Journal articles on the topic 'Emotion Upregulation'

Existing research reveals the academic profession to be stressful and emotion-laden. Recent evidence further shows job-related stress and emotion regulation to impact faculty well-being and productivity. The present study recruited 414 Canadian faculty members from 13 English-speaking research-intensive universities. We examined the associations between perceived stressors, emotion regulation strategies, including reappraisal, suppression, adaptive upregulation of positive emotions, maladaptive downregulation of positive emotions, as well as adaptive and maladaptive downregulation of negative emotions, and well-being outcomes (emotional exhaustion, job satisfaction, quitting intentions, psychological maladjustment, and illness symptoms). Additionally, the study explored the moderating role of stress, gender, and years of experience in the link between emotion regulation and well-being as well as the interactions between adaptive and maladaptive emotion regulation strategies in predicting well-being. The results revealed that cognitive reappraisal was a health-beneficial strategy, whereas suppression and maladaptive strategies for downregulating positive and negative emotions were detrimental. Strategies previously defined as adaptive for downregulating negative emotions and upregulating positive emotions did not significantly predict well-being. In contrast, strategies for downregulating negative emotions previously defined as dysfunctional showed the strongest maladaptive associations with ill health. Practical implications and directions for future research are also discussed.

In stressful situations such as the COVID-19-pandemic, unpleasant emotions are expected to increase while pleasant emotions will likely decrease. Little is known about the role cognitive appraisals, information management, and upregulating pleasant emotions can play to support emotion regulation in a pandemic. In an online survey (N = 1682), we investigated predictors of changes in pleasant and unpleasant emotions in a German sample (aged 18–88 years) shortly after the first restrictions were imposed. Crisis self-efficacy and felt restriction were predictors of changes in unpleasant emotions and joy alike. The application of emotion up-regulation strategies was weakly associated with changes in joy. Among the different upregulation strategies, only “savouring the moment” predicted changes in joy. Our study informs future research perspectives assessing the role of upregulating pleasant emotions under challenging circumstances.

Peroxisome proliferator-activator receptors (PPARs) regulate lipid and glucose metabolism, control inflammatory processes, and modulate several brain functions. Three PPAR isoforms have been identified, PPARα, PPARb/d, and PPARg, which are expressed in different tissues and cell types. Hereinafter, we focus on PPARα involvement in the pathophysiology of neuropsychiatric and neurodegenerative disorders, which is underscored by PPARα localization in neuronal circuits involved in emotion modulation and stress response, and its role in neurodevelopment and neuroinflammation. A multiplicity of downstream pathways modulated by PPARα activation, including glutamatergic neurotransmission, upregulation of brain-derived neurotrophic factor, and neurosteroidogenic effects, encompass mechanisms underlying behavioral regulation. Modulation of dopamine neuronal firing in the ventral tegmental area likely contributes to PPAR effects in depression, anhedonia, and autism spectrum disorder (ASD). Based on robust preclinical evidence and the initial results of clinical studies, future clinical trials should assess the efficacy of PPARα agonists in the treatment of mood and neurodevelopmental disorders, such as depression, schizophrenia, and ASD.

Objective. Electroacupuncture (EA) is reported effective in alleviating pain-related emotion; however, the underlying mechanism of its effects still needs to be elucidated. The NPS-NPSR system has been validated for the involvement in the modulation of analgesia and emotional behavior. Here, we aimed to investigate the role of the NPS-NPSR system in the anterior cingulate cortex (ACC), hypothalamus, and central amygdala (CeA) in the use of EA to relieve affective pain modeled by complete Freund’s adjuvant- (CFA-) evoked conditioned place aversion (C-CPA). Materials and Methods. CFA injection combined with a CPA paradigm was introduced to establish the C-CPA model, and the elevated O-maze (EOM) was used to test the behavioral changes after model establishment. We further explored the expression of NPS and NPSR at the protein and gene levels in the brain regions of interest by immunofluorescence staining and quantitative real-time PCR. Results. We observed that EA stimulation delivered to the bilateral Zusanli (ST36) and Kunlun (BL60) acupoints remarkably inhibited sensory pain, pain-evoked place aversion, and anxiety-like behavior. The current study showed that EA significantly enhanced the protein expression of this peptide system in the ACC and hypothalamus, while the elevated expression of NPSR protein alone was just confined to the affected side in the CeA. Moreover, EA remarkably upregulated the mRNA expression of NPS in CeA, ACC, and hypothalamus and NPSR mRNA in the hypothalamus and CeA. Conclusions. These data suggest the effectiveness of EA in alleviating affective pain, and these benefits may at least partially be attributable to the upregulation of the NPS-NPSR system in the ACC and hypothalamus.

We investigated whether depressed patients who received fMRI-based neurofeedback are able to upregulate the activity in brain areas devoted to positive emotion processing and thereby establish improvements in mood state. Eight medicated patients with major depression participated in four separate fMRI sessions, each of which consisted of an emotion localiser and three neurofeedback runs. Target areas were selected individually with a functional localiser that identified the region most responsive to positive affective images. The target areas were in uni- or bilateral prefrontal cortex, insula or amygdala. During neurofeedback runs, patients received real-time feedback about activation levels in the target area. Each patient learnt to increase target area activity over successive sessions. Depression scores on the 17-item Hamilton Depression Rating Scale improved significantly. No such improvement was seen in a non-neurofeedback control group (N = 8) that was matched for symptom severity, demographics and medication and used the same cognitive/affective strategies that were employed successfully by the neurofeedback group, but outside the scanner. This group difference in treatment effects was supported by a significant interaction between the factors time (pre/post-intervention) and group (neurofeedback/controls) on the repeated measures ANOVA (F(1,14) = 10.15, p = .007). The neurofeedback group showed increasing activity in the ventral striatum and regions involved in cognitive control as training progressed. Upregulation of brain areas responsive to positive affective cues through fMRI-neurofeedback is thus a promising tool in the treatment of depression. The novelty of the present approach consists in the combination of biological and cognitive factors in the same intervention.

The serotonin-1A (5-HT 1A ) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre- and post-synaptic 5-HT 1A receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre- versus post-synaptic 5-HT 1A receptors could provide better tools for their selective regulation. This review examines the transcription factors that regulate brain region-specific basal and stress-induced expression of the 5-HT 1A receptor gene ( Htr1a ). A functional polymorphism, rs6295 in the Htr1a promoter region, blocks the function of specific repressors Hes1, Hes5 and Deaf1, resulting in increased 5-HT 1A autoreceptor expression in animal models and humans. Its association with altered 5-HT 1A expression, depression, anxiety and antidepressant response are related to genotype frequency in different populations, sample homogeneity, disease outcome measures and severity. Preliminary evidence from gene × environment studies suggests the potential for synergistic interaction of stress-mediated repression of 5-HT 1A heteroreceptors, and rs6295-induced upregulation of 5-HT 1A autoreceptors. Targeted therapeutics to inhibit 5-HT 1A autoreceptor expression and induce 5-HT 1A heteroreceptor expression may ameliorate treatment of anxiety and major depression.

Depression is often associated with co-occurring neurocognitive deficits in executive function (EF), processing speed (PS) and emotion regulation (ER), which impact treatment response. Cognitive training targeting these capacities results in improved cognitive function and mood, demonstrating the relationship between cognition and affect, and shedding light on novel targets for cognitive-focused interventions. Computerized cognitive training (CCT) is one such new intervention, with evidence suggesting it may be effective as an adjunct treatment for depression. Parallel research suggests that mindfulness training improves depression via enhanced ER and augmentation of self-referential processes. CCT and mindfulness training both act on anti-correlated neural networks involved in EF and ER that are often dysregulated in depression—the cognitive control network (CCN) and default-mode network (DMN). After practicing CCT or mindfulness, downregulation of DMN activity and upregulation of CCN activity have been observed, associated with improvements in depression and cognition. As CCT is posited to improve depression via enhanced cognitive function and mindfulness via enhanced ER ability, the combination of both forms of training into mindfulness-enhanced CCT (MCCT) may act to improve depression more rapidly. MCCT is a biologically plausible adjunct intervention and theoretical model with the potential to further elucidate and target the causal mechanisms implicated in depressive symptomatology. As the combination of CCT and mindfulness has not yet been fully explored, this is an intriguing new frontier. The aims of this integrative review article are four-fold: (1) to briefly review the current evidence supporting the efficacy of CCT and mindfulness in improving depression; (2) to discuss the interrelated neural networks involved in depression, CCT and mindfulness; (3) to present a theoretical model demonstrating how MCCT may act to target these neural mechanisms; (4) to propose and discuss future directions for MCCT research for depression.

Reappraisal is an adaptive emotion regulation strategy while the role of self-perspective in reappraisal process of depressed patients is largely unknown in terms of goals (valence/arousal) and tactics (detachment/immersion). In this study, 12 depressed individuals and 15 controls were scanned with MRI during which they either attend naturally to emotional stimuli, or adopt detachment/immersion strategy. Behaviorally, no group differences in self-reported emotion regulation effectiveness were found. In addition, we observed that (1) patients were less able to downregulate amygdala activation with recruitment of more dorsal lateral prefrontal cortex (dlPFC) when adopting detachment strategy regardless of valence, and this preserved ability to regulate emotion was inversely associated with severity of symptoms; (2) patients had deficits in upregulating amygdala activation when adopting immersion strategy, with less inferior frontal gyrus (IFG) activation and strengthening coupling of dlPFC and ventral medial prefrontal cortex (vmPFC) with amygdala; (3) comparison between groups yielded that patients showed stronger vmPFC activation under either self-detached or self-immersed condition. In conclusion, impaired modulatory effects of amygdala in depressed patients are compensated with strengthening cognitive control resources, with dissociable effects for different self-perspectives in reappraisal. These results may help clarify the role of self-perspective underlying reappraisal in major depression.

