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1.
Predictors for self‐directed aggression in Italian prisoners include externalizing behaviors,childhood trauma and the serotonin transporter gene polymorphism 5‐HTTLPR
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E. Gorodetsky V. Carli M. Sarchiapone A. Roy D. Goldman M.‐A. Enoch 《Genes, Brain & Behavior》2016,15(5):465-473
Suicidal behavior and self‐mutilation can be regarded as the expression of self‐directed aggression and both are common in prison populations. We investigated the influence of externalizing behaviors, depressive symptoms, childhood trauma, 5‐HTTLPR variants on self‐directed aggression (N = 145) in a group of 702 male Italian prisoners. Participants were comprehensively evaluated, including for psychiatric disorders, impulsive traits, lifetime aggressive behavior [Brown‐Goodwin Lifetime History of Aggression (BGHA)], hostility, violent behavior during incarceration, depressive symptomatology [Hamilton Depression Rating Scale (HDRS)], childhood trauma [Childhood Trauma Questionnaire (CTQ)]. Logistic regression analysis showed false discovery rate corrected independent main effects of externalizing behaviors: BGHA (P = 0.001), violent behavior in jail (P = 0.007), extraversion (P = 0.015); HDRS (P = 0.0004), Axis I disorders (P = 0.015), CTQ (P = 0.004) and 5‐HTTLPR genotype (P = 0.02). Carriers of 5‐HTTLPR high (LALA), intermediate (LALG, SLA) activity variants were more likely to have exhibited self‐directed aggression relative to the low activity (LGLG, SLG, SS) variant: high/low: odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.27–4.68, P = 0.007; intermediate/low: OR = 1.96, 95% CI 1.09–3.68, P = 0.025. The CTQ main effect was driven by physical abuse. There was no interactive effect of 5‐HTTLPR and CTQ. Secondary logistic regression analyses in (1) all suicide attempters (N = 88) and (2) all self‐mutilators (N = 104), compared with controls showed that in both groups, childhood trauma (P = 0.008–0.01), depression (P = 0.0004–0.001) were strong predictors. BGHA, violent behavior in jail predicted self‐mutilation (P = 0.002) but not suicide attempts (P = 0.1). This study was able to distinguish differing influences on self‐directed aggression between groups of closely related predictor variables within the externalizing behavioral domain. 5‐HTTLPR had an independent, variant dosage effect. 相似文献
2.
Serotonin transporter gene variants are known to interact with stressful life experiences to increase chances of developing affective symptoms, and these same variants have been shown to influence amygdala reactivity to affective stimuli in non-psychiatric populations. The impact of these gene variants on affective neurocircuitry in anxiety and mood disorders has been studied less extensively. Utilizing a triallelic assay (5-HTTLPR and rs25531) to assess genetic variation linked with altered serotonin signaling, this fMRI study investigated genetic influences on amygdala and anterior insula activity in 50 generalized anxiety disorder patients, 26 of whom also met DSM-IV criteria for social anxiety disorder and/or major depressive disorder, and 39 healthy comparison subjects. A Group x Genotype interaction was observed for both the amygdala and anterior insula in a paradigm designed to elicit responses in these brain areas during the anticipation of and response to aversive pictures. Patients who are S/LG carriers showed less activity than their LA/LA counterparts in both regions and less activity than S/LG healthy comparison subjects in the amygdala. Moreover, patients with greater insula responses reported higher levels of intolerance of uncertainty, an association that was particularly pronounced for patients with two LA alleles. A genotype effect was not established in healthy controls. These findings link the serotonin transporter gene to affective circuitry findings in anxiety and depression psychopathology and further suggest that its impact on patients may be different from effects typically observed in healthy populations. 相似文献
3.
