5-HTTLPR and COMTval158met genotype gate amygdala reactivity and habituation

Amygdala reactivity is a heritable trait, potentiated in affective disorders and associated with both the 5-HTTLPR and the COMTval158met polymorphism.Fifty-four healthy volunteers selected a priori based on gender and 5-HTTLPR/rs25531 and COMTval158met genotypes performed a passive viewing task of angry facial expressions using fMRI. Amygdala reactivity and habituation were investigated using the a priori anatomical region of interest (ROI) approach. Furthermore, salivary cortisol and skin conductance responses were recorded.We observed an effect of 5-HTTLPR on right amygdala reactivity (s-carrier > l/l) and COMTval158met on left amygdala reactivity (met/met > val-carrier). We provide preliminary evidence that different amygdala habituation curves may partly underlie the differences between 5-HTTLPR and not COMT genotype groups. Further, exploratory analyses find no evidence for additive or interaction effects.Our results support that 5-HTTLPR s-carriers and COMT met/met carriers may be more sensitive to the detection of biologically and socially relevant information and suggest a mechanism behind this for the 5-HTTLPR.     

Family Based Association Analyses between the Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Neuroticism,Anxiety and Depression

We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register (559 parents and 1,245 offspring). Subjects had participated between one and five times in a survey study measuring neuroticism, anxiety and depression. Offspring of these families were also approached to participate in a psychiatric interview diagnosing DSM-IV major depression. Within-family and total association between 5-HTTLPR and these traits were tested. Only three of the 36 tests showed a significant effect of 5-HTTLPR (P < 0.05). These effects were in opposite directions, i.e. both negative and positive regression coefficients were found for the s allele. No additive effect of the s allele was found for DSM-IV depression. Our results strongly suggest that there is no straightforward association between 5-HTTLPR and neuroticism, anxiety and depression. Edited by Stacey Cherny     

Interaction of 5-HTTLPR genotype and unipolar major depression in the emergence of aggressive/hostile traits

Objective

The 5-HTTLPR polymorphism has been associated both with depression and aggression/hostility. The multidirectional association between depression, aggression and the s allele may be important, since all these phenomena are related to suicidal behavior. Our aim was to investigate the association between 5-HTTLPR and aggressive/hostile traits in depressed patients and controls.

Methods

137 depressive and 118 control women completed the Buss-Durkee Hostility Inventory and were genotyped for 5-HTTLPR. BDHI scores in the different groups were investigated by Generalized Linear Model Analysis. Association between dependent and independent variables in the model was tested by the likelihood ratio Chi-square statistic.

Results

Diagnosis and genotype showed a significant association with several aggressive/hostile traits. Interaction of the two main effects was also significant in case of several subscales. Post hoc analyses indicated a significant association between BDHI subscales and s allele only in the depressed group.

Limitation

Only women were studied and since gender differences are present both in aggressive behavior and putatively in the behavioral effects of 5-HTTLPR genotype, our findings pertain only to females.

Conclusion

Our results indicate a robust relationship between aggression/hostility and 5-HTTLPR genotype, but this association is more marked in the presence of depression. The presence of the s allele thus not only contributes to a higher risk of depression, but in depressives also leads to higher aggression/hostility. Our results have important implications for suicide research, since the s allele is associated with violent suicide, and this association may be mediated through the emergence of increased aggression/hostility in depressed patients carrying the s allele.     

5-HTTLPR genotype and gender, but not chronic fluoxetine administration, are associated with cortical TREK1 protein expression in rhesus macaques

TREK1 is a widely expressed background potassium channel. Similar to mice treated with selective serotonin reuptake inhibitors (SSRIs), TREK1 knockout mice are resistant to depression-like behavior and have elevated serotonin levels leading to speculation that TREK1 inhibition may contribute to the therapeutic effects of SSRIs. This study examined how chronic fluoxetine administration and a common functional polymorphism in the serotonin-transporter-linked promoter region (5-HTTLPR) influence cortical TREK1 expression in 24 rhesus monkeys. The short rh5-HTTLPR allele as well as female gender were associated with reduced cortical TREK1 protein expression but chronic SSRI administration had no effect. These results suggest that serotonin may influence TREK1, but that chronic SSRI treatment does not result in long lasting changes in cortical TREK1 protein expression. TREK1 gender differences may be related to gender differences in serotonin and require further research.     

