Pathological Anxiety Research Articles

The effect of anxiety on gait: a threat-of-scream study.

It is known that fear responses to clearly identified threats can inhibit motion, slowing down gait and inducing postural freezing. Nonetheless, it is less clear how anxiety, which emerges during threat anticipation, affects gait parameters. In the present work, we used a threat-of-scream paradigm to study the effects of anxiety on gait. Twenty-five participants (15 female, aged 23.4 ± 1.8) were instructed to walk on a 5-m walking track, while motion was recorded in 3D, via a VICON system. Four alternating blocks, two "threat" and two "safe" blocks of 10 trials each, were signaled by colored stripes on a screen in front of the walking path. Participants were informed that they could hear a human scream in their headphones at any time during threat blocks, which were in fact always delivered during walking. On the contrary, no screams were delivered in the safe blocks. Results indicated that participants reported higher subjective anxiety during threat vs. safe blocks. Furthermore, increases in self-reported anxiety from safe to threat showed significant moderate correlations with increased stride speed and length, decreased stride time and decreased stance phase duration. Increases in anxiety were also moderately correlated with increased arm/leg swing amplitude, an effect that was fully mediated by increased stride speed. Overall, these results indicate that anxiety invigorates motion in healthy subjects, by increasing speed. These results are discussed in terms of the recent advancements in the understanding of defensive behavior, its neural correlates and on clinical implications relative to pathological anxiety.

ANXIETY SYNDROME IN PREGNANT WOMEN WITH OBESITY AND GESTATIONAL DIABETES MELLITUS

Introduction. Over the past three years, the population of Ukraine has faced chronic stress due to ongoing military actions within its borders. In current conditions, psychoemotional disorders in patients with somatic pathology are often underestimated, with physiological states being confused with pathological anxiety. This oversight can lead to ineffective treatment, worsening patient conditions, and negative prognoses. As a result, the diagnosis and treatment of anxiety syndrome, particularly in pregnant women with both obstetric and extragenital pathology under chronic stress, is a pressing issue in modern obstetrics. The purpose of this study was to assess the presence of anxiety syndrome in pregnant women of the Kharkiv region with obesity and gestational diabetes mellitus during martial law. Materials and methods. To achieve the objective of this study, 85 women aged 24 to 39 years were examined at 30–42 weeks of pregnancy. The main group consisted of 63 pregnant women with obesity and gestational diabetes mellitus, further divided into three clinical subgroups: the first group included 24 women with gestational diabetes mellitus, the second group comprised 16 women with pre-pregnancy obesity, and the third group consisted of 23 women with both gestational diabetes mellitus and obesity. The control group included 22 women without somatic or obstetric pathology. The GAD-7 questionnaire was used to assess the overall level of anxiety. Results and discussion. All participants answered the questionnaire with scores of 2–3 points, indicating significant anxiety levels, as total scores reached 14 points or higher. Notably, the average anxiety scores in the groups with gestational diabetes mellitus, obesity, and gestational diabetes mellitus with obesity were similar—16.5±2.3, 17.9±1.8, and 17.6±2.5, respectively— and were significantly higher than those of the control group, which averaged 4.4±2.6 (p < 0.05). Thus, all women in the main group (63 pregnant women) exhibited clear signs of anxiety, including irritability (95.2%), restlessness (79.4%), inability to relax (74.6%), and anticipation of dreadful events (66.0%). These symptoms were more pronounced in women with obesity compared to those with gestational diabetes mellitus without obesity. Conclusion. Under martial law conditions, pregnant women with comorbidity of gestational diabetes mellitus and obesity exhibit a significantly higher level of anxiety compared to women with a physiological pregnancy, although the latter also experience anxiety disorders, but to a lesser degree. Assessing anxiety disorders in pregnant women with gestational diabetes mellitus and obesity using the GAD-7 scale enables timely detection of these issues, even remotely. This facilitates appropriate referrals to specialists such as psychologists, psychotherapists, or psychiatrists, and allows for the early initiation of necessary therapy.

Transcranial Alternating Current Stimulation: A Novel Neuromodulatory Treatment for Anxiety and Related Disorders.

