The role of brain-derived neurotrophic factor genotype, parental depression, and relationship discord in predicting early-emerging negative emotionality

The brain-derived neurotrophic factor (BDNF) gene is a plausible candidate for early-emerging negative emotionality (NE), and evidence suggests that the effects of this gene may be especially salient in the context of familial risk for child maladjustment. We therefore examined whether the single-nucleotide polymorphism producing a valine-to-methionine substitution at codon 66 (val66met) of the BDNF gene was associated with childhood NE, in the context of parental depression and relationship discord. A sample of 413 three-year-old children was assessed for NE using standardized laboratory measures. The children's parents completed clinical interviews as well as a measure of marital satisfaction. Children with at least one BDNF methionine (met) allele exhibited elevated NE when a parent had a history of depressive disorder or when relationship discord was reported by a parent. In contrast, this allele was associated with especially low NE when parental depression was absent and when the parental relationship was not discordant. Our findings suggest that the BDNF met allele confers increased child sensitivity to both positive and negative familial influences.     

Influence of maternal depression on children's brooding rumination: Moderation by CRHR1 TAT haplotype

There is growing evidence that brooding rumination plays a key role in the intergenerational transmission of major depressive disorder (MDD) and may be an endophenotype for depression risk. However, less is known about the mechanisms underlying this role. Therefore, the goal of the current study was to examine levels of brooding in children of mothers with a history of MDD (n = 129) compared to children of never depressed mothers (n = 126) and to determine whether the variation in a gene known to influence hypothalamic-pituitary-adrenal axis functioning—corticotropin-releasing hormone receptor 1 (CRHR1) —would moderate the link between maternal MDD and children's levels of brooding. We predicted children of mothers with a history of MDD would exhibit higher levels of brooding than children of mothers with no lifetime depression history but that this link would be stronger among children carrying no copies of the protective CRHR1 TAT haplotype. Our results supported these hypotheses and suggest that the development of brooding among children of depressed mothers, particularly children without the protective CRHR1 haplotype, may serve as an important mechanism of risk for the intergenerational transmission of depression.     

Serum levels of brain-derived neurotrophic factor (BDNF), BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine in Japanese patients with major depressive disorder (MDD)

Object We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapine's effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients. METHODS: Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively. RESULTS: Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG). Discussion The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels. Conclusion Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.     

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。     

Brooding Rumination and Risk for Depressive Disorders in Children of Depressed Mothers

The goal of the current study was to examine the role of brooding rumination in children at risk for depression. We found that children of mothers with a history of major depression exhibited higher levels of brooding rumination than did children of mothers with no depression history. Examining potential mechanisms of this risk, we found no evidence for shared genetic influences (BDNF or 5-HTTLPR) or modeling of mothers’ rumination. However, we did find that children with a history of prior depressive disorders exhibited higher current levels of brooding rumination than children with no depression history. Importantly, children’s brooding predicted prospective onsets of new depressive episodes over a 20-month follow-up even when we statistically controlled for depressive symptom levels at the initial assessment, suggesting that the predictive effect of brooding rumination in children was not due simply to co-occurring depressive symptoms.     

Increased parasympathetic activity and ability to generate positive emotion: The influence of the BDNF Val66Met polymorphism on emotion flexibility

Cross-species behavioral research suggests that a single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene (rs6265, Val66Met), influences behavioral inflexibility. This SNP has not yet been linked to variability in emotion-related behaviors, despite broader evidence suggesting an association may be present. This investigation explored the role of the BDNF Val66Met polymorphism in emotion response behaviors measured during a lab-based emotional provocation. Specifically, the influence of BDNF Val66Met in emotion flexibility was explored in a sample of healthy adults (N?=?120), emotion responses were recorded during the emotional provocation on multiple dimensions, in response to emotionally-evocative videos of negative then positive valence. These results suggest that Met carriers exhibit decreased parasympathetic responding, and reduced ability to generate positive emotion, relative to Val homozygotes. These findings are the first to suggest an association between the Met allele and a pattern of responding indicative of emotion inflexibility that might afford greater risk for psychopathology.     