Background Cognitive reappraisal is a strategy for emotional regulation, important in the context of anxiety disorders. It is not known whether anxiolytic effects of benzodiazepines affect cognitive reappraisal. Aims We aimed to investigate the effect of 25 mg oxazepam on cognitive reappraisal. Methods In a preliminary investigation, 33 healthy male volunteers were randomised to oxazepam or placebo, and then underwent an experiment where they were asked to use cognitive reappraisal to upregulate or downregulate their emotional response to images with negative or neutral emotional valence. We recorded unpleasantness ratings, skin conductance, superciliary corrugator muscle activity, and heart rate. Participants completed rating scales measuring empathy (Interpersonal Reactivity Index, IRI), anxiety (State-Trait Anxiety Inventory, STAI), alexithymia (Toronto Alexithymia Scale-20, TAS-20), and psychopathy (Psychopathy Personality Inventory-Revised, PPI-R). Results Upregulation to negative-valence images in the cognitive reappraisal task caused increased unpleasantness ratings, corrugator activity, and heart rate compared to downregulation. Upregulation to both negative- and neutral-valence images caused increased skin conductance responses. Oxazepam caused lower unpleasantness ratings to negative-valence stimuli, but did not interact with reappraisal instruction on any outcome. Self-rated trait empathy was associated with stronger responses to negative-valence stimuli, whereas self-rated psychopathic traits were associated with weaker responses to negative-valence stimuli. Conclusions While 25 mg oxazepam caused lower unpleasantness ratings in response to negative-valence images, we did not observe an effect of 25 mg oxazepam on cognitive reappraisal.

Transdiagnostic cognitive-behavioral therapy for emotional disorders (ED) has proven to be effective. However, current transdiagnostic treatment protocols address only the regulation of negative affectivity, and they do not include treatment components to more directly target the regulation of positive affectivity. In this study, we propose to evaluate the preliminary efficacy and acceptability of a transdiagnostic treatment protocol for ED that includes, as an innovative feature, a specific treatment component to directly upregulate positive affectivity based on positive psychology interventions. A total of 24 participants were randomized to either a transdiagnostic treatment protocol ( n = 12) or a transdiagnostic treatment protocol with an additional component designed to regulate positive affectivity ( n = 12). Participants completed measures of anxiety, depression, positive and negative affectivity, and quality of life, as well as treatment acceptability at pre- and posttreatment and at the 3-month follow-up. Both interventions led to improvements in all measures at posttreatment, and these outcomes were maintained at the 3-month follow-up, with large effect sizes for all measures. The effect sizes for positive affect were larger in the condition that included the component to upregulate positive affectivity. Attrition rate was low, and both treatment protocols were well accepted by participants. The results obtained in this study indicate the feasibility of testing the treatment protocol in a larger, randomized, controlled trial, and they suggest the potential of including treatment components for directly upregulating positive affectivity in future research on transdiagnostic treatment protocols for ED.

Abstract Introduction Sleep disturbance is a risk factor for the development of mood disorders and up to 90% of mood disorder patients report sleep problems. However, the neural mechanisms by which poor sleep contributes to mood disorders are not well understood. We investigated whether sleep disturbance was associated with dysregulation of positive and negative affect systems, including passive reactivity and active emotion regulation. Methods Participants (n=55, Mage=24.4 years, 53% female) selected for high, medium, and low scores on the PROMIS Sleep Disturbance scale completed a cognitive reappraisal task in an fMRI scanner. Participants were presented with International Affective Picture Stimuli (30 positive, 30 negative, 15 neutral) and were instructed to either passively view or actively up- or down-regulate their emotional experience. We tested five conditions: view-positive, upregulate-positive, view-negative, downregulate-negative, view-neutral. Participants also completed objective (i.e., 7-day actigraphy) and self-report (i.e., Insomnia Severity Index [ISI]) measures of sleep prior to the scan. Analyses in AFNI were constrained within an emotion regulation network, identified using a Neurosynth mask, and treated as a single region of interest. Voxelwise (puncorr<.005) and clusterwise thresholds (p<.05) were used to correct for multiple comparisons. Results Actigraphy-assessed sleep duration was associated with supplementary motor area (SMA) activity when upregulating positive affect relative to passively viewing positive images (k=44 voxels, clusterwise p=.04); participants who slept less showed greater SMA activity. ISI score was marginally associated with dorsolateral prefrontal cortex (dlPFC) activity when downregulating negative affect relative to an implicit baseline (k=30 voxels, clusterwise p=.10); individuals with greater insomnia severity showed more dlPFC activity. PROMIS Sleep Disturbance showed no significant associations. Conclusion Markers of poor sleep (i.e., lower sleep duration, greater insomnia severity) were associated with heightened SMA and dlPFC activity during cognitive reappraisal. This may suggest inefficiency in modulating positive affect via verbal and motor processes (i.e., SMA) and negative affect via cognitive control (i.e., dlPFC). Alternatively, individuals with poor sleep may have greater emotional reactivity to modulate. Mood disorders are commonly associated with increased negative affect and blunted positive affect. Our findings suggest a plausible neural substrate for how sleep disturbance contributes to dysregulation of these systems. Support (If Any) NIMH R21 MH102412.

An optimal coordination between parents and their offspring involves a sequence of reciprocal behaviors to ensure the adequate care of the young, which is critical for a healthy physical, emotional, and social development. Parental deprivation, particularly an impaired child-mother attachment, induces lasting changes in emotional as well as in cognitive capacities in later life. We assessed in the South American precocial species,Octodon degus, whether alterations of glutamatergic function of the limbic system induced by parental deprivation may be a neural correlate for such behavioral changes. Further, we analyzed whether the mother's voice can protect from separation-induced changes of brain function. Changes of N-methyl-D-aspartate (NMDA) receptor expression were examined in the following three groups of 2-week-oldOctodon deguspups: (I) control animals who remained undisturbed with the family; (II) animals who were repeatedly separated from the family and individually placed in an unfamiliar environment for behavioral analysis (open field); and (III) animals who were treated like the group described under (lI) but were presented with maternal vocalizations during separation. Relative to those in the control group I, the animals in group II showed an upregulation of NMDA receptor density in the (a)anterior cingulate, prelimbic, infralimbic, and anterior insular cortices; (b)CA1/stratum radiatum; (c)CA1/stratum lacunosum moleculare and CA3/stratum radiatum; and (d)in the basomedial amygdaloid nucleus. Presentation of the maternal call during the separation period (group III) suppressed the separation-induced NMDA receptor upregulation in all regions. The results demonstrate that early life events can influence the expression of transmitter receptors and that maternal behavior, acting to control the pup's socio-emotional environment, is a key factor for regulating such developmental events.

AbstractPeripheral inflammatory conditions, including those localized to the gastrointestinal tract, are highly comorbid with psychiatric disorders such as anxiety and depression. These behavioral symptoms are poorly managed by conventional treatments for inflammatory diseases and contribute to quality of life impairments. Peripheral inflammation is associated with sustained elevations in circulating glucocorticoid hormones, which can modulate central processes, including those involved in the regulation of emotional behavior. The endocannabinoid (eCB) system is exquisitely sensitive to these hormonal changes and is a significant regulator of emotional behavior. The impact of peripheral inflammation on central eCB function, and whether this is related to the development of these behavioral comorbidities remains to be determined. To examine this, we employed the trinitrobenzene sulfonic acid-induced model of colonic inflammation (colitis) in adult, male, Sprague Dawley rats to produce sustained peripheral inflammation. Colitis produced increases in behavioral measures of anxiety and elevations in circulating corticosterone. These alterations were accompanied by elevated hydrolytic activity of the enzyme fatty acid amide hydrolase (FAAH), which hydrolyzes the eCB anandamide (AEA), throughout multiple corticolimbic brain regions. This elevation of FAAH activity was associated with broad reductions in the content of AEA, whose decline was driven by central corticotropin releasing factor type 1 receptor signaling. Colitis-induced anxiety was reversed following acute central inhibition of FAAH, suggesting that the reductions in AEA produced by colitis contributed to the generation of anxiety. These data provide a novel perspective for the pharmacological management of psychiatric comorbidities of chronic inflammatory conditions through modulation of eCB signaling.

We have studied the adrenergic mechanisms of immediate-early gene (IEG) induction in the discrete types of cardiac cells with the use of in situ hybridization histochemistry in an immobilization-stress model in conscious rats. Expression of c- fos, fos B, c- jun, jun B, NGFI-A, and NGFI-B mRNA was rapidly upregulated in the endothelial, myocardial, and smooth muscle cells of coronary vessels by 15–45 min after the onset of immobilization. Simultaneous blockade of both α- and β-adrenoceptors completely abolished expression of IEGs in these cardiac cells. Application of an α-agonist or β-agonist alone to the perfused rat heart under constant pressure elicited the upregulation of IEGs in a fashion similar to that of emotional stress. These data suggest that activation of either α- or β-adrenoceptor is sufficient to evoke expression of these genes and that there may be cross talk in signal transduction downstream from α- and β-adrenoceptors in cardiac cells.

