Role In Anxiety Disorders Research Articles

The relationship between dietary sugar consumption and anxiety disorders: A systematic review.

High-sugar intake is a risk factor for chronic diseases such as cardiovascular disease and type 2 diabetes, but less is known about its role in anxiety disorders. This systematic review aimed to systematically synthesise and assess the existing evidence regarding the association between dietary sugars intake and anxiety disorders. Following PRISMA guidelines, a systematic search of PubMed, MEDLINE, Embase, APA PsycArticles and APA PsycINFO was conducted up to 19th August 2022. Study quality was assessed by the Newcastle-Ottawa scale (NOS) and the Cochrane risk of bias tool. Eleven studies (10 cross-sectional and 1 randomised controlled trial [RCT]) were included. Seven cross-sectional studies had very good quality or good quality, and the quality of the RCT was at low risk of bias. These studies examined sugar-sweetened beverages (n = 7), sugar-sweetened foods (n = 4) and/or added sugar (n = 5). The findings suggest a possible positive relationship of added sugar consumption with anxiety disorders, with age as a potential moderator in such association. No conclusions can be drawn on the associations between sugar-sweetened beverages, sugar-sweetened foods consumption and anxiety disorders. Due to the included studies being mostly cross-sectional, the conclusions drawn from the existing evidence should be interpreted with caution. The longitudinal design is warranted to investigate any causal relationship and the potential mechanisms underlying these heterogeneous results. The potential difference in effect at different ages observed in this review should be further examined.

Comparative evaluation of the antianxiety effects of Vitamin C, buspirone, and diazepam in rats

Background: Anxiety is one of the common mental disorders. Non-fatal health loss is one of the consequences of anxiety disorders. Oxidative stress may also play a role in anxiety disorders. As an antioxidant, Vitamin C can create stable ascorbate free radicals and lower reactive oxygen species. In addition, Vitamin C can prevent damage caused by free radicals. Oxidative stress can also lead to depression, schizophrenia, and bipolar disorder. Aim and Objectives: The aim and objectives of the study are to compare the antianxiety effects of Vitamin C, buspirone, and diazepam in albino rats using elevated plus maze and hole board apparatus. Materials and Methods: 36 albino rats of either sex were divided into 6 groups of 6 rats each and drugs were administered orally. Group 1 received distilled water 10 ml/kg, Group 2 received Vitamin C 200 mg/kg, Group 3 received buspirone 10 mg/kg, Group 4 received diazepam 1 mg/kg, Group 5 received buspirone 10 mg/kg + Vitamin C 200 mg/kg, and Group 6 received diazepam 1 mg/kg + Vitamin C 200 mg/kg. Antianxiety effects of these drugs were tested after 14 days of drug administration using hole board apparatus and elevated plus maze. The methods used for statistical analysis were mean, standard deviation, confidence interval, median, interquartile range (IQR), frequency and percentage, ANOVA, Kruskal–Wallis test, and Fisher’s exact test. Results: On average time spent in open arms by Group 5 was 98.00 sec (IQR: 19.75–138.00) which was higher than other groups, but it was not statistically significant (P = 0.845). The time spent in closed arms in seconds by Group 4 was 245 ± 28.863, which was higher than other groups, but it was not statistically significant (P = 0. 805). On average head dip by Group 5 was 9.83 ± 4.708, which was higher than other groups, but it was not statistically significant (P = 0.141). Conclusion: Group 5 rats that received buspirone and Vitamin C, followed by Group 6 rats that received diazepam and Vitamin C had spent more time and had more entries into the open arms. Furthermore, Groups 5 and 6 animals had a greater number of head dips in the hole board apparatus compared to the behavior of all animals in other groups. Buspirone and diazepam are known anxiolytics. When these drugs were given in combination with Vitamin C, the antianxiety behaviors in rats were more compared to the drugs given alone in the present study but it was not statistically significant.

Bile acid signalling and its role in anxiety disorders.