Association of polymorphisms in BDNF, MTHFR, and genes involved in the dopaminergic pathway with memory in a healthy Chinese population

The contribution of genetic factors to the memory is widely acknowledged. Research suggests that these factors include genes involved in the dopaminergic pathway, as well as the genes for brain-derived neurotrophic factor (BDNF) and methylenetetrahydrofolate reductase (MTHFR). The activity of the products of these genes is affected by single nucleotide polymorphisms (SNPs) within the genes. This study investigates the association between memory and SNPs in genes involved in the dopaminergic pathway, as well as in the BDNF and MTHFR genes, in a sample of healthy individuals. The sample includes 134 Taiwanese undergraduate volunteers of similar cognitive ability. The Chinese versions of the Wechsler Memory Scale (WMS-III) and Wechsler Adult Intelligence Scale (WAIS-III) were employed. Our findings indicate that the BDNF Met66Val polymorphism and dopamine receptor D3 (DRD3) Ser9Gly polymorphism are associated significantly with long-term auditory memory. Further analysis detects no significant associations in the other polymorphisms and indices. Future replicated studies with larger sample sizes, and studies that consider different ethnic groups, are encouraged.     

The BDNFval66met polymorphism and individual differences in temperament in 4-month-old infants: A pilot study

Individual differences in infants’ temperament are under genetic control. We investigated the association between brain-derived-neurotrophic-factor (BDNF_val66met) polymorphism and temperament in 63 full-term infants. Met-carriers (N = 25) had lower Regulatory capacities compared to val-homozygotes (N = 38). These findings suggest that the BDNF polymorphism affects early temperament individual differences.     

COMT基因rs6267多态性与母亲教养行为对青少年身体攻击和关系攻击的交互作用

遗传与环境如何交互作用影响儿童青少年的攻击行为是当前攻击研究中的重要前沿课题之一。近年来, 分子遗传学关于人类攻击的研究已拓展到对不同攻击亚类(身体攻击和关系攻击)的遗传基础的探讨。本研究运用问卷法与DNA分型技术, 对1258名儿童进行为时4年(四年级—七年级)的追踪调查, 考察COMT基因rs6267多态性与母亲教养行为对青少年身体攻击和关系攻击的交互作用以及性别在其中的调节作用。结果发现, COMT基因rs6267多态性与母亲教养行为仅交互作用于男青少年的身体攻击, 母亲教养行为显著预测GG 基因型男青少年的身体攻击, 但对T等位基因男青少年身体攻击的预测作用并不显著。COMT基因rs6267多态性与母亲教养行为对青少年关系攻击的交互作用不显著。本研究结果表明, 身体攻击和关系攻击具有不同遗传基础和发生机制。     

MAOA基因rs6323多态性与母亲支持性教养对青少年抑郁的交互作用：素质-压力假说与不同易感性假说的检验

抑郁的遗传与环境交互作用(G×E)机制已成为富有挑战性的前沿课题之一。然而,既有G×E研究大多关注遗传基因与不利环境的交互作用,相对忽视了积极环境的影响。本研究以1025名青少年为被试,运用问卷法与 DNA分型技术,采用间隔3年的追踪设计(T1小学六年级—T2初中三年级),考察 MAOA基因rs6323多态性与母亲支持性教养对青少年抑郁的交互作用以及性别在其中的调节作用,并同时采用新兴的探索性与验证性方法检验G×E交互作用的素质–压力假说与不同易感性假说。结果显示, MAOA基因rs6323多态性与母亲支持性教养行为交互作用于女青少年的抑郁,母亲支持性教养显著负向预测 GG 基因型女青少年的抑郁,但对 TT基因型女青少年抑郁的预测作用并不显著,该交互作用符合不同易感性假说。MAOA基因 rs6323多态性与母亲支持性教养对男青少年的抑郁无显著交互作用。本研究发现推进了抑郁遗传机制的研究,并为不同易感性假说提供新的研究证据。     