Osteoarthritis and its associated comorbidities are important clinical problems that have a negative impact on the quality of life, and its treatment remains unresolved. We investigated whether the systemic administration of slow-releasing hydrogen sulfide (H2S) donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), alleviates chronic osteoarthritis pain and the associated emotional disorders. In C57BL/6 female mice with osteoarthritis pain induced by the intra-articular injection of monosodium iodoacetate, we evaluated the effects of repeated administration of A-ITC and P-ITC on the (i) mechanical allodynia and grip strength deficits; (ii) emotional conducts; and (iii) glial activity and expression of inducible nitric oxide synthase (NOS2), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and antioxidant enzymes (heme oxygenase 1, NAD(P)H:quinone oxidoreductase-1, glutathione S-transferase mu 1 and alpha 1) in the hippocampus. The administration of A-ITC and P-ITC inhibited the mechanical allodynia, the grip strength deficits, and the depressive-like behaviors accompanying osteoarthritis. Both treatments inhibited microglial activation, normalized the upregulation of NOS2 and PI3K/p-Akt, and maintained high levels of antioxidant/detoxificant enzymes in the hippocampus. Data suggest that treatment with low doses of slow-releasing H2S donors might be an interesting strategy for the treatment of nociception, functional disability, and emotional disorders associated with osteoarthritis pain.

Malnutrition represents a major problem in the clinical management of the inflammatory bowel disease (IBD). Presently, our understanding of the cross-link between eating behavior and intestinal inflammation is still in its infancy. Crohn’s disease patients with active disease exhibit strong hedonic desires for food and emotional eating patterns possibly to ameliorate feelings of low mood, anxiety, and depression. Impulsivity traits seen in IBD patients may predispose them to palatable food intake as an immediate reward rather than concerns for future health. The upregulation of enteroendocrine cells (EEC) peptide response to food intake has been described in ileal inflammation, which may lead to alterations in gut–brain signaling with implications for appetite and eating behavior. In summary, a complex interplay of gut peptides, psychological, cognitive factors, disease-related symptoms, and inflammatory burden may ultimately govern eating behavior in intestinal inflammation.

Allergic rhinitis (AR) is a major concern in personal and public health, which negatively affects emotions and behavior, leading to cognitive deficits, memory decline, poor school performance, anxiety, and depression. Several cellular and molecular mediators are released in the inflammatory process of AR and activate common neuroimmune mechanisms, involving emotionally relevant circuits and the induction of anxiety. Responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to allergic processes have been reported, which may also include responsiveness of the hippocampus, cortex, and other brain regions. Here, we have used an optimized rat model of AR to explore whether the disease has a relationship with inflammatory responses in the hippocampus. AR was established in adult rats by ovalbumin sensitization, and the expression of various inflammatory substances in the hippocampus was measured by specific assays. Comparison between experimental and various control groups of animals revealed an association of AR with significant upregulation of substance P, microglia surface antigen (CD11b), glial fibrillary acid protein (GFAP), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) in the hippocampus. Thus, we hypothesize that the AR challenge may activate these inflammatory mediators in the hippocampus, which in turn contribute to the abnormal behavior and neurological deficits associated with AR.

FKBP51 is a key stress-responsive regulator of the hypothalamic–pituitary–adrenal axis. To elucidate the contribution of rs1360780 FKBP5 C/T alleles to aging and longevity, we genotyped FKBP5 in a cohort of 800 non-demented and Alzheimer’s disease (AD) subjects of different age, taking into account the allele state of ApoE ε4, the major risk factor for AD. Furthermore, we searched for the association of FKBP5 with subcohorts of non-demented subjects evaluated for anxiety and resting-state quantitative EEG characteristics, associated with cognitive, emotional, and functional brain activities. We observed that increased state anxiety scores depend on the combination of the FKBP5 and ApoE genotypes and on the DNA methylation state of the FKBP5 promoter and ApoE genotype. We also found a significant gender-dependent correlation between FKBP5 promoter methylation and alpha-, delta-, and theta-rhythms. Analysis of the FKBP5 expression in an independent cohort revealed a significant upregulation of FKBP5 in females versus males. Our data suggest a synergistic effect of the stress-associated (FKBP5) and neurodegeneration-associated (ApoE) gene alleles on anxiety and the gender-dependent effect of FKBP5 on neurophysiological brain activity.

AbstractPsychopathy is an extreme form of antisocial behavior, with about 1% prevalence in the general population, and 10–30% among incarcerated criminal offenders. Although the heritability of severe antisocial behavior is up to 50%, the genetic background is unclear. The underlying molecular mechanisms have remained unknown but several previous studies suggest that abnormal glucose metabolism and opioidergic neurotransmission contribute to violent offending and psychopathy. Here we show using iPSC-derived cortical neurons and astrocytes from six incarcerated extremely antisocial and violent offenders, three nonpsychopathic individuals with substance abuse, and six healthy controls that there are robust alterations in the expression of several genes and immune response-related molecular pathways which were specific for psychopathy. In neurons, psychopathy was associated with marked upregulation of RPL10P9 and ZNF132, and downregulation of CDH5 and OPRD1. In astrocytes, RPL10P9 and MT-RNR2 were upregulated. Expression of aforementioned genes explained 30–92% of the variance of psychopathic symptoms. The gene expression findings were confirmed with qPCR. These genes may be relevant to the lack of empathy and emotional callousness seen in psychopathy, since several studies have linked these genes to autism and social interaction.

Central neuropathic pain is not only characterized by reflexive pain responses, but also emotional or affective nonreflexive pain responses, especially in women. Some pieces of evidence suggest that the activation of the neuroimmune system may be contributing to the manifestation of mood disorders in patients with chronic pain conditions, but the mechanisms that contribute to the development and chronicity of CNP and its associated disorders remain poorly understood. This study aimed to determine whether neuroinflammatory factor over-expression in the spinal cord and supraspinal structures may be associated with reflexive and nonreflexive pain response development from acute SCI phase to 12 weeks post-injury in female mice. The results show that transient reflexive responses were observed during the SCI acute phase associated with transient cytokine overexpression in the spinal cord. In contrast, increased nonreflexive pain responses were observed in the chronic phase associated with cytokine overexpression in supraspinal structures, especially in mPFC. In addition, results revealed that besides cytokines, the mPFC showed an increased glial activation as well as CX3CL1/CX3CR1 upregulation in the neurons, suggesting the contribution of neuron-glia crosstalk in the development of nonreflexive pain responses in the chronic spinal cord injury phase.

Background Emotional disorders (EDs) are among the most prevalent mental disorders. Existing evidence-based psychological treatments are not sufficient to reduce the disease burden of mental disorders. It is therefore essential to implement innovative solutions to achieve a successful dissemination of psychological treatment protocols, and in this regard, the use of information and communication technologies such as the internet can be very useful. Furthermore, the literature suggests that not everyone with an ED receives the appropriate treatment. This situation has led to the development of new intervention proposals based on the transdiagnostic perspective, which attempts to address the underlying processes common to EDs. Most of these transdiagnostic interventions focus primarily on downregulating negative affectivity (NA), and less attention has been paid to strengths and the upregulation of positive affectivity, despite its importance for well-being and mental health. Objective This study aims to evaluate the efficacy of a transdiagnostic internet-based treatment for EDs in a community sample. Methods A 3-armed randomized controlled trial was conducted. A total of 216 participants were randomly assigned to a transdiagnostic internet-based protocol (TIBP), a TIBP+ positive affect (PA) component, or a waiting list (WL) control group. The treatment protocol contained core components mainly addressed to downregulate NA (ie, present-focused emotional awareness and acceptance, cognitive flexibility, behavioral and emotional avoidance patterns, and interoceptive and situational exposure) as well as a PA regulation component to promote psychological strengths and enhance well-being. Data on depression, anxiety, quality of life, neuroticism and extraversion, and PA/NA before and after treatment were analyzed. Expectations and opinions of treatment were also analyzed. Results Within-group comparisons indicated significant pre-post reductions in the two experimental conditions. In the TIBP+PA condition, the effect sizes were large for all primary outcomes (d=1.42, Beck Depression Inventory [BDI-II]; d=0.91, Beck Anxiety Inventory [BAI]; d=1.27, Positive and Negative Affect Schedule-Positive [PANAS-P]; d=1.26, Positive and Negative Affect Schedule-Negative [PANAS-N]), whereas the TIBP condition yielded large effect sizes for BDI-II (d=1.19) and PANAS-N (d=1.28) and medium effect sizes for BAI (d=0.63) and PANAS-P (d=0.69). Between-group comparisons revealed that participants who received one of the two active treatments scored better at posttreatment than WL participants. Although there were no statistically significant differences between the two intervention groups on the PA measure, effect sizes were consistently larger in the TIBP+PA condition than in the standard transdiagnostic protocol. Conclusions Overall, the findings indicate that EDs can be effectively treated with a transdiagnostic intervention via the internet, as significant improvements in depression, anxiety, and quality of life measures were observed. Regarding PA measures, promising effects were found, but more research is needed to study the role of PA as a therapeutic component. Trial Registration ClinicalTrials.gov NCT02578758; https://clinicaltrials.gov/ct2/show/NCT02578758 International Registered Report Identifier (IRRID) RR2-10.1186/s12888-017-1297-z

Increasing evidence associates indoor fungal exposure with deleterious central nervous system (CNS) health, such as cognitive and emotional deficits in children and adults, but the specific mechanisms by which it might impact the brain are poorly understood. Mice were exposed to filtered air, heat-inactivated Aspergillus versicolor (3 × 105 spores), or viable A. versicolor (3 × 105 spores) via nose-only inhalation exposure 2 times per week for 1, 2, or 4 weeks. Analysis of cortex, midbrain, olfactory bulb, and cerebellum tissue from mice exposed to viable A. versicolor spores for 1, 2, and 4 weeks revealed significantly elevated pro-inflammatory ( Tnf and Il1b) and glial activity ( Gdnf and Cxc3r1) gene expression in several brain regions when compared to filtered air control, with the most consistent and pronounced neuroimmune response 48H following the 4-week exposure in the midbrain and frontal lobe. Bulk RNA-seq analysis of the midbrain tissue confirmed that 4 weeks of A. versicolor exposure resulted in significant transcriptional enrichment of several biological pathways compared to the filtered air control, including neuroinflammation, glial cell activation, and regulation of postsynaptic organization. Upregulation of Drd1, Penk, and Pdyn mRNA expression was confirmed in the 4-week A. versicolor exposed midbrain tissue, highlighting that gene expression important for neurotransmission was affected by repeated A. versicolor inhalation exposure. Taken together, these findings indicate that the brain can detect and respond to A. versicolor inhalation exposure with changes in neuroimmune and neurotransmission gene expression, providing much needed insight into how inhaled fungal exposures can affect CNS responses and regulate neuroimmune homeostasis.

