Chronic Anxiety Research Articles

The Role of the Cerebellar and Vestibular Networks in Anxiety Disorders and Depression: the Internal Model Hypothesis

Clinical data and animal studies confirmed that the cerebellum and the vestibular system are involved in emotions. Nowadays, no real consensus has really emerged to explain the clinical symptoms in humans and behavioral deficits in the animal models. We envisage here that the cerebellum and the vestibular system play complementary roles in emotional reactivity. The cerebellum integrates a large variety of exteroceptive and proprioceptive information necessary to elaborate and to update the internal model: in emotion, as in motor processes, it helps our body and self to adapt to the environment, and to anticipate any changes in such environment in order to produce a time-adapted response. The vestibular system provides relevant environmental stimuli (i.e., gravity, self-position, and movement) and is involved in self-perception. Consequently, cerebellar or vestibular disorders could generate « internal fake news» (due to lack or false sensory information and/or integration) that could, in turn, generate potential internal model deficiencies. In this case, the alterations provoke false anticipation of motor command and external sensory feedback, associated with unsuited behaviors. As a result, the individual becomes progressively unable to cope with the environmental solicitation. We postulate that chronically unsuited, and potentially inefficient, behavioral and visceral responses to environmental solicitations lead to stressful situations. Furthermore, this inability to adapt to the context of the situation generates chronic anxiety which could precede depressive states.

The Relationship Between Hospitalization Frequency of Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Anxiety and Depression.

Depression and anxiety are common in patients with COPD (chronic obstructive pulmonary disease), and anxiety and depression can increase the risk of hospitalization and the acute exacerbation of chronic obstructive pulmonary disease. The relationship between the frequency of hospitalization for acute exacerbation of COPD (AECOPD) and the anxiety and depression of patients is not fully understood. This study aims to analyze the relationship between the frequency of hospitalizations and anxiety and depression of patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A collection of 309 AECOPD patients admitted to the emergency department in our hospital from 2019 to 2020 were divided into anxiety group A and depression group D according to the Hospital Anxiety and Depression Scale (HADS) score and divided into A1 and D1 negative groups (≤7 Score), A2 and D2 suspicious groups (8–10 points), A3 and D3 confirmed groups (≥11 points) for paired analysis of anxiety and depression correlation and difference and comparison of the frequency of hospitalization in each group within 2 years. The results found that anxiety and depression were significantly positively correlated (r = 0.654, p = 0.000). Intra-group comparison shows that the difference between the anxiety-diagnosed and non-diagnosed groups and the depression subgroups are statistically p < 0.05; the comparison between the anxiety subgroup and the depression subgroup showed that there was a statistical difference between the confirmed group and the non-diagnosed group (p < 0.01). In short, AECOPD anxiety is positively correlated with depression, and depression is affected by the frequency of hospitalization earlier and gradually, and anxiety should be prioritized in the acute phase.

Acquisition learning is stronger for aversive than appetitive events

Appetitive and aversive learning are both key building blocks of adaptive behavior, yet knowledge regarding their differences is sparse. Using a capsaicin heat pain model in 36 healthy participants, this study directly compared the acquisition and extinction of conditioned stimuli (CS) predicting pain exacerbation and relief. Valence ratings show stronger acquisition during aversive compared to appetitive learning, but no differences in extinction. Skin conductance responses and contingency ratings confirmed these results. Findings were unrelated to individual differences in pain sensitivity or psychological factors. Our results support the notion of an evolutionarily hardwired preponderance to acquire aversive rather than appetitive cues as is protective for acute aversive states such as pain but may contribute to the development and maintenance of clinical conditions such as chronic pain, depression or anxiety disorders.

Protective and Risk Factors at the Intersection of Chronic Pain, Depression, Anxiety, and Somatic Amplification: A Latent Profile Approach