Specificity of parental bonding and rumination in depressive and anxious emotional distress

We examined how different dimensions of rumination may mediate the impact of parental bonding (lack of care and overprotectiveness) on negative emotional symptomatology (anxiety and depression). Survey data from participants were analyzed using structural equation modeling. Results indicated that brooding rumination fully mediated the relationship between maternal care and depressive and anxious symptomatology. These findings suggest that to the extent that maternal caregivers are low in warmth and support, offspring are more likely to develop a brooding style of ruminative thinking associated with heightened emotional distress. This research supports the growing body of evidence suggesting that cognitive variables form a pathway between troublesome parent/child interactions and psychopathology.     

CHRM2基因rs1824024多态性与青少年早期抑郁的关系

运用问卷法与DNA分型技术,以127名高和低抑郁组初中生为被试,考察CHRM2基因rs1824024多态性与青少年早期抑郁的关系,重点探讨负性生活事件、青少年性别与年级的调节作用。结果发现,CHRM2基因rs1824024多态性与女青少年的抑郁边缘显著关联,T等位基因携带者患高抑郁的风险较低,但该位点与男青少年的抑郁无关;在那些经历低水平负性生活事件的青少年中,T等位基因携带者患高抑郁的可能性边缘显著低于GG型基因携带者;rs1824024多态性与年级对青少年早期抑郁无显著交互作用。     

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.     

Ukrainian Application of the Children's Somatization Inventory: Psychometric Properties and Associations With Internalizing Symptoms

This paper examines the psychometric properties of the Children's Somatization Inventory (CSI) in 600 10–12-year old children in Kyiv, Ukraine, replicating and extending the original findings from a sample in Nashville, Tennessee (J. Garber et al. 1991). The Kyiv children had significantly lower CSI total scores and reported significantly fewer symptoms than the American children. The Kyiv mothers, however, reported significantly more somatization symptoms in their children than did the American mothers. A factor analysis of the children's data yielded four similar factors encompassing pseudoneurologic, cardiovascular, gastrointestinal, and pain/weakness symptoms. Consistent with the findings from the Nashville study, the CSI was significantly related to the children's self-reports of health and depressive and anxiety symptoms and to maternal reports of child depression and anxiety symptoms. In addition, although more children with the highest CSI scores (25+) reported various illness experiences than those with 0–1 symptoms, no differences were found in the school absentee records. Thus, the results were congruent with the findings of the Nashville study, indicating that the CSI reliably measured somatization in this Ukrainian sample.     

The Influence of the BDNF Val66Met Polymorphism on Mechanisms of Semantic Priming: Analyses with Drift-Diffusion Models of Masked and Unmasked Priming

Automatic and strategic processes in semantic priming can be investigated with masked and unmasked priming tasks. Unmasked priming is thought to enable strategic processes due to the conscious processing of primes, while masked priming exclusively depends on automatic processes due to the invisibility of the prime. Besides task properties, interindividual differences may alter priming effects. In a recent study, masked and unmasked priming based on mean response time (RT) and error rate (ER) differed as a function of the BDNF Val66Met polymorphism (Sanwald et al., 2020). The BDNF Val66Met polymorphism is related to the integrity of several cognitive executive functions and might thus influence the magnitude of priming. In the present study, we reanalyzed this data with drift-diffusion models. Drift-diffusion models conjointly analyze single trial RT and ER data and serve as a framework to elucidate cognitive processes underlying priming. Masked and unmasked priming effects were observed for the drift rates ν, presumably reflecting semantic preactivation. Priming effects on nondecision time t0 were especially pronounced in unmasked priming, suggesting additional conscious processes to be involved in the t0 modulation. Priming effects on the decision thresholds a may reflect a speed-accuracy tradeoff. Considering the BDNF Val66Met polymorphism, we found lowered drift rates and decision thresholds for Met allele carriers, possibly reflecting a superficial processing style in Met allele carriers. The present study shows that differences in cognitive tasks between genetic groups can be elucidated using drift-diffusion modeling.     