Christoph Kraus Pia Baldinger Christina Rami-Mark Gregor Gryglewsky Georg S. Kranz Daniela Haeusler Andreas Hahn Wolfgang Wadsak Markus Mitterhauser Dan Rujescu Siegfried Kasper Rupert Lanzenberger 《PloS one》2014,9(9)
Background
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) may impact on the in-vivo binding of important serotonergic structures such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT1A) receptor. Previous positron emission tomography (PET) studies on the association between Val66Met and 5-HTT and 5-HT1A binding potential (BPND) have demonstrated equivocal results.Methods
We conducted an imaging genetics study investigating the effect of Val66Met genotype on 5-HTT or 5-HT1A BPND in 92 subjects. Forty-one subjects (25 healthy subjects and 16 depressive patients) underwent genotyping for Val66Met and PET imaging with the 5-HTT specific radioligand [11C]DASB. Additionally, in 51 healthy subjects Val66Met genotypes and 5-HT1A binding with the radioligand [carbonyl-11C]WAY-100635 were ascertained. Voxel-wise and region of interest-based analyses of variance were used to examine the influence of Val66Met on 5-HTT and 5-HT1A BPND.Results
No significant differences of 5-HTT nor 5-HT1A BPND between BDNF Val66Met genotype groups (val/val vs. met-carrier) were detected. There was no interaction between depression and Val66Met genotype status.Conclusion
In line with previous data, our work confirms an absent effect of BDNF Val66Met on two major serotonergic structures. These results could suggest that altered protein expression associated with genetic variants, might be compensated in vivo by several levels of unknown feedback mechanisms. In conclusion, Val66Met genotype status is not associated with changes of in-vivo binding of 5-HTT and 5-HT1A receptors in human subjects. 相似文献4.
5.
Unilateral hypoxic-ischemia results in the frequent occurrence of interictal spikes, and occasionally sustained ictal discharges
accompanied by a reduction in paired-pulse inhibition within the non-lesioned dentate gyrus. To elucidate the roles of serotonin
(5-hydroxytryptamine [5-HT]) in an epileptogenic insult, we investigated the changes in 5-HT receptors and serotonin transporter
(5-HTT) immunoreactivities within the lesioned and contralateral hippocampus following unilateral hypoxic-ischemia. During
epileptogenic periods following hypoxic-ischemia, both 5-HT1A and 5HT1B receptor immunoreactivities were decreased within the lesioned and the non-lesioned hippocampus. However, 5-HTT immunoreactivity
was transiently increased within the hippocampus bilaterally. These findings indicate that alteration of the 5-HT system results
in a “diaschisis” pattern, and may contribute to neuronal death and the development of emotional disorders in epileptic patients
accompanied by psychological stress. 相似文献
6.
Objective: There is considerable evidence that cortisol secretion is associated with obesity. The regulation of the 5‐hydroxytryptamine receptor 2A (5‐HT2A) gene might play an essential role because it is involved in the control of cortisol secretion. Therefore, we examined the potential impact of the 5‐HT2A ?1438G/A promoter polymorphism on obesity and estimates of insulin, glucose, and lipid metabolism as well as circulating hormones, including salivary cortisol, in 284 unrelated Swedish men born in 1944. Research Methods and Procedures: The subjects were genotyped by using polymerase chain reaction amplification of the promoter region of the gene for 5‐HT2A followed by digestion of the reaction product with the restriction enzyme MspI. Results: The frequencies were 0.39 for allele ?1438A and 0.61 for allele ?1438G. Homozygotes for the ?1438G allele had, in comparison with ?1438A/A subjects, higher body mass index, waist‐to‐hip ratio, and abdominal sagittal diameter. Moreover, cortisol escape from 0.25‐mg dexamethasone suppression was found in subjects with the ?1438A/G genotype. Serum leptin, fasting insulin, and glucose, as well as serum lipids, were not different across the ?1438G/A genotype groups. Discussion: From these results, we suggest the possibility that an abnormal production rate of the 5‐HT2A gene product might lead to the development of abdominal obesity. The pathophysiology could involve stress factors that destabilize the serotonin‐hypothalamic‐pituitary‐adrenal system in those with genetic vulnerability in the serotonin receptor gene. 相似文献
7.
Pretty Mary Abraham Korah P Kuruvilla Jobin Mathew Anitha Malat Shilpa Joy CS Paulose 《Journal of biomedical science》2010,17(1):78
Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find
the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT2A receptor subtype, gene expression studies on 5-HT2A, 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed
a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters Bmax and Kd showed a significant decrease (p < 0.001) whereas 5-HT2A receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p < 0.001) in diabetic rats compared to control. Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, Bmax , Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin
through its transporter significantly increased (p < 0.001) anxiety-related traits in diabetic rats which were corrected by
combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal
serotonergic function. This has clinical significance in the management of diabetes. 相似文献
8.
