Illness Behavior Research Articles

Nobiletin-rich kososan, a Kampo formula, prevents the onset of apathy-like behavior and neuroinflammation in sickness behavior mouse model induced by increasing doses of lipopolysaccharide.

Infectious diseases are often concomitant with symptoms of lassitude and emotional disturbances, including depression, the so-called sickness behavior. Kososan, a Kampo (traditional Japanese herbal) formula, has been clinically used for depressive mood, with demonstrated efficacy in stress-induced depressive-like behavior mouse models. Additionally, our previous study has shown that nobiletin-rich kososan (NKS) prevents aging-related depressive-like behaviors and neuroinflammation in mice. Here, we examined whether NKS alleviates depressive-like behavior and neuroinflammation in a mouse model of sickness behavior induced by lipopolysaccharide (LPS). Repeated oral administration of NKS and the positive control antidepressant paroxetine (Paro) significantly prevented this behavior. NKS and Paro significantly increased the anti-inflammatory milieu in the hippocampus and prefrontal cortex (PFC), as well as brain microglia, of LPS-injected mice. The expression of the vascular tight junction protein claudin-5 was also significantly increased by the treatment with NKS, but not with Paro, in the hippocampus and PFC of LPS-injected mice. In vitro analysis using brain microvascular endothelial cells (BMVECs) showed that incubation with 5% serum derived from mice orally administered NKS resulted in a significant increase in the expression of anti-inflammatory heme oxygenase 1 as well as autophagic flux markers. Moreover, the claudin-5 levels in BMVECs were also increased under LPS-stimulated conditions. These results suggest that NKS exerts prophylactic effects against the LPS-induced apathy-like behavior, partly mediated by the increase in the anti-inflammatory milieu and in the levels of tight junction proteins in the brain. This study provides scientific evidence supporting the potential efficacy of NKS in preventing post-infection depression.

Biologging in a free-ranging mammal reveals apparent energetic trade-offs among physiological and behavioural components of the acute-phase response.

The acute-phase response (APR) is an adaptive emergency life-history stage, wherein vertebrates exhibit fever and anorexia to survive an infection. However, induced immune responses are energetically costly, and sick animals may reduce physical activity to compensate. Tests of this predicted energetic trade-off in free-ranging animals are rare due to difficulties in measuring individual physiology and behaviour under immune challenge in natural settings. However, recent advances in biologging technology now make such studies possible. We surgically implanted heart rate/temperature loggers in free-ranging adult male Arctic ground squirrels, fitted the squirrels with collar-mounted accelerometers and light/temperature loggers, and injected animals with lipopolysaccharide (LPS) to simulate an immune challenge. LPS-injected squirrels exhibited approximately 1°C overnight fevers accompanied by slightly elevated (10 bpm) heart rates; LPS-injected squirrels also spent 19% less of their time aboveground the following day and reduced overall movement by 40% compared with saline-injected controls. Thus, we found support for an energetic trade-off between functional immune responses (fever and anorexia) and lethargic sickness behaviour within the APR of a free-ranging mammal. Moreover, our results suggest animal-borne devices can play an important role in future studies of vertebrate immunity and disease dynamics.

Traditional and Religious Beliefs on Mental Illness and Help-Seeking Behaviour in Ife Central LGA, Ogun State

Traditional and Religious Beliefs on Mental Illness and Help-Seeking Behaviour in Ife Central LGA, Ogun State

Using Latent Class Analysis to Characterize Sickness Signaling in Relation to Familism and Public and Private Religiosity in a Stratified US Sample.

