Partial replication of two rumination-related candidate gene studies

Two recent papers associated candidate genes with brooding rumination, a possible cognitive endophenotype for depression, in children ages 8–14 years. Stone et al. reported that BDNF val66met polymorphism predicted brooding in adolescence. Woody et al. reported that children carrying at least one copy of a CRHR1 TAT haplotype reported less brooding than their peers in the presence of maternal depression. We attempted to replicate and extend these findings in a sample of twins aged 12–16 years. We analyzed the BDNF val66met (rs6265) polymorphism and two (rs242924 and rs7209436) out of three single nucleotide polymorphisms (SNPs) that Woody et al. used to create a CRHR1 haplotype. We controlled for maternal history of depression and clustering within families. Unlike Stone et al., we found higher brooding among BDNF Met carriers. This main effect was qualified by an interaction with pubertal status, with the effect driven by more physically mature participants. Similar to Woody et al., we found an interaction between CRHR1 SNPs and maternal depression, with the homozygous minor genotype acting as a protective factor against brooding in the presence of maternal depression. Findings provide partial support for the influence of candidate genes in two environmentally sensitive systems on brooding.     

MTHFR and ACE gene polymorphisms and risk of vascular and degenerative dementias in the elderly

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as degenerative dementia. Among genetic factors, role of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes as putative risk factors has been examined but the outcome of these studies remain inconclusive. Present study attempted to see the importance of ACE alu insertion/deletion and MTHFR C677T polymorphisms as genetic predisposers to dementia. The study comprised of 80 vascular dementia patients, 90 degenerative dementia patients and 170 age matched controls. All were genotyped for ACE, MTHFR and APOE polymorphisms using PCR-RFLP method. Frequency of ACE D allele was seemingly high in dementia cases (26.7%) when compared to controls (11.2%). However, after adjusting for age and APOE E4^*, none of the ACE alleles showed good correlation. MTHFR genotypes or alleles also did not show any correlation. Our study suggests no true correlation of ACE or MTHR genes with dementia in elderly.     

MTHFR and ACE gene polymorphisms and risk of vascular and degenerative dementias in the elderly

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as degenerative dementia. Among genetic factors, role of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes as putative risk factors has been examined but the outcome of these studies remain inconclusive. Present study attempted to see the importance of ACE alu insertion/deletion and MTHFR C677T polymorphisms as genetic predisposers to dementia. The study comprised of 80 vascular dementia patients, 90 degenerative dementia patients and 170 age matched controls. All were genotyped for ACE, MTHFR and APOE polymorphisms using PCR-RFLP method. Frequency of ACE D allele was seemingly high in dementia cases (26.7%) when compared to controls (11.2%). However, after adjusting for age and APOE E4^*, none of the ACE alleles showed good correlation. MTHFR genotypes or alleles also did not show any correlation. Our study suggests no true correlation of ACE or MTHR genes with dementia in elderly.     

Factor structure of the Wechsler Adult Intelligence Scale-III in schizophrenia

This report examines and compares the factor structure of the new edition of the Wechsler Adult Intelligence Scale (WAIS-III) in a sample of chronic schizophrenia and schizoaffective disorder outpatients (n = 120) and an age-matched sample of individuals drawn from the WAIS-III standardization sample (n = 200). Exploratory and confirmatory factor analyses similar to those reported by the developers of the scale suggested that a model of WAIS-III performance with correlated factors for verbal comprehension, perceptual organization, working memory, and processing speed fit the data from the schizophrenia sample as well as it fit the nonclinical comparison sample and fit the data from both samples better than alternative models.     

Sex differences in spatial ability reflected in performance on IQ subtests by black or white examinees

Sex differences in spatial ability were investigated using scores on the performance subtests of the Wechsler Intelligence Scale for Children. The sample consisted of 832 adolescents, evenly divided by race (black or white) and sex. Within both racial groups, males outscored females on all of the spatially-oriented subtests, but females outscored males on a subtest emphasizing rote memory. The similarity of patterning of sex differences within each racial group might be interpreted as indicating that something more than social experience alone is involved in this phenomenon.     

The joint WAIS-III and WMS-III factor structure: development and cross-validation of a six-factor model of cognitive functioning

During the standardization of the Wechsler Adult Intelligence Scale (3rd ed.; WAIS-III) and the Wechsler Memory Scale (3rd ed.; WMS-III) the participants in the normative study completed both scales. This "co-norming" methodology set the stage for full integration of the 2 tests and the development of an expanded structure of cognitive functioning. Until now, however, the WAIS-III and WMS-III had not been examined together in a factor analytic study. This article presents a series of confirmatory factor analyses to determine the joint WAIS-III and WMS-III factor structure. Using a structural equation modeling approach, a 6-factor model that included verbal, perceptual, processing speed, working memory, auditory memory, and visual memory constructs provided the best model fit to the data. Allowing select subtests to load simultaneously on 2 factors improved model fit and indicated that some subtests are multifaceted. The results were then replicated in a large cross-validation sample (N = 858).     