Anxiety disorder is a prevalent neuropsychiatric disorder that afflicts 7.3%~28.0% of the world's population. Bile acids are synthesized by hepatocytes and modulate metabolism via farnesoid X receptor (FXR), G protein-coupled receptor (TGR5), etc. These effects are not limited to the gastrointestinal tract but also extend to tissues and organs such as the brain, where they regulate emotional centers and nerves. A rise in serum bile acid levels can promote the interaction between central FXR and TGR5 across the blood-brain barrier or activate intestinal FXR and TGR5 to release fibroblast growth factor 19 (FGF19) and glucagon-like peptide-1 (GLP-1), respectively, which in turn, transmit signals to the brain via these indirect pathways. This review aimed to summarize advancements in the metabolism of bile acids and the physiological functions of their receptors in various tissues, with a specific focus on their regulatory roles in brain function. The contribution of bile acids to anxiety via sending signals to the brain via direct or indirect pathways was also discussed. Different bile acid ligands trigger distinct bile acid signaling cascades, producing diverse downstream effects, and these pathways may be involved in anxiety regulation. Future investigations from the perspective of bile acids are anticipated to lead to novel mechanistic insights and potential therapeutic targets for anxiety disorders.

Aberrant functional connectivity of the bed nucleus of the stria terminalis and its age dependence in children and adolescents with social anxiety disorder.

Social anxiety disorder (SAD) is a prevalent and impairing mental disorder among children and adolescents. The bed nucleus of the stria terminalis (BNST) plays a critical role in anxiety disorders, including valence surveillance and hypervigilance for potential threats. However, the role of BNST and its related functional network in children and adolescents with SAD has not been fully investigated. This study examined the aberration of BNST's functional connectivity and its age dependence in adolescents with SAD. Using a sample of 75 SAD patients and 75 healthy controls (HCs) children aged 9-18 years old, we delineated the group-by-age interaction of BNST-seeded functional connectivity (FC) during resting state and movie-watching. The relationships between BNST-seeded FC and clinical scores were also examined. During movie viewing, the FC between the right BNST and the left amygdala, bilateral posterior cingulate cortex (PCC), bilateral superior temporal cortex, and right pericalcarine cortex showed a diagnostic group-by-age interaction. Compared to HCs, SAD patients showed a significant enhancement of the above FC at younger ages. Meanwhile, they showed an age-dependent decrease in FC between the right BNST and left amygdala. Furthermore, for SAD patients, FC between the right BNST and left amygdala during movie viewing was positively correlated with separation anxiety scores. The right BNST plays an essential role in the aberrant brain functioning in children and adolescents with SAD. The atypicality of BNST's FC has remarkable age dependence in SAD, suggesting an association of SAD with neurodevelopmental traits.

The effect of imagery rescripting on prospective mental imagery of a feared social situation

Background and objectivesNegative mental imagery appears to play a role in anxiety disorders and can involve aversive memories or anticipated future threats. Modulating aversive memories through imagery rescripting generally reduces negative memory appraisals and associated anxiety. This pre-registered two-day analog study investigated whether imagery rescripting of aversive memories also reduces negative imagery of future threats. MethodsOn Day 1, socially anxious individuals (N = 52) were randomly assigned to imagery rescripting of an aversive memory or progressive relaxation (control condition). Before each intervention, they were asked to imagine a feared social situation that may happen in their future and evaluate this situation. They also rated the aversive memory before and after the intervention phase. The feared future situation was again evaluated at follow-up on Day 2. ResultsUnexpectedly, no group differences were found on the main outcome measures. That is, negative memory appraisals reduced after both interventions. Likewise, in both groups, negative details decreased, and positive details increased in prospective mental imagery, and anxiety and avoidance towards the imagined event decreased. On the exploratory measures, the imagery rescripting group showed increased positive appraisals of memory and future threat, and decreased negative future-threat appraisals, compared to the progressive relaxation group. LimitationsNo passive control group was included, so potential time or placebo effects cannot be precluded. ConclusionsThe interventions had similar effects on the main outcomes and influenced mental imagery of future threats. Some differences were found on the exploratory measures that warrant further investigation with a passive control condition.

To explore the potential molecular mechanism of complex rose-bergamot essential oil on anti-anxiety with facial spots based on network pharmacology.

