Bi Zhu

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 Ravens 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.

Sex Modulates the Associations Between the COMT Gene and Personality Traits

Previous research has shown inconsistent findings regarding the relations between the functional Val158Met polymorphisms of the catechol-O-methyltransferase (COMT) gene and individual differences in personality traits. This study attempts to overcome some of the weaknesses of previous research, namely, small sample sizes, clinical samples, ethnic stratification, wide age ranges, neglecting sex differences, and single measures of personality traits. A large sample (n=556, 250 male, 306 female) of healthy Chinese college students (mean age=20.5±1 years) was given a battery of personality scales, including the temperament and character inventory-revised, the behavioral inhibition system and behavioral approach system scale, the Beck depression inventory, and the Beck anxiety inventory. Factor analysis of the affect-related personality traits revealed two factors that corresponded to positive (PEM) and negative emotionality (NEM). We found a consistent COMT-by-sex interaction effect on affect-related personality traits. Compared with males with Met/Met alleles, males with Val/Val alleles showed significantly higher scores on NEM, but lower scores on PEM. Females, however, showed an opposite but nonsignificant pattern. Our results supported the role of the COMT gene in personality traits for males and contributed to the growing literature on sex differences in gene–behavior connections.

COMT rs4680 Met is not always the 'smart allele': Val allele is associated with better working memory and larger hippocampal volume in healthy Chinese.

Catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism plays a crucial role in regulating brain dopamine level. Converging evidence from Caucasian samples showed that, compared with rs4680 Val allele, the Met allele was linked to lower COMT activity, which in turn was linked to better cognitive performance such as working memory (WM) and to a larger hippocampus (a brain region important for WM). However, some behavioral studies have shown that the function of rs4680 appears to vary across different ethnic groups, with Chinese subjects showing an opposite pattern as that for Caucasians (i.e. the Val allele is linked to better cognitive functions related to WM in Chinese). Using a sample of healthy Han Chinese college students (ages from 19 to 21 years), this study investigated the association of COMT Val158Met genotype with behavioral data on a two-back WM task (n = 443, 189M/254F) and T1 MRI data (n = 320, 134M/186F). Results showed that, compared to the Met allele, the Val allele was associated with larger hippocampal volume (the right hippocampus: β = -0.118, t = -2.367, P = 0.019, and the left hippocampus: β = -0.099, t = -1.949, P = 0.052) and better WM performance (β = -0.110, t = -2.315, P = 0.021). These results add to the growing literature on differentiated effects of COMT rs4680 polymorphism on WM across populations and offer a brain structural mechanism for such population-specific genetic effects.

Contributions of Dopamine-Related Genes and Environmental Factors to Highly Sensitive Personality: A Multi-Step Neuronal System-Level Approach

Traditional behavioral genetic studies (e.g., twin, adoption studies) have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL) with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation) to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system) genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP). 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth) that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphisms main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001). Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional behavioral genetics and the lack of reproducible genetic effects observed currently from molecular genetic studies.

COMT Val158Met polymorphism interacts with stressful life events and parental warmth to influence decision making.

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 Val158Met 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.

The relationship between DRM and misinformation false memories.

This research investigated the relationship between false memories induced by two different paradigms (misinformation and Deese–Roediger–McDermott [DRM]). The misinformation effect refers to the phenomenon that a person’s recollection of a witnessed event can be altered after exposure to misleading information about the event. DRM false memory represents the intrusion of words that are semantically related but not actually presented in the study session. Subjects (N = 432) completed both misinformation and DRM false memory tests. Results showed a small but significant correlation (r = .12, p = .02) between the misinformation and DRM false memories. Furthermore, using signal detection theory, we found that the discrimination ability index (d′) was related to both the misinformation and DRM false memories (r = −.12 and −.13, p = .01), while the response bias was related only to DRM false memory (r = −.46, p < .001). These results suggest that misinformation and DRM false memories generally involve different mechanisms and that their shared mechanism may involve the global discrimination ability.

Fiber connectivity between the striatum and cortical and subcortical regions is associated with temperaments in Chinese males

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.

The NTSR1 gene modulates the association between hippocampal structure and working memory performance.

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.

Genetic variations in the dopaminergic system and alcohol use: a system‐level analysis

Alcohol use is highly heritable and has been associated with many gene variants, including those related to dopamine (DA). However, single gene association studies have shown inconsistent and small effects. Using a system‐level approach, the current study aimed to estimate the overall effect of genetic variations in the DA system on alcohol use among male drinkers. One hundred seventy‐six male college students who reported to have ever drunk alcohol were enrolled. Alcohol use was measured using the Alcohol Use Disorders Identification Test. Ninety‐eight representative polymorphisms in all major DA neurotransmitter genes were genotyped. Using analysis of variance, we identified six single‐nucleotide polymorphisms (SNP)s that made statistically significant contributions to alcohol use. Next, main effects and interactions of these SNPs were assessed using multiple regression. The final model accounted for approximately 20% of the variance for alcohol use. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be low, p ranging from 0.024 to 0.048. These results confirmed that DA‐related gene variants made strong contributions to reported alcohol use and suggest that multiple regression can be a promising way to explore the genetic basis for multi‐gene‐determined human behaviors.

Haplotype polymorphism in the alpha-2B-adrenergic receptor gene influences response inhibition in a large Chinese sample.

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, Cohens 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.