Investigating heart rate variability measures during pregnancy as predictors of postpartum depression and anxiety: an exploratory study.

Perinatal affective disorders are common, but standard screening measures reliant on subjective self-reports might not be sufficient to identify pregnant women at-risk for developing postpartum depression and anxiety. Lower heart rate variability (HRV) has been shown to be associated with affective disorders. The current exploratory study aimed to evaluate the predictive utility of late pregnancy HRV measurements of postpartum affective symptoms. A subset of participants from the BASIC study (Uppsala, Sweden) took part in a sub-study at pregnancy week 38 where HRV was measured before and after a mild stressor (n = 122). Outcome measures were 6-week postpartum depression and anxiety symptoms as quantified by the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Anxiety Inventory (BAI). In total, 112 women were included in a depression outcome analysis and 106 women were included in an anxiety outcome analysis. Group comparisons indicated that lower pregnancy HRV was associated with depressive or anxious symptomatology at 6 weeks postpartum. Elastic net logistic regression analyses indicated that HRV indices alone were not predictive of postpartum depression or anxiety outcomes, but HRV indices were selected as predictors in a combined model with background and pregnancy variables. ROC curves for the combined models gave an area under the curve (AUC) of 0.93 for the depression outcome and an AUC of 0.83 for the anxiety outcome. HRV indices predictive of postpartum depression generally differed from those predictive of postpartum anxiety. HRV indices did not significantly improve prediction models comprised of psychological measures only in women with pregnancy depression or anxiety.

Mood and physiological effects of visual stimulation with images of the natural environment in individuals with depressive and anxiety disorders.

BACKGROUND: Nature therapies are gaining attention as non-pharmacological treatments for depressive and anxiety disorders, but research on their effectiveness in patients is limited. This study investigates the mood-improving effects of visual stimulation with natural environmental images in patients with depressive and anxiety disorders. METHODS: We conducted a randomized crossover comparison trial involving 60 right-handed adult participants with depressive or anxiety disorders and receiving outpatient treatment. Visual stimuli of natural environments consisted of green-themed nature images, while the control stimuli featured urban scenes dominated by buildings. The stimulation lasted for 3 min, during which orbital prefrontal brain activity was measured using a 2-channel Near-infrared Spectroscopy (NIRS) system, and heart rate variability was assessed using fingertip accelerated plethysmography. RESULTS: Mood enhancement effects were observed in both the depressive and anxiety disorder groups following visual stimulation with nature images. In the depression group, orbital prefrontal oxygenated hemoglobin concentration significantly increased after visual stimulation with nature images, while there were no significant changes in the anxiety group. However, in the anxiety group, a correlation was found between reduced orbital prefrontal oxygenated hemoglobin in response to nature images and increased mood-enhancement. Furthermore, the severity of depressive symptoms did not significantly affect the intervention effects, whereas heightened anxiety symptoms was associated with a smaller mood enhancement effect. DISCUSSION: Our study demonstrates the benefits of nature image stimulation for patients with depressive and anxiety disorders. Differential orbital prefrontal brain activity impacts notwithstanding, both conditions exhibited mood enhancement, affirming the value of nature image stimulation.

Changes in SLITRK1 Level in the Amygdala Mediate Chronic Neuropathic Pain-Induced Anxio-Depressive Behaviors in Mice.

BACKGROUND: Comorbid chronic neuropathic pain (NPP) and anxio-depressive disorders (ADD) have become a serious global public-health problem. The SLIT and NTRK-like 1 (SLITRK1) protein is important for synaptic remodeling and is highly expressed in the amygdala, an important brain region involved in various emotional behaviors. We examined whether SLITRK1 protein in the amygdala participates in NPP and comorbid ADD. METHODS: A chronic NPP mouse model was constructed by L5 spinal nerve ligation; changes in chronic pain and ADD-like behaviors were measured in behavioral tests. Changes in SLITRK1 protein and excitatory synaptic functional proteins in the amygdala were measured by immunofluorescence and Western blot. Adeno-associated virus was transfected into excitatory synaptic neurons in the amygdala to up-regulate the expression of SLITRK1. RESULTS: Chronic NPP-related ADD-like behavior was successfully produced in mice by L5 ligation. We found that chronic NPP and related ADD decreased amygdalar expression of SLITRK1 and proteins important for excitatory synaptic function, including Homer1, postsynaptic density protein 95 (PSD95), and synaptophysin. Virally-mediated SLITRK1 overexpression in the amygdala produced a significant easing of chronic NPP and ADD, and restored the expression levels of Homer1, PSD95, and synaptophysin. CONCLUSION: Our findings indicated that SLITRK1 in the amygdala plays an important role in chronic pain and related ADD, and may prove to be a potential therapeutic target for chronic NPP-ADD comorbidity.