In response to contracting an infection, individuals usually display a suite of external signs (including sickness behavior) as an outward indication of illness. This context-dependent phenomenon seems to weigh the benefits and costs of eliciting sympathy by indicating sickness versus hiding signs of illness to avoid exposing others to potential infection. In a dynamically social species like humans, non-kin may be as likely to respond to these signs with care as family members, particularly fellow church members. We explore the relative contributions of religiosity and familism in shaping self-reported sickness signaling styles as two dimensions central to human altruism using latent class analysis (LCA). LCA was used to characterize the signaling styles of the study participants. Data come from a large 2018 survey (n = 1259) of sickness and health behaviors among US adults. We used denomination public (church attendance) and private religiosity (time spent in prayer, meditation, etc.) and the God Locus of Health Control scale to assess the impact of God on health. Sickness signaling style was assessed with the SicknessQ and three additional items. Covariates included age, gender, education, and income. We identified four classes (Familiar, Moderate, Gregarious, and Stoic) tied to signaling styles. The Familiar Signaling class displayed sickness verbally to familiar others, were the oldest, and were least guided by an internal sense of religion. The Moderate Signaling class was younger and had lower public and private religiosity (except regarding health issues) than the Stoic and Gregarious Signaling classes. The Gregarious class signaled to both close others and strangers and scored highest in familism and religiosity. The Stoic class did not verbally signal but indicated sickness worsening when around both close others and strangers, were less likely to be married or endorse private religiosity, and were least likely to recall recent illness as severe. The signaling classes strongly resembled aspects of the introvert-ambivert-extrovert spectrum. We conclude that variation is important at multiple levels, including personality types, and potentially prevents the loss of immunological diversity.

Sick and detached: Does experimental inflammation impact on movement synchrony in humans?

Interpersonal connectedness is a central feature of human interaction that can be compromised during illness. Nonverbal signals play a crucial role in this context, and humans, like other animals, have evolved a behavioral immune system that enables individuals to detect subtle cues of sickness in others. Conversely, sick individuals often tend to avoid social interaction, a key component of sickness behavior. The coordination of body movements between two individuals (movement synchrony) is a measure of the quality of relationships that could provide insight into an interlocutor’s sickness state. In the present study, we explored the effect lipopolysaccharide (LPS) administration, a naturalistic stimulus for inflammation-induced sickness, on movement synchrony in healthy volunteers randomly assigned to a double-blind interview with a non-treated interviewer conducted 2.5 h after intravenous injection of either LPS (n = 26) or placebo (n = 25). Movement synchrony was assessed by automated video analysis of subject’s and interviewer’s head movements. Lagged cross-correlations were used to objectively quantify coordination in dyads and to assess patterns of temporal movement-synchronization. Data analysis revealed that dyads with subjects under placebo displayed a pattern of movement coordination comparable to that seen in previous studies. However, dyads with subjects under LPS showed a loss of simultaneous movement (i.e. moving at the same time) with the interview partner, which is normally the temporal domain providing the highest level of synchrony. Together, the findings suggest that immediate social interaction is attenuated when one interlocutor is exposed to systemic inflammation, while the other is unaffected. This effect can be attributed to both sickness behavior on one hand and correlates of the behavioral immune system on the other hand.

The role of immunity in comorbid pain and depression

The narrative review aims to shed light on the influence of inflammation in the comorbid chronic pain and major depressive disorder (MDD). This connection is known to be multifactorial, with a dynamic interaction between genetic and epigenetic factors. However, a growing body of evidence has shown that the co-presence of MDD and pain is underlain by immune mechanisms involved in the persistence of the inflammatory process. In particular, the cytokines released following activation of the innate immune system during inflammation cause changes at the endocrine level that result in glucocorticoid resistance, as well as altering the synthesis and metabolism of some central nervous system (CNS) mediators. Cytokines appear to generate neuroinflammation by activating normally protective microglia. Various other mechanisms, including changes in the function of the glutamatergic, GABAergic, and serotonergic systems are also implicated, but inflammation-induced reduction of BDNF (brain-derived neurotrophic factor) appears to be the deciding factor. In turn, neuroinflammation leads to sickness behavior, which is characterized by anhedonia and social withdrawal. This review explored these mechanisms, which may be at the root of comorbid pain and MDD. Although intriguing, however, most available evidence comes from animal studies, and rigorous clinical exploration is warranted.