ObjectiveResearch indicates a complex nexus between chronic pain, depression, anxiety, and somatic amplification (PDAS) symptoms, marked by high rates of co-morbidity and mutually maintaining mechanisms. Although recent frameworks have attempted to explain co-occurrence rates of pain and other comorbid disorders, the interrelations between PDAS and their impacts on pain outcomes have not been adequately examined with a person-centered approach. Using nationally representative data, this study assessed the heterogeneity in PDAS symptomatology and examined links among risk and protective factors in different profiles.MethodsData were derived from 1027 participants in the National Survey of Midlife Development in the United States (MIDUS) who completed telephone interviews or self-report measures that assessed PDAS, various sources of social supports (family, friends, spouses/partners, religion, coworkers, and supervisors), and the number of healthcare visits.ResultsWe found heterogeneity in symptom severity rather than symptom type across classes over time. Regardless of comorbidity severity, people reported similar levels of somatic symptoms, which may help clinicians more effectively diagnose comorbidity issues among chronic pain patients. As PDAS symptomatology increased by group, the perceived levels of social support decreased. Membership in a higher symptom severity class was associated with being female, younger age, and an increase in medical, but not mental health visits.LimitationsLimitations included the use of a cross-sectional design, reliance on self-report measures, and a sample largely comprised of Whites.ConclusionPDAS co-occurs across classes, which may relate to shared risk and protective factors. This study lays the foundation to investigate similar questions for overlapping symptoms that occur during the same period, which would shed light on whether—among middle to older age adults—these disorders are attributable to a common mechanism and if they may inform transdiagnostic treatments.

Association of maternal depression and anxiety with toddler social-emotional and cognitive development in South Africa: a prospective cohort study

ObjectiveA robust literature has identified associations between prenatal maternal depression and adverse child social-emotional and cognitive outcomes. The majority of prior research is from high-income countries despite increased reporting of...

The Role of Acupuncture in Reducing Pain Scale Scoring in Geriatric Patients with Acute Pain: A Literature Review

Background: Pain is one of the problems commonly found in geriatric population in the world, causing reduction in quality of life and functionality, and increasing socioeconomic burden. The geriatric population are vulnerable to inadequate analgesia, which increase the risk of forming chronic pain, frailty, depression and anxiety, and increased morbidity. Objective: To review several studies that explain the role of acupuncture in reducing pain scale scoring in geriatric patients with acute pain. Method: Literature searching of studies published between January 2011 to June 2020 was done on the Google Scholar and PubMed databases using the keywords “acupuncture,” “manual acupuncture,” “electroacupuncture,” “laserpuncture,” “laser acupuncture,” “ear acupuncture,” “battlefield acupuncture,” “pain,” and “acute pain.” Randomized controlled trials using pain scales as outcome measurement with the population sample having acute pain and using acupuncture modalities as its treatment were included. Non-English studies that cannot be accessed in full text and did not show number of sample, baseline characteristics, and outcome values, and studies with the mean age of the participants below 60 years were excluded. Result: Seven studies were found and analyzed. The pain scale scoring used included Visual Analog Scale (VAS) (n = 4), Numeric Rating Scale (NRS) (n = 1), McGill Pain Questionnaire (MPQ) (n = 2), and Brief Pain Inventory (BPI) (n = 2), with some studies using more than 1 scale. Conclusion: Acupuncture was found to reduce pain scale scoring of VAS, NRS, MPQ, and BPI significantly, whether statistically or clinically.

Chronic facial inflammatory pain-induced anxiety is associated with bilateral deactivation of the rostral anterior cingulate cortex

Patients with chronic pain, especially orofacial pain, often suffer from affective disorders, including anxiety. Previous studies largely focused on the role of the caudal anterior cingulate cortex (cACC) in affective responses to pain, long-term potentiation (LTP) in cACC being thought to mediate the interaction between anxiety and chronic pain. But recent evidence indicates that the rostral ACC (rACC), too, is implicated in processing affective pain. However, whether such processing is associated with neuronal and/or synaptic plasticity is still unknown. We addressed this issue in a chronic facial inflammatory pain model (complete Freund's adjuvant model) in rats, by combining behavior, Fos protein immunochemistry and ex vivo intracellular recordings in rACC slices prepared from these animals. Facial mechanical allodynia occurs immediately after CFA injection, peaks at post-injection day 3 and progressively recovers until post-injection days 10–11, whereas anxiety is delayed, being present at post-injection day 10, when sensory hypersensitivity is relieved, but, notably, not at post-injection day 3. Fos expression reveals that neuronal activity follows a bi-phasic time course in bilateral rACC: first enhanced at post-injection day 3, it gets strongly depressed at post-injection day 10. Ex vivo recordings from lamina V pyramidal neurons, the rACC projecting neurons, show that both their intrinsic excitability and excitatory synaptic inputs have undergone long-term depression (LTD) at post-injection day 10. Thus chronic pain processing is associated with dynamic changes in rACC activity: first enhanced and subsequently decreased, at the time of anxiety-like behavior. Chronic pain-induced anxiety might thus result from a rACC deactivation-cACC hyperactivation interplay.