Sevinc Sarinc Ulasli Fusun Oner Eyuboglu Hasibe Verdi Fatma Belgin Atac 《Molecular biology reports》2013,40(10):5625-5633
Different biochemical pathways and cellular mechanisms play role in the pathogenesis of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). Alveolar hypoxia is not the only determinant of vascular remodeling, genetic factors are thought to have additive effects. We aimed to investigate the effects of endothelial nitric oxide synthase (eNOS A/B), angiotensin converting enzyme (ACE I/D) and serotonin transporter (5-HTT L/S) gene polymorphisms on development and severity of PH in COPD patients. 50 COPD patients without PH (group 1); 30 COPD patients with PH confirmed with echocardiography (group 2) and 49 healthy subjects (group 3) as control group were included to the study. eNOS A/B, ACE I/D and 5-HTT L/S gene polymorphisms and allele frequencies of COPD patients with and without PH and healthy subjects were determined. Functional parameters and echocardiographic measurements were recorded. Patients with PH were also assessed in two subgroups according to the severity of pulmonary arterial pressure (PAP). Significant differences among three groups in the distribution of 5-HTT genotype and allele frequency were present (respectively p = 0.002; p = 0.021). In group 2, LL and LS genotype rate was 93.3 % with a frequency of 71.2 % L allele and 28.3 % of S allele. 5-HTT LL genotype was present in 88.9 % of patients with PAP ≥50 mmHg significantly (p = 0.012). Other genotype distributions were not significantly different between two subgroups. The results of this study can suggest that COPD patients with L allele of 5-HTT may have higher risk for the development of PH and patients with LL genotype of 5-HTT may present higher PAP. We also demonstrated that eNOS and ACE gene polymorphisms were not associated with the development and severity of PH in our study population. Further studies with larger numbers of patients are needed to explore these relationships. 相似文献
9.
No association between the serotonin transporter-linked promoter region polymorphism and either schizophrenia or density of the serotonin transporter in human hippocampus. 总被引:1,自引:0,他引:1
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L. Naylor B. Dean A. Pereira A. Mackinnon A. Kouzmenko D. Copolov 《Molecular medicine (Cambridge, Mass.)》1998,4(10):671-674
BACKGROUND: Allelic association case-control analysis of a deletion/insertion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has suggested associations with unipolar disorder, bipolar disorder, depression, and Alzheimer's disease. Moreover, the heterozygous long form of the 5-HTTLPR has been associated with increased levels of mRNA for the serotonin transporter (5-HTT) and increased serotonin uptake in lymphoblastic cell lines. This study attempts to determine whether there is an association between 5-HTTLPR genotype and schizophrenia or the binding of [3H]paroxetine to the human hippocampal 5-HTT. MATERIALS AND METHODS: DNA from the cerebellum from 58 schizophrenic and 62 control subjects was used to genotype the 5-HTTLPR. In addition, the relationship between 5-HTTLPR genotype and the affinity and density of [3H]paroxetine binding to the hippocampal 5-HTT was assessed. RESULTS: There were no associations between 5-HTTLPR allotype or genotype and/or the parameters of [3H]paroxetine binding to the hippocampal 5-HTT. CONCLUSIONS: Our data suggest that 5-HTTLPR genotype neither confers an increased susceptibility for schizophrenia nor dictates the expression of the 5-HTT in the human hippocampus. 相似文献
10.
11.
Summary. Implications of exercise on serotonergic neuromodulation in the brain have been investigated in two studies. Acute paroxetine
(selective serotonin (5-HT) reuptake inhibitor) administration to endurance athletes, who performed a cycle ergometer test
to exhaustion at moderate intensity, reduced time to exhaustion and post exercise cognitive performance in comparison to trials
with placebo or BCAA administration. Furthermore, during a 3-week moderate endurance training of sedentary males basaline
values of Bmax of 5-HT transporters (5-HTT) and 5-HT2A receptors (5-HT2AR) on isolated platelet membranes increased while plasma prolactin (PRL) concentrations decreased as well as mood and physical
efficiency improved. In contrast, after an excessive training program over four weeks, well-trained endurance athletes showed
no change of Bmax of 5-HTT, but a decline of 5-HT2AR density and an increase in basal plasma PRL concentration. Mood was impaired and central fatigue increased. Thus, the impact
of exercise on 5-HT neurotransmission may depend on training state of athletes and extent of exertion. The theoretical background
of the implication of exercise and the effect of long lasting exhaustive exercise in athletes on mental and physical efficiency
or central fatigue are evaluated. The significance of the primary disturbance of central neuromodulation and dysfunction of
5-HTT, 5-HT receptor subtypes and the phosphoinositol signal transduction as well as the limited modulation capacity of the
5-HT system in overstrain are also addressed.
Received December 1, 1999 / Accepted February 1, 2000 相似文献
12.
