Oxytocin increases anxiety to unpredictable threat.
Ontology highlight
ABSTRACT:
SUBMITTER: Grillon C
PROVIDER: S-EPMC3930442 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Publications
Oxytocin increases anxiety to unpredictable threat.
Grillon C C Krimsky M M Charney D R DR Vytal K K Ernst M M Cornwell B B
Molecular psychiatry 20121113 9
Similar Datasets
Project description:Anxiety is elicited by excessive apprehension about unpredictable threats. However, the neural circuit governing unpredictable threat induced anxiety remains unclear. Here, we found ventral bed nucleus of the stria terminalis (vBNST) GABAergic neurons displayed selective activation to unpredictable threats by means ofthrough coordinated excitatory input from insular cortex (IC) glutamergic neurons and inhibitory input from lateral nucleus of the amygdala (CeL) somatostatin (SOM) neurons. Using activity-dependent neuronal tagging technology, we found that unpredictable threat responsive cells in vBNST drive freezing and anxiety via projections to ventral lateral periaqueductal grey (vlPAG) and median nucleus of the amygdala (CeM) respectively. Finally, we identified KCNQ3 plays an essential role in hyperactivity of vBNST GABAergic neurons and induced anxiety. These data identified a forward inhibitory circuit that determine the selective activation of vBNST in unpredictable threat and anxiety, and suggest that Kcnq3 KCNQ3 channel acts as a promising target in treatment of anxiety disorder following unpredictable stress.
2024-02-19 | GSE255670 | GEO
Project description:Coordinated excitatory and inhibitory circuits governing unpredictable threat induced anxiety
| PRJNA1076124 | ENA
Project description:The threat of predictable and unpredictable aversive events was developed to assess short-duration (fear) and long-duration (anxiety) aversive states in humans. A typical experiment consists of three conditions: a safe condition (neutral (N)), during which participants are safe from aversive stimuli, and two threat conditions-one in which aversive events are administered predictably (P) (i.e., signaled by a threat cue), and one in which aversive stimuli are administered unpredictably (U). During the so-called NPU-threat test, ongoing change in aversive states is measured with the startle reflex. The NPU-threat test has been validated in pharmacological and clinical studies and can be implemented in children and adults. Similar procedures have been applied in animal models, making the NPU-threat test an ideal tool for translational research. The procedure is relatively short (35 min), simple to implement and generates consistent results with large effect sizes.
| S-EPMC3446242 | biostudies-literature
Project description:BackgroundDelineating specific clinical phenotypes of anxiety disorders is a crucial step toward better classification and understanding of these conditions. The present study sought to identify differential aversive responses to predictable and unpredictable threat of shock in healthy comparisons and in non-medicated anxiety patients with and without a history of panic attacks (PAs).Method143 adults (72 healthy controls; 71 patients with generalized anxiety disorder (GAD) or/and social anxiety disorder (SAD), 24 with and 47 without PAs) were exposed to three conditions: 1) predictable shocks signaled by a cue, 2) unpredictable shocks, and 3) no shock. Startle magnitude was used to assess aversive responses.ResultsAcross disorders, a PA history was specifically associated with hypersensitivity to unpredictable threat. By disorder, SAD was associated with hypersensitivity to predictable threat, whereas GAD was associated with exaggerated baseline startle.ConclusionsThese results identified three physiological patterns. The first is hypersensitivity to unpredictable threat in individuals with PAs. The second is hypersensitivity to predictable threat, which characterizes SAD. The third is enhanced baseline startle in GAD, which may reflect propensity for self-generated anxious thoughts in the absence of imminent danger. These results inform current thinking by linking specific clinical features to particular physiology profiles.