Given the high prevalence and socioeconomic burden of anxiety disorders, there is an urgent need for effective, fast-acting, cost-efficient treatment alternatives to traditional psychotherapy. Transcranial alternating current stimulation (tACS), a noninvasive brain stimulation technique that modulates endogenous brain oscillations via the application of sinusoidal currents to the scalp, emerges as a promising neuromodulatory treatment. We reviewed oscillatory neuropsychopathology in anxiety, examined current evidence of tACS interventions for anxiety and related disorders, and proposed novel simulation targets and protocols. We emphasize the need for rigorously designed clinical trials to systematically investigate the neuropsychological effects of different tACS protocols on diverse populations with pathological anxiety.

Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala

Nicotine intake is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in rodents and humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n = 88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to enhanced physiological arousal to learned threats and overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates of adaptive aversive learning in line with the risk for the development of pathological anxiety.

Aberrant TSC-Rheb axis in Oxytocin receptor+ cells mediate stress-induced anxiety.

Stress is a major risk for the onset of several maladaptive processes including pathological anxiety, a diffuse state of heightened apprehension over anticipated threats1. Pathological anxiety is prevalent in up to 59% of patients with Tuberous Sclerosis complex (TSC)2, a neurodevelopmental disorder (NDD) caused by loss-of-function mutations in genes for Tuberin (Tsc2) and/or Hamartin (Tsc1) that together comprise the eponymous protein complex. Here, we generated cell type-specific heterozygous knockout of Tsc2 in cells expressing oxytocin receptor (OTRCs) to model pathological anxiety-like behaviors observed in TSC patient population. The stress of prolonged social isolation induces a sustained negative affective state that precipitates behavioral avoidance, often by aberrant oxytocin signaling in the limbic forebrain3,4. In response to social isolation, there were striking sex differences in stress susceptibility in conditional heterozygote mice when encountering situations of approach-avoidance conflict. Socially isolated male mutants exhibited behavioral avoidance in anxiogenic environments and sought more social interaction for buffering of stress. In contrast, female mutants developed resilience during social isolation and approached anxiogenic environments, while devaluing social interaction. Systemic and medial prefrontal cortex (mPFC)-specific inhibition of downstream effector of TSC, the integrated stress response (ISR), rescued behavioral approach toward anxiogenic environments and conspecifics in male and female mutant mice respectively. Further, we found that Tsc2 deletion in OTRCs leads to OTR-signaling elicited network suppression, i.e., hypofrontality, in male mPFC, which is relieved by inhibiting the ISR. Our findings present evidence in support of a sexually dimorphic role of prefrontal OTRCs in regulating emotional responses in anxiogenic environments, which goes awry in TSC. Our work has broader implications for developing effective treatments for subtypes of anxiety disorders that are characterized by cell-autonomous ISR and prefrontal network suppression.

Partner symptom accommodation in generalized anxiety disorder: a preliminary examination of correlates with symptoms and cognitive behavioural therapy outcome.

Symptom accommodation is suggested to maintain anxiety pathology and interfere with treatment effectiveness for anxiety and related disorders. However, little is known about symptom accommodation in generalized anxiety disorder (GAD). This study investigated the associations between romantic partner symptom accommodation, GAD symptoms, intolerance of uncertainty (IU), relationship satisfaction, and cognitive behavioural therapy (CBT) outcomes from the perspective of the person with GAD. One hundred and twelve people with GAD participated in group CBT and completed measures at pre- and post-treatment. All participants endorsed that their partner engaged in symptom accommodation to some extent, and the most commonly endorsed type was providing reassurance. Greater self-reported partner symptom accommodation was associated with greater GAD symptoms, chronic worry severity, IU, and relationship satisfaction at baseline. Partner symptom accommodation was found to significantly decrease over treatment; however, less improvement in symptom accommodation from pre- to post-treatment was associated with worse treatment outcomes. This study is the first to show that partner symptom accommodation is prevalent in adults with GAD and to elucidate the presentation and frequency of behaviours. The findings provide preliminary evidence that targeting partner symptom accommodation in treatment may improve CBT outcomes.