619 Pain Management in Burn and Wound Patients: Effects of Acupuncture in Pain Score and Medication

IntroductionPain management in burn patients is a complex ongoing problem. Opioid and non-opioid medications have historically been used as the primary pain management modality in burn care. Considering the ongoing opioid epidemic, a multidisciplinary holistic approach is needed for pain management. Acupuncture has been recognized to help in different settings such as chronic back pain, neurological problems, depression, and anxiety.We hypothesize that burn and wound patients receiving acupuncture will have a decrease in opioids and non-opioid medications on acupuncture day (ACd) compared to non-acupuncture day (n-ACd) and a reduction of pain scores before and after acupuncture.MethodsA prospective observational study in all patients admitted to the burn service was made. We exclude patients that were unable to provide consent or age 6 years and younger.A numeric pain score (1-10) was collected from the patients before and after each acupuncture session; if patients were sleeping after acupuncture pain score was collected when they woke up. A prospective collection of daily opioids and non-opioids medications was made. Opioids were converted to daily morphine equivalents (MME).ResultsFrom February to August 2021, 53 patients on the burn service were treated with acupuncture for a total of 185 sessions. The median age was 49 years (IQR:32.5-63.0). Median TBSA for burn patients was 3.3% (IQR:1.5-8.1). The number of sessions per patient ranged from 1-12 with a median of 3 (IQR1.7-4). Before acupuncture, the median pain score was 5 (IQR:2.6-6.4), and after treatment was it was 1.5 (IQR:0.2-2.8).Of 185 sessions, 49 (26%) of those sessions, patients fell asleep afterward. Median morphine use on ACd was 26.6 MME (15.8-62.1) vs. n-ACd 27.35 MME (15.5-65.3). For non-opioid medication, the median of acetaminophen on ACd 1007.5mg (313.39 -1950) vs. n-ACd 1381.25mg (642.5-2535).After adjusting for TBSA and chronic opioid use, patients were given a daily mean of 391 MME CI: (1201.12-419.12 p=0.334) less in ACd vs. n-ACd. In addition, acetaminophen had a daily mean of 395.12mg CI: (130.05, 660.19 p=0.005) less in ACd vs. n-ACd.Overall, acupuncture was associated with a significant lower pain score with a mean of 2.799 points less.ConclusionsAcupuncture seems to abrogate pain in burn and wound patients, as demonstrated by doses of pain medication. While there was no significant difference in opioid medications, there was a significant difference in acetaminophen, indicating that additional education of a tiered approach to pain medications is essential to reduce unnecessary opioid use.

Cav3.1-driven bursting firing in ventromedial hypothalamic neurons exerts dual control of anxiety-like behavior and energy expenditure

The central nervous system has evolved to coordinate the regulation of both the behavior response to the external environment and homeostasis of energy expenditure. Recent studies have indicated the dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both innate behavior and energy homeostasis for coping stress. However, how dmVMH neurons control neuronal firing pattern to regulate chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we found enhanced neuronal activity in VMH after chronic stress, which is mainly induced by increased proportion of burst firing neurons. This enhancement of VMH burst firing is predominantly mediated by Cav3.1 expression. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects, suggested that Cav 3.1 as a crucial regulator. Interestingly, we found that fluoxetine (anxiolytics) could block the increase of Cav3.1 expression to inhibit the burst firing, and then rescued the anxiety-like behaviors and energy expenditure changes. Collectively, our study first revealed an important role of Cav3.1-driven bursting firing of dmVMH neurons in the control of anxiety-like behavior and energy expenditure, and provided potential therapeutic targets for treating the chronic stress-induced emotional malfunction and metabolism disorders.

Prevalence, Comorbidities, and Risk Factors of Erectile Dysfunction: Results from a Prospective Real-World Study in the United Kingdom.