Cholecystokinin and gastrin as immune modulating hormones: Implications and applications

Cholecystokinin (CCK) and gastrin are gastrointestinal hormones traditionally recognised for their roles in digestion. However, it has been recognised that these hormones may also modulate immune function. Here, we examine the immune-modulating effects of CCK and gastrin, and explore the functional significance of this dual role. In addition to the direct effect of these hormones on immune cell function, we discuss why hormones that regulate complex physiological and behavioural aspects of digestion might also influence immune responses. Notably, recent findings highlight the importance of these hormones in promoting a tolerogenic hepatic environment, particularly as the liver encounters gut-derived inflammogens following a meal. Additionally, the neuro-immune crosstalk mediated by CCK suggests that this hormone may influence immune responses indirectly via the gut-brain axis, especially in the context of infection or inflammation. Furthermore, the role of CCK in inducing feeding cessation and satiety appears to be repurposed during sickness behaviour, such as the loss of appetite during infection. Collectively, these observations suggest that nutritional strategies, including permissive underfeeding or fasting, could have important clinical implications. A deeper understanding of the dual roles of CCK and gastrin in digestion and immunity may pave the way for novel therapeutic approaches that leverage these pathways for improved disease management and treatment outcomes.

Study of Rates and Factors Associated to Psychosomatic Syndromes Assessed Using the Diagnostic Criteria for Psychosomatic Research across Different Clinical Settings

Introduction: Diagnostic Criteria for Psychosomatic Research (DCPR) serve as an instrument for identifying and classifying specific psychosomatic syndromes that are not adequately encompassed in standard nosography. The present study aimed at measuring the prevalence of DCPR syndromes in different clinical settings and exploring factors associated to such diagnoses. Methods: A cross-sectional and nationwide study recruited 6,647 patients in different clinical settings: 306 were diagnosed with fibromyalgia (FM), 333 with irritable bowel syndrome, 1,109 with migraine, 2,550 with coronary heart disease (CHD), and 2,349 with type 2 diabetes (T2D). Participants underwent DCPR diagnostic interview and were assessed for depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder 7-Item Scale), and subjective well-being (World Health Organization-5 Well-Being Index). The PsychoSocial Index was used to evaluate global well-being, stress, and abnormal illness behavior. The prevalence of DCPR diagnoses was calculated, and factors associated to such diagnoses were analyzed by logistic regression. Results: Alexithymia (64.47%), irritable mood (20.55%), and demoralization (15.60%) were the most prevalent psychosomatic syndromes, with demoralization being most common in FM (49.02%). The factors associated to DCPR diagnoses encompassed high anxiety or abnormal illness behavior, and poor well-being. Notably, stress was found to be associated specifically to FM and T2D, with OR of 1.24 (95% CI: 1.06–1.46) and 1.26 (95% CI: 1.18–1.36), respectively. Conclusion: DCPR is a clinically helpful complementary assessment tool in need of being widely implemented in clinical settings in order to have a comprehensive picture of the patients.

Scrolling through adolescence: a systematic review of the impact of TikTok on adolescent mental health.

Amidst rising concerns about mental health in adolescents, the role of social media (SM), particularly highly visual platforms such as TikTok, has become a growing focus of investigation. In the extant literature, conclusive evidence is limited by the aggregate analysis of very heterogeneous SM platforms. This systematic scoping review examines the relationship between TikTok and mental health in adolescents. Additionally, it aims to highlight potential interactions between typical developmental processes and the unique aspects of TikTok, exploring their relevance to mental health within this demographic. Following PRISMA guidelines, a systematic search across PubMed, Scopus, Web of Knowledge, and PsychINFO yielded 20 studies that met the inclusion criteria, encompassing a total of 17,336 subjects from 10 countries. The retrieved studies analyzed four main topics related to TikTok use, i.e., the overall impact on adolescents' mental health, risk of problematic use and behavioral addiction, consequences on body image and self-esteem, and possible spreading of mental illness behaviors. While TikTok offers creative opportunities for self-expression and peer connection, the literature raises concerns about its potential negative effects on teens, such as lower life satisfaction, increased risk of "contagion" of certain psychiatric symptoms, and problematic usage patterns. Significant variations in study methodologies and outcome measures were observed. In the current era of evolving SM landscapes, a comprehensive approach informed by developmentally grounded research is critically needed to further understand the interplay between SM and adolescent mental health, providing insights for health authorities and policymakers.