Introduction Cognitive reappraisal (CR) is a cognitive regulation strategy aimed at changing how people think about certain stimuli in order to change their emotional impact. CR strategies have been used in research to try to change eating behaviors and other food-related responses. This study is the first to use a behavioral measurement to examine the effect of CR on food attentional bias (FAB) in people with elevated FAB. Objectives It was hypothesized that CR would reduce FAB. Ninety-five participants were randomly assigned to one of three groups: CR, upregulation (UP) or controls (CN). Methods All participants performed a computerized Visual Dot Probe (VDP) task using food stimuli to measure their FAB before and after the manipulation. The CR group recited five sentences aimed at curtailing the reward of high caloric food. Participants in the UP group recited five sentences aimed at strengthening the reward of high caloric food. The CN group recited five mundane sentences about their day. Participants also self-reported on eating disordered symptomology and BMI. Results People with elevated FAB had more disordered eating than people low on FAB. A significant interaction was observed between group and time (pre/post-test), with the lowest FAB levels in the CR group following the manipulation. Conclusions CR, a self-administered strategy can be effective in reducing FAB. CR may be an effective strategy for developing resistance to tempting food stimuli and curbing high caloric food intake. Being highly attentive to food cues may contribute to obesity. The attentional bias paradigm can be used to detect early signs of FAB. Disclosure No significant relationships.

The amygdala contributes toward emotional processes such as fear, anxiety, and social cognition. Furthermore, evidence suggests that increased excitability of basolateral amygdala (BLA) principal neurons underlie certain neuropsychiatric disorders. Gain-of-function mutations in neuronal L-type calcium channels (LTCCs) are linked to neurodevelopmental diseases, including autism spectrum disorders (ASDs). While LTCCs are expressed throughout the BLA, direct evidence for increased LTCC activity affecting BLA excitability and potentially contributing to disease pathophysiology is lacking. In this study, we utilized a pharmacological approach to examine the contributions of LTCCs to BLA principal cell excitability and synaptic activity at immature (postnatal day 7, P7) and juvenile (P21) developmental stages. Acute upregulation of LTCC activity in brain slices by application of the agonist ( S)-Bay K 8644 resulted in increased intrinsic excitability properties including firing frequency response, plateau potential, and spike-frequency adaptation selectively in P7 neurons. Contrastingly, for P21 neurons, the main effect of ( S)-Bay K 8644 was to enhance burst firing. ( S)-Bay K 8644 increased spontaneous inhibitory synaptic currents at both P7 and P21 but did not affect evoked synaptic currents at either stage. ( S)-Bay K 8644 did not alter P7 spontaneous excitatory synaptic currents, although it increased current amplitude in P21 neurons. Overall, the results provide support for the notion that alteration of LTCC activity at specific periods of early brain development may lead to functional alterations to neuronal network activity and subsequently contribute to underlying mechanisms of amygdala-related neurological disorders. NEW & NOTEWORTHY The role of L-type calcium channels (LTCCs) in regulating neuronal electrophysiological properties during development remains unclear. We show that in basolateral amygdala principal neurons, an increase of LTCC activity alters both neuronal excitability and synaptic activity. The results also provide evidence for the distinct contributions of LTCCs at different stages of neurodevelopment and shed insight into our understanding of LTCC dysfunction in amygdala-related neurological disorders.