The microvibrations of the body,an index for examination stress

Summary Changes of whole-body microvibrations (MV) were quantitatively analyzed in 123 voluntary subjects during two examination situations and compared with the results obtained during the ensuing vacation. The force oscillations in the three space directions were measured during quiet bipedal standing and simultaneously recorded as a time function with the rectified and integrated force-time function (= rectified impulse). The rectified impulses related to body weight were used as a measure for the MV.Immediately before the examinations, all the subjects showed high values. These decreased significantly in the control measurement if the subjects passed the exams, but remained relatively high in the subjects who failed. In all three measurements, smokers and candidates who took tranquillizers before the exams show higher MV values than do the other subjects. Females are less tense than males, a difference particularly significant in the vertical (z) direction. The rectified impulse in this direction correlates positively with the estimated cardiac output. Body weight and body length show a positive correlation with the MV values in the horizontal forward-backward (x) and vertical (z) direction.The measurement of the whole-body MV enables quantitative evaluation of the complex load due to an examination situation. The hypothesis that different types of stress or personality affect given directions in space requires further investigation.Dedicated to Professor O. A. M. Wyss on the occasion of his 75th birthday     

Lack of association between the serotonin transporter promoter polymorphism (5-HTTLPR) and personality traits in asymptomatic patients with panic disorder

The serotonin transporter promoter polymorphism (5-HTTLPR) has been investigated regarding its association with neuroticism, which, in its turn, is a personality dimension often found in patients with panic disorder (PD). It has been recently evidenced that the long 5-HTTLPR polymorphism has a genetic variation (Lg), which is related to its lower expression. The objective of this study was to assess the association between the 5-HTTLPR polymorphism in the triallelic system and the neurotic personality traits in patients in PD remission. Sixty-seven Caucasian patients with PD diagnosis according to the DSM-IV-TR assessed with the MINI (mini international neuropsychiatric interview) were included. The MMPI (Minnesota multiphasic personality inventory) was used to assess the personality. The remission of PD symptoms was defined as CGI (clinical global impression) 相似文献   

Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) in the rat after immobilization stress

An increase of 100% in urinary 5-hydroxyindoleacetic acid, as a measure of release and catabolism of serotonin, is associated with the stress of 18 hr of restraint. Seventy percent of the rats developed gastric ulcers. Increased urinary 5-hydroxyindoleacetic acid levels were not observed in rats deprived of food for 42 hr.     

Cortisol responses to emotional stress in men: association with a functional polymorphism in the 5HTR2C gene

The serotonin 5HTR2C receptor has been shown to mediate HPA axis activation during stress. We hypothesized that a functional polymorphism (rs6318) of the 5HTR2C gene would be associated with HPA axis response to a laboratory stress protocol. The present sample consisted of 41 men (22 African Americans, 19 Caucasians). We found that at rest men with the more active rs6318 Ser23 C allele had similar cortisol values compared to those with the less active Cys23 G allele. During laboratory stress, however, men with the Ser23 C allele exhibited the predicted significantly higher cortisol levels (p < 0.001), as well as larger increases in anger (p = 0.08) and depressive mood (p = 0.006) ratings, compared to the Cys23 G carriers. The increase in cortisol was significantly related to the increases in ratings of anger and depression assessed before and after the emotion induction, and these correlations became nonsignificant when rs6318 genotype was covaried. We conclude that genetic variation in 5HTR2C may be associated with HPA axis activation and stimulated by emotional stress, and also with both psychological and physiological endophenotypes that increase the risk of cardiovascular disease and type-2 diabetes.     

Lack of association between the 5-HTTLPR and the error-related negativity (ERN)

The error-related negativity (ERN) is a negative waveform that occurs approximately 50 ms after an incorrect response. Pharmacological manipulations and theoretical accounts suggest that the ERN reflects reward-related dopamine activity; however, it is likely that several neurotransmitters contribute to the generation of the ERN. Two studies have found an association between the ERN and the serotonin transporter-linked promoter region (5-HTTLPR) polymorphism. In order to investigate this further, 86 participants performed an arrow version of the flanker task and were genotyped for the 5-HTTLPR and the A/G SNP (rs25531) located within the L allele. Despite using multiple methods to group subjects by genotype and score the ERN, no reliable associations between the ERN and the 5-HTTLPR were found. The current study casts doubt on the relationship between ERN and 5-HTTLPR; reasons for this discrepancy with previous work are discussed.     

