Modulation Of Anxiety Research Articles

The role of Rajyoga meditation for modulation of anxiety and serum cortisol in patients undergoing coronary artery bypass surgery: A prospective randomized control study.

Introduction:Rajyoga meditation is a form of mind body intervention that is promoted by the Brahma Kumaris World Spiritual University. This form of meditation can be easily performed without rituals or mantras and can be practiced anywhere at any time. The practice of Rajyoga meditation can have beneficial effects on modulating anxiety and cortisol level in patients undergoing major cardiac surgery.Materials and Methods:A prospective randomized control study was carried out in a single tertiary care center. One hundred and fifty patients undergoing elective coronary artery bypass surgery were enrolled in the study. The patients were randomized in two groups namely, Group 1 (Rajyoga group) and Group 2 (Control Group). Anxiety was measured on a visual analog scale 1–10 before the start of Rajyoga training or patient counseling (T1), on the morning of the day of surgery (T2), on the 2nd postoperative day (T3), and on the 5th postoperative day (T4). The serum cortisol level was measured in the morning of the day of surgery (T1), on the 2nd postoperative day (T2) and on the 5th postoperative day (T3), respectively.Results:In the study, it was seen that the anxiety level of the patients before the surgery (T1) and on the day of surgery (T2) were comparable between the two groups. However on the 2nd postoperative day (T3), the patients who underwent Rajyoga training had lower anxiety level in comparison to the control group (3.12 ± 1.45 vs. 6.12 ± 0.14, P < 0.05) and on the 5th postoperative day (T4) it was seen that Rajyoga practice had resulted in significant decline in anxiety level (0.69 ± 1.1 vs. 5.6 ± 1.38, P < 0.05). The serum cortisol level was also favorably modulated by the practice of Rajyoga meditation.Conclusion:Mindbody intervention is found to effective in reducing the anxiety of the patients and modulating the cortisol level in patients undergoing wellknown stressful surgery like coronary artery bypass surgery.

Impact of Life History on Fear Memory and Extinction.

Behavioral profiles are strongly shaped by an individual's whole life experience. The accumulation of negative experiences over lifetime is thought to promote anxiety-like behavior in adulthood (“allostatic load hypothesis”). In contrast, the “mismatch hypothesis” of psychiatric disease suggests that high levels of anxiety-like behavior are the result of a discrepancy between early and late environment. The aim of the present study was to investigate how different life histories shape the expression of anxiety-like behavior and modulate fear memory. In addition, we aimed to clarify which of the two hypotheses can better explain the modulation of anxiety and fear. For this purpose, male mice grew up under either adverse or beneficial conditions during early phase of life. In adulthood they were further subdivided in groups that either matched or mismatched the condition experienced before, resulting in four different life histories. The main results were: (i) Early life benefit followed by late life adversity caused decreased levels of anxiety-like behavior. (ii) Accumulation of adversity throughout life history led to impaired fear extinction learning. Late life adversity as compared to late life benefit mainly affected extinction training, while early life adversity as compared to early life benefit interfered with extinction recall. Concerning anxiety-like behavior, the results do neither support the allostatic load nor the mismatch hypothesis, but rather indicate an anxiolytic effect of a mismatched early beneficial and later adverse life history. In contrast, fear memory was strongly affected by the accumulation of adverse experiences over the lifetime, therefore supporting allostatic load hypothesis. In summary, this study highlights that anxiety-like behavior and fear memory are differently affected by specific combinations of adverse or beneficial events experienced throughout life.