Two- and three-factor solutions of the WAIS-III

The third edition of the Wechsler Adult Intelligence Scale manual reports four-factor solutions for the WAIS-III, and subsequent research has validated four-factor solutions for a variety of samples. These four factors consistently correspond to the four Factor Indexes that are yielded by the WAIS-III. However, the WAIS-III still provides Verbal and Performance IQs, in addition to the Indexes, making it desirable to examine two-factor solutions as well. In addition, because the Wechsler literature includes much interpretation of three-factor solutions, these solutions were likewise examined. Principal factor analysis followed by Varimax and Oblimin rotations of two and three factors were performed on data for the total WAIS-III sample ages 16 to 89 years (N=2,450). The two-factor solutions were viewed as a construct validation of Wechsler's two separate IQs, although the Working Memory subtests tended to load higher on the Performance scale than on their intended scale (Verbal); three-factor solutions were interpreted within the context of Horn's expanded fluid-crystallized theory and research on working memory. Both the two- and three-factor Varimax-rotated solutions were related to similar factor analyses conducted previously for the Wechsler Adult Intelligence Scale-Revised and the Wechsler Intelligence Scale for Children-III. Coefficients of congruence between like-named factors consistently exceeded .90, and usually .98, across different Wechsler batteries.     

Variant BDNF (Val66Met) impact on brain structure and function

Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are a unique family of polypeptide growth factors that influence differentiation and survival of neurons in the developing nervous system. In adults, BDNF is important in regulating synaptic plasticity and connectivity in the brain. Recently, a common single-nucleotide polymorphism in the human BDNF gene, resulting in a valine to methionine substitution in the prodomain (Val66Met), has been shown to lead to memory impairment and susceptibility to neuropsychiatric disorders. An understanding of how this naturally occurring polymorphism affects behavior, anatomy, and cognition in adults is an important first step in linking genetic alterations in the neurotrophin system to definable biological outcomes in humans. We review the recent literature linking this BDNF polymorphism to cognitive impairment in the context of in vitro and transgenic animal studies that have established BDNF’s central role in neuronal functioning in the adult brain.     

A confirmatory factor analysis of the WISC-III in a clinical sample with cross-validation in the standardization sample.

Maximum likelihood confirmatory factor analysis was applied to the Wechsler Intelligence Scale for Children-Third Edition (WISC-III; Wechsler, 1991) data of a mixed clinical sample of 318 children. Analyses were designed to determine which of nine hypothesized oblique factor solutions could best explain intelligence as measured by the WISC-III in the clinical sample. Competing latent variable models were identified in previous studies, and results in the clinical sample were cross-validated by testing all models in the WISC-III standardization sample (n = 2200). Findings in both the clinical and standardization samples supported a five-factor model including Verbal Comprehension, Constructional Praxis, Visual Reasoning, Freedom from Distractibility, and Processing Speed factors. The Visual Reasoning factor was defined primarily by Picture Arrangement, whereas Mazes did not appear to improve model fit. Potential opportunities and pitfalls with regard to the interpretation of the proposed Visual Reasoning factor are discussed.     

Effects of Age,Domain, and Processing Demands on Memory Span: Evidence for Differential Decline

Analysis of cross-sectional data from the normative sample of the Wechsler Memory Scale - Third Edition (WMS-III) revealed different patterns of age-related differences in memory span measures depending on the type of memory item, processing demands, and the age of the older adult group. Regression of memory span on age revealed that the slope for Spatial Span raw scores was significantly more negative than the slope for Digit Span raw scores. There was no significant difference, however, either between the slopes for forward and backward Digit Span or between the slopes for forward and backward Spatial Span. Regression of Letter-Number Sequencing raw scores on age showed a distinctive, curvilinear pattern. Taken together, the present findings suggest that at least two mechanisms are involved in age-related differences in memory span. One mechanism, associated with a relatively linear decrease in memory span as a function of age, may differentially affect the storage of different types of information (e.g., sequences of digits vs. spatial locations). The other mechanism, evidenced by the curvilinear trend in Letter-Number Sequencing scores, may be tentatively attributed to a decline in executive aspects of working memory that becomes increasingly pronounced with age.     