Objectives Assessment of erectile dysfunction (ED) burden could improve health outcomes associated with underlying cardiometabolic and psychological causes of ED. This study provided updated real-world evidence (RWE) on ED epidemiology and quantified healthcare resource utilization (HCRU) and health-related quality of life (HRQoL) burden among men with ED in the UK. Methods This cross-sectional, prospective real-world evidence study was conducted via a self-reported Internet survey in 2018 in the UK general population. Prevalence of ED was estimated; HCRU and HRQoL were compared between men with ED versus without ED via bivariate analysis. Results Of 12,490 men included, 41.5% reported ED; 7.5% of men reported severe ED; ED was most prevalent in Wales (44.3%). Men with ED were older (54.1 ± 14.5 vs. 46.8 ± 14.1 years) and often reported modifiable lifestyle risk factors, including smoking (32.8% vs. 26.3%), drinking alcohol (76.1% vs. 71.0%), not exercising (21.7% vs. 19.4%), and being overweight or obese (64.9% vs. 54.6%). Additionally, men with ED more often reported ≥1 comorbid chronic conditions (73.7% vs. 47.7%), including hypertension (31.8% vs. 16.3%), hyperlipidemia (27.6% vs. 14.0%), depression (24.3% vs. 14.6%), anxiety (23.3% vs. 16.6%), and diabetes (15.9% vs. 6.1%) versus men without ED (all, p < 0.001). Nearly half of men with ED (45.3%) were not undergoing treatment for cardiometabolic or psychological comorbidities. Furthermore, men with ED more often reported ≥1 visit to physicians/nurse practitioners and pharmacists in the past year and had significantly lower SEAR total and domain scores than men without ED (all, p < 0.001). Conclusion ED was highly prevalent in the UK affecting over a quarter of younger men. Cardiometabolic and psychological conditions were common among men with ED and often remained untreated. Higher proportions of modifiable lifestyle risk factors observed among men with ED present an opportunity for healthcare providers to help mitigate the risk of cardiometabolic diseases and incidence of ED.

Effect of Medical Marijuana Card Ownership on Pain, Insomnia, and Affective Disorder Symptoms in Adults

Despite the legalization and widespread use of cannabis products for a variety of medical concerns in the US, there is not yet a strong clinical literature to support such use. The risks and benefits of obtaining a medical marijuana card for common clinical outcomes are largely unknown. To evaluate the effect of obtaining a medical marijuana card on target clinical and cannabis use disorder (CUD) symptoms in adults with a chief concern of chronic pain, insomnia, or anxiety or depressive symptoms. This pragmatic, single-site, single-blind randomized clinical trial was conducted in the Greater Boston area from July 1, 2017, to July 31, 2020. Participants were adults aged 18 to 65 years with a chief concern of pain, insomnia, or anxiety or depressive symptoms. Participants were randomized 2:1 to either the immediate card acquisition group (n = 105) or the delayed card acquisition group (n = 81). Randomization was stratified by chief concern, age, and sex. The statistical analysis followed an evaluable population approach. The immediate card acquisition group was allowed to obtain a medical marijuana card immediately after randomization. The delayed card acquisition group was asked to wait 12 weeks before obtaining a medical marijuana card. All participants could choose cannabis products from a dispensary, the dose, and the frequency of use. Participants could continue their usual medical or psychiatric care. Primary outcomes were changes in CUD symptoms, anxiety and depressive symptoms, pain severity, and insomnia symptoms during the trial. A logistic regression model was used to estimate the odds ratio (OR) for CUD diagnosis, and linear models were used for continuous outcomes to estimate the mean difference (MD) in symptom scores. A total of 186 participants (mean [SD] age 37.2 [14.4] years; 122 women [65.6%]) were randomized and included in the analyses. Compared with the delayed card acquisition group, the immediate card acquisition group had more CUD symptoms (MD, 0.28; 95% CI, 0.15-0.40; P < .001); fewer self-rated insomnia symptoms (MD, -2.90; 95% CI, -4.31 to -1.51; P < .001); and reported no significant changes in pain severity or anxiety or depressive symptoms. Participants in the immediate card acquisition group also had a higher incidence of CUD during the intervention (17.1% [n = 18] in the immediate card acquisition group vs 8.6% [n = 7] in the delayed card acquisition group; adjusted odds ratio, 2.88; 95% CI, 1.17-7.07; P = .02), particularly those with a chief concern of anxiety or depressive symptoms. This randomized clinical trial found that immediate acquisition of a medical marijuana card led to a higher incidence and severity of CUD; resulted in no significant improvement in pain, anxiety, or depressive symptoms; and improved self-rating of insomnia symptoms. Further investigation of the benefits of medical marijuana card ownership for insomnia and the risk of CUD are needed, particularly for individuals with anxiety or depressive symptoms. ClinicalTrials.gov Identifier: NCT03224468.