P.2.b.037 - Lurasidone for major depressive disorder with mixed features: effect of baseline depression severity on clinical outcome

Harm avoidance is a personality trait characterized by excessive worrying and fear of uncertainty, which has repeatedly been related to anxiety disorders. Converging lines of research in rodents and humans point towards an involvement of the nicotinic cholinergic system in the modulation of anxiety. Most notably, the rs1044396 polymorphism in the CHRNA4 gene, which codes for the α4 subunit of the nicotinic acetylcholine receptor, has been linked to negative emotionality traits including harm avoidance in a recent study. Against this background, we investigated the association between harm avoidance and the rs1044396 polymorphism using data from N=1673 healthy subjects, which were collected in the context of the German multi-centre study ׳Genetics of Nicotine Dependence and Neurobiological Phenotypes׳. Homozygous carriers of the C-allele showed significantly higher levels of harm avoidance than homozygous T-allele carriers, with heterozygous subjects exhibiting intermediate scores. The effect was neither modulated by age or gender nor by smoking status. By replicating previous findings in a large population-based sample for the first time, the present study adds to the growing evidence suggesting an involvement of nicotinic cholinergic mechanism in anxiety and negative emotionality, which may pose an effective target for medical treatment.

25.2 SOCIAL BUFFERING OF CONDITIONED AND INNATE FEAR RESPONSES

The social modulation of fear and anxiety represents a highly conserved trait. Humans and rodents display decreases in fear, anxiety, and stress responses when a conspecific is present. The neural basis of this is not well understood.

Baroreflex sensitivity and chronic pain : Pathogenetic significance and clinical implications

The interaction of cardiovascular dynamics and pain perception is an important component of intrinsic pain regulation. In healthy subjects acute pain stimuli cause increased sympathetic arousal and increased mean arterial pressure. Arterial baroreceptors sense phasic blood pressure changes and relay the information to the lower brainstem via the dorsomedial nucleus tractus solitarius (dmNTS). Projections in the brainstem and also higher cortical areas result in elevation of blood pressure as part of the autonomic nervous system as well as modulation of sleep, anxiety and pain. In healthy subjects there is an inverse relationship between blood pressure and pain sensitivity but this relationship is impaired in chronic pain patients. Persistent stress, pain behavior and classical and operant conditioning mechanisms reduce baroreflex sensitivity (BRS) and dmNTS activity in asubgroup of patients. This leads to adecrease of autonomic regulatory function as well as reduced pain inhibition. Importantly, baroreflex function can be modulated by cognitive and affective processes. This article reviews the role of the baroreflex arc as apossible crucial factor in the development and maintenance of chronic pain. The importance of learning mechanisms is described. Mechanism-based individualized treatment approaches for patients with hypertensive stress reactivity are also critically discussed.

Anxiety and depression with neurogenesis defects in exchange protein directly activated by cAMP 2-deficient mice are ameliorated by a selective serotonin reuptake inhibitor, Prozac.

Intracellular cAMP and serotonin are important modulators of anxiety and depression. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) also known as Prozac, is widely used against depression, potentially by activating cAMP response element-binding protein (CREB) and increasing brain-derived neurotrophic factor (BDNF) through protein kinase A (PKA). However, the role of Epac1 and Epac2 (Rap guanine nucleotide exchange factors, RAPGEF3 and RAPGEF4, respectively) as potential downstream targets of SSRI/cAMP in mood regulations is not yet clear. Here, we investigated the phenotypes of Epac1 (Epac1−/−) or Epac2 (Epac2−/−) knockout mice by comparing them with their wild-type counterparts. Surprisingly, Epac2−/− mice exhibited a wide range of mood disorders, including anxiety and depression with learning and memory deficits in contextual and cued fear-conditioning tests without affecting Epac1 expression or PKA activity. Interestingly, rs17746510, one of the three single-nucleotide polymorphisms (SNPs) in RAPGEF4 associated with cognitive decline in Chinese Alzheimer's disease (AD) patients, was significantly correlated with apathy and mood disturbance, whereas no significant association was observed between RAPGEF3 SNPs and the risk of AD or neuropsychiatric inventory scores. To further determine the detailed role of Epac2 in SSRI/serotonin/cAMP-involved mood disorders, we treated Epac2−/− mice with a SSRI, Prozac. The alteration in open field behavior and impaired hippocampal cell proliferation in Epac2−/− mice were alleviated by Prozac. Taken together, Epac2 gene polymorphism is a putative risk factor for mood disorders in AD patients in part by affecting the hippocampal neurogenesis.

Trait Anxiety Is Associated with Negative Interpretations When Resolving Valence Ambiguity of Surprised Faces.