Further analyses of the effects of practice,dropout, sex,socio-economic advantage,and recruitment cohort differences during the University of Manchester longitudinal study of cognitive change in old age

A sample of 4,314 volunteers who, when first recruited, were aged from 41 to 93 years were quadrennially tested from 2 to 4 occasions during the next 4 to 20 years on the Cattell Culture Fair intelligence test, 2 tests of information-processing speed, the Wechsler Adult Intelligence Scale (WAIS) vocabulary test, and 3 memory tests. After significant effects of practice, sex, demographics, socio-economic advantage, and recruitment cohort had been identified and considered, performance on all tests declined with age. These age-related declines accelerated for the Cattell and WAIS, 2 tests of information speed, and 2 of the memory tests. For all tests individuals' trajectories of age-related change diverged with increasing age but, unexpectedly, were not affected by demographic factors. Practice gains from an initial experience of the cognitive tests remained undiminished as the interval before the second experience increased from 4 to 8 + years.     

人类情绪记忆的行为遗传学与神经遗传学研究进展述评

情绪记忆及其增强效应存在广泛的个体差异,这种个体差异可能有其神经与遗传基础。近来的行为遗传学与神经遗传学证实人类ADRA2B基因缺失突变以及BDNF Val66Met基因的多态性与情绪记忆增强及其神经机制的个体差异相联系。本文重点介绍与人类情绪记忆相关的这两种基因,梳理了行为与神经遗传学研究的最新进展,指出未来应关注更多候选基因,并重视多个脑区之间的交互作用;还应使用情绪面孔刺激探索BDNF Val66Met基因多态性对情绪记忆编码和提取的影响等。     

COMT genotype influences prefrontal response to emotional distraction

Early studies of genetic effects on brain activity have been conducted to investigate primarily either the influence of polymorphisms in dopaminergic genes, especially the catechol-O-methyltransferase (COMT) gene, on prefrontal cognitive processes such as working memory, or that of polymorphisms in the serotonin transporter gene on the amygdala response to threatening stimuli. Here, we address genetic influences on the neural systems underlying cognitive-affective interactions. Specifically, we assess the effect of the COMT val¹⁵⁸met polymorphism on frontal regulation of attention under emotional distraction. Healthy volunteers were scanned while performing a house-matching task with affectively negative versus neutral distractors. Effects of val allele load were examined on frontal regions associated with attentional control and emotion regulation, and on parahippocampal regions associated with perception of houses. As we predicted, val load correlated positively with activity in control- and task-related regions during performance under emotional distraction. These findings provide an initial step toward identifying genetic contributions to interindividual variability in recruitment of mechanisms that regulate affective processing.     

An alternative to the search for single polymorphisms: toward molecular personality scales for the five-factor model

There is growing evidence that personality traits are affected by many genes, all of which have very small effects. As an alternative to the largely unsuccessful search for individual polymorphisms associated with personality traits, the authors identified large sets of potentially related single nucleotide polymorphisms (SNPs) and summed them to form molecular personality scales (MPSs) with from 4 to 2,497 SNPs. Scales were derived from two thirds of a large (N = 3,972) sample of individuals from Sardinia who completed the Revised NEO Personality Inventory (P. T. Costa, Jr., & R. R. McCrae, 1992) and were assessed in a genomewide association scan. When MPSs were correlated with the phenotype in the remaining one third of the sample, very small but significant associations were found for 4 of the 5e personality factors when the longest scales were examined. These data suggest that MPSs for Neuroticism, Openness to Experience, Agreeableness, and Conscientiousness (but not Extraversion) contain genetic information that can be refined in future studies, and the procedures described here should be applicable to other quantitative traits.     

Influence of brain-derived neurotrophic factor and catechol O-methyl transferase polymorphisms on effects of meditation on plasma catecholamines and stress

Meditation may show differential effects on stress and plasma catecholamines based on genetic polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol O-methyl transferase (COMT). Eighty adults (40 men, 40 women; mean age 26 years) who practiced meditation regularly and 57 healthy control adults (35 men, 22 women; mean age 26 years) participated. Plasma catecholamines (norepinephrine (NE), epinephrine (E), and dopamine (DA)) concentrations were measured, and a modified form of the Stress Response Inventory was administered. The results were analyzed using two-way analysis of covariance (ANCOVA) with control and meditation subjects, gene polymorphism as factors, and meditation duration as the covariate. Two-way ANCOVA showed a significant interaction between control and meditation subjects, and BDNF Val66Met polymorphism on DA/NE+DA/E (p = 0.042) and NE/E+NE/DA (p = 0.046) ratios. A significant interaction was found for control and meditation subjects with COMT Val158Met polymorphism and plasma NE concentrations (p = 0.009). Post hoc ANCOVA in the meditation group, adjusted for meditation duration, showed significantly higher plasma NE concentrations for COMT Met carriers than COMT Val/Val subjects (p = 0.025). Significant differences of stress levels were found between the control and meditation subjects in BDNF Val/Met (p < 0.001) and BDNF Met/Met (p = 0.003), whereas stress levels in the BDNF Val/Val genotype did not differ between the control and meditation groups. This is the first evidence that meditation produces different effects on plasma catecholamines according to BDNF or COMT polymorphisms.     