To explore the potential mechanism of complex rose-bergamot essential oil against anxiety accompanied with facial spots through network pharmacology. The components of rose and bergamot essential oils were determined by GC-MS and obtained from literature, and their action targets were predicted by PubChem, SwissADME and SwissTargetPrediction databases. Using "Anxiety disorder" and "Facial pigmentation" as keywords, the relevant targets of anxiety disorder and facial spots were mined in the databases of DrugBank, TTD, GeneCards, and OMIM. The intersection targets of complex rose-bergamot essential oil and anxiety accompanied with facial spots diseases were obtained by making Venn diagram, respectively. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of intersection targets were carried out through STRING platform, Metascape, and KEGG Mapper databases. The "complex essential oil- component- target- pathway" network was constructed by Cytoscape software. The key active compounds and core targets were docked by AutoDock software. A total of 34 active components of complex rose-bergamot essential oil and 405 corresponding targets were obtained. The intersection targets of complex essential oil with anxiety disorder and facial spot were 88 and 34, respectively, and the related KEGG pathways were 137 and 123 items, respectively. Neroli acetate, Neroli alcohol, and Linalool in complex rose-bergamot essential oil could play a therapeutic role in anxiety disorder by regulating key targets such as SLC6A4, GRIN2B and DRD2 to participate in the neuroactive ligand-receptor interaction and serotonergic synapse and other pathways, they also could play a role in the treatment of facial spots by regulating key targets such as EGFR, VEGFA, and PIK3CA in the PI3K-AKT, JAK-STAT and other signal pathways. The molecular docking between the key compounds and the core targets showed that the binding energy was less than 0kcal /mol, indicating that the compound and the target could bind stably. Complex rose-bergamot essential oil can play a role in the treatment of anxiety disorder with facial spots through the synergistic mechanism of multicomponent, multitarget, and multipathway.

Highly Demand Working Memory Intervention Weakens a Reactivated Threat Memory and the Associated Cognitive Biases

Anxiety disorders are the most frequent type of mental disorder. Threat-conditioning memory plays a central role in anxiety disorders, impacting complex cognitive systems by modifying behavioral responses to fearful stimuli and inducing an overestimation of potential threats. Here, we analyzed the reminder-dependent amnesia on physiological responses, unconditioned stimulus (US) expectancy ratings, and measures of cognitive bias towards the threat of a threat-conditioning memory.Subjects received differential threat-conditioning. Twenty-four hours later, after reactivation of the memory of threat-conditioning, one group performed a high demand working memory task (HWM) and a second group a low demand working memory task (LWM). A third group only performed the HWM task. Retention of conditioned threat memory was tested on Day 3 in an extinction session followed by a reinstatement test. Tasks targeting stimulus representation, valuation, and attentional bias towards threat were performed. We show that the reminder-dependent intervention with an HWM weakened memory retention as expressed in skin conductance response (SCR) and faded the representation and valuation towards the threat, but it did not affect US expectancy or attentional bias. Our findings provide evidence for the experimental psychopathology approach opening the possibility to weaken both Threat conditioning memory and the systems associated with the maintenance of anxiety features.

Do Metacognitions of Children and Adolescents with Anxiety Disorders Change after Intensified Exposure Therapy?

Metacognitive beliefs have repeatedly proven to play a role in anxiety disorders in children and adolescents, but few studies have investigated whether they change after cognitive behavioral therapy. This longitudinal intervention study explores whether positive and negative metacognitive beliefs in particular change after exposure-focused treatment, and if metacognitive changes predict reductions in anxiety symptoms. A sample of 27 children between 8 and 16 years of age with a primary diagnosis of specific phobia, separation-anxiety disorder or social phobia completed assessments of anxiety symptoms, metacognitive beliefs, worry and repetitive negative thoughts before and after 11 sessions of intensified exposure treatment. Metacognitive beliefs did not change significantly after intensified exposure, but post-hoc power analysis revealed a lack of power here. Change in negative metacognitive beliefs correlated with a change in anxiety symptoms, but did not independently contribute as a predictor variable. Differences between subsamples showed that patients with separation-anxiety disorder scored higher on negative metacognitive beliefs than those with specific or social phobia. Consideration of metacognition, and negative metacognitive beliefs in particular could help us further improve the understanding and treatment of anxiety disorders in children and adolescents and should therefore receive more attention in psychotherapy research.