Preliminary evidence for altered brain-heart coherence during anxiogenic movies

Abstract During states of anxiety, fundamental threat circuitry in the brain can increase heart rate via alterations in autonomic balance (increased sympathetic activity and parasympathetic withdrawal) and may serve to promote interoceptive integration and awareness of cardiac signals. Moreover, evidence indicates pathological anxiety could be associated with increased communication between the brain and the heart. Yet, this phenomenon remains not well understood. For instance, studies in this area have been conducted within the confines of tightly controlled experimental paradigms. Whether anxiety impacts brain-heart communication outside of such experimental settings, and in relatively more naturalistic contexts, is less clear. Here, we used a suspenseful movie fMRI paradigm to study induced anxiety (n = 29 healthy volunteers; Caltech Conte dataset; Kliemann et al., 2022). We predicted that brain responses across an anxiety-relevant “defensive response network” (amygdala, hypothalamus, periaqueductal gray, bed nucleus of the stria terminalis, dorsomedial prefrontal cortex, ventromedial prefrontal cortex, subgenual anterior cingulate, and anterior insula; Abend et al., 2022) would show increased coherence with heart rate as participants watched a suspenseful movie clip compared to a non-suspenseful movie clip. Counter to our predictions, we found decreased coherence between heart rate and brain responses during increased anxiety, namely in amygdala-prefrontal circuitry. We suggest these alterations may be underpinned by parasympathetic withdrawal and/or decreased interoceptive awareness during suspenseful movie-watching.

Psychometric Evaluation of a Measure of Posttraumatic Safety Behaviors

Despite evidence that safety behaviors function as transdiagnostic causal maintenance factors for anxiety pathology, there has been relatively less empirical investigation of trauma-related safety behaviors in the development and maintenance of posttraumatic stress disorder. This paper introduces the development and preliminary psychometric evaluation of the Posttraumatic Safety Behaviors Inventory (PSBI), a 10-item self-report assessment of trauma-relevant safety behaviors. Two samples totaling 597 trauma survivors (61.8% female; Mage = 40.0; 76.2% White/Caucasian) recruited through Amazon Mechanical Turk completed the PSBI. Exploratory and confirmatory factor analyses identified a three-factor structure consisting of Avoidance, Coping with Negative Thoughts and Emotions, and Coping with Threats to Physical Safety. The PSBI also demonstrated favorable measurement invariance, construct validity, internal consistency, and test-retest reliability. Taken together, our preliminary findings suggest that the PSBI is an efficient, psychometrically sound assessment tool for posttraumatic safety behaviors. With further psychometric validation, the PSBI promises to aid researchers and clinicians in the identification and monitoring of trauma-relevant safety behaviors.

<i>Curcuma Longa</i> (Turmeric) Supplements Improved Fasting Blood Glucose Level and Anxiety-Like Behavior in Diabetic Wistar Rats

Turmeric is a spice derived from the rhizomes of Curcuma longa (C. longa) which is a member of the ginger family (Zingiberaceae). Curcuma longa is widely used for food spices, preservatives, and coloring agents. Anxiety disorders are the most frequently occurring mental disorders, they encompass a group of conditions that share extreme or pathological anxiety as the principal disturbance of mood or emotional tone. This study aimed to evaluate the effect of C. longa supplements on fasting blood glucose levels and anxiety-like behavior in diabetic Wistar rats. Twenty (20) rats were randomly assigned into five (5) groups of four each (N=4). Group I served as control and received distilled water (1 ml/kg), groups II, III, IV and V were diabetic and received glibenclamide (1mg/kg), and C. longa supplements at 2.5%, 5% and 10% respectively. Diabetes was induced using intraperitoneal injection of freshly dissolved alloxan monohydrate (150 mg/kg). All administrations were made for 21 days. Fasting blood glucose levels and anxiety-like behavior were determined using a digital glucometer and elevated plus maze test respectively. Based on the results obtained from this study, there was significant (p < 0.05) improvement in fasting blood glucose levels across all supplemented doses of C. longa (2.5%, 5% and 10% at 9.33 ± 0.46 mmol/L, 11.20 ± 0.68 mmol/L and 11.00 ± 0.40 mmol/L respectively) compared to control group (18.13 ± 1.28 mmol/L). Time spent in the opened arm was also increased significantly (p < 0.05) in 5% (18.25 1.18 s) and 10% (19.25 1.49 s) groups after 21 days of supplementation compared to before the commencement of supplementation (9.75 ± 1.11 s and 10.25 ± 1.49 s respectively). These findings suggested that the C. longa supplement improved fasting blood glucose and anxiety-like behavior in diabetic Wistar rats.

GABAergic synapses from the ventral lateral septum to the paraventricular nucleus of hypothalamus modulate anxiety.

Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxiety-like behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv-PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA-PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic-PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders.