Prophylactic clemastine treatment improves influenza A virus-induced cognitive dysfunction in mice

Respiratory infection by influenza A virus (IAV) is known to cause systemic inflammation, neuroinflammation, and cognitive impairment. We previously found that experimental infection with IAV affected oligodendrocyte homeostasis, which was associated with altered expression of genes involved in myelin maintenance as well as the lipidome. In this study, we sought to determine if clemastine, an antihistamine with myelin promoting properties, could reverse the effects of IAV on oligodendrocyte (OL) specific genes, as well as mitigate infection-induced cognitive impairment. Male and female C57BL/6J mice were randomized into experimental groups based on clemastine treatment, infection, and sex. Treatment with vehicle or clemastine (10 mg/kg/d) commenced seven days prior to inoculation with either saline or IAV and continued throughout the experiment. Body weight was measured throughout the infection. Spatial learning and memory were assessed by Morris water maze. Sickness behavior was assessed by measuring burrowing response. Immune cell responses were determined by flow cytometry, RT-qPCR, antigen recall assays and ELISA, and viral load assessed by RT-qPCR. Hippocampal levels of neuroinflammatory (Tnf, Cdkn1a) and myelin (Plp1, Mag, Ugt8a) genes were determined by RT-qPCR. Mice infected with IAV developed weight loss, impaired cognitive flexibility, reduced burrowing behavior, altered lung immune cell infiltration, increased circulating anti-viral IgM and IgG levels and increased T cell responses to IAV epitopes. Infection increased hippocampal levels of genes associated with neuroinflammation and decreased levels of genes involved in myelination. Clemastine treatment resulted in earlier recovery of weight loss in males and increased IgM levels for both sexes, but neither affected expression levels of Tnf or Cdkn1a, nor rescued changes to oligodendrocyte genes. However, treatment mitigated infection-induced neurocognitive impairment.

Physical activity and psychosocial status among Egyptian healthcare professionals: a cross-sectional study

BackgroundThe Egyptian health system faces numerous challenges, including overpopulation, limited resources, and high patient load. Long working hours, inadequate sleep, and exposure to traumatic events further strain health care workers. This study aims to investigate the association between physical activity and psychosocial status of healthcare professionals in Egypt.MethodsThis cross-sectional study was conducted in Egypt from 20th March to 20th April 2023. An online self-administered survey was used to recruit 647 healthcare professionals. The International Physical Activity Questionnaire (IPAQ) and Psychosocial Index (PSI) were used to measure physical activity and psychosocial status, respectively.ResultsAmong the 647 participants, 82% were aged 24–30 years, with 49.9% females and 66.5% doctors. Only 41% engaged in physical activity, and among them, only 5.7% exercised more than three times per week. The median work hours per week were 36, and based on the Total Work MET, participants were classified into high (32%), moderate (40%), and low (28%) physical activity levels. Half of the participants experienced highly stressful lives, while only 40% reported good-to-excellent well-being. Physical activity correlated with psychological distress (r = 0.116, p = 0.003) and abnormal illness behaviors (r = 0.081, p = 0.038), while average working hours per week correlated with psychological distress (r = 0.084, p = 0.033) and sleep disturbance (r = 0.14, p < 0.001).ConclusionIn this study, physical activity levels varied among participants, and the majority of participants had a poor psychological status. Additionally, physical activity significantly correlated with psychological distress and abnormal illness behaviors, while average working hours per week correlated with psychological distress and sleep disturbance.