AbstractAnoxybacillus (A. flavithermus, A. kamchatkensis subsp. asachharedens, A. caldiproteolyticus and A. tepidamans) and Geobacillus (two strains of G. thermodenitrificans, G. thermoglucosidans and G. vulcanii) isolates and reference strains in whole milk were evaluated for their biofilm production on six different abiotic surfaces. G. thermodenitrificans DSM 465T had the highest cell counts (>4 log10 CFU cm?2) on glass and stainless steel (SS) at 55 and 65?°C, respectively. G. thermodenitrificans D195 had the highest counts on SS at 55?°C (>5 log10 CFU cm?2) and polyvinyl chloride (PVC) at 65?°C (>4 log10 CFU cm?2), indicating the existence of strain variation. The ideal surfaces for all strains were SS and glass at 55?°C, but their preferences were polystyrene and SS at 65?°C. Moreover, Anoxybacillus members were more prone to form biofilms in skim milk than in semi-skim and whole milk, whereas the results were the opposite for Geobacillus. Both the attachment and sporulation of Geobacillus in whole milk was higher than in semi-skim or skim milk. This study proposes that the surface material, temperature and milk type had a cumulative effect on biofilm formation. 相似文献
13.
Trond Brattelid Eirik Qvigstad Lise R. Moltzau Silje V. S. Bekkevold Dagny L. Sandnes Jon Arne K. Birkeland Tor Skomedal Jan-Bj?rn Osnes Ivar Sjaastad Finn Olav Levy 《PloS one》2012,7(9)
A positive inotropic responsiveness to serotonin, mediated by 5-HT4 and 5-HT2A receptors, appears in the ventricle of rats with post-infarction congestive heart failure (HF) and pressure overload-induced hypertrophy. A hallmark of HF is a transition towards a foetal genotype which correlates with loss of cardiac functions. Thus, we wanted to investigate whether the foetal and neonatal cardiac ventricle displays serotonin responsiveness. Wistar rat hearts were collected day 3 and 1 before expected birth (days -3 and -1), as well as day 1, 3, 5 and 113 (age matched with Sham and HF) after birth. Hearts from post-infarction HF and sham-operated animals (Sham) were also collected. Heart tissue was examined for mRNA expression of 5-HT4, 5-HT2A and 5-HT2B serotonin receptors, 5-HT transporter, atrial natriuretic peptide (ANP) and myosin heavy chain (MHC)-α and MHC-β (real-time quantitative RT-PCR) as well as 5-HT-receptor-mediated increase in contractile function ex
vivo (electrical field stimulation of ventricular strips from foetal and neonatal rats and left ventricular papillary muscle from adult rats in organ bath). Both 5-HT4 mRNA expression and functional responses were highest at day -3 and decreased gradually to day 5, with a further decrease to adult levels. In HF, receptor mRNA levels and functional responses reappeared, but to lower levels than in the foetal ventricle. The 5-HT2A and 5-HT2B receptor mRNA levels increased to a maximum immediately after birth, but of these, only the 5-HT2A receptor mediated a positive inotropic response. We suggest that the 5-HT4 receptor is a representative of a foetal cardiac gene program, functional in late foetal development and reactivated in heart failure. 相似文献
14.
5‐HTTLPR genotype potentiates the effects of war zone stressors on the emergence of PTSD,depressive and anxiety symptoms in soldiers deployed to iraq
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Michael J. Telch Christopher G. Beevers David Rosenfield Han-Joo Lee Albert Reijntjes Robert E. Ferrell Ahmad R. Hariri 《World psychiatry》2015,14(2):198-206
Exposure to war zone stressors is common, yet only a minority of soldiers experience clinically meaningful disturbance in psychological function. Identification of biomarkers that predict vulnerability to war zone stressors is critical for developing more effective treatment and prevention strategies not only in soldiers but also in civilians who are exposed to trauma. We investigated the role of the serotonin transporter linked polymorphic region (5‐HTTLPR) genotype in predicting the emergence of post‐traumatic stress disorder (PTSD), depressive and anxiety symptoms as a function of war zone stressors. A prospective cohort of 133 U.S. Army soldiers with no prior history of deployment to a war zone, who were scheduled to deploy to Iraq, was recruited. Multilevel regression models were used to investigate associations between 5‐HTTLPR genotype, level of war zone stressors, and reported symptoms of PTSD, depression and anxiety while deployed to Iraq. Level of war zone stressors was associated with symptoms of PTSD, depression and anxiety. Consistent with its effects on stress responsiveness, 5‐HTTLPR genotype moderated the relationship between level of war zone stressors and symptoms of emotional disturbance. Specifically, soldiers carrying one or two low functioning alleles (S or LG) reported heightened symptoms of PTSD, depression and anxiety in response to increased levels of exposure to war zone stressors, relative to soldiers homozygous for the high functioning allele (LA). These data suggest that 5‐HTTLPR genotype moderates individual sensitivity to war zone stressors and the expression of emotional disturbance including PTSD symptoms. Replication of this association along with identification of other genetic moderators of risk can inform the development of biomarkers that can predict relative resilience vs. vulnerability to stress. 相似文献
15.
