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The U-Shaped Relationship between HPA Axis Genes and Aggression: A Psychobiological Perspective
Ding Xiaofan, Cao Yanmiao, Ji Linqin, Zhang Wenxin
Journal of Psychological Science ›› 2026, Vol. 49 ›› Issue (3) : 600-611.
PDF(1534 KB)
PDF(1534 KB)
The U-Shaped Relationship between HPA Axis Genes and Aggression: A Psychobiological Perspective
Aggression, which is a common and remarkably damaging problem, has its roots in stress-responsive systems. Although children display a wide range of individual differences in the hypothalamic-pituitary-adrenal (HPA) axis function, numerous initial conditions of stress reactivity may reach the same end state. In other words, both hyper- and hypo-responses to stress tend to induce heightened risks for aggressive behavior. Informed by the concept of equifinality in developmental psychopathology, this study, through its focus on hypothalamic-pituitary-adrenocortical (HPA) genetic susceptibility, examines the nonlinear (U-shaped) relationship between stress responsiveness and the severity of aggression. Additionally, since it remains unclear whether the equifinality phenomenon is evident in distal behavioral phenotypes or proximal endophenotypes, this study also evaluated, on the basis of “psychobiological model of antisocial behavior” framework, a mediated moderation model to examine the effects of the HPA axis genes on aggression, as moderated by the parent-child relationship and mediated by impulsivity.
A total of 530 participants (mean age 19.35 ± 1.59 years at Time 1, 53.4% females) completed two assessments at a one-year interval. Data on self-reported aggression, parent-child relationship, and impulsivity were collected, and DNA was extracted from saliva. All of the measures exhibited good reliability. The multilocus genetic profile score (MGPS) was calculated using four polymorphisms within HPA axis-related genes, namely NR3C2 gene rs2070951 polymorphism, CRHR1 gene rs110402 polymorphism, COMT gene rs4680 polymorphism, and BDNF gene rs6265 polymorphism. For each participant, genotyping of the four HPA axis genes was performed using improved multiplex ligation detection reaction. This was followed by a series of hierarchical regressions that were conducted to examine the U-shaped relationship between MGPS and aggression, and the moderating role of parent-child relationships and the mediating role of impulsivity was tested in a mediated moderation model. To test the robustness of the results, a series of sensitivity analysis were conducted. Specifically, the mediated moderation models of each polymorphism were examined to explain the power of MGPS approach. Besides, an internal replication and meta-analysis were conducted by randomly splitting the total sample into two subsamples.
The U-shaped relation between HPA MGPS and aggression was not observed. However, a quadratic, U-shaped relationship was observed between the additive genetic risk of HPA and aggression. Both low and high MPGS carriers exhibited high levels of aggression when exposed to higher levels of parent-child conflict. Nevertheless, parent-child cohesion did not exhibit such moderating effects. Furthermore, the moderating effect was mediated by impulsivity. Similarly, there was a significant quadratic relationship between MGPS and impulsivity when parent-child conflicts were at comparatively high levels, with results displaying a U-shaped relationship. However, an inverted U-shaped relationship between MGPS and impulsivity was observed when parent-child conflicts were relatively lower. Impulsivity was a significant risk factor for aggression, with high impulsivity predicting high levels of aggression. The sensitive analysis revealed that the additive genetic risk of HPA accounted for a more significant effect than any single gene. The mediated moderation model was replicated in both two subsamples.
These findings inform our understanding of how additive genetic variants in the HPA axis and its response to adversity are involved in the etiology of aggressive behavior. It is likely that, because of the U-shaped relationship, the association between HPA genetic function and aggression is more complex than what the general perspectives — “the more the genetic risk variants, the higher the likelihood of aggressive behavior.” Moreover, these findings provide support for the phenomenon of equifinality in developmental psychopathology. Domain-specific findings regarding the differences in parent-child conflicts and the cohesion model imply that the U-shaped function of HPA genes cannot be generalized to positive environmental influences.