Fear generalization predicts post-traumatic stress symptoms: A two-year follow-up study in Dutch fire fighters

IntroductionExcessive fear generalization has been associated with pathological anxiety, including posttraumatic stress disorder (PTSD). However, studies investigating the longitudinal relationship between generalization and the development of anxiety symptomatology are scarce. This study aims to test the predictive value of fear generalization for PTSD symptoms in a high-risk profession sample and to explore the relationship between generalization and neuroticism, which are both linked to PTSD. MethodLongitudinal data from a multi-wave study in 529 Dutch fire-fighters were used. Fear generalization, PTSD symptoms and neuroticism were assessed at baseline. PTSD symptoms were reevaluated at six, 12, 18, and 24 months. Generalization was assessed in a differential conditioning paradigm by measuring expectancies of an aversive outcome when presented with stimuli similar to previously conditioned stimuli. ResultsHigher expectancy ratings towards stimuli most similar to safety signals predicted PTSD symptoms at follow-up after controlling for baseline PTSD symptoms, whereas higher expectancy ratings towards stimuli most similar to danger signals was associated with neuroticism. Neuroticism weakened the predictive power of fear generalization when considered simultaneously. DiscussionThese findings suggest that heightened fear generalization is associated with the development of anxiety and trauma-related symptoms. Targeting problematic fear generalization may be a promising intervention approach.

The impact of video calls on the anxiety level among patients’ caregivers at Viet Duc Hospital during covid-19 pandemics

Objectives: To assess the impact of video call on the anxiety level of caregivers at the intensive care unit 2 at Viet Duc Hospital during COVID-19 pandemics. Research participants and methods: Intervention study comparing 2 groups on 62 caregivers of patients who were treated at Intensive Care Unit 2 of Viet Duc Hospital from January 2022 to November 2022 based on Zung Self-Rating Anxiety Scale. Results: Assessing the level of anxiety in the video call group: Severe anxiety was 71%, no pathological anxiety and very severe anxiety was 0%. Among the research participants in the video call group, the proportion of people who felt panicked for no reasons accounted for 71%, and 61.3% felt more impatient and anxious than usual, those felt limbs swaying, trembling, weak and easily tired, breathing in and out easily were 3.2%, 3.1%, 3.2% respectively. Anxiety level in video calls at mild to moderate anxiety accounted for the highest rate of 93.5%; The rate of very severe anxiety is 0%. Conclusion: Video calls for caregivers significantly reduced anxiety proportion compared to non-video calls.

Dropout From Psychological Interventions for Pathological Health Anxiety: A Three-Level Meta-Analysis of Randomized Controlled Trials.

This study aimed to provide the first comprehensive evidence on the prevalence and predictors of dropout in psychological interventions for pathological health anxiety. A database search in Web of Science, EMBASE, PubMed, Scopus, PsycINFO and the Cochrane Central Register of Controlled Trials identified 28 eligible randomized controlled trials (40 intervention conditions; 1783 participants in the intervention condition), published up to 18 June 2024. Three-level meta-analytic results showed a weighted average dropout rate of 9.67% (95% confidence interval [CI] [6.49%, 14.17%]), with dropout equally likely from treatment and control conditions (odds ratio = 1.07, 95% CI [0.80, 1.44]). Moderator analyses indicated no statistically significant effects of study, participant, treatment or therapist characteristics, except for the country of study. These findings suggest that the average dropout rate is relatively low compared with those reported for other mental health conditions and highlight the importance of considering cultural and societal factors when evaluating treatment adherence. Future research should continue to explore the complex and multifaceted factors influencing dropout to improve the design and implementation of psychological interventions for pathological health anxiety.

Heightened facial muscle reactivity in preadolescent girls with pathological anxiety

AbstractObjectivesAnticipatory anxiety and heightened responses to uncertainty are central features of anxiety disorders (ADs) that contribute to clinical impairment. Anxiety symptoms typically emerge during childhood, and even subthreshold‐AD symptoms are associated with distress and risk for future psychopathology. This study compared facial emotional response to threat and uncertainty between preadolescent girls with ADs, girls with subthreshold‐AD symptoms, and controls.MethodsFacial emotional responding was characterized in preadolescent girls (age 8–11) with a range of anxiety symptoms: no/low anxiety (controls, n = 41), subthreshold‐AD (n = 73), and DSM‐5 diagnoses of separation, social, and/or generalized ADs (n = 45). A threat anticipation paradigm examined how image valence (negative/neutral) and image anticipation (uncertain/certain timing) impacted activity of the corrugator supercilii, a forehead muscle implicated in the “frown” response that is modulated by emotional stimuli (negative > neutral). Corrugator magnitude and corrugator timecourse were compared between groups.ResultsFindings demonstrate greater corrugator activity during anticipation and viewing of negative stimuli, as well as increased corrugator reactivity in subthreshold‐AD and AD girls. Timecourse analyses of negative versus neutral stimuli revealed that AD and subthreshold‐AD girls had greater uncertainty‐related increases in corrugator activity compared to controls.ConclusionResults extend the physiological characterization of childhood pathological anxiety, highlighting the impact of subthreshold‐AD symptoms.