Mechanisms underlying hemodynamic and neuroendocrine stress reactivity at different phases of the menstrual cycle

This study examined the association of menstrual cycle phase with stress reactivity as well as the hormonal and neuroendocrine mechanisms contributing to cycle effects. Fifty‐seven women underwent a modified Trier Social Stress Test during the early follicular, late follicular, and luteal phases of the menstrual cycle. Greater increases in cardiac index (CI) and greater decreases in vascular resistance index (VRI) during speech were observed in the luteal phase relative to other phases, while greater increases in epinephrine (EPI) was observed during the late follicular and luteal phases compared to the early follicular phase. Luteal phase estradiol predicted luteal EPI reactivity but not CI or VRI reactivity, while luteal phase EPI reactivity predicted luteal phase CI and VRI reactivity. Thus, cycle‐related changes in EPI reactivity may be a stronger determinant of cycle effects on hemodynamic reactivity than sex hormones per se.     

Effects of Environmental Stress and Gender on Associations among Symptoms of Depression and the Serotonin Transporter Gene Linked Polymorphic Region (5-HTTLPR)

The short (s) variant of the serotonin transporter (5-HTT) gene linked functional polymorphic region (5-HTTLPR) is associated with depression. Stressful life events, gender, and race have been shown to moderate this association. We examined the relationship between 5-HTTLPR genotype and symptoms of depression in two samples. Study 1 = 288 participants from a study of caregiver stress; and Study 2 = 142 participants from a study examining psychosocial stressors, genetics, and health. Main effects of 5-HTTLPR on symptoms of depression were examined, along with moderation by stress (caregiving status or low childhood socioeconomic status (SES), gender, and race. The 5-HTTLPR × stress group × gender interaction was significant in both samples (P < 0.003, and P < 0.008, respectively). For females, the s allele, combined with caregiving stress (Study 1) or low childhood SES (Study 2), was associated with higher depression scores as compared to participants in the non-stressor group and those with the long (l) allele; whereas, in males, the l allele, combined with a stressor, was associated with higher depression scores as compared to those in the non-stressor group and those with the s allele. Findings from two independent samples suggest that the association of 5-HTTLPR with depression varies according to gender and stressful life events. Edited by Tatiana Foroud.     

Blunted cardiovascular and cortisol reactivity to acute psychological stress: A summary of results from the Dutch Famine Birth Cohort Study

The Dutch Famine Birth Cohort Study is a large population based study of late middle aged, overall healthy men and women whose health has been followed from 50 to 65 years of age. In a sample of 725 cohort members, an extensive psychological stress protocol was performed during which cardiovascular and cortisol responses were measured. In line with many previous studies, results showed that increased blood pressure responsiveness to the stress protocol was associated with an increased risk for hypertension 5 years later. However, decreased cardiovascular and/or cortisol stress reactivity were associated with obesity and the risk of becoming obese, symptoms of depression and anxiety, a poor self-reported health, poor lung function, and poor cognitive function (all p for statistical tests < 0.05). These associations generally survived adjustment for a range of potential confounders, including resting cardiovascular and cortisol activity, commitment to the stress tasks, sex, age, smoking and use of medication. Results from these studies agree with recent evidence that low biological reactivity to acute psychological stress may not always be beneficial for health but instead seems to be a marker for a range of negative health outcomes. Future studies have to point out whether low stress reactivity precedes or follows these negative health outcomes.     

Neural and behavioral responses to threatening emotion faces in children as a function of the short allele of the serotonin transporter gene

Recent evidence suggests that a genetic polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) mediates stress reactivity in adults. Little is known, however, about this gene-brain association in childhood and adolescence, generally conceptualized as a time of heightened stress reactivity. The present study examines the association between 5-HTTLPR allelic variation and responses to fearful and angry faces presented both sub- and supraliminally in participants, ages 9-17. Behaviorally, carriers of the 5-HTTLPR short (s) allele exhibited significantly greater attentional bias to subliminally presented fear faces than did their long (l)-allele homozygous counterparts. Moreover, s-allele carriers showed greater neural activations to fearful and angry faces than did l-allele homozygotes in various regions of association cortex previously linked to attention control in adults. These results indicate that in children and adolescents, s-allele carriers can be distinguished from l-allele homozygotes on the basis of hypervigilant behavioral and neural processing of negative material.     