aggression / HPA axis genes / parent-child relationship / impulsivity / U-shaped relationship
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童年期的不良经历似乎增加了个体对压力刺激的敏感性, 从而可能影响其终身的社会适应。许多研究表明, HPA轴系统基因可能在调节环境因素与社会适应之间发挥作用。然而, 过去单个基因与环境相互作用对社会适应的影响存在争议。本研究针对青少年样本(14.15 ± 0.63岁; N = 700), 采用多位点遗传谱评分(multilocus genetic profile scores, MGPS)计算HPA轴系统多基因得分, 利用纵向数据探究其与童年期创伤和亲子关系之间的相互作用, 并预测青少年的社会适应(包括抑郁症状、亲社会行为和自伤行为)。研究结果显示, 青少年的社会适应(包括抑郁症状和亲社会行为)是遗传(HPA轴系统MGPS)、远端环境(童年期创伤)和近端环境(亲子关系)三者相互作用的结果。随着遗传风险评分的增加, 童年期创伤和亲子关系之间的交互作用也增加, 这意味着遭受过童年期创伤的个体, 亲子关系对社会适应的影响会更加显著, 符合差别易感性模型。行为学实验进一步揭示了遗传和环境因素对青少年社会适应的潜在机制。
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Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear.Copyright © 2017 Elsevier Ltd. All rights reserved.
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Hypothalamic pituitary adrenal (HPA) axis activity may be a mechanism linking early adversity to child mental health difficulties. However, there is a dearth of longitudinal evidence for the association between HPA axis activity and mental health among children in low-resource contexts. The goal of this study is to examine linear and curvilinear associations between HPA axis activity during infancy and mental health difficulties in early childhood among children in rural Pakistan. Participants included 104 children (46% male) from the Bachpan study, a longitudinal cohort embedded within a maternal depression trial in Pakistan. We examined the associations between hair-derived cortisol and dehydroepiandosterone (DHEA) at 12 months old and mental health difficulties, measured with the Strengths and Difficulties Questionnaire (SDQ), at 36 months old. There was a significant quadratic association between hair cortisol and SDQ scores, with results showing a U-shaped relationship (i.e., having relatively high or low cortisol predicted increased mental health difficulties). DHEA showed a quadratic association with SDQ scores with an inverted U-shaped relationship (i.e., high and low DHEA was associated with decreased mental health difficulties). Results provide evidence of longitudinal and curvilinear effects of cortisol and DHEA during infancy on mental health difficulties in early childhood.
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The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to elicit fear (N = 33) or frustration (N = 32), or a validity check condition (N = 8). This was followed by a 60-min controlled regulation phase. A total of 17 saliva samples for cortisol analysis were collected including 12 post-stress samples at 5-min intervals. Reactive and proactive aggression levels were assessed via the teacher-completed Aggression Behavior Teacher Checklist (Dodge and Coie, J Pers Soc Psychol, 53(6), 1146-1158, 1987). Reactive aggression significantly predicted total and peak post-stress cortisol regardless of stress modality. Proactive aggression was not a predictor of any cortisol index. Examination of pure reactive, proactive, combined, or non-aggressive children indicated that reactive aggressive children had higher cortisol reactivity than proactive and non-aggressive children. Our data suggest that while an overactive HPA-axis response to stress is associated with reactive aggression, stress induced HPA-axis variability does not seem to be related to proactive aggression.
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Altered reactivity to stress, either in the direction of exaggerated reactivity or diminished reactivity, may signal a dysregulation of systems intended to maintain homeostasis and a state of good health. Evidence has accumulated that diminished reactivity to psychosocial stress may signal poor health outcomes. One source of diminished cortisol and autonomic reactivity is the experience of adverse rearing during childhood and adolescence. The Oklahoma Family Health Patterns Project has examined a cohort of 426 healthy young adults with and without a family history of alcoholism. Regardless of family history, persons who had experienced high degrees of adversity prior to age 16 had a constellation of changes including reduced cortisol and heart rate reactivity, diminished cognitive capacity, and unstable regulation of affect, leading to behavioral impulsivity and antisocial tendencies. We present a model whereby this constellation of physiological, cognitive, and affective tendencies is consistent with altered central dopaminergic activity leading to changes in brain function that may foster impulsive and risky behaviors. These in turn may promote greater use of alcohol other drugs along with adopting poor health behaviors. This model provides a pathway from early life adversity to low stress reactivity that forms a basis for risky behaviors and poor health outcomes. Published by Elsevier B.V.
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The effects of various doses (40 microg/kg/hr, 300 microg/kg/hr, 600 microg/kg/hr or placebo) of hydrocortisone on tasks assessing working and declarative memory function were measured in 4 groups of 10 young men. During the infusion, participants were given an item-recognition working memory task, a paired-associate declarative memory task, and a continuous performance task used to control possible concomitant effects of corticosteroids on vigilance. The results revealed significant acute effects of the highest dose of hydrocortisone on working memory function, without any significant effect on declarative memory function or arousal-vigilance performance. These results suggest that working memory is more sensitive than declarative memory to the acute elevations of corticosteroids, which could explain the detrimental effects of corticosteroids on acquisition and consolidation of information, as reported in the literature.