Understanding the heterogeneity of anxiety using a translational neuroscience approach.

Anxiety disorders affect millions of people worldwide and present a challenge in neuroscience research because of their substantial heterogeneity in clinical presentation. While a great deal of progress has been made in understanding the neurobiology of fear and anxiety, these insights have not led to effective treatments. Understanding the relationship between phenotypic heterogeneity and the underlying biology is a critical first step in solving this problem. We show translation, reverse translation, and computational modeling can contribute to a refined, cross-species understanding of fear and anxiety as well as anxiety disorders. More specifically, we outline how animal models can be leveraged to develop testable hypotheses in humans by using targeted, cross-species approaches and ethologically informed behavioral paradigms. We discuss reverse translational approaches that can guide and prioritize animal research in nontraditional research species. Finally, we advocate for the use of computational models to harmonize cross-species and cross-methodology research into anxiety. Together, this translational neuroscience approach will help to bridge the widening gap between how we currently conceptualize and diagnose anxiety disorders, as well as aid in the discovery of better treatments for these conditions.

Multiscale neural signatures of major depressive, anxiety, and stress-related disorders.

The extent of shared and distinct neural mechanisms underlying major depressive disorder (MDD), anxiety, and stress-related disorders is still unclear. We compared the neural signatures of these disorders in 5,405 UK Biobank patients and 21,727 healthy controls. We found the greatest case­control differences in resting-state functional connectivity and cortical thickness in MDD, followed by anxiety and stress-related disorders. Neural signatures for MDD and anxiety disorders were highly concordant, whereas stress-related disorders showed a distinct pattern. Controlling for cross-disorder genetic risk somewhat decreased the similarity between functional neural signatures of stress-related disorders and both MDD and anxiety disorders. Among cases and healthy controls, reduced within-network and increased between-network frontoparietal and default mode connectivity were associated with poorer cognitive performance (processing speed, attention, associative learning, and fluid intelligence). These results provide evidence for distinct neural circuit function impairments in MDD and anxiety disorders compared to stress disorders, yet cognitive impairment appears unrelated to diagnosis and varies with circuit function.

The magnitude and effect of work-life imbalance on cognition and affective range among the non-western population: A study from Muscat.

The temporal relationship between work-life balance/imbalance, occupational burnout, and poor mental health outcomes have been widely explored. Little has been forthcoming on cognitive functioning among those with work-life imbalance. This study aimed to explore the rate of work-life imbalance and the variation in neuropsychological functioning. The relationship between affective ranges (anxiety and depressive symptoms) and work-life balance was also explored. The target population in this study are Omani nationals who were referred for psychometric evaluation. The study employs neuropsychology measures tapping into attention and concentration, learning and remembering, processing speed, and executive functioning. Subjective measures of cognitive decline and affective ranges were also explored. A total of 168 subjects (75.3% of the responders) were considered to be at a work-life imbalance. Multivariate analysis showed that demographic and neuropsychological variables were significant risk factors for work-life imbalance including age and the presence of anxiety disorder. Furthermore, participants indicating work-life imbalance were more likely to report cognitive decline on indices of attention, concentration, learning, and remembering. This study reveals that individuals with work-life imbalance might dent the integrity of cognition including attention and concentration, learning and remembering, executive functioning, and endorsed case-ness for anxiety.

Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome.

(1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS.