The current research examines whether trait anxiety is associated with negative interpretation bias when resolving valence ambiguity of surprised faces. To further isolate the neuro-cognitive mechanism, we presented angry, happy, and surprised faces at broad spatial frequency (BSF), high spatial frequency (HSF), and low spatial frequency (LSF) and asked participants to determine the valence of each face. High trait anxiety was associated with more negative interpretations of BSF (i.e., intact) surprised faces. However, the modulation of trait anxiety on the negative interpretation of surprised faces disappeared at HSF and LSF. The current study provides evidence that trait anxiety modulates negative interpretations of BSF surprised faces. However, the negative interpretation of LSF surprised faces appears to be a robust default response that occurs regardless of individual differences in trait anxiety.

Dopamine D1 receptor activity is involved in the increased anxiety levels observed in STZ-induced diabetes in rats

Epidemiological surveys have indicated that anxiety disorders are more frequent in diabetic patients than in the general population. Similar results have been shown in animal studies using the streptozotocin (STZ)-induced diabetes model. The mechanisms underlying this relationship are not clearly understood, but it has been suggested that alterations in the dopaminergic neurotransmission, which plays an important role in the amygdaloid modulation of fear and anxiety, may be involved. The aim of this study was to ascertain whether or not the amygdaloid DA D1 receptors are involved in the increase of anxiety-like behavior observed in “diabetic” animals. Adult Wistar male rats were injected with STZ (50mg/kg, i.p.) in two consecutive days and subjected to the Shock-Probe Burying Test 10days after the beginning of treatment. STZ-treated rats showed a significant increase in immobility/freezing behavior whereas no effects were elicited in latency to bury, burying behavior itself and the number of shocks received during testing as compared with non-diabetic controls. These results suggest the triggering of a passive coping response in the STZ-treated rats. Interestingly, immobility/freezing behavior was reversed following the intra-amygdaloid dopamine D1 receptor blockade by the local microinfusion of SCH23390 (100ng/side). Autoradiographic experiments showed a selective increase of [3H]-SCH23390 binding in the ventral intercalated paracapsular islands of STZ-treated rats when compared to the non-treated control group. Our results suggest that a hyperdopaminergic state involving DA D1 receptors within the amygdala may have a role in the increase of anxiety observed in diabetic rats.

Functional lateralization of the medial prefrontal cortex in the modulation of anxiety in mice: Left or right?

It has been suggested that the left medial prefrontal cortex (LmPFC) has an inhibitory role in controlling the right mPFC (RmPFC), thereby reducing the deleterious effects of stressors on emotional states. Here, we investigated the effects on anxiety of bilateral or unilateral injections of NOC-9 [a nitric oxide (NO) donor] and cobalt chloride (CoCl2; a synaptic inhibitor) into the mPFC of mice exposed to the elevated plus-maze (Experiments 1 and 2). The effects of restraint or social defeat on anxiety in undrugged mice were recorded at 5 min or 24 h after exposure to the stress (Experiment 3). Experiment 4 investigated the effects of LmPFC injection of CoCl2 combined with restraint or social defeat on anxiety, which was recorded 24 h later. Although intra-RmPFC NOC-9 produced anxiogenesis, its injection into the LmPFC, or bilaterally, did not change anxiety. Intra-RmPFC or -LmPFC injection of CoCl2 produced anxiolytic- and anxiogenic-like effects, respectively. Both restraint and social defeat produced anxiogenesis at 5 min, but defeated mice did not display anxiety 24 h after the stress. Although intra-LmPFC CoCl2 did not change anxiety, which was recorded 24 h later in non-stressed mice, this synaptic inhibitor produced a clear, anxiogenic-like effect in defeated (but not restrained) mice. These results suggest that (i) nitrergic activation of the RmPFC increases anxiety, which in turn is inhibited by NO production within the LmPFC; (ii) neuronal inhibition of the RmPFC or LmPFC elicits anxiolysis and anxiogenesis, respectively; and (iii) inactivation of the LmPFC results in recrudescence of anxiety induced by social defeat stress.

