Major depressive disorder (MDD) presents as a multifaceted syndrome with complex pathophysiology and variable treatment responses, posing significant challenges in clinical management. Neuroinflammation is known to play pivotal mechanism in depression, linking immune responses with central nervous system (CNS) dysfunction. This review explores the interplay between peripheral and central inflammatory processes in MDD, emphasizing discrepancies in biomarker validity and specificity. While peripheral markers like cytokines have historically been investigated as proxies for neuroinflammation, their reliability remains contentious due to inconsistent findings, lack of correlation with neuroinflammatory markers, the influence of confounding variables, and the role of regulatory mechanism within the CNS. Additionally, the human brain shows a pattern of regionalized inflammation. Current methodologies for investigating neuroinflammation in humans in vivo, including neural-derived extracellular vesicles (EVs) and positron emission tomography (PET) neuroimaging using translocator protein, offer promising avenues while facing substantial limitations. We propose that future research in MDD may benefit from combined microglia-derived EV-TSPO PET neuroimaging analyses to leverage the strengths and mitigate the limitations of both individual methods.

Maternal inflammation during pregnancy increases the offspring's risk of developing autism, ADHD, schizophrenia, and depression. Epidemiologic studies have demonstrated that maternal infections stimulate the production of interleukin-6 (IL-6), which can cross the placenta and fetal blood-brain barrier to alter brain development with functional and behavioral consequences. To model the effects of increased IL-6 between weeks 24-30 of human gestation, we injected male and female mice with 75 ng IL-6 twice daily, from P3 to P6. Our published studies have shown that this increases circulating IL-6 two-fold, alters post-pubescent ultrasonic vocalization patterns, reduces sociability, and increases self-grooming. However, most neurodevelopmental disorders in humans manifest in children as young as 2 years of age. Hence, a critical unexplored question is whether behavioral changes in immune activation models can be detected in pre-pubescent mice. Therefore, we evaluated early communication, sociability, and repetitive behaviors in pre-pubescent mice following the IL-6 treatment. A second open question is whether the cellular and behavioral changes are secondary to systemic or neuroinflammation. To address this question, we profiled 18 cytokines and chemokines in the circulation and CNS and evaluated eight immune cell types in P7 male and female brains following systemic IL-6 administration. We found an increase in ultrasonic vocalizations with simpler morphologies produced by the IL-6-injected male pups and a decrease in frequency in the female vocalizations upon removal from the nest at P7. The IL-6-treated male pups also socially interacted less when introduced to a novel mouse vs. controls as juveniles and spent almost twice as much time grooming themselves, a phenotype not present in the females. Tactile sensitivity was also increased, but only in the IL-6-treated female mice. The IL-6-treated mice had increased circulating IL-6 and IL-7 and reduced IL-13 at P7 that were no longer elevated at P14. There were no changes in brain levels of IL-6, IL-10, IL-13 or IL-17A mRNAs at P7. Altogether, these studies show that changes in the three core behavioral domains associated with several psychiatric disorders can be detected early in pre-pubescent mice following a transient developmental increase in IL-6. Yet, these behavioral alterations do not require neuroinflammation.

Post-COVID-19 Syndrome (PCS) is defined as symptoms persisting beyond 12 weeks from the onset of symptoms. Notably, COVID-19 has been associated with long-term effects on the brain and mental health. This cross-sectional study aims to investigate depression, fatigue, sleep quality, and cognitive dysfunction, particularly working memory, in individuals with PCS compared to a healthy control group.

Between April and December 2021, 45 COVID-19 individuals and 60 healthy individuals met the eligibility criteria. Demographic information and the Montreal Cognitive Assessment were collected. Two visual working memory tasks, Delayed Match-to-Sample (DMS) and n-back, were performed, along with self-report questionnaires: Beck Depression Inventory, Modified Fatigue Impact Scale, and Pittsburgh Sleep Quality Index.

A total of 105 participants were enrolled. Findings reveal that the PCS group exhibited notably higher levels of cognitive impairment (13.3% vs. 1.6%, p = 0.04), depression (53.9% vs. 25.9%, p = 0.03), and sleep disturbances (53.9% vs. 18.6%, p = 0.01) compared to the healthy control group. Sleep latency and sleep duration were particularly affected. No significant differences in working memory function were observed between the two groups (p = 0.90 for DMS and p = 0.98 for n-back).