Multidimensional assessment of anxiety through the State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA): From dimensionality to response prediction across emotional contexts.

The assessment of mal-adaptive anxiety is crucial, considering the associated personal, economic, and societal burden. The State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) is a self-report instrument developed to provide multidimensional anxiety assessment in four dimensions: trait-cognitive, trait-somatic, state-cognitive and state-somatic. This research aimed to extend STICSA's psychometric studies through the assessment of its dimensionality, reliability, measurement invariance and nomological validity in the Portuguese population. Additionally, the predictive validity of STICSA-Trait was also evaluated, through the analysis of the relationship between self-reported trait anxiety and both the subjective and the psychophysiological response across distinct emotional situations. Similarly to previous studies, results supported both a four-factor and two separated bi-factor structures. Measurement invariance across sex groups was also supported, and good nomological validity was observed. Moreover, STICSA trait-cognitive dimension was associated with differences in self-reported arousal between groups of high/low anxiety, whereas STICSA trait-somatic dimension was related to differences in both the subjective and psychophysiological response. Together, these results support STICSA as a useful instrument for a broader anxiety assessment, crucial for an informed diagnosis and practice.

ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders.

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

Editorial: Toward Neurobiological-Based Treatments of Depression and Anxiety: A Potential Case for the Nucleus Accumbens.

Depression and anxiety disorders together account for the majority of mental health disorders in childhood and adolescence, and are often comorbid.1 The frequent co-occurrence of these disorders has motivated clinicians and researchers to consider dimensional taxonomy models that focus on neurobiological substrates that explain transdiagnostic constructs of functioning (eg, reward processing abnormalities). Such an approach would redefine not only depression and anxiety disorders but could also revolutionize clinical care, as such biobehavioral targets, rather than a traditional primary diagnosis, could serve as the basis for treatment planning. In this issue of the Journal, Auerbach et al.2 examined whether and how a key structure involved in reward processing, the nucleus accumbens (NAcc), is altered in adolescents aged 14 to 17 years with depression and/or anxiety (including generalized anxiety, separation anxiety, social anxiety, specific phobia, agoraphobia, and panic) disorders, and whether NAcc morphometry and function would improve prediction of 6-month symptomatology. As part of the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) initiative,3 the researchers compared 129 adolescents with primary diagnoses of depression and/or anxiety and 64 psychiatrically healthy controls on gray matter volumes of the NAcc and on functional activation of the NAcc during a monetary incentive delay task using magnetic resonance imaging (MRI) protocols harmonized with the Human Connectome project (http://www.humanconnectomeproject.com/). Compared to healthy adolescents, depressed/anxious adolescents exhibited significantly smaller volumes of the NAcc and blunted NAcc responses to reward receipt. Among the 88 depressed/anxious adolescents and 57 healthy controls who provided symptom data 6 months later, the researchers also found that inclusion of NAcc volumes, but not reward-related responses of the NAcc on the task, significantly improved statistical prediction of subsequent depression symptoms.

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders.

Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

Processing of fMRI-related anxiety and bi-directional information flow between prefrontal cortex and brain stem.

Brain-heart synchronization is fundamental for emotional-well-being and brain-heart desynchronization is characteristic for anxiety disorders including specific phobias. Recording BOLD signals with functional magnetic resonance imaging (fMRI) is an important noninvasive diagnostic tool; however, 1-2% of fMRI examinations have to be aborted due to claustrophobia. In the present study, we investigated the information flow between regions of interest (ROI's) in the cortex and brain stem by using a frequency band close to 0.1 Hz. Causal coupling between signals important in brain-heart interaction (cardiac intervals, respiration, and BOLD signals) was studied by means of Directed Transfer Function based on the Granger causality principle. Compared were initial resting states with elevated anxiety and final resting states with low or no anxiety in a group of fMRI-naïve young subjects. During initial high anxiety the results showed an increased information flow from the middle frontal gyrus (MFG) to the pre-central gyrus (PCG) and to the brainstem. There also was an increased flow from the brainstem to the PCG. While the top-down flow during increased anxiety was predominant, the weaker ascending flow from brainstem structures may characterize a rhythmic pacemaker-like activity that (at least in part) drives respiration. We assume that these changes in information flow reflect successful anxiety processing.