Overgeneralization of conditioned fear in patients with social anxiety disorder.

While abnormal responses to threat, including overgeneralization to conditioned fear, have been postulated to play a critical role in pathological anxiety, the relevance of previous findings to social anxiety disorder (SAD) is unclear. We investigated conditioned and generalized fear responses in patients with SAD using socially relevant stimuli. A total of 26 patients with SAD and 25 healthy controls participated in a fear conditioning and generalization paradigm consisting of two neutral faces as conditioned stimuli (CS+ or CS-) and an angry face with contemptuous comments as unconditioned stimuli. Eight morphed faces of two conditioned stimuli in each continuum were given to test generalization. Behavioral data and physiological responses were acquired. Successful conditioning was observed in the risk ratings for both groups, while only a marginal indication of conditioning was noted in physiological measures. During the generalization phase, patients rated the risk higher than CS- when the stimuli close to CS- contained a portion of CS+ features. Larger skin conductance responses to this stimulus were linked to higher fear of negative evaluation. In addition, patients spent a longer time evaluating safe and ambiguous stimuli than healthy controls and exhibited consistently high levels of subjective arousal. Taken together, our findings suggest that SAD patients may exhibit a tendency towards overgeneralization of fear responses and show distinct patterns in processing generalized threat stimuli compared to healthy controls. Even though overgeneralization was not evident in physiological measures, it is necessary to consider this behavioral characteristic in the clinical management of patients with SAD.

Anxiety and school avoidance in an 8-year-old child with epilepsy

Anxiety is ubiquitous in school age children. Co-occurring medical illness adds to the complexity of identifying pathologic anxiety as opposed to that of typical development such as with social interactions or academic pressures. Anxiety may also occur in the context of cognitive difficulties or inattention, both of which may be exacerbated by epilepsy or by anti-seizure medicines themselves. Treatment strategies may require patience and long-term observations to account for the typical range of stressors that may be expected with disease progression or with development through childhood. This section illustrates the challenge of diagnosis and management of anxiety in the context of epilepsy in a school aged child and addresses nuances that neurology clinicians need to consider. Practical strategies for management including stepwise options for pharmacologic treatment will be emphasized.

THE INFLUENCE OF 2-OXOINDOLINE-3-GLYOXYLIC ACID DERIVATIVES ON THE NEUROPHYSIOLOGICAL REACTIONS OF RATS IN THE “BLACK AND WHITE CHAMBER” TEST

The number of patients with an anxiety pathology is constantly growing, which requires the search and development of new remedies for protection. The aim of this research is to establish the presence of anxiolytic activity in derivatives of 2-oxoindolin-3-glyoxylic acid basedon testing animals in the “black-and-white chamber” test. Materials and methods. Experiments were performed on 150 adult male rats. The 2-oxoindoline derivatives were suspended ex tempore (water for injection and Tween-80) and administered to rats at a dose of 12 mg/kg intraperitoneally 1 hour before testing. The control group received a solvent with an emulsifier. Diazepam (2 mg/kg) served as a reference preparation. Behavior was studied in the “black and white chamber” test. Results. Compound 2 significantly reduced the residence time in the light compartment of the chamber. Substance 18 reduced the latent period of the first peek by 1.4 times (p<0.01), significantly increased the number and time of peeking, reduced the latent period of exit by 1.6 times (p<0.001), increased the number of exits and the time spent in the illuminated part of the device and significantly increased the percentage of rats peeking or exiting from the dark compartment and also reduced the number of boluses by 1.9-fold (p<0.001) compared to the control. Substance 2-T only increased the total time of peeking, compound K significantly reduced the number of boluses, and compound 3.85 increased the latent period of the first peek by 1.5 times (p<0.002), substance G increased the number of peeks by 1.7 times ( p<0.05), the time of stay in the light compartment of the camera by 2.5 times (p<0.001) and reduced the number of boluses by 1.3 times compared to the injection control (p<0.05). Conclusion. Administration of the IK compound significantly prolonged the latency of the first peek and exit, as well as significantly reduced the number of boluses compared to the control. 100% of animals peeked into the illuminated compartment of the chamber. Derivatives of 2-oxoindoline with the laboratory codes 18, G, and IК changed the neurophysiological reactions of animals in a similar way to the classic anxiolytic diazepam.