CRF receptor type 1 (but not type 2) located within the amygdala plays a role in the modulation of anxiety in mice exposed to the elevated plus maze

The amygdala (Amy) is an important center that processes threatening stimuli. Among the neurotransmitters implicated in the control of emotional states, the corticotrophin releasing factor (CRF) is an important modulator, acting at CRF1 and CRF2 receptors. Few studies have investigated the role of CRF and its receptors in the Amy on anxiety in mice. Here, we investigated the effects of intra-Amy (aimed at the basolateral nucleus) injections of CRF (37.5 and 75pmol/0.1μl), urocortin 3 (UCn3, a selective CRF2 agonist; 4, 8, 16 or 24pmol/0.1μl), CP376395 (a selective CRF1 antagonist; 0.375, 0.75 or 1.5nmol/0.1μl), antisauvagine-30 (ASV-30, a selective CRF2 antagonist; 1 or 3nmol/0.1μl) on the behavior of mice exposed to the elevated plus maze (EPM). Both spatiotemporal (e.g., percentage of open-arm entries and percentage of open-arm time; %OE and %OT) and complementary [e.g., frequency of protected and unprotected stretched attend postures (pSAP and uSAP) and head dips (pHD and uHD); frequency and time spent on open arm end exploration (OAEE)] measures were recorded during a 5-min test in the EPM. While intra-Amy injections of CRF decreased %OE, %OT and OAEE, suggesting an anxiogenic-like action, UCn3 (all doses) did not change any behavior. In contrast, injections of CP376395 (0.75nmol) produced an anxiolytic-like effect, by increasing %OT and OAEE and decreasing pSAP and pHD. Neither spatiotemporal nor complementary measures were changed by intra-Amy ASV-30. These results suggest that CRF plays a marked anxiogenic role at CRF1 receptors in the amygdala of mice exposed to the EPM.

Modulation of anxiety and fear via distinct intrahippocampal circuits.

Recent findings indicate a high level of specialization at the level of microcircuits and cell populations within brain structures with regards to the control of fear and anxiety. The hippocampus, however, has been treated as a unitary structure in anxiety and fear research despite mounting evidence that different hippocampal subregions have specialized roles in other cognitive domains. Using novel cell-type- and region-specific conditional knockouts of the GABAA receptor α2 subunit, we demonstrate that inhibition of the principal neurons of the dentate gyrus or CA3 via α2-containing GABAA receptors (α2GABAARs) is required to suppress anxiety, while the inhibition of CA1 pyramidal neurons is required to suppress fear responses. We further show that the diazepam-modulation of hippocampal theta activity shows certain parallels with our behavioral findings, suggesting a possible mechanism for the observed behavioral effects. Thus, our findings demonstrate a double dissociation in the regulation of anxiety versus fear by hippocampal microcircuitry.

Noradrenaline microinjected into the dorsal periaqueductal gray matter causes anxiolytic-like effects in rats tested in the elevated T-maze

AimsThe dorsal periaqueductal gray matter (dPAG) is involved in the integration of behavioral and cardiovascular responses caused by fear and anxiety situations. Some studies suggest an involvement of noradrenergic neurotransmission in the dPAG in anxiety modulation, however, there is no evidence about its role in panic attacks. The goal of this work was to study the effect of NA microinjection in dPAG in rats submitted to the elevated T-maze (ETM). Materials and methodsMale Wistar had a cannula implanted in the PAG where it was injected NA in the doses of 1, 3, 15, 45nmol/50nl or artificial cerebrospinal fluid previous the ETM test. Key findings.NA intra-dPAG decreased inhibitory avoidance behavior in the ETM without changing escape, indicating only an anxiolytic-like effect. Furthermore, the microinjection of NA did not change the general exploratory activity of the animals submitted to the open field test, suggesting that the anxiolytic-like effect is not due to an increase in exploratory activity. SignificanceThe results indicate an involvement of noradrenergic neurotransmission in the dPAG in defensive reactions associated with generalized anxiety, but not as main mechanisms for the panic, in rats submitted to the elevated T-maze providing support for other research aimed at improving the treatment of generalized anxiety.