The role of shame and guilt in social anxiety disorder

• Shame plays an important role in the understanding of social anxiety disorders. • Shame contributes significantly to the variation in social anxiety disorders over and above depression. • Guilt does not seem to have a notable association with social anxiety disorder, at least not contextual-legitimate guilt. For maladaptive forms of guilt, further research is required. Research suggests that shame and guilt may play a role in anxiety disorders. For social anxiety disorder (SAD), however, only a few studies investigated patients with the primary diagnosis of SAD. Thus, further research on shame and guilt in SAD is required. A secondary analysis of Data from the SOPHO-NET multicenter treatment study was performed. In a large sample of N = 495 patients with the primary diagnosis of SAD the relationship between shame and guilt with symptoms of social anxiety, depression, and interpersonal problems was examined by means of correlation analysis and additionally, a hierarchical linear regression analysis. To assess SAD, the German version of the Structured Clinical Interview for DSM-IV was used. Shame and guilt were assessed by the Test of Self-Conscious Affect. Results showed significant associations between internal shame and SAD symptoms, depression, and interpersonal problems. Internal shame contributed significantly to the variation in SAD symptoms over and above depression. Contextual-legitimate guilt was neither correlated with SAD symptoms nor with interpersonal problems. For depression, a significant but very small correlation with SAD symptoms was found that did not persist after controlling for internal shame by partial correlation. Internal shame but not contextual-legitimate guilt plays a role in SAD. It seems to be not only associated with symptoms of social anxiety but also with depression and interpersonal problems. Future studies should examine whether a focus on internal shame may be useful in treating SAD.

Neural Processing of Cognitive Control in an Emotionally Neutral Context in Anxiety Patients.

Impaired cognitive control plays a crucial role in anxiety disorders and is associated with deficient neural mechanisms in the fronto-parietal network. Usually, these deficits were found in tasks with an emotional context. The present study aimed at investigating electrophysiological and vascular signatures from event-related brain potentials (ERPs) and functional near-infrared spectroscopy (fNIRS) in anxiety patients versus healthy controls during an inhibition task integrated in an emotionally neutral context. Neural markers were acquired during the completion of a classical Eriksen flanker task. The focus of data analysis has been the ERPs N200 and P300 and fNIRS activations in addition to task performance. No behavioral or neural group differences were identified. ERP findings showed a larger N2pc and a delayed and reduced P300 for incongruent stimuli. The N2pc modulation suggests the reorienting of attention to salient stimuli, while the P300 indicates longer lasting stimulus evaluation processes due to increased task difficulty. FNIRS did not result in any significant activation potentially suggesting a contribution from deeper brain areas not measurable with fNIRS. The missing group difference in our non-emotional task indicates that no generalized cognitive control deficit but rather a more emotionally driven deficit is present in anxiety patients.

Intranasal oxytocin decreases fear generalization in males, but does not modulate discrimination threshold.

A previously acquired fear response often spreads to perceptually or conceptually close stimuli or contexts. This process, known as fear generalization, facilitates the avoidance of danger, and dysregulations in this process play an important role in anxiety disorders. Oxytocin (OT) has been shown to modulate fear learning, yet effects on fear generalization remain unknown. We employed a randomized, placebo-controlled, double-blind, between-subject design during which healthy male participants received either intranasal OT or placebo (PLC) following fear acquisition and before fear generalization with concomitant acquisition of skin conductance responses (SCRs). Twenty-four to 72h before the fear learning and immediately after the fear generalization task, participants additionally complete a discrimination threshold task. Relative to PLC, OT significantly reduced perceived risk and SCRs towards the CS+ and GS1 (the generalization stimulus that is most similar to CS+) during fear generalization, whereas the discrimination threshold was not affected. Together, the results suggest that OT can attenuate fear generalization in the absence of effects on discrimination threshold. This study provides the first evidence for effects of OT on fear generalization in humans and suggests that OT may have therapeutic potential in anxiety disorders characterized by dysregulated fear generalization.