Evaluation of New Derivatives of 2,4-dioxobutanoic Acid Salts in Behavioral Studies of Laboratory Animals

Introduction. Correction of pathological anxiety is currently an important task of modern pharmacology, since anxiety disorders are among the most common mental illnesses. Taking into account the trend of a constant increase in the incidence of anxiety and depressive disorders (ADD) in the world, the urgency of searching for various tools for studying this group of diseases and creating safe, highly effective drugs for the pharmacotherapy of ADD is growing.Aim. The study of new derivatives of salts of 2,4-dioxobutanoic acids containing fragments of benzimidazole and pyrimidine cycles on behavioral reactions of animals.Materials and methods. The salts of 4-methoxyphenyl-4-oxobut-2-enoic acid with heterocyclic amines synthesized by us were used as objects of research. Behavioral reactions of animals to the introduction of the studied compounds were evaluated using a number of tests: "open field", light/dark box", "extrapolation escape task", "forced swim".Results and discussion. The results of the experiments made it possible to identify a potentially active compound 1b, which showed an improvement in a number of indicators of motor activity of animals and an anti-anxiety effect. In addition, with the introduction of substance 1b, there is a manifestation of antidepressant activity in an acute stress situation.Conclusion. The effect of compounds 1a, 1b obtained for the first time on the behavioral reactions of animals was studied. The "structure-activity" analysis was carried out with the establishment of the priority of further targeted synthesis of salts of 2,4-dioxobutane acid derivatives containing a fragment of 2-aminopyrimidine. A compound with a neuropsychotropic activity profile has been identified, which is recommended for further in-depth study.

Cancer-related fatigue trajectories up to 5 years after curative treatment for oesophageal cancer

BackgroundWhether cancer-related fatigue develops differently after curative-intended oesophageal cancer treatment and the related modifiable factors are unclear.MethodsThis population-based and longitudinal cohort included 409 oesophageal cancer patients who underwent curative oesophagectomy in 2013–2020 in Sweden. The main outcome was cancer-related fatigue trajectories with measurements at 1, 1.5, 2, 2.5, 3, 4 and 5 years postoperatively by validated EORTC QLQ-FA12 questionnaire, and analysed using growth mixture models. Weighted logistic regressions provided odds ratios (OR) with 95% confidence intervals (95% CI) for underlying sociodemographic, clinical, and patient-reported outcome factors in relation to the identified trajectories.ResultsTwo distinct overall cancer-related fatigue trajectories were identified: low level of persistent fatigue and high level of increasing fatigue, with 64% and 36% of patients, respectively. The odds of having high level of fatigue trajectory were increased by Charlson comorbidity index (≥ 2 versus 0: OR = 2.52, 95% CI 1.07–5.94), pathological tumour Stage (III–IV versus 0-I: OR = 2.52, 95% CI 1.33–4.77), anxiety (OR = 7.58, 95% CI 2.20–26.17), depression (OR = 15.90, 95% CI 4.44–56.93) and pain (continuous score: OR = 1.02, 95% CI 1.01–1.04).ConclusionsLong-term trajectories with high level of increasing cancer-related fatigue and the associated modifiable factors were identified after oesophageal cancer treatment. The results may facilitate early identification and targeted intervention for such high-risk patients.

Recent advances in anxiety disorders: Focus on animal models and pathological mechanisms.

Anxiety disorders have become one of the most severe psychiatric disorders, and the incidence is increasing every year. They impose an extraordinary personal and socioeconomic burden. Anxiety disorders are influenced by multiple complex and interacting genetic, psychological, social, and environmental factors, which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety. The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology, and the development of new drugs. Therefore, a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease. This review summarizes animal models and the pathogenesis of anxiety disorders, and discusses the current research status to provide insights for further study of anxiety disorders.