Convergence, preliminary findings and future directions across the four human connectome projects investigating mood and anxiety disorders.

In this paper we provide an overview of the rationale, methods, and preliminary results of the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders. The first study, "Dimensional connectomics of anxious misery" (HCP-DAM), characterizes brain-symptom relations of a transdiagnostic sample of anxious misery disorders. The second study, "Human connectome Project for disordered emotional states" (HCP-DES), tests a hypothesis-driven model of brain circuit dysfunction in a sample of untreated young adults with symptoms of depression and anxiety. The third study, "Perturbation of the treatment resistant depression connectome by fast-acting therapies" (HCP-MDD), quantifies alterations of the structural and functional connectome as a result of three fast-acting interventions: electroconvulsive therapy, serial ketamine therapy, and total sleep deprivation. Finally, the fourth study, "Connectomes related to anxiety and depression in adolescents" (HCP-ADA), investigates developmental trajectories of subtypes of anxiety and depression in adolescence. The four projects use comparable and standardized Human Connectome Project magnetic resonance imaging (MRI) protocols, including structural MRI, diffusion-weighted MRI, and both task and resting state functional MRI. All four projects also conducted comprehensive and convergent clinical and neuropsychological assessments, including (but not limited to) demographic information, clinical diagnoses, symptoms of mood and anxiety disorders, negative and positive affect, cognitive function, and exposure to early life stress. The first round of analyses conducted in the four projects offered novel methods to investigate relations between functional connectomes and self-reports in large datasets, identified new functional correlates of symptoms of mood and anxiety disorders, characterized the trajectory of connectome-symptom profiles over time, and quantified the impact of novel treatments on aberrant connectivity. Taken together, the data obtained and reported by the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders describe a rich constellation of convergent biological, clinical, and behavioral phenotypes that span the peak ages for the onset of emotional disorders. These data are being prepared for open sharing with the scientific community following screens for quality by the Connectome Coordinating Facility (CCF). The CCF also plans to release data from all projects that have been pre-processed using identical state-of-the-art pipelines. The resultant dataset will give researchers the opportunity to pool complementary data across the four projects to study circuit dysfunctions that may underlie mood and anxiety disorders, to map cohesive relations among circuits and symptoms, and to probe how these relations change as a function of age and acute interventions. This large and combined dataset may also be ideal for using data-driven analytic approaches to inform neurobiological targets for future clinical trials and interventions focused on clinical or behavioral outcomes.

Assessing the effect of interaction between C-reactive protein and gut microbiome on the risks of anxiety and depression.

Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3321 independent single nucleotide polymorphism (SNP) loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113,693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114,219). At last, 11 candidate CRP × gut microbiome interaction with suggestive significance was detected for PHQ-9 score, such as F_Ruminococcaceae (ß = - 0.009, P = 2.2 × 10-3), G_Akkermansia (ß = - 0.008, P = 7.60 × 10-3), F_Acidaminococcaceae (ß = 0.008, P = 1.22 × 10-2), G_Holdemanella (ß = - 0.007, P = 1.39 × 10-2) and O_Lactobacillales (ß = 0.006, P = 1.79× 10-2). 16 candidate CRP × gut microbiome interaction with suggestive significance was detected for GAD-7 score, such as O_Bacteroidales (ß = 0.010, P = 4.00× 10-4), O_Selenomonadales (ß = - 0.010, P = 1.20 × 10-3), O_Clostridiales (ß = 0.009, P = 2.70 × 10-3) and G_Holdemanella (ß = - 0.008, P = 4.20 × 10-3). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiomes for them.

Error-related negativity predicts increases in anxiety in a sample of clinically anxious female children and adolescents over 2 years.