TPH2基因rs4570625多态性和母亲权威教养对创造力的交互作用

采用基因分型技术、自我报告及表现性评价对409名健康的中国汉族大学生的基因型、母亲教养方式、一般智力和创造力进行测量,综合运用分层回归分析和显著性区域分析（regions of significance, RoS）方法探讨了TPH2基因rs4570625多态性与母亲权威教养对创造力的交互作用及其交互作用模式。结果发现：（1）在创造力的流畅性和独创性维度上,rs4570625多态性和母亲权威存在显著的交互作用。（2）RoS分析结果均支持差别易感模型,T等位基因是母亲权威的“可塑性”基因。这些发现将有助于从遗传和环境相互作用的角度解释个体创造力差异的起源。     

Examining the Link Between Infant Attachment and Child Conduct Problems in Grade 1

Abtract  We examined the extent to which infant attachment status is directly related to child conduct problems 6 years later, and assessed the potential mediating roles of hostile parenting and maternal depression. The sample included 84 adolescent mothers and their children (45 girls, 39 boys). Infant attachment status was assessed using the Strange Situation when the study children were 1-year-old. Hostile parenting was coded during a parent–child interaction task when the study children were 4.5-years-old. Maternal depression was self-rated, also when the study children were 4.5-years-old, using the Beck Depression Inventory. Mothers reported child conduct problems at Grade 1 on the Child Behavior Checklist. Infant attachment status at 1 year of age was directly related to child conduct problems but not to hostile parenting or maternal depression. Neither hostile parenting nor maternal depression mediated the relationship between infant attachment status and child conduct problems. However, the pattern of relations differed by attachment security. For securely attached children, maternal depression, but not hostile parenting, was directly related to conduct problems. For insecurely attached children, hostile parenting, but not maternal depression, was directly related to child conduct problems. Implications for intervention and future research are discussed.     

Attention biases and habituation of attention biases are associated with 5-HTTLPR and COMTval158met

Fundamental biases in affective information processing are modulated by individual differences in the emotional response to environmental stimuli that may be partly based on the individual’s genetic make-up. To extend prior dot probe studies on attention genetics, we used a visual-search paradigm (VSP) with pictures of angry and happy faces of both sexes as targets, neutral faces as distractors, and a varying set size. Participants were selected a priori depending on their 5-HTTLPR (s/s, s/l, l/l; on a constant rs25531 A-allele background) and COMTval158met (val/val, valmet, met/met) genotypes and were matched for sex and age. We demonstrate a bias towards angry male faces (as opposed to happy male faces) irrespective of 5-HTTLPR genotype in the first experimental block that was maintained during the second experimental block only in carriers of the s-allele, which implies differential habituation processes. While a bias towards angry male faces was observed irrespective of COMTval158met genotype, only individuals with the val/val genotype exhibited a bias towards a happy female face (as opposed to an angry female face). In sum, our results both replicate and extend prior findings in the field of attention genetics and add important pieces of information to the research on attentional biases in emotion processing.     

父母教养行为与青少年早期抑郁的关系：多基因与负性生活事件的调节作用

以745名青少年为被试,采用多基因×多环境设计,考察COMT Val158Met、5-HTR1A C-1019G和BDNF Val66Met基因多态性的多基因累加得分与负性生活事件在父母教养行为与青少年早期抑郁之间的调节作用及其性别差异。结果发现,多基因累加得分与负性生活事件仅能显著调节父亲积极教养行为对青少年抑郁的预测作用,且该调节作用只存在于男青少年群体中。研究结果丰富了抑郁的多基因遗传机制研究,为制定青少年早期抑郁的干预措施提供了理论依据。