Differential effects of mild chronic stress on cortisol and S-IgA responses to an acute stressor

While acute stress is adaptive in the short term, chronic stress may interfere with HPA axis functioning and self-regulation that can, in turn, alter the body's immune response. Several studies suggest that acute and chronic stress consistently increase cortisol levels; however, the same cannot be said about S-IgA levels. We tested the effects of a mild chronic stress (an academic exam period), on cortisol and S-IgA responses to an acute stress. Exposure to an acute stressor significantly increases cortisol levels during periods of no-stress, but not during mild chronic stress, while S-IgA levels consistently increase during both sessions. Furthermore, we find that during the period of chronic mild stress, the perception of stress is related to increased cortisol response to an acute stressor. Combined, these findings shed light on the impact of increased background stress on acute stress responses.     

VP7 Gene of human rotavirus A genotype G5: Phylogenetic analysis reveals the existence of three different lineages worldwide

Group A rotavirus (RV-A) genotype G5, which is common in pigs, was also detected in children with severe diarrhea in Brazil, Argentina, Paraguay, Cameroon, China, Thailand, and Vietnam. To evaluate the evolutionary relationship among RV-A G5 strains, the VP7 and VP4 genes of 28 Brazilian RV-A G5 human strains, sampled between 1986 and 2005, were sequenced and compared with other RV-A G5 strains currently circulating worldwide in animals and humans. The phylogenetic analysis of RV-A G5 VP7 gene strains demonstrates the existence of three main lineages: (a) Lineage I: Brazilian strains grouped with three porcine strains from Thailand; (b) Lineage II: porcine, bovine, and equine strains from different regions; (c) Lineage III: human strains isolated in Asia and Africa, and two porcine strains from Argentina. The VP8* (*non-typable) subunit of VP4 gene sequencing showed that all P[8] strains fell into three major genetic lineages: P[8]-1; P[8]-2; and P[8]-3. These results showed that the RV-A G5 strains circulating in humans are the result of two independent zoonotic transmission events, most likely from pigs.     

Salivary alpha-amylase response to acute psychosocial stress: the impact of age

The impact of stress on health varies across the different stages of human life. Aging is associated with psychobiological changes that could limit our ability to cope with stressors. Therefore, it is crucial to clarify the physiological mechanisms that underlie the stress response and the changes that occur in them as we age. Our aim was to investigate age differences in the salivary alpha amylase (sAA) response to stress, and its relationship with other typical stress biomarkers such as cortisol and heart rate (HR). Sixty-two participants divided into two age groups (younger group: N = 31, age range: 18-35 years; older group: N = 31, age range: 54-71 years) were exposed to the Trier Social Stress Test and a control condition in a crossover design. No age differences were found in the sAA or HR responses to stress. However, the sAA global output was higher in older than younger adults. Additionally, in the stress condition, the total amount of cortisol released was positively related to the total sAA released, while the HR increase was positively related to the sAA increase. Our results do not support the existence of an attenuated autonomic nervous system response to stress in older adults, but rather a heightened sympathetic tone. Furthermore, we found further evidence of the coordination between the hypothalamus-pituitary-adrenal system and the autonomic nervous system in their response to acute psychosocial stress.     

Brief Reports: Further evidence for an association between self‐reported health and cardiovascular as well as cortisol reactions to acute psychological stress

In a recent study, the association between cardiovascular reactions to acute psychological stress and self‐reported health was examined. Participants with excellent or good self‐reported health exhibited higher cardiovascular reactivity than those who reported fair or poor health. We investigated this association in a population‐based cohort of whom 725 men and women, aged 55–60 years, participated in a standardized psychological stress test. We measured continuous blood pressure and heart rate as well as cortisol reactivity. Good subjective health was associated with higher cardiovascular and cortisol reactions to psychological stress. Results of the present study confirm those of the previously reported study showing that greater cardiovascular reactivity may not always be associated with negative health outcomes. In addition, the same holds for cortisol reactivity.