| S-EPMC5665581 | biostudies-literature
Project description:Stress response neuroadaptation has been repeatedly implicated in animal addiction models for many drugs, including nicotine. Programmatic laboratory research that examines the stress response of nicotine-deprived humans is necessary to confirm that stress neuroadaptations observed in animal models generalize to humans.Two experiments tested the prediction that nicotine deprivation selectively increases startle response associated with anxiety during unpredictable threat but not fear during imminent, predictable threat. Dependent smokers (n = 117) were randomly assigned to 24-hour nicotine-deprived or nondeprived groups and participated in one of two experiments wherein electric shock was administered either unpredictably (noncontingent shock; Experiment 1) or predictably (cue-contingent shock; Experiment 2).Nicotine deprivation increased overall startle response in Experiment 1, which involved unpredictable administration of shock. Age of first cigarette and years of daily smoking were significant moderators of this deprivation effect. Self-reported withdrawal symptoms also predicted startle response during unpredictable shock. In contrast, nicotine deprivation did not alter overall or fear-potentiated startle in Experiment 2, which involved predictable administration of shock.These results provide evidence that startle response during unpredictable threat may be a biomarker of stress neuroadaptations among smokers in nicotine withdrawal. Contrast of results across unpredictable versus predictable shock experiments provides preliminary evidence that these stress neuroadaptations manifest selectively as anxiety during unpredictable threat rather than in every stressful context. Individual differences in unpredictable threat startle response associated with withdrawal symptoms, age of first cigarette, and years daily smoking link this laboratory biomarker to clinically relevant indexes of addiction risk and relapse.
| S-EPMC2949532 | biostudies-literature
Project description:Converging lines of evidence suggest that heightened responding to unpredictable threat may be an important neurobiological marker of internalizing psychopathology (IP). Prior data also indicate that aversive responding to uncertainty may be mediated by hyperactivation of several brain regions within the frontolimbic circuit, namely the anterior insula (aINS) and the dorsal anterior cingulate cortex (dACC). To date, however, the majority of this research has been focused on individual diagnoses and it is unclear whether abnormal neural reactivity to unpredictable threat is observed within heterogeneous, transdiagnostic IP patient populations, as theory would suggest. The aim of the current study was to therefore examine the neural correlates of temporally unpredictable (U) and predictable (P) threat in a sample of healthy controls (n = 24) and patients with a broad range of IP diagnoses (n = 51). We also examined whether symptom severity measures of fear and distress/misery dimensions correlated with neural reactivity to U- and P-threat. All participants completed a modified version of a well-validated threat-of-shock task during functional magnetic resonance imaging (fMRI). Across all participants, U- and P-threat elicited heightened activation in the aINS and brainstem, while P-threat alone also activated the dACC. Relative to healthy controls, patients displayed greater activation in the right aINS during U-threat, and greater right brainstem activation during P-threat. In addition, we found that brainstem activity during U-threat correlated with fear, but not distress/misery, psychopathology. Taken together, these preliminary results suggest that exaggerated aINS reactivity during U-threat and brainstem reactivity during P-threat may have the potential to become important transdiagnostic biomarkers of IP; however, future research efforts are needed to corroborate and expand the present findings.
| S-EPMC6476657 | biostudies-literature
Project description:Cognitive affective neuroscience tasks that are straightforward to administer, measure key constructs of interest, and can be used in different lab settings and with multiple psychophysiological methods can lead to a more complete understanding of experimental effects. The no-threat, predictable threat, unpredictable threat (NPU-threat) task assesses constructs of interest to both clinical and basic affective science literatures, is relatively brief to administer, and has been used across labs with a number of different measurements (e.g., startle eyeblink, fMRI, corrugator response, subjective ratings). ERPs provide another means of assessing neurobiological reactivity during the NPU-threat task, but to date such measures have been underutilized. That is, no study has yet evaluated cue-elicited ERPs in the NPU-threat task. Here, cue-elicited ERPs were assessed in 78 participants who completed a version of the NPU-threat task previously shown to reliably moderate startle eyeblink amplitudes. Results showed larger P2 amplitudes for unpredictable versus predictable trials, increased P3s and late positive potentials for threatening versus no-threat trials, as well as larger stimulus preceding negativities for threatening versus no-threat trials (driven primarily by predictable threat cues). In line with prior work, we observed enhanced startle eyeblink for threatening versus no-threat trials and for unpredictable compared to predictable threat interstimulus intervals. In addition, the probe-elicited P3 was suppressed for predictable and unpredictable compared to no-threat trials. Therefore, cue-elicited ERPs, which can be recorded alongside other measures in the NPU-threat task (e.g., startle), may provide useful indices of temporally distinct stages of predictable and unpredictable threat processing.