Neural and self-report indices of cognitive reappraisal moderate the association between sensitivity to uncertain threat and problem alcohol use

Exaggerated reactivity to threats that are uncertain (U-threat) is a risk factor for problem alcohol use. Data suggest that exaggerated reactivity to U-threat is associated with chronic anxiety and motivation for coping-oriented drinking. Not all individuals with high U-threat reactivity engage in excessive drinking and theory and research suggest that individual differences in emotion regulation, particularly frequency and effectiveness of cognitive reappraisal, are potential moderators of this well-established link. The aim of the current study was to test this hypothesis using a multimodal laboratory design. A total of 83 volunteers with depression and/or anxiety completed a well-validated threat sensitivity task and two complimentary assessments of cognitive reappraisal. Threat sensitivity was measured using startle eyeblink potentiation during threat-of-electric shock. Cognitive reappraisal was measured using self-report and estimates of prefrontal cortex activation (PFC; i.e., ventrolateral, dorsolateral and dorsomedial) during instructed reappraisal during functional magnetic resonance imaging. Results revealed self-reported and PFC indices of reappraisal were correlated within-subjects. Additionally, self-reported and ventrolateral (vlPFC) activation during reappraisal moderated the association between reactivity to U-threat and problem alcohol use. Across both measures, at low engagement in reappraisal, greater startle reactivity to U-threat was associated with greater problem alcohol use. At high engagement in reappraisal, there was no association between U-threat reactivity and problem alcohol use. Together, the findings reveal that exaggerated reactivity to U-threat may be a particularly robust risk factor for problem alcohol use in the context of impaired or ineffective emotion regulation.

Examining the psychometric properties of brief screening measures of depression and anxiety in chronic pain: The Patient Health Questionnaire 2-item and Generalized Anxiety Disorder 2-item.

ObjectiveIndividuals with chronic pain experience anxiety and depressive symptoms at rates higher than the general population. The Patient Health Questionnaire 2‐item (PHQ‐2) and Generalized Anxiety Disorder 2‐item (GAD‐2) are brief screening measures of depression and anxiety, respectively. These brief scales are well‐suited for use in routine care due to their brevity and ease of administration, yet their psychometric properties have not been established in heterogeneous chronic pain samples when administered over the Internet.Materials and MethodsUsing existing data from randomized controlled trials of an established Internet‐delivered pain management program (n = 1333), we assessed the reliability, validity, diagnostic accuracy, and responsiveness to treatment change in the PHQ‐2 and GAD‐2, as well as the long‐form counterparts. Exploratory analyses were conducted to obtain cutoff scores using those participants with diagnostic data (n = 62).ResultsThe PHQ‐2 and GAD‐2 demonstrated appropriate reliability (eg, Cronbach's α = 0.79–0.84), validity (eg, higher scores in individuals with a diagnosis; p < 0.001), and responsiveness to treatment change (eg, pre‐ to post‐treatment scores, p < 0.001). The psychometric properties of the short forms compared well with the longer forms. Cutoff scores on the short forms were consistent with general population samples, while cutoff scores on the long forms were higher than previously observed using general population samples. All four scales favored specificity over sensitivity.ConclusionsThe PHQ‐2 and GAD‐2 demonstrated acceptable psychometric properties in the current sample, as did the long forms. Based on our findings, the PHQ‐2 and GAD‐2 can be used as screening tools with chronic pain samples when administered over the Internet.

Gender Differences in the Association between Physical Inactivity and Mental-Health Conditions in People with Vision or Hearing Impairment.

This study aimed to examine associations between physical inactivity and mental health in Spanish adults with vision or hearing difficulties and explored differences between men and women. Data from the Spanish National Health Survey in 2017 were analyzed (n = 23,089 adults, 15–103 years, mean age 53.4 ± 18.9 years, 45.9% men). Physical inactivity (exposure) was evaluated with the International Physical Activity Questionnaire Short Form. Participants self-reported whether they had previously suffered from depression, chronic anxiety and other mental-health complications (outcomes). Associations between physical inactivity and mental-health complications were assessed with multivariable logistic regression in people with difficulty seeing and hearing, after grouping by gender and adjusting for age, body-mass index, education level, living as a couple, smoking and alcohol consumption. The overall multivariable logistic-regression analyses showed that women with vision impairment showed significant associations between physical inactivity and depression (OR 1.403, 95% CI 1.015–1.940) and other mental-health complications (OR 2.959, 95% CI 1.434–6.104). In the overall analyses, there were no significant associations in men and in people with hearing impairment. The age-stratified analyses showed that inactive people with visual impairment who were <65 years old had a higher risk of mental-health conditions. In conclusion, physical activity has been shown to be important in the prevention of mental-health complications. Healthcare practitioners and policy makers should look at appropriate strategies to increase levels of physical activity in people with vision loss, especially in women and in those <65 years old.