Juruaça virus taxonomy, tolerance and resistance to infection, and inflammatory response modulation in murine model

Juruaça virus (JUAV), previously unclassified, was isolated from bats and administered to neonatal and adult BALB/c mice to investigate acute and chronic disease progression. In this study, we conducted genomic sequencing to achieve taxonomic classification and utilized these models to explore the inflammatory response and sickness behavior in both neonatal and adult mice. Neonates received a single intranasal instillation of infected brain homogenate (20 µL), whereas 31-day-old mice were given the same volume intranasally for three consecutive days. Control groups were administered equal volumes of uninfected brain homogenate. Our findings reveal that intranasal JUAV infection-induced acute meningoencephalitis and death in neonates, while adult mice exhibited chronic infection with variable clinical signs, inflammatory mediator production, histopathological changes, and neuropathological features. Interestingly, only some adult mice showed sickness behavior post-infection, and among these, a subset continued to decline and die. The differential tissue damage observed in mice with and without overt disease symptoms suggests mechanisms of resistance or tolerance, where exceeding tolerance capacity resulted in pathological outcomes, including chronic dysfunction or death. This study provides the first evidence of JUAV’s capability to infect mammals, demonstrating its distinct impact on bats and variable effects in neonatal and adult mice. We provisionally classified JUAV as closely related to the clade containing tombus-like virus 6 found in mute swan feces. Our research highlights the importance of understanding viral–host interactions and the inflammatory responses that contribute to disease variability, offering insights into tolerance and resistance mechanisms based on inflammatory response modulation.

Subclinical attention-deficit hyperactivity disorder symptoms and unhealthy lifestyle behaviours.

Literature emphasises the importance of identifying and intervening in the adoption of unhealthy lifestyle behaviours (ULBs) during adolescence at an early stage, to mitigate their long-term detrimental effects. Among the possible associated factors contributing to ULBs, attention-deficit hyperactivity disorder (ADHD) has been shown to play an important role. However, little is known about ADHD subclinical manifestations. The present study aimed to bridge the gap in the literature and shed light on the relationship between subclinical ADHD and early adoption of ULBs during adolescence. Through a clinimetric approach, prevalence of ULBs, severity of ADHD symptoms and psychosocial factors (i.e. allostatic overload, abnormal illness behaviour, quality of life, psychological well-being) were investigated among adolescents. The associations between different degrees of ADHD, ULBs and psychosocial factors were also explored. This multicentre cross-sectional study involved 440 adolescents (54.5% females; mean age 14.21 years) from six upper secondary schools. Participants completed self-report questionnaires on sociodemographic characteristics, ULBs, ADHD symptoms and psychosocial factors. The most common ULBs were energy drinks/alcohol consumption and problematic smartphone use. Of the sample, 22% showed subclinical ADHD and 20.2% showed clinical ADHD. The subclinical ADHD group showed several ULBs (i.e. altered mindful eating, impaired quality of sleep, problematic technology use) and psychosocial factors, akin to those of ADHD group and different from peers without ADHD symptoms. Since subclinical ADHD manifestation is associated with ULBs, similarly to clinical ADHD, identifying subthreshold symptoms during adolescence is crucial, as it could improve health-related outcomes in adulthood across different domains.

Symptom clusters and network analysis in patients with gynecologic cancer undergoing chemotherapy: A cross-sectional study

ObjectivesThis study aimed to explore the complex relationships among symptoms and symptom clusters in patients with gynecologic cancer receiving chemotherapy using symptom network analysis, and to identify core symptoms and core symptom clusters. MethodsA cross-sectional study was conducted at the Affiliated Hospital of Jiangnan University from December 2023 to June 2024, including 221 patients with gynecologic tumors. Participants completed demographic and clinical information questionnaires and the Chinese version of the MD Anderson Symptom Inventory (MDASI-C). Univariate analysis and multiple linear regression were used to screen covariates, exploratory factor analysis to determine symptom clusters, and network analysis to identify core symptoms and core symptom clusters. ResultsA total of 221 patients were included, with an average age of 58.73 years (SD ​= ​11.50). Fatigue (n ​= ​197, 89.1%) and lack of appetite (n ​= ​192, 86.9%) were the most common symptoms, while fatigue (mean ​= ​4.17, SD ​= ​2.07) and distress (mean ​= ​3.43, SD ​= ​2.20) were the most severe symptoms. Several distinct symptom clusters were identified: sickness behavior, gastrointestinal, psychological, and side-effect clusters. In the constructed network, fatigue emerged as the most central symptom (rs ​= ​1.28), while the sickness behavior cluster was identified as the most central symptom cluster (rs ​= ​1.11). ConclusionsPatients with gynecologic cancer undergoing chemotherapy commonly experience a range of symptoms. Our findings suggest that targeted interventions focusing on the sickness behavior symptom cluster may help reduce the overall symptom burden and assist caregivers in developing more effective symptom management strategies.