The study highlights the higher prevalence of sleep disturbance, depression, and cognitive impairment in the PCS phase, with inflammation likely playing a significant role. Moreover, the study suggests that untreated depression and sleep disturbances may pose long-term risks for dementia. Understanding the underlying mechanisms is crucial for developing effective interventions and support for individuals recovering from the infection. Prospective longitudinal studies with larger and more diverse samples are warranted to confirm and expand upon these findings.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is defined by myocardial infarction criteria with < 50% stenosis and no clear cause. While mental health disorders are linked to cardiovascular risk, their impact on MINOCA outcomes is not well studied.

We conducted a retrospective cohort study using the National Inpatient Sample (NIS) from 2017 to 2021, identifying hospitalized MINOCA patients with and without mental health disorders using ICD-10-CM codes. Propensity score matching and inverse probability weighting (IPW) were employed to adjust for confounders and balance baseline characteristics. Multivariable logistic regression estimated adjusted odds ratios and 95% confidence intervals for in-hospital outcomes.

Among 4300 propensity-matched pairs (8600 patients), MINOCA patients with mental health disorders had higher in-hospital mortality (2.26% vs 1.21%, p < 0.001) and increased risk of sudden cardiac arrest (1.51% vs 0.65%, p < 0.001). They were also more likely to develop pulmonary embolism (1.54% vs 0.65%, p < 0.001) and acute kidney injury (25.45% vs 20.24%, p < 0.001).

Mental health disorders are independently associated with higher in-hospital mortality and adverse cardiovascular outcomes among MINOCA patients. These findings highlight the urgent need for integrated cardiovascular and psychiatric care, emphasizing early screening, multidisciplinary management, and targeted interventions to improve patient outcomes.

Psychological stress is the most common psychological comorbidity and a significant triggering factor of vitiligo. Moderate to severe psychological stress can markedly affect the efficacy of vitiligo treatment. However, the specific mechanisms underlying its involvement remain insufficiently studied.

Chronic unpredictable mild stress (CUMS)-induced major depressive disorder (MDD)-like behavior was modeled in C57BL/6 mice alongside wild-type mice to investigate differences in vitiligo pathogenesis. White spot tissues from mouse tails were subjected to high-throughput transcriptomic sequencing (RNA-seq). In vitro experiments utilized β-galactosidase, P16, and P21 to assess IFN-γ-induced senescence. The effects of exogenous IL-6 on fibroblast senescence were assessed, and the role of blocking the IL-6 autocrine loop with an IL-6R inhibitor in reversing IFN-γ-induced fibroblast senescence was evaluated.

CUMS-induced MDD -like mice exhibited significantly lower body mass index and sugar-water preference index compared to wild-type mice, and their vitiligo severity was markedly increased. Transcriptomic sequencing revealed significant upregulation of cellular senescence and JAK-STAT signaling pathways in white spot tissues of depressive-like vitiligo mice. In vitro findings indicated that IFN-γ induced fibroblast senescence via activation of the JAK2-STAT3 signaling pathway, which subsequently promoted melanocyte apoptosis and increased IL-6 secretion and IL-6R expression. Exogenous IL-6 further activated the JAK2-STAT3 signaling pathway, induced fibroblast senescence, and synergistically intensified IFN-γ-induced fibroblast senescence.

Excessive activation of the IL-6 autocrine loop, synergizing with IFN-γ to aggravate fibroblast senescence and promote melanocyte apoptosis. Blocking the IL-6 autocrine loop may serve as an effective approach to mitigate the impact of CUMS on vitiligo pathogenesis and treatment efficacy.