The activation and blockage of CRF type 2 receptors of the medial amygdala alter elevated T-maze inhibitory avoidance, an anxiety-related response

Previous results show that the activation of CRF type 1 (CRFR1) receptors of the medial amygdala (MeA) induces anxiogenic-like effects. The present study investigates the role played by medial amygdala CRF type 2 receptors (CRFR2) in the modulation of anxiety and panic-related responses. Male Wistar rats were administered into the MeA with the CRFR2 agonist urocortin 2 (0.5 e 1.0μg/0.2μl, experiment 1) or with the CRFR2 antagonist astressin 2-B (60ng/0.2μl, experiment 2) and 10min later tested in the elevated T-maze (ETM) for inhibitory avoidance and escape measurements. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. In a third experiment, the effects of the combined treatment with urocortin 2 (1.0μg/0.2μl) and a sub-effective dose of astressin 2-B (30ng/0.2μl) were also investigated. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Results showed that urocortin 2, in the highest dose administered (1.0μg/0.2μl), facilitated ETM avoidance, an anxiogenic-like effect. Astressin 2-B, also in the highest dose (60ng/0.2μl), significantly decreased avoidance latencies, an anxiolytic-like effect. The lower dose of astressin 2-B (30ng/0.2μl) did not induce anxiolytic-like effects but was able to counteract the anxiogenic-like effects of urocortin 2. None of the compounds administered altered escape responses or locomotor activity measurements. These results suggest that CRFR2 in the medial amygdala, as CRFR1, selectively modulate an anxiety-related response.

Social media modulation of mood and anxiety in adolescents with chronic visible skin conditions

Chronic skin diseases are often associated with psychiatric disorders, and psychological factors such as stress can affect the management of skin conditions. In adolescents, skin diseases can have a profound impact on body image, self-esteem and social interactions. Social media is a mode of communication increasingly used, especially among adolescents. It has been shown to have detrimental effect by the negative influence of peers through social network interactions as well as positive effects by allowing support and access to care. The posting of pictures of individuals by others in social media may make this mode of communication particularly distressful for teens with a visible skin condition; they cannot control the photos being shared with the group and are reminded of the visibility of their skin condition through these postings. To determine how social media may impact mental health and skin disease management in adolescents’ with chronic visible skin conditions, we conducted a survey of patients in the ambulatory setting. This cross-sectional study is based on an anonymous survey in teens, age 12 to 19, with various levels of chronic visible skin conditions. It explores the influences of social media on incidence and or severity of both psychiatric and dermatological health status as self-reported by patients. Acne, psoriasis, and atopic dermatitis are often associated with poor quality of life even with moderate skin disease. Taking in account the impact of social media on these pathologies is especially critical among adolescents due to their wide use and relevance in this population.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats.

The heme oxygenase-carbon monoxide pathway has been shown to play an important role in many physiological processes and is capable of altering nociception modulation in the nervous system by stimulating soluble guanylate cyclase (sGC). In the central nervous system, the locus coeruleus (LC) is known to be a region that expresses the heme oxygenase enzyme (HO), which catalyzes the metabolism of heme to carbon monoxide (CO). Additionally, several lines of evidence have suggested that the LC can be involved in the modulation of emotional states such as fear and anxiety. The purpose of this investigation was to evaluate the activation of the heme oxygenase-carbon monoxide pathway in the LC in the modulation of anxiety by using the elevated plus maze test (EPM) and light-dark box test (LDB) in rats. Experiments were performed on adult male Wistar rats weighing 250-300 g (n=182). The results showed that the intra-LC microinjection of heme-lysinate (600 nmol), a substrate for the enzyme HO, increased the number of entries into the open arms and the percentage of time spent in open arms in the elevated plus maze test, indicating a decrease in anxiety. Additionally, in the LDB test, intra-LC administration of heme-lysinate promoted an increase on time spent in the light compartment of the box. The intracerebroventricular microinjection of guanylate cyclase, an sGC inhibitor followed by the intra-LC microinjection of the heme-lysinate blocked the anxiolytic-like reaction on the EPM test and LDB test. It can therefore be concluded that CO in the LC produced by the HO pathway and acting via cGMP plays an anxiolytic-like role in the LC of rats.