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Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.
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Genes are major contributors to many psychiatric diseases, but their mechanisms of action have long seemed elusive. The intermediate phenotype concept represents a strategy for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in psychiatric disease. Using imaging genetics as an example, we illustrate recent advances, challenges and implications of linking genes to structural and functional variation in brain systems related to cognition and emotion.
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| [46] |
Depression has been linked to increased cortisol reactivity and differences in limbic brain volumes, yet the mechanisms underlying these alterations are unclear. One main hypothesis is that stress causes these effects. This is supported by animal studies showing that chronic stress or glucocorticoid administration can lead to alterations in hippocampal and amygdala structures. Relatedly, life stress is cited as one of the major risk factors for depression and candidate gene studies have related variation in stress-system genes to increased prevalence and severity of depression. The present study tested the hypothesis that genetic profile scores combining variance across 10 single nucleotide polymorphisms from four stress-system genes (CRHR1, NR3C2, NR3C1, and FKBP5) and early life stress would predict increases in cortisol levels during laboratory stressors in 120 preschool-age children (3-5 years old), as well as hippocampal and amygdala volumes assessed with MRI in these same children at school age (7-12 years old). We found that stress-system genetic profile scores positively predicted cortisol levels while the number of stressful/traumatic life events experienced by 3-5 years old negatively predicted cortisol levels. The interaction of genetic profile scores and early life stress predicted left hippocampal and left amygdala volumes. Cortisol partially mediated the effects of genetic variation and life stress on limbic brain volumes, particularly on left amygdala volume. These results suggest that stress-related genetic and early environmental factors contribute to variation in stress cortisol reactivity and limbic brain volumes in children, phenotypes associated with depression in adulthood.
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| [47] |
Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology.(c) 2015 APA, all rights reserved).
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| [48] |
The purpose of the present study was to revise the Barratt Impulsiveness Scale Version 10 (BIS-10), identify the factor structure of the items among normals, and compare their scores on the revised form (BIS-11) with psychiatric inpatients and prison inmates. The scale was administered to 412 college undergraduates, 248 psychiatric inpatients, and 73 male prison inmates. Exploratory principal components analysis of the items identified six primary factors and three second-order factors. The three second-order factors were labeled Attentional Impulsiveness, Motor Impulsiveness, and Nonplanning Impulsiveness. Two of the three second-order factors identified in the BIS-11 were consistent with those proposed by Barratt (1985), but no cognitive impulsiveness component was identified per se. The results of the present study suggest that the total score of the BIS-11 is an internally consistent measure of impulsiveness and has potential clinical utility for measuring impulsiveness among selected patient and inmate populations.
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| [49] |
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| [50] |
This study tested two competing models of differential susceptibility and diathesis-stress in a prospective longitudinal study of African American youths (N = 935). It examined whether individual variations in the functioning of the hypothalamic–pituitary–adrenocortical axis at age 11 interact with middle childhood parent–child relationship quality to predict mental and physical health problems in adolescence (ages 11–15 years old). Adolescent boys with lower levels of cortisol reactivity to laboratory challenges had the highest levels of internalizing problems if they experienced a high conflictual relationship with their parents. Equally low-reactive boys, however, reported the lowest number of physical illnesses if their relationship with their parents was characterized by high levels of intimacy and support.
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| [51] |
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| [52] |
In this study, we used a stress test to investigate endocrinological and subjective stress responses of 8- to 14-year-old children with internalizing or externalizing disorders and healthy controls. The sample (N = 170) consisted of clinical and community children. Parents were given a diagnostic interview to diagnose their children's psychiatric condition. We measured saliva cortisol and subjectively experienced arousal in children before and after the Trier Social Stress Test for Children. Children also rated their performance immediately after the stress test, and 1 hr later they rated their positive and negative thoughts about this stressful event. Children with internalizing or externalizing disorders exhibited a blunted cortisol response compared to healthy controls. Depressed children rated their test performance lower and reported more negative thoughts after the test in comparison to healthy controls, anxious children reported more arousal before and after the task, and children with externalizing disorders reported more positive thoughts. In regression analyses, cortisol and subjective stress responses were both predictive of psychiatric disorders. The study extends previous work on the relation between psychiatric disorders and children's stress responses to an experimentally induced stress task by including a broad range of psychiatric disorders and by integrating endocrinological and subjective stress responses.