| S-EPMC6150785 | biostudies-literature
Project description:Stress can impair cognitive performance, as commonly observed in cognitive performance anxiety (CPA; e.g., test anxiety). Cognitive theories indicate that stress impairs performance by increasing attention to negative thoughts, a phenomenon also known as threat-interference. These theories are mainly supported by findings related to self-report measures of threat-interference or trait anxiety. Our main aim was to test, for the first time in a single study, the hypotheses that acute CPA-related stress negatively affects both working memory (WM) performance and objectively assessed threat-interference during performance. In addition, we aimed to assess the validity of a new stress-induction procedure that was developed to induce acute CPA. Eighty-six females were randomly assigned to a CPA-related stress group (n = 45) or a control group. WM performance and threat-interference were assessed with an n-back task (2-back and 3-back memory loads), using CPA-related words as distracters. The stress group showed higher state anxiety and slower WM performance. Both effects were moderated by trait CPA: the effects were stronger for individuals with higher trait CPA. Finally, trait CPA moderated the effect of stress on threat-interference during higher cognitive load: individuals with higher trait CPA in the stress group showed higher threat-interference. We conclude that acute CPA increases threat-interference and impairs WM performance, especially in vulnerable individuals. The role of threat-interference, cognitive load, and trait anxiety should be taken into account in future research. Finally, our method (combining our stressor and modified n-back task) is effective for studying stress-cognition interactions in CPA.
| S-EPMC6366876 | biostudies-literature
Project description:Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala, leading to increased fear and social anxiety. Several studies have demonstrated the prosocial effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of subchronic oxytocin on EEG activity in amygdala of mice during performance of the three-chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, whereas oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate prosocial and social anxiety pathways may mediate social preference.
| S-EPMC4518468 | biostudies-literature
Project description:BackgroundEstrogen increases dramatically during pregnancy but quickly drops below prepregnancy levels at birth and remains suppressed during the postpartum period. Clinical and rodent work suggests that this postpartum drop in estrogen results in an estrogen withdrawal state that is related to changes in affect, mood, and behavior. How estrogen withdrawal affects oxytocin (OT) neurocircuitry has not been examined.MethodsWe used a hormone-simulated pseudopregnancy followed by estrogen withdrawal in Syrian hamsters, a first for this species. Ovariectomized females were given daily injections to approximate hormone levels during gestation and then withdrawn from estrogen to simulate postpartum estrogen withdrawal. These hamsters were tested for behavioral assays of anxiety and anhedonia during estrogen withdrawal. Neuroplasticity in OT-producing neurons in the paraventricular nucleus of the hypothalamus and its efferent targets was measured.ResultsEstrogen-withdrawn females had increased anxiety-like behaviors in the elevated plus maze and open field tests but did not differ from control females in sucrose preference. Furthermore, estrogen-withdrawn females had more OT-immunoreactive cells and OT messenger RNA in the paraventricular nucleus of the hypothalamus and an increase in OT receptor density in the dorsal raphe nucleus. Finally, blocking OT receptors in the dorsal raphe nucleus during estrogen withdrawal prevented the high-anxiety behavioral phenotype in estrogen-withdrawn females.ConclusionsEstrogen withdrawal induces OT neuroplasticity in the paraventricular nucleus of the hypothalamus and dorsal raphe nucleus to increase anxiety-like behavior during the postpartum period. More broadly, these experiments suggest Syrian hamsters as a novel organism in which to model the effects of postpartum estrogen withdrawal on the brain and anxiety-like behavior.
| S-EPMC8052262 | biostudies-literature