This review aimed to explore the association between metabolically healthy obesity (MHO) and the risk of depression. Databases (EMBASE, PubMed, Web of Science, Cochrane Library) were searched up to 20 June 2024. Observational studies were included if they compared groups with MHO, metabolically unhealthy nonobesity, and metabolically unhealthy obesity to groups with metabolically healthy nonobesity for the risk of depression. The random-effect model was used to calculate the pooled odds ratios (ORs). Subgroup analyses and meta-regressions were conducted according to age, study design, definition of MHO, BMI cut-off value, depression assessment method, geographic location, ethnicity, development status, and gender to explore the sources of heterogeneity. Three cohorts and 9 cross-sectional studies (N = 1,277,267 participants) were included in this review. Individuals with MHO (OR 1.08 [95% CI 1.04, 1.12], I² = 88.3%), metabolically unhealthy nonobesity (OR 1.15 [95% CI 1.04, 1.28], I² = 99.6%), and metabolically unhealthy obesity (OR 1.30 [95% CI 1.12, 1.51], I² = 99.8%) had an increased risk of depression than individuals with metabolically healthy nonobesity. The association between MHO and risk of depression was stronger in women (OR = 1.14; 95% CI: 1.08-1.20) and populations from North America (OR = 1.26; 95% CI: 1.01-1.58) and Europe (OR = 1.23; 95% CI: 1.07-1.41). Inconsistencies in MHO definitions and BMI cutoff values across studies were important sources of heterogeneity (subgroup analysis: PQ = 29.87, p = 0.001; meta-regression: p = 0.015, R² = 100%). MHO was associated with an increased risk of depression, particularly among women and populations from North America and Europe. These high-risk groups need personalized interventions. Standardizing definition for MHO could enhance comparability across studies. Future prospective cohort studies are needed to validate our findings by including populations from developing nations and employing rigorous definitions.

Background: Patients with psoriasis often experience psychiatric comorbidities, such as depression and anxiety. These comorbidities can lead to poorer adherence to treatment regimens, reduced effectiveness of therapies, and a heightened disease burden. This study aims to explore the scientific output related to psoriasis, depression, and anxiety using a comprehensive analysis combining bibliometric statistical methods. Methods: The study performed a bibliometric analysis of publications related to psoriasis, depression, and anxiety between 1974 and December 2023. This study employed the Latent Dirichlet Allocation (LDA) algorithm to identify key research topics and used the HJ-Biplot technique to visualize the relationships between publications and research indicators. The inclusion criteria were limited to English-language research articles. Results: Over 49 years, the analysis identified 5059 documents published across 1151 sources. The annual growth rate for research was 12.26%. The Journal of the European Academy of Dermatology and Venereology and The British Journal of Dermatology were found to be the leading journals in this field. The United States emerged as the top contributor, followed by China, Italy, and Germany. The most prevalent research topics were inflammation and cellular function, with a significant focus on patient treatment and the impact of depression and anxiety. Conclusions: This bibliometric analysis underscores the increasing of studies on the comorbidities of depression and anxiety in patients with psoriasis. This study provides a comprehensive overview of research trends and emerging topics in this field, offering valuable insights for future investigations.

It has been shown that the microflora of the gastrointestinal tract undergoes changes in obese individuals. The present study aimed to investigate the effect of kefir fortified with two strains, Lactobacillus helveticus and Bifidobacterium longum, on depression, appetite, oxidative stress, and inflammatory parameters in overweight and obese elderly individuals.

This study was a double-blind, randomized, and placebo-controlled clinical trial conducted on 67 elderly men aged over 65, who were randomly divided into two groups. One group (n = 35) received one bottle (240 cc) of regular kefir as a placebo, while the intervention group (n = 32) received one bottle of probiotic-fortified kefir for eight weeks. Depression and appetite were evaluated using the Geriatric Depression Scale-15 (GDS-15) and a validated Visual Analogue Scale (VAS), respectively. Oxidative stress parameters were assessed using the standard calorimetric method, and inflammatory parameters were measured via the enzyme-linked immunosorbent assay method (ELISA). The differences between the two groups were compared using the independent samples T-test.

The median age of participant in both groups was 65 years. A significant difference in depression scores and the mean change between the two groups was observed after eight weeks (p = 0.001 and p = 0.042, respectively). Within-group comparison revealed a significant increase in appetite scores in both groups (p < 0.05 for both). Moreover, a significant difference in the changes in total antioxidant capacity (TAC) was noted (p = 0.009). However, no significant differences were observed in other oxidative and inflammatory parameters between the two groups (p˃0.05 for all).