BACKGROUND: An increased neural response to making errors has emerged as a biomarker of anxiety. Error negativity (Ne) or errorrelated negativity (ERN) is an event-related potential generated when people commit errors; the Ne/ERN is greater among people with anxiety and predicts increases in anxiety. However, no previous study has examined whether the Ne/ERN can be used as a prognostic indicator among people with current anxiety. The present study addressed this gap by examining whether the Ne/ERN prospectively predicts increases in anxiety symptoms in clinically anxious children and adolescents. METHODS: The sample included 34 female participants between the ages of 8 and 14 years who met the criteria for a clinical anxiety disorder based on clinical interview. The Ne/ERN was measured using a flanker task. RESULTS: Increased Ne/ERN at baseline predicted increases in total anxiety symptoms 2 years later, even when accounting for baseline symptoms. The Ne/ERN predicted increases in the symptom domains of generalized anxiety, social anxiety and harm avoidance/perfectionism, but not panic, separation anxiety, school avoidance or physical symptoms. LIMITATIONS: The sample size was small, which may have inflated the false discovery rate. To mitigate this possibility, we used multiple self-report measures, and the results for the 2 measures (as well as their symptom domains) converged. CONCLUSION: These data suggest that the Ne/ERN can delineate specific risk trajectories, even among those who already meet the criteria for a clinical anxiety disorder. Considering the need for prognostic markers among people with clinical anxiety, the current findings are an important and novel extension of previous work.

Resilience and Hope Among Yazidi Women Released From ISIS Enslavement.

ABSTRACT: This study aimed to explore the levels of resilience and hope among Yazidi women who survived captivity by Islamic State of Iraq and Syria (ISIS) and to examine its relationship with posttraumatic stress disorder (PTSD), generalized anxiety, and depressive symptoms. In this cross-sectional study, 139 formerly enslaved Yazidi women were assessed. The mean scores of resilience and hope were below the suggested cutoff means (M = 2.47, SD = 0.48, R = 1-5) and (M = 31.6, SD = 11.7, R = 8-64), respectively. Sociodemographic variables were not related to resilience and hope, other than those women who stayed in captivity for more than a 3-year period who reported significantly lower levels of hope (M = 28.36, SD = 11.69). Formerly enslaved Yazidi women who display higher levels of PTSD, generalized anxiety, and depression exhibit significantly lower levels of resilience and hope. Resilience and hope are therefore important concepts to explore in traumatized populations.

Apocynin Prevents Anxiety-Like Behavior and Histone Deacetylases Overexpression Induced by Sub-Chronic Stress in Mice.

Anxiety disorders are common mental health diseases affecting up to 7% of people around the world. Stress is considered one of the major environmental risk factors to promote anxiety disorders through mechanisms involving epigenetic changes. Moreover, alteration in redox balance and increased reactive oxygen species (ROS) production have been detected in anxiety patients and in stressed-animal models of anxiety. Here we tested if the administration of apocynin, a natural origin antioxidant, may prevent the anxiety-like phenotype and reduction of histone acetylation induced by a subchronic forced swimming stress (FSS) paradigm. We found that apocynin prevented the enhanced latency time in the novelty-suppressed feeding test, and the production of malondialdehyde induced by FSS. Moreover, apocynin was able to block the upregulation of p47phox, a key subunit of the NADPH oxidase complex. Finally, apocynin prevented the rise of hippocampal Hdac1, Hdac4 and Hdac5, and the reduction of histone-3 acetylation levels promoted by FSS exposure. In conclusion, our results provide evidence that apocynin reduces the deleterious effect of stress and suggests that oxidative stress may regulate epigenetic mechanisms.

Generalization gradients for fear and disgust in human associative learning.