Immune challenge affects risk sensitivity and locomotion in mosquitofish (Gambusia holbrooki).

The immune system is crucial in responding to disease-causing pathogens. However, immune responses may also cause stereotypical changes in behaviour known as sickness behaviours, which often include reduced activity. Sickness behaviours are thought to have an important role in conserving energy required to support the immune response; however, little is known about how they manifest over time or in relation to risk, particularly in fishes. Here, we induced an immune response in mosquitofish (Gambusia holbrooki) by inoculating them with Escherichia coli lipopolysaccharide (LPS). We subsequently tested batches of fish at 24 h intervals and examined: locomotory behaviour, tendency to use a refuge and fast-start response immediately following a threat stimulus (measured as peak acceleration). Control and LPS-treated fish behaved similarly on days 1, 3 and 4. However, 2 days post-inoculation, LPS fish swam more slowly and spent more time in the refuge than control fish, although no difference in post-threat peak acceleration was found. Our findings suggest that sickness behaviours peak roughly 2 days following exposure to LPS and are relatively short-lived. Specifically, immune-challenged individuals exhibit reduced locomotion and exploratory behaviour, becoming more risk averse overall while still retaining the ability to respond acutely to a threat stimulus.

Repeated Administration of a Full-Spectrum Cannabidiol Product, Not a Cannabidiol Isolate, Reverses the Lipopolysaccharide-Induced Depressive-Like Behavior and Hypolocomotion in a Rat Model of Low-Grade Subchronic Inflammation.

Background: Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. Methods: We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. Results: The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.

Cognitive behavioural therapy for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis

BackgroundTreatment of fatigue is important for many patients with multiple sclerosis (MS). While pharmacological options have not shown consistent benefit, psychological interventions offer another avenue of treatment. Cognitive behavioural therapy (CBT) involves strategies to change maladaptive cognition and illness behaviours that modulate how patients with MS respond to fatigue. The aim of this study was to perform a systematic review and meta-analysis to determine the effectiveness of CBT for the treatment of fatigue in patients with MS. MethodsFive databases (Cochrane Central Register of Controlled Trials, MEDLINE/PubMed, Embase, Emcare and PsycINFO) were searched up until 31 July 2023. Randomised controlled trials involving adult patients with MS and fatigue, comparing CBT with another intervention or usual treatment were included. Studies were required to measure fatigue severity and/or the impact of fatigue as the primary outcome(s). Each study was assessed for bias using the Cochrane Risk of Bias tool version 2. Studies with sufficient data were used for meta-analysis to quantify the short- and long-term effects of CBT on MS-related fatigue. The level of certainty provided by the body of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. ResultsEight studies were included in the review and six studies contributed to the meta-analysis. Most studies had a low overall risk of bias. CBT interventions differed in the number, duration and frequency of sessions, mode of delivery and therapist. There were significant short- (standardised mean difference (SMD) -0.58, 95% confidence interval (95%CI) -0.85 to -0.31, P-value < 0.0001) and long-term (SMD -0.36, 95%CI -0.52 to -0.19, P-value < 0.0001) effects supporting CBT. The evidence provided a low level of certainty for the short-term effect because of heterogeneity of results and possible publication bias, while there was high certainty for the long-term result. ConclusionThe study provides secondary evidence that CBT has moderate short-term and small long-term effects in reducing fatigue in patients with MS. CBT should be regarded as a viable evidence-based intervention, particularly in the absence of established alternatives. Future research should identify the ideal characteristics of a fatigue-specific CBT intervention, patient factors that predict treatment response and strategies to maintain initial improvements over time.

Possible roles of neuropeptide/transmitter and autoantibody modulation in emotional problems and aggression.