V E Golimbet V M Alfimova T V Shcherbatykh L I Abramova V G Kaleda E I Rogaev 《Molekuliarnaia biologiia》2001,35(3):397-400
Some studies associate the insertion/deletion polymorphism of the serotonin transporter (5-HTT) gene with anxiety-related personality traits in mentally healthy people, the short (s) allele being associated with a higher neuroticism score. The 5-HTT genotype and neuroticism score were established for 114 affective patients, 87 healthy relatives of endogenous psychosis patients, and for 156 mentally healthy people without familial psychiatric history. The effects of sex and age on the association between the two parameters was studied. Neuroticism proved to be not associated with the 5-HTT genotype. 相似文献
16.
17.
Golimbet V. E. Alfimova M. V. Shcherbatykh T. V. Abramova L. I. Kaleda V. G. Rogaev E. I. 《Molecular Biology》2001,35(3):336-338
Some studies associate the insertion/deletion polymorphism of the serotonin transporter (5-HTT) gene with anxiety-related personality traits in mentally healthy people, the short (s) allele being associated with a higher neuroticism score. The 5-HTT genotype and neuroticism score were established for 114 affective patients, 87 healthy relatives of endogenous psychosis patients, and for 156 mentally healthy people without familial psychiatric history. The effects of sex and age on the association between the two parameters was studied. Neuroticism proved to be not associated with the 5-HTT genotype. 相似文献
18.
《Life sciences》1997,61(21):PL295-PL303
Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals. 相似文献
19.
The brain serotonin (5-HT) system has been implicated in the pathophysiology of anxiety, depression, drug addiction, and schizophrenia. 5-HT2A receptors are involved in the mechanisms of stressinduced psychopathology and impulsive behavior. In this work, we investigated the role of 5-HT2A receptors in the autoregulation of the brain 5-HT system. Chronic treatment with DOI, a 5-HT2A receptor agonist (1.0 mg/kg, i.p./14 days), produced a considerable decrease in the number of 5-HT2A receptor-mediated head twitches in AKR/J mice, indicating the desensitization of 5-HT2A receptors. Chronic DOI treatment did not affect the expression of the 5-HT2A receptor gene in the midbrain, hippocampus and frontal cortex. At the same time, an increase in the expression of the gene encoding a key enzyme of 5-HT synthesis, tryptophan hydroxylase-2 (TPH-2), accompanied with an increase in TPH-2 activity and 5-HT levels, and decreased expression of the serotonin transporter (5-HTT) gene were observed in the midbrain of DOI-treated mice. These results provide new evidence of receptor-gene cross-talk in the brain 5-HT system and implication 5-HT2A receptors in the autoregulation of the brain 5-HT system. 相似文献
20.
Effects of stand age and tree species on canopy transpiration and average stomatal conductance of boreal forests 总被引:6,自引:1,他引:6
We quantified the effect of stand age and tree species composition on canopy transpiration (EC) by analysing transpiration per unit leaf area (EL) and canopy stomatal conductance (GS) for boreal trees comprising a five stand wildfire chronosequence. A total of 196 sap flux sensors were used on 90 trees consisting of Betula papyrifera Marsh (paper birch; present in the youngest stand), Populus tremuloides Michx (quaking aspen), Pinus banksiana Lamb. (jack pine), and Picea mariana (Mill.) (black spruce). While fine roots were positively correlated with stand EC; leaf area index, basal area, and sapwood area were not. Stands less than 70 years old were dominated by Populus tremuloides and Pinus banksiana and stands greater than 70 years old were composed almost entirely of Picea mariana. As Populus tremuloides and Pinus banksiana increased in size and age, they displayed an increasing sapwood to leaf area ratio (AS : AL), a constant minimum leaf water potential (ΨL), and a constant proportionality between GS at low vapour pressure deficit (Dj GSref) and the sensitivity of GS to D (–δ). In contrast, AS : AL, minimum ΨL, and the proportionally between –δ and GSref decreased with height and age in Picea mariana. A GS model that included the effects of D, AS : AL, tree height, and for Picea mariana an increasing soil to leaf water potential gradient with stand age, was able to capture the effects of contrasting hydraulic properties of Picea mariana, Populus tremuloides and Pinus banksiana during stand development after wildfire. 相似文献