Psychodinamic Aspect in Mixed Anxiety and Depression Disorder: a Case Report

Abstract
 Introduction. According to the ICD-10 criteria, mixed anxiety disorders and depression (MADD) are characterized by symptoms of anxiety and subsyndromal depression that occur together, but nothing dominates. A mixture of anxiety and depression disorders have various risk factors that underlie the occurrences. This case report aims to discuss the mixture of anxiety and depression disorders and their background.
 Case Presentation. A man, 23 years old, college student, single, middle down the socio-economic background, lived in a rural area in Yogyakarta, came to consult a psychiatrist at the psychiatric clinic Dr. Sardjito general hospital with complaints felt excessive anxiety and depressed because they were unable to do the thesis. From the psychiatric examination, it was found that men according to age, good self-care, thin body posture, many bowed, often moving his hands, looking nervous, cooperative, intonation and small voice volume, clear articulation, depressed mood, depressed mood, inappropriate affect, realistic thought, worried, worried about moving house, worried about the future, worried about people's assumptions about patients for fear of being blamed, sinful ideas, low self-esteem ideas, ideas of reference, ambivalence, a progression of coherent thought, relevance, good orientation, good memory, mental relations can, there are disturbances in concentration and attention, good impulse control. The patient realizes that what he is thinking is not real and only exists in his mind.
 Conclusion. Psychodynamic aspects have a role in anxiety disorders and depression.

The impact of prior and ongoing threat on the false alarm threshold for facial discrimination

Background and objectivesPerceptual adaptations that facilitate rapid responses to threats can also lead to false alarms, or the failure to discriminate safe stimuli from signals of threat. We examined the impact of varying degrees of threat on false alarms in the perceptual discrimination of faces along the dimension of emotion (Experiment 1) or identity (Experiment 2). MethodsParticipants first trained to discriminate between a target and nontarget face. Next, we tested their ability to identify the target in randomized presentations of the target, the nontarget, and nine novel stimuli morphed in 10% increments of similarity from the target to the nontarget. The task was completed under one of three randomized conditions: 1) Ongoing-Threat paired the target with an aversive outcome in both phases; 2) Prior-Threat paired the target with an aversive outcome in the training phase only; and 3) No-Threat paired the target with a neutral outcome in the training phase only. ResultsIn Experiment 1 (N = 90), Ongoing-Threat lowered the false alarm threshold for facial discrimination based on anger intensity compared to Prior-Threat and No-Threat. In Experiment 2 (N = 90), Ongoing-Threat and Prior-Threat each lowered the false alarm threshold for identity-based discrimination compared to No-Threat. LimitationsThe experiment did not measure generalization of threat responses. ConclusionAssociating a facial expression or identity with threat leads to faster but less accurate discrimination of faces with similar features, particularly under conditions of ongoing threat. These experiments provide an avenue for examining the parameters that impact false alarms, which play a key role in anxiety disorders.

Sleep deprivation increases threat beliefs in human fear conditioning.

SummarySleep disturbances and anxiety disorders exhibit high comorbidity levels, but it remains unclear whether sleep problems are causes or consequences of increased anxiety. To experimentally probe the aetiological role of sleep disturbances in anxiety, we investigated in healthy participants how total sleep deprivation influences fear expression in a conditioning paradigm. In a fear conditioning procedure, one face stimulus (conditioned stimulus [CS+]) was paired with electric shock, whereas another face stimulus was not (unpaired stimulus [CS−]). Fear expression was tested the next morning using the two face stimuli from the training phase and a generalization stimulus (i.e. a morph between the CS+ and CS− stimuli). Between fear conditioning and test, participants were either kept awake in the laboratory for 12 hr (n = 20) or had a night of sleep at home (n = 20). Irrespective of stimulus type, subjective threat expectancies, but not skin conductance responses, were enhanced after sleep deprivation, relative to regular sleep. These results suggest that sleep disturbances may play a role in anxiety disorders by increasing perceived threat.