The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. Available at: https://covid19.who.int/ [Accessed on 23 August 2020] Sim K, Chua HC. The psychological impact of SARS: a matter of heart and mind. CMAJ. 2004; 170:811e2. https://doi.org/10.1503/cmaj.1032003. Wu P, Fang Y, Guan Z, Fan B, Kong J, Yao Z, et al. The psychological impact of the SARS epidemic on hospital employees in China: exposure, risk perception, and altruistic acceptance of risk. Can J Psychiatr. 2009; 54:302e11. https://doi.org/10.1177/070674370905400504. Brooks SK, Webster RK, Smith LE, Woodland L, Wessely S, Greenberg N, et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020; 395:912e20. https://doi.org/10.1016/S0140-6736(20)30460-8. Robertson E, Hershenfield K, Grace SL, Stewart DE. The psychosocial effects of being quarantined following exposure to SARS: a qualitative study of Toronto health care workers. Can J Psychiatr. 2004; 49:403e7. https://doi.org/10.1177/070674370404900612. Barbisch D, Koenig KL, Shih FY. Is there a case for quarantine? Perspectives from SARS to Ebola. Disaster Med Public Health Prep. 2015; 9:547e53. https://doi.org/10.1017/dmp.2015.38. Jeong H, Yim HW, Song YJ, Ki M, Min JA, Cho J, et al. Mental health status of people isolated due to Middle East Respiratory Syndrome. Epidemiol Health. 2016;38: e2016048. https://doi.org/10.4178/epih.e2016048. Liu X, Kakade M, Fuller CJ, Fan B, Fang Y, Kong J, et al. Depression after exposure to stressful events: lessons learned from the severe acute respiratory syndrome epidemic. Compr Psychiatr. 2012; 53:15e23. https://doi.org/10.1016/j.comppsych.2011.02.003 Chadda RK, Deb KS. Indian family systems, collectivistic society and psychotherapy. Indian J Psychiatry. 2013;55: S299‑ https://dx.doi.org/10.4103%2F0019-5545.105555. Grover S, Sahoo S, Mehra A, Avasthi A, Tripathi A, Subramanyan A, et al. Psychological impact of COVID‑19 lockdown: An online survey from India. Indian J Psychiatry. 2020; 62:354-62. https://doi.org/ 10.4103/psychiatry.IndianJPsychiatry _427_20. Hawkley LC, Cacioppo JT. Loneliness matters: a theoretical and empirical review of consequences and mechanisms. Ann Behav Med. 2010; 40: 218–27. https://dx.doi.org/10.1007%2Fs12160-010-9210-8. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. https://doi.org/10.1016/S0140-6736(20)30211-7. Bhandari S, Sharma R, Singh Shaktawat A, Banerjee S, Patel B, Tak A, et al. COVID-19 related mortality profile at a tertiary care centre: a descriptive study. Scr Med. 2020;51(2):69-73. https://doi.org/10.5937/scriptamed51-27126. Baumeister RF, Leary MR. The need to belong: desire for interpersonal attachments as a fundamental human motivation. Psychol Bull. 1995; 117: 497–529. https://doi.org/10.1037/0033-2909.117.3.497. Caspi A, Harrington H, Moffitt TE, Milne BJ, Poulton R. Socially isolated children 20 years later: risk of cardiovascular disease. Arch Pediatr Adolesc Med. 2006; 160(8):805-11. https://doi.org/10.1001/archpedi.160.8.805. Eaker ED, Pinsky J, Castelli WP. Myocardial infarction and coronary death among women: psychosocial predictors from a 20-year follow-up of women in the Framingham Study. Am J Epidemiol. 1992; 135(8):854-64. https://doi.org/10.1093/oxfordjournals.aje.a116381. Luo Y, Hawkley LC, Waite LJ, Cacioppo JT. Loneliness, health, and mortality in old age: a national longitudinal study. Soc Sci Med. 2012 Mar; 74(6):907-14. https://dx.doi.org/10.1016%2Fj.socscimed.2011.11.028. Olsen RB, Olsen J, Gunner-Svensson F, Waldstrøm B. Social networks and longevity. A 14-year follow-up study among elderly in Denmark. Soc Sci Med. 1991; 33(10):1189-95. https://doi.org/10.1016/0277-9536(91)90235-5. Patterson AC, Veenstra G. Loneliness and risk of mortality: a longitudinal investigation in Alameda County, California. Soc Sci Med. 2010; 71(1):181-6. https://doi.org/10.1016/j.socscimed.2010.03.024. Savikko N, Routassalo P, Tilvis RS, Strandberg TE, Pitkalla KH. Predictors and subjective causes of loneliness in an aged population. Arch Gerontol Geriatrics. 2005; 41:3;223-33. https://doi.org/10.1016/j.archger.2005.03.002. Health Advisory for Elderly Population of India during COVID19. Available at: https://www.mohfw.gov.in/pdf/AdvisoryforElderlyPopulation.pdf [Accessed on 13 August 2020]. Dicks D, Myers R, Kling A. Uncus and amygdala lesions: effects on social behavior in the free-ranging rhesus monkey. Science. 1969; 165:69–71. https://doi.org/10.1126/science.165.3888.69. Kanai R, Bahrami B, Duchaine B, Janik A, Banissy MJ, Rees G. Brain structure links loneliness to social perception. Curr Biol. 2012; 22(20):1975-9. https://dx.doi.org/10.1016%2Fj.cub.2012.08.045. Bender AR, Daugherty A, Raz N. Vascular risk moderates associations between hippocampal subfield volumes and memory. J Cogn Neurosci. 2013; 25:1851–62. https://doi.org/10.1162/jocn_a_00435. Raz N. Diabetes: brain, mind, insulin–what is normal and do we need to know? Nat Rev Endocrinol. 2011; 7:636–7. https://doi.org/10.1038/nrendo.2011.149. Colcombe SJ, Erickson KI, Naftali R, Andrew GW, Cohen NJ, McAuley E, et al. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci. 2003; 58:176–80. https://doi.org/10.1093/gerona/58.2.m176. Maass A, Düzel S, Goerke M, Becke A, Sobieray U, Neumann K, et al. Vascular hippocampal plasticity after aerobic exercise in older adults. Mol Psychiatry. 2015; 20, 585–93. https://doi.org/10.1038/mp.2014.114. Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, et al. Loneliness and Risk of Alzheimer Disease. Arch Gen Psychiatry. 2007;64(2):234–240. https://doi.org/10.1001/archpsyc.64.2.234. Kogan JH, Frankland PW, Silva AJ. Long-term memory underlying hippocampus-dependent social recognition in mice. Hippocampus. 2000;10(1):47-56. https://doi.org/10.1002/(sici)1098-1063(2000)10:1%3C47::aid-hipo5%3E3.0.co;2-6. Yorgason JT, España RA, Konstantopoulos JK, Weiner JL, Jones SR. Enduring increases in anxiety-like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats. Eur J Neurosci. 2013;37(6):1022-31. https://doi.org/10.1111/ejn.12113. Bledsoe AC, Oliver KM, Scholl JL, Forster GL. Anxiety states induced by post-weaning social isolation are mediated by CRF receptors in the dorsal raphe nucleus. Brain Res Bull. 2011;85(3-4):117-22. https://dx.doi.org/10.1016%2Fj.brainresbull.2011.03.003. Lukkes JL, Engelman GH, Zelin NS, Hale MW, Lowry CA. Post-weaning social isolation of female rats, anxiety-related behavior, and serotonergic systems. Brain Res. 2012; 1443:1-17. https://dx.doi.org/10.1016%2Fj.brainres.2012.01.005. Ago Y, Araki R, Tanaka T, Sasaga A, Nishiyama S, Takuma K, et al. Role of social encounter-induced activation of prefrontal serotonergic systems in the abnormal behaviors of isolation-reared mice. Neuropsychopharmacology. 2013; 38(8):1535-47. https://doi.org/10.1038/npp.2013.52. Veenema AH. Early life stress, the development of aggression and neuroendocrine and neurobiological correlates: what can we learn from animal models? Front Neuroendocrinol. 2009;30(4):497-518. https://doi.org/10.1016/j.yfrne.2009.03.003. Zhao X, Sun L, Jia H, Meng Q, Wu S, Li N, et al. Isolation rearing induces social and emotional function abnormalities and alters glutamate and neurodevelopment-related gene expression in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(7):1173-1177. https://doi.org/10.1016/j.pnpbp.2009.06.016. Sciolino NR, Bortolato M, Eisenstein SA, Fu J, Oveisi F, Hohmann AG, et al. Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats. Neuroscience. 2010;168(2):371-86. https://dx.doi.org/10.1016%2Fj.neuroscience.2010.04.007. Ghasemi M, Phillips C, Trillo L, De Miguel Z, Das D, Salehi A. The role of NMDA receptors in the pathophysiology and treatment of mood disorders. Neurosci Biobehav Rev. 2014; 47:336-358. https://doi.org/10.1016/j.neubiorev.2014.08.017. Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Fernández AP, Rodrigo J, et al. Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. J Neurochem. 2000;74(2):785-791. https://doi.org/10.1046/j.1471-4159.2000.740785.x. Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2008;63(4):349-352. https://doi.org/10.1016/j.biopsych.2007.05.028. Kalia LV, Kalia SK, Salter MW. NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol. 2008;7(8):742-755. https://dx.doi.org/10.1016%2FS1474-4422(08)70165-0. Waxman EA, Lynch DR. N-methyl-D-aspartate Receptor Subtypes: Multiple Roles in Excitotoxicity and Neurological Disease. The Neuroscientist. 2005; 11(1), 37–49. https://doi.org/10.1177/1073858404269012. Hermes G, Li N, Duman C, Duman R. Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats. Physiol Behav. 2011;104(2):354-9. https://dx.doi.org/10.1016%2Fj.physbeh.2010.12.019. Sestito RS, Trindade LB, de Souza RG, Kerbauy LN, Iyomasa MM, Rosa ML. Effect of isolation rearing on the expression of AMPA glutamate receptors in the hippocampal formation. J Psychopharmacol. 2011;25(12):1720-1729. https://doi.org/10.1177/0269881110385595. Toua C, Brand L, Möller M, Emsley RA, Harvey BH. The effects of sub-chronic clozapine and haloperidol administration on isolation rearing induced changes in frontal cortical N-methyl-D-aspartate and D1 receptor binding in rats. Neuroscience. 2010;165(2):492-499. https://doi.org/10.1016/j.neuroscience.2009.10.039. Alò R, Avolio E, Mele M, Storino F, Canonaco A, Carelli A et al. Excitatory/inhibitory equilibrium of the central amygdala nucleus gates anti-depressive and anxiolytic states in the hamster. Pharmacol Biochem Behav. 2014; 118:79-86. https://doi.org/10.1016/j.pbb.2014.01.007. St JP, Petkov VV. Changes in 5-HT1 receptors in different brain structures of rats with isolation syndrome. General pharmacology. 1990;21(2):223-5. https://doi.org/10.1016/0306-3623(90)90905-2. Miachon S, Rochet T, Mathian B, Barbagli B, Claustrat B. Long-term isolation of Wistar rats alters brain monoamine turnover, blood corticosterone, and ACTH. Brain Res Bull. 1993;32(6):611-614. https://doi.org/10.1016/0361-9230(93)90162-5. Van den Berg CL, Van Ree JM, Spruijt BM, Kitchen I. Effects of juvenile isolation and morphine treatment on social interactions and opioid receptors in adult rats: behavioural and autoradiographic studies. Eur J Neurosci. 1999;11(9):3023-3032. https://doi.org/10.1046/j.1460-9568.1999.00717.x. Vanderschuren LJ, Stein EA, Wiegant VM, Van Ree JM. Social play alters regional brain opioid receptor binding in juvenile rats. Brain Res. 1995;680(1-2):148-156. https://doi.org/10.1016/0006-8993(95)00256-p. Moles A, Kieffer BL, D'Amato FR. Deficit in attachment behavior in mice lacking the mu-opioid receptor gene. Science. 2004;304(5679):1983-1986. https://doi.org/10.1126/science.1095943. Panksepp J, Herman BH, Vilberg T, Bishop P, DeEskinazi FG. Endogenous opioids and social behavior. Neurosci Biobehav Rev. 1980;4(4):473-487. https://doi.org/10.1016/0149-7634(80)90036-6. Gong JP, Onaivi ES, Ishiguro H, Liu Q, Tagliaferro PA, Brusco A, et al. Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res. 2006;1071(1):10-23. https://doi.org/10.1016/j.brainres.2005.11.035. Breivogel CS, Sim-Selley LJ. Basic neuroanatomy and neuropharmacology of cannabinoids. Int Rev Psychiatry 2009; 21:2:113-121. https://doi.org/10.1080/09540260902782760. Haj-Mirzaian A, Amini-Khoei H, Haj-Mirzaian A, Amiri S, Ghesmati M, Zahir M, et al. Activation of cannabinoid receptors elicits antidepressant-like effects in a mouse model of social isolation stress. Brain Res Bull. 2017; 130:200-210. https://doi.org/10.1016/j.brainresbull.2017.01.018. Banach M, Piskorska B, Czuczwar SJ, Borowicz KK. Nitric Oxide, Epileptic Seizures, and Action of Antiepileptic Drugs. CNS & Neurological Disorders - Drug Targets 2011;10: 808. https://doi.org/10.2174/187152711798072347. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829-37, 837a-837d. https://dx.doi.org/10.1093%2Feurheartj%2Fehr304. Hu Y, Wu D, Luo C, Zhu L, Zhang J, Wu H, et al. Hippocampal nitric oxide contributes to sex difference in affective behaviors. PNAS. 2012, 109 (35) 14224-14229. https://doi.org/10.1073/pnas.1207461109. Khan MI, Ostadhadi S, Zolfaghari S, Mehr SE, Hassanzadeh G, Dehpour, A et al. The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test. Neuroscience Letters. 2016; 612:52-61. https://doi.org/10.1016/j.neulet.2015.12.006. Matsumoto K, Puia G, Dong E, Pinna G. GABAA receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: Possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders. Stress. 2007; 10:1:3-12. https://doi.org/10.1080/10253890701200997. Zlatković J, Filipović D. Chronic social isolation induces NF-κB activation and upregulation of iNOS protein expression in rat prefrontal cortex. Neurochem Int. 2013;63(3):172-179. https://doi.org/10.1016/j.neuint.2013.06.002. Haj-Mirzaian A, Amiri S, Kordjazy N, Momeny M, Razmi A, Balaei MR, et al. Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic-pituitary-adrenal axis function. Neuroscience. 2016; 315:271-285. https://doi.org/10.1016/j.neuroscience.2015.12.024. Larson HJ. The biggest pandemic risk? Viral misinformation. Nature 2018; 562:309. https://doi.org/10.1038/d41586-018-07034-4. Zarocostas J. How to fight an infodemic. Lancet 2020; 395:676. https://doi.org/10.1016/S0140-6736(20)30461-X. World Health Organization, 2019. Ebola Virus Disease – Democratic Republic of the Congo. Geneva, Switzerland: WHO. Available at: https://www.who.int/csr/don/28-november-2019-ebola-drc/en/ [Accessed on August 8, 2020] Times of India. Covid-19: doctors gone to collect samples attacked in Indore. Available at: https://timesofindia.indiatimes.com/videos/news/covid-19-doctors-goneto- collect-samples-attacked-in-indore/videoshow/74942153.cms; 2020 [Accessed on August 8, 2020]. Withnall A. Coronavirus: why India has had to pass new law against attacks on healthcare workers. The Independent. April 23, 2020. Semple K. “Afraid to be a nurse”: health workers under attack. The New York Times. 2020 Apr 27. The Economist. Health workers become unexpected targets during COVID-19. The Economist. May 11, 2020. Turan B, Budhwani H, Fazeli PL, Browning WR, Raper JL, Mugavero MJ, et al. How does stigma affect people living with HIV? The mediating roles of internalized and anticipated HIV stigma in the effects of perceived community stigma on health and psychosocial outcomes. AIDS Behav. 2017; 21: 283–291. https://doi.org/10.1007/s10461-016-1451-5. James PB, Wardle J, Steel A, Adams J. An assessment of Ebola-related stigma and its association with informal healthcare utilisation among Ebola survivors in Sierra Leone: a cross sectional study. BMC Public Health. 2020; 20: 182. https://doi.org/10.1186/s12889-020-8279-7. Aljazeera, 2020. Iran: Over 700 Dead after Drinking Alcohol to Cure Coronavirus. Aljazeera. Available at: https://www.aljazeera.com/ news/2020/04/iran-700-dead-drinking-alcohol-cure-coronavirus200427163529629.html. (Accessed June 4, 2020) Delirrad M, Mohammadi AB, 2020. New methanol poisoning outbreaks in Iran following COVID-19 pandemic. Alcohol Alcohol. 55: 347–348. https://doi.org/10.1093/alcalc/agaa036. Hassanian-Moghaddam H, Zamani N, Kolahi A-A, McDonald R, Hovda KE. Double trouble: methanol outbreak in the wake of the COVID-19 pandemic in Iran-a cross-sectional assessment. Crit Care. 2020; 24: 402. https://doi.org/10.1186/s13054-020-03140-w. Soltaninejad K. Methanol Mass Poisoning Outbreak: A Consequence of COVID-19 Pandemic and Misleading Messages on Social Media. Int J Occup Environ Med. 2020;11(3):148-150. https://dx.doi.org/10.34172%2Fijoem.2020.1983. Islam MS, Sarkar T, Khan SH, Kamal AM, Hasan SMM, Kabir A, et al. COVID-19–Related Infodemic and Its Impact on Public Health: A Global Social Media Analysis. Am J Trop Med Hyg. 2020; 00(0):1–9. https://doi.org/10.4269/ajtmh.20-0812. Hawryluck L, Gold W, Robinson S, Pogorski S, Galea S, Styra R. SARS control and psychological effects of quarantine, Toronto, Canada. Emerg Infect Dis. 2004;10(7):1206–1212. https://dx.doi.org/10.3201%2Feid1007.030703. Lee S, Chan LYY, Chau AAM, Kwok KPS, Kleinman A. The experience of SARS-related stigma at Amoy Gardens. Soc Sci Med. 2005; 61(9): 2038-2046. https://doi.org/10.1016/j.socscimed.2005.04.010. Yoon MK Kim SY Ko HS Lee MS. System effectiveness of detection, brief intervention and refer to treatment for the people with post-traumatic emotional distress by MERS: a case report of community-based proactive intervention in South Korea. Int J Ment Health Syst. 2016; 10: 51. https://doi.org/10.1186/s13033-016-0083-5. Reynolds DL, Garay JR, Deamond SL, Moran MK, Gold W, Styra R. Understanding, compliance and psychological impact of the SARS quarantine experience. Epidemiol Infect. 2008; 136: 997-1007. https://dx.doi.org/10.1017%2FS0950268807009156. Marjanovic Z, Greenglass ER, Coffey S. The relevance of psychosocial variables and working conditions in predicting nurses' coping strategies during the SARS crisis: an online questionnaire survey. Int J Nurs Stud. 2007; 44(6): 991-998. https://doi.org/10.1016/j.ijnurstu.2006.02.012. Bai Y, Lin C-C, Lin C-Y, Chen J-Y, Chue C-M, Chou P. Survey of stress reactions among health care workers involved with the SARS outbreak. Psychiatr Serv. 2004; 55: 1055-1057. https://doi.org/10.1176/appi.ps.55.9.1055. Ministry of Health and Family Welfare. Available at: https://www.mohfw.gov.in/pdf/Guidelinesforhomequarantine.pdf [Accessed on 25 August 2020]. Ministry of Health and Family Welfare. Available at: https://www.mohfw.gov.in/pdf/RevisedguidelinesforHomeIsolationofverymildpresymptomaticCOVID19cases10May2020.pdf [Accessed on 25 August 2020]. Ministry of Health and Family Welfare. Available at: https://www.mohfw.gov.in/pdf/AdvisoryformanagingHealthcareworkersworkinginCOVIDandNonCOVIDareasofthehospital.pdf (Accessed on 25 August 2020). Ministry of Health and Family Welfare. Available at: https://www.mohfw.gov.in/pdf/RevisedguidelinesforInternationalArrivals02082020.pdf [Accessed on 25 August 2020]. Cost of the lockdown? Over 10% of GDP loss for 18 states. Available at: https://timesofindia.indiatimes.com/india/cost-of-the-lockdown-over-10-of-gdp-loss-for-18-states/articleshow/76028826.cms [Accessed on 21 August 2020]. Jorda O, Singh SR, Taylor AM. Longer-Run Economic Consequences of Pandemics. Federal Reserve Bank of San Francisco Working Paper. 2020-09. https://doi.org/10.24148/wp2020-09. Firdaus G. Mental well‑being of migrants in urban center of India: Analyzing the role of social environment. Indian J Psychiatry. 2017; 59:164‑ https://doi.org/10.4103/psychiatry.indianjpsychiatry_272_15. National Crime Record Bureau. Annual Crime in India Report. New Delhi, India: Ministry of Home Affairs; 2018. 198 migrant workers killed in road accidents during lockdown: Report. Available at: https://www.hindustantimes.com/india-news/198-migrant-workers-killed-in-road-accidents-during-lockdown-report/story-hTWzAWMYn0kyycKw1dyKqL.html [Accessed on 25 August 2020]. Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis. 2020; 20:689-96. https://doi.org/10.1016/S1473-3099(20)30198-5. Dalton L, Rapa E, Stein A. Protecting the psychological health of through effective communication about COVID-19. Lancet Child Adolesc Health. 2020;4(5):346-347. https://doi.org/10.1016/S2352-4642(20)30097-3. Centre for Disease Control. Helping Children Cope with Emergencies. Available at: https://www.cdc.gov/childrenindisasters/helping-children-cope.html [Accessed on 25 August 2020]. Liu JJ, Bao Y, Huang X, Shi J, Lu L. Mental health considerations for children quarantined because of COVID-19. Lancet Child & Adolesc Health. 2020; 4(5):347-349. https://doi.org/10.1016/S2352-4642(20)30096-1. Sprang G, Silman M. Posttraumatic Stress Disorder in Parents and Youth After Health-Related Disasters. Disaster Med Public Health Prep. 2013;7(1):105-110. https://doi.org/10.1017/dmp.2013.22. Rehman U, Shahnawaz MG, Khan NH, Kharshiing KD, Khursheed M, Gupta K, et al. Depression, Anxiety and Stress Among Indians in Times of Covid-19 Lockdown. Community Ment Health J. 2020:1-7. https://doi.org/10.1007/s10597-020-00664-x. Cao W, Fang Z, Hou, Han M, Xu X, Dong J, et al. The psychological impact of the COVID-19 epidemic on college students in China. Psychiatry Research. 2020; 287:112934. https://doi.org/10.1016/j.psychres.2020.112934. Wang C, Zhao H. The Impact of COVID-19 on Anxiety in Chinese University Students. Front Psychol. 2020; 11:1168. https://dx.doi.org/10.3389%2Ffpsyg.2020.01168. Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, et al. The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus. Lancet Psychiatry 2020;7(3): e14. https://doi.org/10.1016/s2215-0366(20)30047-x. Lai J, Ma S, Wang Y, Cai Z, Hu J, Wei N, et al. Factors associated with mental health outcomes among health care workers exposed to coronavirus disease 2019. JAMA Netw Open 2020;3(3): e203976. https://doi.org/10.1001/jamanetworkopen.2020.3976. Lancee WJ, Maunder RG, Goldbloom DS, Coauthors for the Impact of SARS Study. Prevalence of psychiatric disorders among Toronto hospital workers one to two years after the SARS outbreak. Psychiatr Serv. 2008;59(1):91-95. https://dx.doi.org/10.1176%2Fps.2008.59.1.91. Tam CWC, Pang EPF, Lam LCW, Chiu HFK. Severe acute respiratory syndrome (SARS) in Hongkong in 2003: Stress and psychological impact among frontline healthcare workers. Psychol Med. 2004;34 (7):1197-1204. https://doi.org/10.1017/s0033291704002247. Lee SM, Kang WS, Cho A-R, Kim T, Park JK. Psychological impact of the 2015 MERS outbreak on hospital workers and quarantined hemodialysis patients. Compr Psychiatry. 2018; 87:123-127. https://dx.doi.org/10.1016%2Fj.comppsych.2018.10.003. Koh D, Meng KL, Chia SE, Ko SM, Qian F, Ng V, et al. Risk perception and impact of severe acute respiratory syndrome (SARS) on work and personal lives of healthcare workers in Singapore: What can we learn? Med Care. 2005;43(7):676-682. https://doi.org/10.1097/01.mlr.0000167181.36730.cc. Verma S, Mythily S, Chan YH, Deslypere JP, Teo EK, Chong SA. Post-SARS psychological morbidity and stigma among general practitioners and traditional Chinese medicine practitioners in Singapore. Ann Acad Med Singap. 2004; 33(6):743e8. Yeung J, Gupta S. Doctors evicted from their homes in India as fear spreads amid coronavirus lockdown. CNN World. 2020. Available at: https://edition.cnn.com/2020/03/25/asia/india-coronavirus-doctors-discrimination-intl-hnk/index.html. [Accessed on 24 August 2020] Violence Against Women and Girls: the Shadow Pandemic. UN Women. 2020. May 3, 2020. Available at: https://www.unwomen.org/en/news/stories/2020/4/statement-ed-phumzile-violence-against-women-during-pandemic. [Accessed on 24 August 2020]. Gearhart S, Patron MP, Hammond TA, Goldberg DW, Klein A, Horney JA. The impact of natural disasters on domestic violence: an analysis of reports of simple assault in Florida (1999–2007). Violence Gend. 2018;5(2):87–92. https://doi.org/10.1089/vio.2017.0077. Sahoo S, Rani S, Parveen S, Pal Singh A, Mehra A, Chakrabarti S, et al. Self-harm and COVID-19 pandemic: An emerging concern – A report of 2 cases from India. Asian J Psychiatr 2020; 51:102104. https://dx.doi.org/10.1016%2Fj.ajp.2020.102104. Ghosh A, Khitiz MT, Pandiyan S, Roub F, Grover S. Multiple suicide attempts in an individual with opioid dependence: Unintended harm of lockdown during the COVID-19 outbreak? Indian J Psychiatry 2020; [In Press]. The Economic Times. 11 Coronavirus suspects flee from a hospital in Maharashtra. March 16 2020. Available at: https://economictimes.indiatimes.com/news/politics-and-nation/11-coronavirus-suspects-flee-from-a-hospital-in-maharashtra/videoshow/74644936.cms?from=mdr. [Accessed on 23 August 2020]. Xiang Y, Yang Y, Li W, Zhang L, Zhang Q, Cheung T, et al. Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed. The Lancet Psychiatry 2020;(3):228–229. https://doi.org/10.1016/S2215-0366(20)30046-8. Van Bortel T, Basnayake A, Wurie F, Jambai M, Koroma A, Muana A, et al. Psychosocial effects of an Ebola outbreak at individual, community and international levels. Bull World Health Organ. 2016;94(3):210–214. https://dx.doi.org/10.2471%2FBLT.15.158543. Kumar A, Nayar KR. COVID 19 and its mental health consequences. Journal of Mental Health. 2020; ahead of print:1-2. https://doi.org/10.1080/09638237.2020.1757052. Gupta R, Grover S, Basu A, Krishnan V, Tripathi A, Subramanyam A, et al. Changes in sleep pattern and sleep quality during COVID-19 lockdown. Indian J Psychiatry. 2020; 62(4):370-8. https://doi.org/10.4103/psychiatry.indianjpsychiatry_523_20. Duan L, Zhu G. Psychological interventions for people affected by the COVID-19 epidemic. Lancet Psychiatry. 2020;7(4): P300-302. https://doi.org/10.1016/S2215-0366(20)30073-0. Dubey S, Biswas P, Ghosh R, Chatterjee S, Dubey MJ, Chatterjee S et al. Psychosocial impact of COVID-19. Diabetes Metab Syndr. 2020; 14(5): 779–788. https://dx.doi.org/10.1016%2Fj.dsx.2020.05.035. Wright R. The world's largest coronavirus lockdown is having a dramatic impact on pollution in India. CNN World; 2020. Available at: https://edition.cnn.com/2020/03/31/asia/coronavirus-lockdown-impact-pollution-india-intl-hnk/index.html. [Accessed on 23 August 2020] Foster O. ‘Lockdown made me Realise What’s Important’: Meet the Families Reconnecting Remotely. The Guardian; 2020. Available at: https://www.theguardian.com/keep-connected/2020/apr/23/lockdown-made-me-realise-whats-important-meet-the-families-reconnecting-remotely. (Accessed on 23 August 2020) Bilefsky D, Yeginsu C. Of ‘Covidivorces’ and ‘Coronababies’: Life During a Lockdown. N. Y. Times; 2020. Available at: https://www.nytimes.com/2020/03/27/world/coronavirus-lockdown-relationships.html [Accessed on 23 August 2020]

