humans , Male , Risk Factors , Statistics, Nonparametric , Young Adult
17.
J Psychiatr Res ; 46(9): 1153-60, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22727904

ABSTRACT

Previous case-control and family-based association studies have implicated the SLC6A4 gene in obsessive-compulsive disorder (OCD). Little research, however, has examined this gene's role in obsessive-compulsive symptoms (OCS) in community samples. The present study genotyped seven tag SNPs and two common functional tandem repeat polymorphisms (5-HTTLPR and STin2), which together cover the whole SLC6A4 gene, and investigated their associations with OCS in normal Chinese college students (N = 572). The results revealed a significant gender main effect and gender-specific genetic effects of the SLC6A4 gene on OCS. Males scored significantly higher on total OCS and its three dimensions than did females (ps < .01). The 5-HTTLPR in the promoter region showed a female-specific genetic effect, with the l/l and l/s genotypes linked to higher OCS scores than the s/s genotype (ps < .05). In contrast, a conserved haplotype polymorphism (rs1042173| rs4325622| rs3794808| rs140701| rs4583306| rs2020942) covering from intron 3 to the 3' UTR of the SLC6A4 gene showed male-specific genetic effects, with the CGAAGG/CGAAGG genotype associated with lower OCS scores than the other genotypes (ps < .05). These effects remained significant after controlling for OCS-related factors including participants' depressive and anxiety symptoms as well as stressful life events, and correction for multiple tests. These results are discussed in terms of their implications for our understanding of the sex-specific role of the different sections of the SLC6A4 gene in OCD.


Subject(s)
Genetic Predisposition to Disease , Obsessive-Compulsive Disorder/genetics , Polymorphism, Single Nucleotide/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Sex Characteristics , Asian People/genetics , Female , Humans , Linkage Disequilibrium , Male , Obsessive-Compulsive Disorder/physiopathology , Psychiatric Status Rating Scales , Students , Universities , Young Adult
18.
Neuropsychopharmacology ; 37(5): 1115-21, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22218095

ABSTRACT

Response inhibition refers to the suppression of inappropriate or irrelevant responses. It has a central role in executive functions, and has been linked to a wide spectrum of prevalent neuropsychiatric disorders. Increasing evidence from neuropharmacological studies has suggested that gene variants in the norepinephrine neurotransmission system make specific contributions to response inhibition. This study genotyped five tag single-nucleotide polymorphisms covering the whole alpha-2B-adrenergic receptor (ADRA2B) gene and investigated their associations with response inhibition in a relatively large healthy Chinese sample (N=421). The results revealed significant genetic effects of the ADRA2B conserved haplotype polymorphisms on response inhibition as measured by stop-signal reaction time (SSRT) (F(2, 418)=5.938, p=0.003). Individuals with the AAGG/AAGG genotype (n=89; mean SSRT=170.2 ms) had significantly shorter SSRTs than did those with either the CCAC/AAGG genotype (n=216; mean SSRT=182.4 ms; uncorrected p=0.03; corrected p=0.09) or the CCAC/CCAC genotype (n=116; mean SSRT=195.8 ms; corrected p<0.002, Cohen's d=0.51). This finding provides the first evidence from association research in support of a critical role of the norepinephrine neurotransmission system in response inhibition. A better understanding of the genetic basis of response inhibition would allow us to develop more effective diagnosis, treatment, and prevention of deficient or underdeveloped response inhibition as well as its related prevalent neuropsychiatric disorders.


Subject(s)
Inhibition, Psychological , Polymorphism, Single Nucleotide/genetics , Receptors, Adrenergic, alpha-2/genetics , Analysis of Variance , Asian People/genetics , Female , Gene Frequency , Genotype , Humans , Intelligence , Linkage Disequilibrium/genetics , Male , Reaction Time/genetics , Signal Detection, Psychological/physiology , Young Adult
19.
Neuropharmacology ; 59(6): 518-26, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20659488

ABSTRACT

Risky decision making is a complex process that involves weighing the probabilities of alternative options that can be desirable, undesirable, or neutral. Individuals vary greatly in how they make decisions either under ambiguity and/or under risk. Such individual differences may have genetic bases. Based on previous studies on the genetic basis of decision making, two decision making tasks [i.e., the Iowa Gambling Task (IGT) and Loss Aversion Task (LAT)] were used to test the effect of 5-HTTLPR polymorphism on decision making under ambiguity and under risk in a large Han Chinese sample (572 college students, 312 females). Basic intelligence and memory tests were also included to control for the influence of basic cognitive abilities on decision making. We found that 5-HTTLPR polymorphism significantly influenced performance in both IGT and LAT. After controlling for intelligence and memory abilities, subjects homozygous for s allele had lower IGT scores than l carriers in the first 40 trials of the IGT task. They also exhibited higher loss aversion than l carriers in the LAT task. Moreover, the effects of 5-HTTLPR were stronger for males than for females. These results extend the literature on the important role of emotion in decision making under ambiguity and risk, and shed additional lights on how decision making is influenced by culture as well as sex differences. Combining our results with existing literature, we propose that these effects might be mediated by a neural circuitry that comprises the amygdala, ventromedial prefrontal cortex, and insular cortex. Understanding the genetic factors affecting decision making in healthy subjects may allow us to better identify at-risk individuals, and better target the development of new potential treatments for specific disorders such as schizophrenia, addiction, and depression.


Subject(s)
Decision Making/physiology , Polymorphism, Genetic , Serotonin Plasma Membrane Transport Proteins/genetics , Alleles , Asian People/genetics , Emotions/physiology , Female , Genotype , Humans , Male , Memory/physiology , Neuropsychological Tests , Sex Factors
20.
Chemistry ; 13(15): 4282-92, 2007.
Article in English | MEDLINE | ID: mdl-17323390

ABSTRACT

2-aryl thiocarbamoyl benzimidazolium and imidazolinium inner salts derived from benzimidazole and imidazoline carbenes are unique ambident C-C-S and C-C-N 1,3-dipolar systems, which undergo highly efficient and site-selective cycloaddition reactions with dimethyl acetylenedicarboxylate or dibenzoylacetylene to furnish spiro(imidazole-2,3'-thiophene) derivatives in excellent yields. When treated with ethyl propiolate, methyl acrylate or acrylonitrile, spiro(imidazole-2,3'-pyrrole) derivatives were formed in good yields. Theoretical studies revealed an asynchronous concerted mechanism for both the C-C-S and C-C-N 1,3-dipolar cycloaddition reactions. The site selectivity in the [3+2] cycloaddition reaction of ambident 1,3-dipoles was predictably regulated by both the electronic and steric effects of dipolarophiles.

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