Investigation the protective effect of vitamin C on anxiety and oxidative stress modulation in male rats treated with progesterone

Investigation the protective effect of vitamin C on anxiety and oxidative stress modulation in male rats treated with progesterone

Disruption of Epithalamic Left-Right Asymmetry Increases Anxiety in Zebrafish.

Differences between the left and right sides of the brain are found throughout the animal kingdom, but the consequences of altered neural asymmetry are not well understood. In the zebrafish epithalamus, the parapineal is located on the left side of the brain where it influences development of the adjacent dorsal habenular (dHb) nucleus, causing the left and right dHb to differ in their organization, gene expression, and connectivity. Left-right (L-R) reversal of parapineal position and dHb asymmetry occurs spontaneously in a small percentage of the population, whereas the dHb develop symmetrically following experimental ablation of the parapineal. The habenular region was previously implicated in modulating fear in both mice and zebrafish, but the relevance of its L-R asymmetry is unclear. We now demonstrate that disrupting directionality of the zebrafish epithalamus causes reduced exploratory behavior and increased cortisol levels, indicative of enhanced anxiety. Accordingly, exposure to buspirone, an anxiolytic agent, significantly suppresses atypical behavior. Axonal projections from the parapineal to the dHb are more variable when it is located on the right side of the brain, revealing that L-R reversals do not necessarily represent a neuroanatomical mirror image. The results highlight the importance of directional asymmetry of the epithalamus in the regulation of stress responses in zebrafish.

Replication of the association between CHRNA4 rs1044396 and harm avoidance in a large population-based sample

Harm avoidance is a personality trait characterized by excessive worrying and fear of uncertainty, which has repeatedly been related to anxiety disorders. Converging lines of research in rodents and humans point towards an involvement of the nicotinic cholinergic system in the modulation of anxiety. Most notably, the rs1044396 polymorphism in the CHRNA4 gene, which codes for the α4 subunit of the nicotinic acetylcholine receptor, has been linked to negative emotionality traits including harm avoidance in a recent study. Against this background, we investigated the association between harm avoidance and the rs1044396 polymorphism using data from N=1673 healthy subjects, which were collected in the context of the German multi-centre study ׳Genetics of Nicotine Dependence and Neurobiological Phenotypes׳. Homozygous carriers of the C-allele showed significantly higher levels of harm avoidance than homozygous T-allele carriers, with heterozygous subjects exhibiting intermediate scores. The effect was neither modulated by age or gender nor by smoking status. By replicating previous findings in a large population-based sample for the first time, the present study adds to the growing evidence suggesting an involvement of nicotinic cholinergic mechanism in anxiety and negative emotionality, which may pose an effective target for medical treatment.

Stress, anxiety and central neural modulation of cardiovascular stress response in rats

Stress, anxiety and central neural modulation of cardiovascular stress response in rats

Novel Synthesis and Pharmacological Characterization of NOP Receptor Agonist 8-[(1S,3aS)-2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro 64-6198).

The nociceptin/orphanin FQ opioid peptide (NOP) receptor is a widely expressed GPCR involved in the modulation of pain, anxiety, and motor behaviors. Dissecting the functional properties of this receptor is limited by the lack of systemically active ligands that are brain permeant. The small molecule NOP receptor-selective, full agonist 8-[(1S,3aS)-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro 64-6198) hydrochloride is an active, brain penetrant ligand, but its difficult and cost-prohibitive synthesis limits its widespread use and availability for animal studies. Here, we detail a more efficient and convenient method of synthesis, and use both in vitro and in vivo pharmacological assays to fully characterize this ligand. Specifically, we characterize the pharmacodynamics of Ro 64-6198 in cAMP and G-protein coupling in vitro and examine, for the first time, the effects of nociceptin/orphanin FQ and Ro 64-6198 in arrestin recruitment assays. Further, we examine the effects of Ro 64-6198 on analgesia, anxiety, and locomotor responses in vivo. This new synthesis and pharmacological characterization provide additional insights into the useful, systemically active, NOP receptor agonist Ro 64-6198.