Previous research indicates that excessive fear is a critical feature in anxiety disorders; however, recent studies suggest that disgust may also contribute to the etiology and maintenance of some anxiety disorders. It remains unclear if differences exist between these two threat-related emotions in conditioning and generalization. Evaluating different patterns of fear and disgust learning would facilitate a deeper understanding of how anxiety disorders develop. In this study, 32 college students completed threat conditioning tasks, including conditioned stimuli paired with frightening or disgusting images. Fear and disgust were divided into two randomly ordered blocks to examine differences by recording subjective US expectancy ratings and eye movements in the conditioning and generalization process. During conditioning, differing US expectancy ratings (fear vs. disgust) were found only on CS-, which may demonstrated that fear is associated with inferior discrimination learning. During the generalization test, participants exhibited greater US expectancy ratings to fear-related GS1 (generalized stimulus) and GS2 relative to disgust GS1 and GS2. Fear led to longer reaction times than disgust in both phases, and the pupil size and fixation duration for fear stimuli were larger than for disgust stimuli, suggesting that disgust generalization has a steeper gradient than fear generalization. These findings provide preliminary evidence for differences between fear- and disgust-related stimuli in conditioning and generalization, and suggest insights into treatment for anxiety and other fear- or disgust-related disorders.

Astrocytes in the Ventromedial Hypothalamus Involve Chronic Stress-Induced Anxiety and Bone Loss in Mice.

Chronic stress is one of the main risk factors of bone loss. While the neurons and neural circuits of the ventromedial hypothalamus (VMH) mediate bone loss induced by chronic stress, the detailed intrinsic mechanisms within the VMH nucleus still need to be explored. Astrocytes in brain regions play important roles in the regulation of metabolism and anxiety-like behavior through interactions with surrounding neurons. However, whether astrocytes in the VMH affect neuronal activity and therefore regulate chronic stress-induced anxiety and bone loss remain elusive. In this study, we found that VMH astrocytes were activated during chronic stress-induced anxiety and bone loss. Pharmacogenetic activation of the Gi and Gq pathways in VMH astrocytes reduced and increased the levels of anxiety and bone loss, respectively. Furthermore, activation of VMH astrocytes by optogenetics induced depolarization in neighboring steroidogenic factor-1 (SF-1) neurons, which was diminished by administration of N-methyl-D-aspartic acid (NMDA) receptor blocker but not by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker. These results suggest that there may be a functional "glial-neuron microcircuit" in VMH nuclei that mediates anxiety and bone loss induced by chronic stress. This study not only advances our understanding of glial cell function but also provides a potential intervention target for chronic stress-induced anxiety and bone loss therapy.

Effectiveness of a nurse-led hospital-to-home transitional care intervention for older adults with multimorbidity and depressive symptoms: A pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a nurse-led hospital-to-home transitional care intervention versus usual care on mental functioning (primary outcome), physical functioning, depressive symptoms, anxiety, perceived social support, patient experience, and health service use costs in older adults with multimorbidity (≥ 2 comorbidities) and depressive symptoms. DESIGN AND SETTING: Pragmatic multi-site randomized controlled trial conducted in three communities in Ontario, Canada. Participants were allocated into two groups of intervention and usual care (control). PARTICIPANTS: 127 older adults (≥ 65 years) discharged from hospital to the community with multimorbidity and depressive symptoms. INTERVENTION: This evidence-based, patient-centred intervention consisted of individually tailored care delivery by a Registered Nurse comprising in-home visits, telephone follow-up and system navigation support over 6-months. OUTCOME MEASURES: The primary outcome was the change in mental functioning, from baseline to 6-months. Secondary outcomes were the change in physical functioning, depressive symptoms, anxiety, perceived social support, patient experience, and health service use cost, from baseline to 6-months. Intention-to-treat analysis was performed using ANCOVA modeling. RESULTS: Of 127 enrolled participants (63-intervention, 64-control), 85% had six or more chronic conditions. 28 participants were lost to follow-up, leaving 99 (47 -intervention, 52-control) participants for the complete case analysis. No significant group differences were seen for the baseline to six-month change in mental functioning or other secondary outcomes. Older adults in the intervention group reported receiving more information about health and social services (p = 0.03) compared with the usual care group. CONCLUSIONS: Although no significant group differences were seen for the primary or secondary outcomes, the intervention resulted in improvements in one aspect of patient experience (information about health and social services). The study sample fell below the target sample (enrolled 127, targeted 216), which can account for the non-significant findings. Further research on the impact of the intervention and factors that contribute to the results is recommended. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03157999.