Synergistic effects between ADORA2A and DRD2 genes on anxiety disorders in children with ADHD

The prevalence of anxiety disorders in patients with Attention Deficit/Hyperactivity Disorder (ADHD) is around 15–40%, three times higher than in the general population. The dopaminergic system, classically associated with ADHD, interacts directly with the adenosinergic system through adenosine A2A receptors (A2A) and dopamine D2 receptors (D2) forming A2A-D2 heterodimers. Both dopaminergic and adenosinergic systems are implicated in anxiety disorders. Therefore, the aims of this study were: a) to investigate the main effects of ADORA2A and DRD2 gene variants on anxiety disorders in an ADHD sample of children and adolescents; b) to test potential synergism between ADORA2A and DRD2 genes on the same outcome; c) to explore ADORA2A variants functionality using an in silico approach. The sample consists of 478 children and adolescents with ADHD and their parents, totalizing 1.239 individuals. An association between the ADORA2A rs2298383 TT genotype with the presence of anxiety disorders (P = .004) and an interaction between ADORA2A-DRD2 risk haplotypes with the same outcome (P = .005) was detected. The in silico analyses showed that rs2298383 has the highest score for regulatory function among all variants in the ADORA2A gene described up to date. Altogether, the present findings suggested that the ADORA2A gene and the interaction of ADORA2A and DRD2 genes may play a role in anxiety disorders in children and adolescents with ADHD.

A psychometric comparison of anxiety-relevant attention measures

ABSTRACTBackground and Objectives: Preferential attention to threat, emotional response inhibition, and attentional control each purportedly play a key role in anxiety disorders. Divergent psychometric properties among attention measures may produce differential detection of anxiety-related associations and treatment-related changes. However, no studies have directly compared the psychometric properties of these attention measures in the same sample.Design: Eighty-five young adults (M = 19.41 years, SD = 1.47, 48 Females) completed a cognitive task battery and a subset of 60 participants (M = 19.42 years, SD = 1.48, 33 Females) completed the task battery again approximately two weeks later.Method: To assess preferential attention to threat, emotional response inhibition, and attentional control, the cognitive task battery included a dot-probe task, emotion and gender Stroop tasks, and a flanker task. Tasks varied in how attention was directed and if emotional stimuli were included. Internal consistency and test-retest reliability were compared across measures.Results: Within the same sample, internal consistency and reliability differed across attention measures. Explicit attention measures (emotional Stroop and flanker) exhibited stronger internal consistency and greater test-retest reliability compared to implicit measures (dot-probe and gender Stroop).Conclusions: These results inform clinical research using attention measures to assess anxiety-related differences and treatment response.

Increased mortality among people with anxiety disorders: total population study.

Anxiety disorders and depression are the most common mental disorders worldwide and have a striking impact on global disease burden. Although depression has consistently been found to increase mortality; the role of anxiety disorders in predicting mortality risk is unclear. To assess mortality risk in people with anxiety disorders. We used nationwide Danish register data to conduct a prospective cohort study with over 30 million person-years of follow-up. In total, 1066 (2.1%) people with anxiety disorders died during an average follow-up of 9.7 years. The risk of death by natural and unnatural causes was significantly higher among individuals with anxiety disorders (natural mortality rate ratio (MRR) = 1.39, 95% CI 1.28-1.51; unnatural MRR = 2.46, 95% CI 2.20-2.73) compared with the general population. Of those who died from unnatural causes, 16.5% had comorbid diagnoses of depression (MRR = 11.72, 95% CI 10.11-13.51). Anxiety disorders significantly increased mortality risk. Comorbidity of anxiety disorders and depression played an important part in the increased mortality.

Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala

Stress and glucocorticoids stimulate the rapid mobilization of endocannabinoids in the basolateral amygdala (BLA). Cannabinoid receptors in the BLA contribute to anxiogenesis and fear-memory formation. We tested for rapid glucocorticoid-induced endocannabinoid regulation of synaptic inhibition in the rat BLA. Glucocorticoid application to amygdala slices elicited a rapid, nonreversible suppression of spontaneous, but not evoked, GABAergic synaptic currents in BLA principal neurons; the effect was also seen with a membrane-impermeant glucocorticoid, but not with intracellular glucocorticoid application, implicating a membrane-associated glucocorticoid receptor. The glucocorticoid suppression of GABA currents was not blocked by antagonists of nuclear corticosteroid receptors, or by inhibitors of gene transcription or protein synthesis, but was blocked by inhibiting postsynaptic G-protein activity, suggesting a postsynaptic nongenomic steroid signaling mechanism that stimulates the release of a retrograde messenger. The rapid glucocorticoid-induced suppression of inhibition was prevented by blocking CB1 receptors and 2-arachidonoylglycerol (2-AG) synthesis, and it was mimicked and occluded by CB1 receptor agonists, indicating it was mediated by the retrograde release of the endocannabinoid 2-AG. The rapid glucocorticoid effect in BLA neurons in vitro was occluded by prior in vivo acute stress-induced, or prior in vitro glucocorticoid-induced, release of endocannabinoid. Acute stress also caused an increase in anxiety-like behavior that was attenuated by blocking CB1 receptor activation and inhibiting 2-AG synthesis in the BLA. Together, these findings suggest that acute stress causes a long-lasting suppression of synaptic inhibition in BLA neurons via a membrane glucocorticoid receptor-induced release of 2-AG at GABA synapses, which contributes to stress-induced anxiogenesis. We provide a cellular mechanism in the basolateral amygdala (BLA) for the rapid stress regulation of anxiogenesis in rats. We demonstrate a nongenomic glucocorticoid induction of long-lasting suppression of synaptic inhibition that is mediated by retrograde endocannabinoid release at GABA synapses. The rapid glucocorticoid-induced endocannabinoid suppression of synaptic inhibition is initiated by a membrane-associated glucocorticoid receptor in BLA principal neurons. We show that acute stress increases anxiety-like behavior via an endocannabinoid-dependent mechanism centered in the BLA. The stress-induced endocannabinoid modulation of synaptic transmission in the BLA contributes, therefore, to the stress regulation of anxiety, and may play a role in anxiety disorders of the amygdala.

Long-term NMDAR antagonism correlates reduced astrocytic glutamate uptake with anxiety-like phenotype.

The role of glutamate N-methyl-D-aspartate receptor (NMDAR) hypofunction has been extensively studied in schizophrenia; however, less is known about its role in anxiety disorders. Recently, it was demonstrated that astrocytic GLT-1 blockade leads to an anxiety-like phenotype. Although astrocytes are capable of modulating NMDAR activity through glutamate uptake transporters, the relationship between astrocytic glutamate uptake and the development of an anxiety phenotype remains poorly explored. Here, we aimed to investigative whether long-term antagonism of NMDAR impacts anxiety-related behaviors and astrocytic glutamate uptake. Memantine, an NMDAR antagonist, was administered daily for 24 days to healthy adult CF-1 mice by oral gavage at doses of 5, 10, or 20 mg/kg. The mice were submitted to a sequential battery of behavioral tests (open field, light–dark box and elevated plus-maze tests). We then evaluated glutamate uptake activity and the immunocontents of glutamate transporters in the frontoparietal cortex and hippocampus. Our results demonstrated that long-term administration of memantine induces anxiety-like behavior in mice in the light–dark box and elevated plus-maze paradigms. Additionally, the administration of memantine decreased glutamate uptake activity in both the frontoparietal cortex and hippocampus without altering the immunocontent of either GLT-1 or GLAST. Remarkably, the memantine-induced reduction in glutamate uptake was correlated with enhancement of an anxiety-like phenotype. In conclusion, long-term NMDAR antagonism with memantine induces anxiety-like behavior that is associated with reduced glutamate uptake activity but that is not dependent on GLT-1 or GLAST protein expression. Our study suggests that NMDAR and glutamate uptake hypofunction may contribute to the development of conditions that fall within the category of anxiety disorders.

Shame proneness in symptom dimensions of obsessive-compulsive disorder.

Although one study has noted that shame may play a significant role in anxiety disorders (Fergus, Valentiner, McGratch, & Jencius, 2010), the literature does not address the appearance of shame within specific dimensions of obsessive-compulsive disorder (OCD). In this study, shame is assessed within four common symptom dimensions of OCD: contamination, harm, unacceptable thoughts, and symmetry. The authors hypothesized that shame would be significantly related to unacceptable thoughts and harm, but not other dimensions. Ninety-one individuals with OCD completed the Dimensional Obsessive-Compulsive Scale (measuring severity of OCD symptom dimensions) and the Test of Self-Conscious Affect (assessing shame proneness). Results indicated a positive significant relationship between shame and harm, but not unacceptable thoughts. Additionally, a significant correlation was found between shame and symmetry. This is possibly due to a relationship between perfectionism and symmetry (Wu & Cortesi, 2009). These findings suggest that shame is related to certain dimensions of OCD and may deserve consideration in relation to treatment.