Psychological adverse effects of anxiety and stress in treating patients with cancer

Psychological factors such as chronic stress, anxiety and depression are major risks that could lead to cancer if not promptly treated. These risks could also cause cancer to become more aggressive and hence more resistant to anti-tumor therapy.

Association between long-term usage of acetylcholinesterase inhibitors and lung cancer in the elderly: a nationwide cohort study

This retrospective cohort study aimed to evaluate the association between acetylcholinesterase inhibitors (AChEI) usage and the risk of lung cancer. Data from 116,106 new users of AChEI and 348,318, at a ratio of 1:3, matched by age, sex, and index-year, between 2000 and 2015 controls were obtained from the Taiwan Longitudinal Health Insurance Database in this cohort study. The Cox regression model was used to compare the risk of lung cancer. The adjusted hazard ratio (aHR) of lung cancer for AChEI users was 1.198 (95% confidence interval [CI] = 0.765–1.774, p = 0.167). However, the adjusted HR for patients aged ≥ 65 was adjusted to HR: 1.498 (95% CI = 1.124–1.798, p < 0.001), in contrast to the comparison groups. In addition, patients with comorbidities such as pneumonia, bronchiectasis, pneumoconiosis, pulmonary alveolar pneumonopathy, hypertension, stroke, coronary artery disease, diabetes mellitus, chronic kidney disease, depression, anxiety, smoking-related diseases, dementia, and seeking medical help from medical centers and regional hospitals, were associated with a higher risk in lung cancer. Furthermore, longer-term usage of rivastigmine (366–730 days, ≥ 731 days) and galantamine (≥ 731 days) was associated with the risk of lung cancer. AChEI increased the risk of lung cancer in the older aged patients, several comorbidities, and a longer-term usage of rivastigmine and galantamine. Therefore, physicians should estimate the risks and benefits of AChEI usage and avoid prescribing antidepressants concurrently.

Kolaviron ameliorates chronic unpredictable mild stress-induced anxiety and depression: involvement of the HPA axis, antioxidant defense system, cholinergic, and BDNF signaling.

This study sought to investigate the beneficial effect of kolaviron (KV) (a biflavonoid) isolated from Garcinia kola seed on chronic unpredictable mild stress (CUMS)-induced anxiety- and depressive-like behavior. Male albino mice were randomly divided into six groups (n=8) as follows; Group I: vehicle-control unstressed; Group II: CUMS-control; Group III-V: CUMS+KV 1, 5 or 50mg/kg, respectively, Group VI: KV (50mg/kg, p.o.) unstressed mice. Animals were subjected to CUMS for 14days, followed by estimation of depressive- and anxiety-like behavior from days 14-16. This was followed by biochemical assays for oxidative stress, hypothalamo-pituitary axis, cholinergic, and BDNF signaling. CUMS caused significant reduction in time spent in open arms of elevated plus maze test (EPM) and increase in immobility time in tail suspension test (TST) and forced swim test (FST) ameliorated by KV treatments. KV administration also attenuated CUMS-induced malondialdehyde/nitrite generation and decrease in antioxidant enzymes activities in the prefrontal cortex and hippocampus. CUMS increased serum corticosterone, acetylcholinesterase activity, and reduced BDNF level in the PFC and hippocampus were attenuated by KV administration. KV prevented CUMS induced anxiety- and depression-like behavior in mice through enhancement of antioxidant defense mechanisms, neurotrophic factors, and cholinergic systems.