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| [53] |
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| [54] |
It has been hypothesized that sensation seeking and impulsivity, which are often conflated, in fact develop along different timetables and have different neural underpinnings, and that the difference in their timetables helps account for heightened risk taking during adolescence. In order to test these propositions, the authors examined age differences in sensation seeking and impulsivity in a socioeconomically and ethnically diverse sample of 935 individuals between the ages of 10 and 30, using self-report and behavioral measures of each construct. Consistent with the authors' predictions, age differences in sensation seeking, which are linked to pubertal maturation, follow a curvilinear pattern, with sensation seeking increasing between 10 and 15 and declining or remaining stable thereafter. In contrast, age differences in impulsivity, which are unrelated to puberty, follow a linear pattern, with impulsivity declining steadily from age 10 on. Heightened vulnerability to risk taking in middle adolescence may be due to the combination of relatively higher inclinations to seek excitement and relatively immature capacities for self-control that are typical of this period of development.
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| [55] |
Previous studies have postulated that the error-related negativity (ERN) may reflect individual differences in impulsivity; however, none have used a longitudinal framework or evaluated impulsivity as a multidimensional construct. The current study evaluated whether ERN amplitude, measured in childhood and adolescence, is predictive of impulsiveness during adolescence.Seventy-five children participated in this study, initially at ages 7-9 years and again at 12-18 years. The interval between testing sessions ranged from 5 to 9 years. The ERN was extracted in response to behavioural errors produced during a modified visual flanker task at both time points (i.e. childhood and adolescence). Participants also completed the Barratt Impulsiveness Scale - a measure that considers impulsiveness to comprise three core sub-traits - during adolescence.At adolescence, the ERN amplitude was significantly larger than during childhood. Additionally, ERN amplitude during adolescence significantly predicted motor impulsiveness at that time point, after controlling for age, gender, and the number of trials included in the ERN. In contrast, ERN amplitude during childhood did not uniquely predict impulsiveness during adolescence.These findings provide preliminary evidence that ERN amplitude is an electrophysiological marker of self-reported motor impulsiveness (i.e. acting without thinking) during adolescence.Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
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| [56] |
There is evidence that cortisol influences cognitive and affective processes such as selective attention and memory for emotional events, yet the effects of glucocorticoids on attentional inhibition in humans remain unknown. Consequently, this double-blind study examined dose-dependent effects of exogenous glucocorticoids on the inhibition of emotional information. Sixty-three university students (14 male, 49 female) ingested either a placebo pill or hydrocortisone (10mg or 40mg), and completed a negative priming task assessing the inhibition of pictures depicting angry, sad, and happy faces. The 10mg, but not the 40mg hydrocortisone dose elicited increased inhibition for angry faces relative to placebo. Thus, moderate glucocorticoid elevations may have adaptive effects on emotional information processing, whereas high glucocorticoid elevations appear to attenuate this effect, consistent with the view that there are dose-dependent effects of glucocorticoids on cognition.Copyright © 2010 Elsevier B.V. All rights reserved.
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| [57] |
A model examining the effects of an increasing number of maltreatment subtypes experienced on antisocial behavior, as mediated by impulsivity and moderated by a polygenic index of dopaminergic genotypes, was investigated. An African American sample of children (N= 1,012,Mage = 10.07) with and without maltreatment histories participated. Indicators of aggression, delinquency, and disruptive peer behavior were obtained from peer- and counselor-rated measures to form a latent variable of antisocial behavior; impulsivity was assessed by counselor report. Five genotypes in four dopaminergic genes (dopamine receptors D4, D2, known asDRD4, DRD2; dopamine active transporter 1, known asDAT1; and catechol-O-methyltransferase, known asCOMT) conferring heightened environmental sensitivity were combined into one polygenic index. Using structural equation modeling, a first-stage, moderated-mediation model was evaluated. Age and sex were entered as covariates, both as main effects and in interaction with maltreatment and the gene index. The model had excellent fit: χ2(32,N= 1,012) = 86.51,p<.001; comparative fit index = 0.982, Tucker–Lewis index = 0.977, root mean square error of approximation = 0.041, and standardized root mean square residual = 0.022. The effect of maltreatment subtypes on antisocial behavior was partially mediated by impulsivity (β = 0.173,p<.001), and these relations were moderated by the number of differentiating dopaminergic genotypes. Specifically, a significant Gene × Environment interaction (β = 0.016,p=.013) indicated that the relation between maltreatment and impulsivity was stronger as children evinced more differentiating genotypes, thereby strengthening the mediational effect of impulsivity on antisocial behavior. These findings elucidate the manner by which maltreated children develop early signs of antisocial behavior, and the genetic mechanisms involved in greater vulnerability for maladaptation in impulse control within the context of child maltreatment.