AbstractBrain aging proceeds with cellular and molecular changes in the limbic system. Aging-dependent changes might affect emotion and stress coping, yet the underlying mechanisms remain unclear. Here, we show aged (18-month-old) mice exhibit upregulation of NADPH oxidase and oxidative stress in the hippocampus, which mirrors the changes in young (2-month-old) mice subjected to chronic stress. Aged mice that lack p47phox, a key subunit of NADPH oxidase, do not show increased oxidative stress. Aged mice exhibit depression-like behavior following weak stress that does not produce depressive behavior in young mice. Aged mice have reduced expression of the epigenetic factor SUV39H1 and its upstream regulator p-AMPK, and increased expression of Ppp2ca in the hippocampus—changes that occur in young mice exposed to chronic stress. SUV39H1 mediates stress- and aging-induced sustained upregulation of p47phox and oxidative stress. These results suggest that aging increases susceptibility to stress by upregulating NADPH oxidase in the hippocampus.

Abstract Background and Objectives Despite well-documented cognitive and physical declines with age, older adults tend to report higher emotional wellbeing than younger adults, even during the Coronavirus Disease-2019 (COVID-19) pandemic. To understand this paradox, as well as investigate the effects of specific historical contexts, the current study examined age differences in emotion regulation related to the events of 2020 in the United States. We predicted that, due to older adults’ theorized greater prioritization of hedonic goals and avoidance of arousal, older adults would report more positivity-upregulation and acceptance tactics than younger adults. Research Design and Methods 81 younger adults (ages 18-25) and 85 older adults (age 55+) completed a retrospective survey on their emotion regulation tactic usage for three specific events: the COVID-19 pandemic outbreak, the killing of George Floyd, and the presidential election. Results Older adults tended to rely most on acceptance-focused tactics, while younger adults tended to rely on a more even variety of tactics. However, age differences in tactic preferences varied by event, possibly due to younger adults’ greater emotion regulation flexibility. Discussion and Implications Older adults’ higher emotional well-being may not be primarily a result of age differences in positivity-related emotion regulation tactics, but more about differences in acceptance use.

Despite the existence of several emotion regulation studies using neurofeedback, interactions among a small number of regions were evaluated, and therefore, further investigation is needed to understand the interactions of the brain regions involved in emotion regulation. We implemented electroencephalography (EEG) neurofeedback with simultaneous functional magnetic resonance imaging (fMRI) using a modified happiness-inducing task through autobiographical memories to upregulate positive emotion. Then, an explorative analysis of whole brain regions was done to understand the effect of neurofeedback on brain activity and the interaction of whole brain regions involved in emotion regulation. The participants in the control and experimental groups were asked to do emotion regulation while viewing positive images of autobiographical memories and getting sham or real (based on alpha asymmetry) EEG neurofeedback, respectively. The proposed multimodal approach quantified the effects of EEG neurofeedback in changing EEG alpha power, fMRI blood oxygenation level-dependent (BOLD) activity of prefrontal, occipital, parietal, and limbic regions (up to 1.9% increase), and functional connectivity in/between prefrontal, parietal, limbic system, and insula in the experimental group. New connectivity links were identified by comparing the brain functional connectivity between experimental conditions (Upregulation and View blocks) and also by comparing the brain connectivity of the experimental and control groups. Psychometric assessments confirmed significant changes in positive and negative mood states in the experimental group by neurofeedback. Based on the exploratory analysis of activity and connectivity among all brain regions involved in emotion regions, we found significant BOLD and functional connectivity increases due to EEG neurofeedback in the experimental group, but no learning effect was observed in the control group. The results reveal several new connections among brain regions as a result of EEG neurofeedback which can be justified according to emotion regulation models and the role of those regions in emotion regulation and recalling positive autobiographical memories.

Abstract Background Little is known about how the obesogenic environment influences emotional states associated with glial responses and neuronal function. Here, we investigated glial reactivation and neuronal electrophysiological properties in emotion-related brain regions of high-fat diet (HFD) and ob/ob mice under chronic stress. Methods The glial reactivation and neuronal activities in emotion-related brain regions were analyzed among normal diet mice (ND), HFD mice, wild-type mice, and ob/ob mice. To further activate or inhibit astrocytes in medial prefrontal cortex (mPFC), we injected astrocytes specific Gq-AAV or Gi-AAV into mPFC and ongoing treated mice with CNO. Results The results showed that obesogenic factors per se had no significant effect on neuronal activities in emotion-related brain regions, or on behavioral performance. However, exposure to a chronic stressor profoundly reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs) in the mPFC; depressive-like behaviors were seen, accompanied by significant upregulation of astrocyte reactivation. We identified resilient and susceptible mice among chronic social defeat stress-exposed HFD mice. As expected, astrocyte reactivity was upregulated, while neuronal activity was depressed, in the mPFC of susceptible compared to resilient mice. Furthermore, activating astrocytes resulted in similar levels of neuronal activity and depressive-like behaviors between resilient and susceptible mice. Additionally, inhibiting astrocyte reactivation in the mPFC of HFD mice upregulated neuronal activities and inhibited depressive-like behaviors. Conclusions These observations indicate that obesogenic factors increase the risk of depression, and improve our understanding of the pathological relationship between obesity and depression. Graphical Abstract