The effects of Wechsler Intelligence Scale for Children-Fourth Edition cognitive abilities on math achievement

This study used structural equation modeling to examine the effect of Stratum III (i.e., general intelligence) and Stratum II (i.e., Comprehension-Knowledge, Fluid Reasoning, Short-Term Memory, Processing Speed, and Visual Processing) factors of the Cattell-Horn-Carroll (CHC) cognitive abilities, as operationalized by the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV; Wechsler, 2003a) subtests, on Quantitative Knowledge, as operationalized by the Wechsler Individual Achievement Test, Second Edition (WIAT-II; Wechsler, 2002) subtests. Participants came from the WISC-IV/WIAT-II linking sample (n=550). We compared models that predicted Quantitative Knowledge using only Stratum III factors, only Stratum II factors, and both Stratum III and Stratum II factors. Results indicated that the model with only the Stratum III factor predicting Quantitative Knowledge best fit the data.     

Three factors of the comprehensive system for the Rorschach and their relationship to Wechsler IQ scores in an adolescent sample

Principal axis factor analyses of the Rorschach Comprehensive System (CS) in a clinical sample of 152 adolescents yielded three clearly defined factors: Synthesized Complexity (defined by Zf, DQ+, and F%), Productivity (defined by R, D, and Dd), and Form Quality (defined by X+%, F+%, and X-%). Variables on the Synthesized Complexity and Form Quality factors were generally correlated with Wechsler Full Scale IQ, Verbal IQ, and Performance IQ scores. Overall, the factors in this adolescent sample replicated factors identified in earlier studies with adults. Implications for clinical practice are discussed.     

Individual differences in false memory from misinformation: Cognitive factors

This research investigated the cognitive correlates of false memories that are induced by the misinformation paradigm. A large sample of Chinese college students (N=436) participated in a misinformation procedure and also took a battery of cognitive tests. Results revealed sizable and systematic individual differences in false memory arising from exposure to misinformation. False memories were significantly and negatively correlated with measures of intelligence (measured with Raven's Advanced Progressive Matrices and Wechsler Adult Intelligence Scale), perception (Motor-Free Visual Perception Test, Change Blindness, and Tone Discrimination), memory (Wechsler Memory Scales and 2-back Working Memory tasks), and face judgement (Face Recognition and Facial Expression Recognition). These findings suggest that people with relatively low intelligence and poor perceptual abilities might be more susceptible to the misinformation effect.     

联想学习与工作记忆在流体智力发展中的作用

以115名7、10、13岁儿童为研究对象,采用配对联想学习、倒序背数、字母-数字排序、图画概念和矩阵推理等测验,考察联想学习与工作记忆在流体智力发展中的作用。结果发现:联想学习与工作记忆在流体智力发展中均起着重要的作用,然而,在不同年龄上,两者对流体智力的作用并不相同。具体来说,在7岁时,联想学习对流体智力的作用显著,而工作记忆的作用不显著;到10岁和13岁时,工作记忆对流体智力的作用显著,而联想学习的作用不再显著。从效应量来看,随着年龄的增长,联想学习对流体智力的作用逐渐减小,而工作记忆的作用则逐渐增加。     

Factor analysis of Wechsler Adult Intelligence Scale-Revised in developmentally disabled persons

The results of previous studies on the factorial structure of Wechsler Intelligence Scales are somewhat inconsistent across normal and pathological samples. To study specific clinical groups, such as developmentally disabled persons, it is useful to examine the factor structure in appropriate samples. A factor analysis was carried out using the principal component method and the Varimax orthogonal rotation on the Wechsler Adult Intelligence Scale (WAIS-R) in a sample of 203 developmentally disabled persons, with a mean age of 25 years 4 months. Developmental disability ranged from mild to moderate. Partially contrasting with previous studies on normal samples, results found a two-factor solution. Wechsler's traditional Verbal and Performance scales seems to be more appropriate for this sample than the alternative three-factor solution.