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| [58] |
Inconsistencies exist in literature examining hypothalamic-pituitary-adrenal (HPA) axis activity in children and adults who have experienced childhood abuse. Hence, the extent and manner to which childhood abuse may disrupt HPA axis development is largely unknown. To address these inconsistencies, the developmental course of nonstress cortisol in a long-term longitudinal study was assessed at six time points from childhood through adolescence and into young adulthood to determine whether childhood abuse results in disrupted cortisol activity. Nonstress, morning cortisol was measured in 84 females with confirmed familial sexual abuse and 89 nonabused, comparison females. Although dynamically controlling for co-occurring depression and anxiety, hierarchical linear modeling (HLM) showed that relative to comparison females, the linear trend for abused females was significantly less steep when cortisol was examined across development from age 6 to age 30, t (1, 180) = -2.55, p <.01, indicating attenuation in cortisol activity starting in adolescence with significantly lower levels of cortisol by early adulthood, F (1, 162) = 4.78, p <.01. As a more direct test of the attenuation hypothesis, supplemental HLM analyses of data arrayed by time since the disclosure of abuse indicated that cortisol activity was initially significantly higher, t (1, 425) = 2.18, p <.05, and slopes were significantly less steep t (1, 205) = -2.66, p <.01, for abused females. These findings demonstrate how the experience of childhood abuse might disrupt the neurobiology of stress, providing some support for the attenuation hypothesis that victims of abuse may experience cortisol hyposecretion subsequent to a period of heightened secretion.
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| [59] |
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| [60] |
Stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in secretion of corticosteroids which facilitate behavioural adaptation. These effects exerted by corticosteroids are mediated by two brain corticosteroid receptor types, the mineralocorticoid receptor (MR), with a high affinity already occupied under basal conditions and the glucocorticoid receptor (GR), with a low affinity only activated during stress. Here, we studied MR gene haplotypes constituted by the two single nucleotide polymorphisms MR-2G/C (rs2070951) and MRI180V (rs5522). The haplotypes showed differences in cortisol-induced gene transcription and protein expression while the structural variant MRI180V did not affect ligand binding. Moreover, in a well characterized cohort of 166 school teachers these haplotypes have been associated with perceived chronic stress (Trier Inventory for the Assessment of Chronic Stress, TICS) and, in a subgroup of 47 subjects, with ACTH, cortisol and heart rate responses to acute psychosocial stress (Trier Social Stress Test, TSST). MR haplotypes were significantly associated with the TICS scales "excessive demands at work" and "social overload". Subjects homozygous for haplotype MR-2C/MRI180, which in vitro showed highest expression and transactivational activity, displayed the highest salivary cortisol (p<0.001), plasma cortisol (p=0.010), plasma ACTH (p=0.003) and heart rate (p=0.018) responses. It is concluded that the investigated MR haplotypes modulate cortisol-induced gene transcription in vitro. Moreover, these haplotypes may contribute to individual differences in perceived chronic stress as well as neuroendocrine and cardiovascular stress responses.Copyright © 2010 Elsevier Ltd. All rights reserved.
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| [61] |
Recent research implicates the catechol-O-methyltransferase (COMT) ValMet polymorphism in stress sensitivity, through modulation of hypothalamic-pituitary-adrenal (HPA) function. In healthy samples, Met homozygosity has been associated with greater HPA activity (i.e., cortisol) and stress sensitivity, though findings are mixed among clinical samples. To date, there are no reports examining baseline or longitudinal changes in HPA activity as a function of COMT genotype in youth. This study tested the hypothesis that COMT genotype would be associated with cortisol secretion in normal and at-risk adolescents; specifically, that COMT genotype would be linked in a dose-response manner such that Met homozygotes would have the highest salivary cortisol levels, followed by heterozygotes, then Val homozygotes. In addition, this study examined the relation of COMT genotype with longitudinal changes in cortisol.This study examined the association of COMT with salivary cortisol across a 1-year period in healthy and at-risk adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision Axis II diagnoses.Results indicated higher cortisol levels for Met homozygotes (compared with heterozygotes and Val homozygotes) at the 1-year follow-up, and increased mean cortisol levels across a 1-year period among Met carriers, suggesting that COMT associates with differences in cortisol secretion during adolescence.Findings are discussed with respect to COMT genotype as a potential genetic indicator of psychiatric risk that modulates developmental changes in HPA activity.
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| [62] |
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| [63] |
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