Joint Analysis of EEG and fMRI datasets can bring new insight into brain mechanisms. In this paper, we employed the recently introduced Correlated Coupled Tensor Matrix Factorization (CCMTF) method for analysis of the emotion regulation paradigm based on EEG frontal asymmetry neurofeedback in the alpha frequency band with simultaneous fMRI. CCMTF method assumes that the co-variations of the common dimension (temporal dimension) between EEG and fMRI are correlated and not necessarily identical. The results of the CCMTF method suggested that EEG and fMRI had similar covariations during the transition of brain activities from resting states to task (view and upregulation) states and these covariations followed an increasing trend. The fMRI shared spatial component showed activations in the limbic system, DLPFC, OFC, and VLPC regions, which were consistent with the previous studies and were linked to EEG frequency patterns in the range of 1–15 Hz with a correlation value close to 0.75. The estimated regions from the CCMTF method were then used as the candidate nodes for dynamic functional connectivity (dFC) analysis, in which the changes in connectivity from view to upregulation states were examined. The results of the dFC analysis were compared with a Normalized Mutual information (NMI) based approach in two different frequency ranges (1–15 and 15–40 Hz) as the NMI method was applied to the vectors of dFC nodes of EEG and fMRI data. The results of the two methods illustrated that the relation between EEG and fMRI datasets was mostly in the frequency range of 1–15 Hz. These relations were both in the brain activations and the dFCs between the two modalities. This paper suggests that the CCMTF method is a capable approach for extracting the shared information between EEG and fMRI data and can reveal new information about brain functions and their connectivity without solving the EEG inverse problem or analyzing different frequency bands.

Abstract Humor has been considered an effective emotion regulation strategy, and some behavioral studies have examined its superior effects on negative emotion regulation. However, its neural mechanisms remain unknown. Our functional magnetic resonance imaging study directly compared the emotion regulation effects and neural bases of humorous coping (reappraisal) and ordinary reappraisal following exposure to negative pictures. The behavioral results suggested that humorous reappraisal was more effective in downregulating negative emotions and upregulating positive emotions both in the short and long term. We also found 2 cooperative neural pathways involved in coping with negative stimuli by means of humor: the “hippocampal–thalamic–frontal pathway” and the “amygdala–cerebellar pathway.” The former is associated with the restructuring of mental representations of negative situations and accompanied by an insightful (“Aha!”) experience, while the latter is associated with humorous emotional release and accompanied by an expression of laughter (“Haha!”). Furthermore, the degree of hippocampal functional connectivity with both the thalamus and frontal cortex was positively correlated with changes in positive emotion, and this result implied that the degree of emotion regulation could be strongly directly related to the depth of cognitive reconstruction. These findings highlight that regulating negative emotions with humor involves cognitive restructuring and the release of positive emotions.

Chronic stress appears to alter DNA methylation and DNA methyltransferases (DNMTs) in brain regions related to emotion. Collapsin response mediator protein-2 (CRMP2) mediates the development of depression by regulating microtubule dynamics. In this study, rats were subjected to chronic unpredictable mild stress (CUMS). At the end of the CUMS procedure, normal saline or fluoxetine was administered to the rats. Moreover, normal saline or the 5-aza-2’-deoxycytidine (5-aza) was administered to the hippocampal CA1 region of the rats. Behavioral tests were performed to evaluate the depressive-like phenotypes. The CRMP2 DNA methylation levels and cytoskeletal microtubular system-related biomarkers were detected by several molecular biology techniques. The results showed that the rat model of depression was successfully established by exposure to CUMS, and fluoxetine treatment exerted an antidepressant-like effect. We observed the upregulation of DNMT1 and DNMT3a in the hippocampus of stressed rats. CUMS induced a decrease in CRMP2 expression and an increase in phosphorylated CRMP2 (pCRMP2) expression in the hippocampus of rats. The rate of DNA methylation in the CpG island of the CRMP2 promoter region in the hippocampus of stressed rats was significantly higher than that in control rats. Moreover, CUMS significantly decreased the interaction between CRMP2 and α-tubulin and decreased the microtubule dynamics. Chronic fluoxetine treatment reversed these changes. Also, hypomethylation induced by 5-aza injection into the hippocampal CA1 region caused antidepressant-like effects and increased CRMP2 expression and microtubule dynamics. These results suggested that CRMP2 DNA methylation may be involved in regulating the cytoskeletal microtubular system and mediating depressive-like behaviors.

Background: Upregulation of the endocannabinoid enzyme fatty acid amide hydrolase (FAAH) has been linked to abnormal activity in frontoamygdalar circuits, a hallmark of posttraumatic stress disorder. We tested the hypothesis that FAAH levels in the amygdala were negatively correlated with functional connectivity between the amygdala and prefrontal cortex, subserving stress and affect control. Methods: Thirty-one healthy participants completed positron emission tomography (PET) imaging with the FAAH probe [C-11]CURB, and resting-state functional MRI scans. Participants were genotyped for the FAAH polymorphism rs324420, and trait neuroticism was assessed. We calculated amygdala functional connectivity using predetermined regions of interest (including the subgenual ventromedial prefrontal cortex [sgvmPFC] and the dorsal anterior cingulate cortex [dACC]) and a seed-to-voxel approach. We conducted correlation analyses on functional connectivity, with amygdala [C-11]CURB binding as a variable of interest. Results: The strength of amygdala functional connectivity with the sgvmPFC and dACC was negatively correlated with [C-11]CURB binding in the amygdala (sgvmPFC: r = −0.38, q = 0.04; dACC: r = –0.44; q = 0.03). Findings were partly replicated using the seed-to-voxel approach, which showed a cluster in the ventromedial prefrontal cortex, including voxels in the dACC but not the sgvmPFC (cluster-level, family-wise error rate corrected p < 0.05). Limitations: We did not replicate earlier findings of a relationship between an FAAH polymorphism (rs324420) and amygdala functional connectivity. Conclusion: Our data provide preliminary evidence that lower levels of FAAH in the amygdala relate to increased frontoamygdalar functional coupling. Our findings were consistent with the role of FAAH in regulating brain circuits that underlie fear and emotion processing in humans.

Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt β-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG via siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC.

AbstractNEU1 sialidase hydrolyzes sialic acids from glycoconjugates in lysosomes. Deficiency of NEU1 causes sialidosis with symptoms including facial dysmorphism, bone dysplasia, and neurodegeneration. However, the effects of NEU1 deficiency on emotional activity have not been explored. Here, we conducted the behavioral analysis using Neu1-knockout zebrafish (Neu1-KO). Neu1-KO zebrafish showed normal swimming similar to wild-type zebrafish (WT), whereas shoaling was decreased and accompanied by greater inter-fish distance than WT zebrafish. The aggression test showed a reduced aggressive behavior in Neu1-KO zebrafish than in WT zebrafish. In the mirror and 3-chambers test, Neu1-KO zebrafish showed more interest toward the opponent in the mirror and multiple unfamiliar zebrafish, respectively, than WT zebrafish. Furthermore, Neu1-KO zebrafish also showed increased interaction with different fish species, whereas WT zebrafish avoided them. In the black–white preference test, Neu1-KO zebrafish showed an abnormal preference for the white region, whereas WT zebrafish preferred the black region. Neu1-KO zebrafish were characterized by a downregulation of the anxiety-related genes of the hypothalamic–pituitary–adrenal axis and upregulation of lamp1a, an activator of lysosomal exocytosis, with their brains accumulating several sphingoglycolipids. This study revealed that Neu1 deficiency caused abnormal emotional behavior in zebrafish, possibly due to neuronal dysfunction induced by lysosomal exocytosis.

AbstractAmong the hallmarks of major depressive disorders (MDD) are molecular, functional, and morphological impairments in the hippocampus. Recent studies suggested a key role for hippocampal GABAergic interneurons both in depression and in the response to its treatments. These interneurons highly express the chromatin-remodeler SMARCA3 which mediates the response to chronic antidepressants in an unknown mechanism. Using cell-type-specific molecular and physiological approaches, we report that SMARCA3 mediates the glutamatergic signaling in interneurons by repressing the expression of the neuronal protein, Neurensin-2. This vesicular protein associates with endosomes and postsynaptic proteins and is highly and selectively expressed in subpopulations of GABAergic interneurons. Upregulation of Neurensin-2 in the hippocampus either by stress, viral overexpression, or by SMARCA3 deletion, results in depressive-like behaviors. In contrast, the deletion of Neurensin-2 confers resilience to stress and induces AMPA receptor localization to synapses. This pathway which bidirectionally affects emotional behavior could be involved in neuropsychiatric disorders, and suggests novel therapeutic approaches.

Abstract Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the aversive perception of pain. However, the underlying mechanisms are largely unknown. We hypothesized that the alteration of metabotropic glutamate receptor 5 (mGluR5) in the brain region underlies such a comorbidity of aversive states. We scanned the brain of chronic neuropathic pain model rats using positron emission tomography (PET) technique with an mGluR5-selective radiotracer [11C] ABP688 and found various brain regions with higher or lower level of mGluR5 compared to control rats. Among the brain areas, a prominent upregulation of mGluR5 was shown in the prelimbic region (PrL) of the medial prefrontal cortex (mPFC) of chronic neuropathic pain animals. A pharmacological blockade of upregulated mGluR5 in the PrL ameliorated the negative symptoms including tactile hypersensitivity and depressive-like behavior, which relieved the subjects from the unpleasant state of chronic neuropathic pain condition. Conversely, lentiviral overexpression of the mGluR5 in the PrL of naïve rats successfully induced comorbid pain and negative moods. Our data provide deeper insight into the shared mechanism of pain perception and negative emotions, identifying a therapeutic target for the treatment of chronic pain and mood disorders.