Prevalence of multimorbidity and associated treatment burden in primary care settings in Kerala: a cross-sectional study in Malappuram District, Kerala, India

Background: Multimorbidity or co-existence of two or more chronic conditions is common and associated with reduced quality of life and increased risk of death. We aimed to estimate the prevalence and pattern of multimorbidity in primary care settings in Kerala and the associated treatment burden, and quality of life. Methods: A cross-sectional survey was conducted among 540 adult participants in Malappuram District, Kerala. A multi-stage cluster sampling method was employed. Hypertension, diabetes, chronic obstructive pulmonary disease, depression and anxiety screening were done by trained medical professionals. The remaining medical conditions were self-reported by the respondent and verified with patient held health records. The health-related quality of life [HRQoL] was measured using the EQ-5D-5L tool. The MTBQ tool was used for measuring the multimorbidity treatment burden. Logistic regression was used to identify variables associated with multi-morbidity. Results: Overall, the prevalence of multi-morbidity was 39.8% (35.7 – 44.1). The prevalence of multi-morbidity among men (42.6%) was relatively higher than that in women (38.1%). Lower educational attainment, higher age group, and overweight or obesity status were independently associated with higher prevalence of multimorbidity. The most common pairs of coexisting chronic conditions reported in the study were hypertension and diabetes in males (66.7%) and females (70.8%). All domains of quality of life were impaired in individuals with multimorbidity. Conclusion: Multimorbidity is a norm and affects two of five participants seeking care in primary care settings in Kerala. The social gradient in the prevalence of multimorbidity was evident with higher prevalence in individuals with low educational attainment. Multimorbidity seriously impairs quality of life and increases treatment burden. The focus of management should move beyond individual diseases, and pivot towards interventions targeting multi-morbidity management, with a specific focus for people living in lower socio-economic strata.

Changes in the structural connectom of the brain in patients with postmastectomy syndrome

Background. After breast cancer treatment, up to 90 % of patients suffer from various neurological and mental disorders, such as vertebrobasilar insufficiency, chronic pain syndrome, anxiety and depression. These disorders can cause structural changes in the white matter tracts of the brain, which can be detected using diffusion tensor magnetic resonance imaging (DT-MRI).Objective. To evaluate structural changes in the white matter tracts of the brain in patients with post-mastectomy syndrome using DT-MRI.Design and methods. The study was carried out on a tomograph with a magnetic field induction force of 3.0 T. 46 patients with neurological disorders in the long-term postoperative period (more than 6 months) after radical mastectomy, chemotherapeutic and/or radiation treatment for breast cancer were examined.Results. According to the results of an intergroup statistical analysis, all 46 patients with post-mastectomy syndrome had differences in quantitative fractional anisotropy in the white matter tracts of the brain compared with the control group (p &lt; 0.01).Conclusion. The use of DT-MRI in patients with post-mastectomy syndrome makes it possible to identify changes in the white matter tracts of the brain that correlate with neurological disorders and a decrease in the quality of life in this cohort of patients. The results obtained indicate the need to improve treatment and rehabilitation approaches in patients receiving treatment for breast cancer.

High trait anxiety in mice is associated with impaired extinction in the contextual fear conditioning paradigm

Trait anxiety is a form of chronic state anxiety that can be part of the individual’s personality and one of the individual factors that increase the risk of developing PTSD. To be able to distinguish between trait and state anxiety in animal models might be challenging, since the tests themselves are often anxiogenic. One possible approach is the use of the free exploratory paradigm (FEP), a model that consists of providing the animal the choice to explore both a familiar and a novel environment. High trait anxiety animals choose to explore more the familiar environment. Thus, the objective of this study was to evaluate if differences in trait anxiety could lead to impairments in acquisition and extinction of fear memory in a contextual fear conditioning protocol. First, Swiss mice were divided into high trait anxiety (HTA) or low trait anxiety (LTA) based on their exploration of the novel environment (%TNS) in the FEP. We observed that the %TNS was stable across three testing sessions. Also, we observed that freezing behavior was not different between HTA and LTA mice in a retrieval session 1 day after the conditioning, which indicates that acquisition was not impaired. However, HTA presented higher freezing time during extinction training and test. Also, HTA presented higher freezing in reinstatement test, but this might be related to the poor extinction learning. Moreover, diazepam (0.25 or 1.0 mg/kg, i.p.) did not prevent the differences in extinction training and test when administer 30 min before conditioning training or 30 min before extinction training, even though diazepam (1.0 mg/kg) had anxiolytic effect in the elevated plus-maze. These results demonstrate that HTA mice presented increase in freezing during extinction training and test, as well as during reinstatement. These results indicate that increased freezing time in HTA mice is not explained by high state anxiety in a specific phase of the fear conditioning, but more likely, the overall high trait anxiety throughout the entire experiment.