The theoretical foundations of understanding psychiatric disorders are undergoing changes. Explaining behaviour and neuroendocrine cell communication leaning towards immunology represents a different approach compared to previous models for understanding complex central nervous system processes. One such approach is the study of immunoglobulins or autoantibodies, and their effect on peptide hormones in the neuro-endocrine system. In the present review, we provide an overview of the literature on neuropeptide/transmitter and autoantibody modulation in psychiatric disorders featuring emotional problems and aggression, including associated illness behaviour. Finally, we discuss the role of psycho-immunology as a growing field in the understanding of psychiatric disorders, and that modulation and regulation by IgG autoAbs represent a relatively new subcategory in psycho-immunology, where studies are currently being conducted.

Leptin reduces LPS‐induced A1 reactive astrocyte activation and inflammation via inhibiting p38‐MAPK signaling pathway

AbstractNeurotoxic A1 reactive astrocytes are induced by inflammatory stimuli. Leptin has been confirmed to have neuroprotective properties. However, its effect on the activation of A1 astrocytes in infectious inflammation is unclear. In the current study, astrocytes cultured from postnatal day 1 Sprague–Dawley rats were stimulated with lipopolysaccharide (LPS) to induce an acute in vitro inflammatory response. Leptin was applied 6 h later to observe its protective effects. The viability of the astrocytes was assessed. A1 astrocyte activation was determined by analyzing the gene expression of C3, H2‐D1, H2‐T23, and Serping 1 and secretion of pro‐inflammatory cytokines IL‐6 and TNF‐α. The levels of phospho‐p38 (pp38) and nuclear factor‐κB (NF‐κB) phosphor‐p65 (pp65) were measured to explore the possible signaling pathways. Additionally, an LPS‐induced inflammatory animal model was established to investigate the in vivo effects of leptin on A1 astrocytic activation. Results showed that in the in vitro culture system, LPS stimulation caused elevated expression of A1 astrocyte‐specific genes and the secretion of pro‐inflammatory cytokines, indicating the activation of A1 astrocytes. Leptin treatment significantly reversed the LPS induced upregulation in a dose‐dependent manner. Similarly, LPS upregulated pp38, NF‐κB pp65 protein and inflammatory cytokines were successfully reduced by leptin. In the LPS‐induced animal model, the amelioratory effect of leptin on A1 astrocyte activation and inflammation was further confirmed, showed by the reduced sickness behaviors, A1 astrocyte genesis and inflammatory cytokines in vivo. Our results demonstrate that leptin efficiently inhibits LPS‐induced neurotoxic activation of A1 astrocytes and neuroinflammation by suppressing p38‐MAPK signaling pathway.

The Role of Online Well-Being Therapy in Overcoming Allostatic Overload in Medical Workers: A Pilot Randomized Controlled Study

Introduction: Stress may lead to allostatic overload. Well-being therapy (WBT) might mitigate it by enhancing psychological well-being and protecting from psychological symptoms. Since no reports are available on the use of WBT in allostatic overload, we evaluated online WBT effects in reducing allostatic overload in medical workers during the coronavirus pandemic. Methods: Sixty-six participants with allostatic overload were enrolled and randomly assigned to eight sessions of online WBT (n = 32) or eight sessions of an online psychoeducation program on healthy lifestyle (CON) (n = 34). The primary outcome was the prevalence rate of allostatic overload in the two groups at session 8 (T2). Secondary analyses were performed on changes in the PsychoSocial Index (PSI) and Psychological Well-Being (PWB) scales scores at the same time points. Generalized estimating equation models were employed. Results: The WBT group showed a significantly lower rate of allostatic overload at T2 than the CON group (28.13% vs. 70.59%, p < 0.001); similar results were found at T1, T3, and T4 (p < 0.001). Compared to CON, WBT produced a significant decrease in psychological distress (p < 0.001) and abnormal illness behavior (p = 0.031), as well as a significant improvement in PWB autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance (p < 0.001). Conclusion: Online WBT may be an effective non-pharmacological therapeutic strategy for individuals with allostatic overload. These findings need to be further validated in different clinical populations.