The results demonstrated the positive impact of two specific strains of Bifidobacterium and Lactobacillus on improving depression in the elderly. However, when comparing the two groups, no significant effects were observed on appetite, inflammation, and oxidative stress parameters, except for TAC.

The prevalence of obesity currently represents a significant public health concern. Besides the physical burden, obesity is also associated with mental health issues. The mutual relationship between mental health issue and surgical outcome remains unclear, particularly in the population of ethnic Chinese patients. The objective of this Taiwanese study aims to evaluate the changes in physical and mental health before and after surgery and investigate the association between surgical outcome and mental health status.

The study population comprised patients who had undergone bariatric surgery at least one year prior (with the follow-up durations predominantly within two years). We collected and compared pre- and post-operative mental health status (using the Chinese Health Questionnaire, CHQ, and the Taiwanese Depressive Questionnaire, TDQ) and physical indicators to evaluate and establish their relationships. Furthermore, formal psychiatric diagnoses were confirmed by psychiatrists to analyze the differences between the groups with and without such diagnoses.

A total of 147 patients were included in the study. Following surgery, notable improvements were observed in physical condition and mental health. The average body mass index (BMI) decreased by 13.46 (SD 8.28), the CHQ scores decreased by 1.52 (SD 2.76), and the TDQ scores decreased by 5.08 (SD 8.58). The prevalence of any psychiatric disorder in these patients was found to be 34%. There was no significant difference in the Percentage of Total Weight Loss (%TWL) between individuals with or without psychiatric disorders. However, patients with psychiatric disorders had higher CHQ and TDQ scores after surgery. In multiple linear regression models, the TDQ-by-follow-up duration interaction was predictive of the %TWL, and both married status and the level of tertiary education were identified as negatively associated factors.

Patients who underwent bariatric surgery exhibited a high prevalence of psychiatric disorders, but the presence of pre-operative psychiatric disorders did not significantly affect weight change after surgery. Despite the improvements in physical and mental health post-surgery, the findings indicate that the impact of depression on effectiveness of bariatric surgery is modulated by the time elapsed since the surgery, emphasizing the importance of ongoing mental health care for these patients.

Not applicable.

Recurrent spontaneous seizures with an extended epileptic discharge are the hallmarks of epilepsy. At present, there are several available anti-epileptic drugs (AEDs) in the market. Still no adequate treatment for epilepsy treatment is available. The main disadvantages of AEDs are their associated adverse effects. It is a challenge to develop new therapies that can reduce seizures by modulating the underlying mechanisms with no adverse effects. In the last decade, the neuromodulatory potential of phytoconstituents has sparked their usage in the treatment of central nervous system disorders. Curcumin is an active polyphenolic component that interacts at cellular and molecular levels. Curcumin's neuroprotective properties have been discovered in recent preclinical and clinical studies due to its immunomodulatory effects. Curcumin has the propensity to modulate signaling pathways involved in cell survival and manage oxidative stress, apoptosis, and inflammatory mechanisms. Further, curcumin can persuade epigenetic alterations, including histone modifications (acetylation/deacetylation), which are the changes responsible for the altered expression of genes facilitating the process of epileptogenesis. The bioavailability of curcumin in the brain is a concern that needs to be tackled. Therefore, nanonization has emerged as a novel drug delivery system to enhance the pharmacokinetics of curcumin. In the present review, we reviewed curcumin's modulatory effects on potential biomarkers involved in epileptogenesis including dendritic cells, T cell subsets, cytokines, chemokines, apoptosis mediators, antioxidant mechanisms, and cognition impairment. Also, we have discussed the nanocarrier systems for encapsulating curcumin, offering a promising approach to enhance bioavailability of curcumin.

Despite earlier research demonstrating the immunomodulatory effects of acute and chronic exercise in many medical illnesses, there is a lack of literature evaluating the acute and chronic effects of exercise on the cytokine levels in individuals with bipolar disorder (BD) or schizophrenia (SCH). This study aims to examine the acute effects of resistance exercise on cytokines and the chronic effects of resistance exercise by 10 weeks on cytokine levels, symptoms of disease, and muscular strength in individuals with BD and SCH. The included individuals (N=10) performed a single session of band-elastic resistance exercises (six exercises, 3 sets of 12-15 repetitions, 60 seconds of interval between sets). A sub-sample (N=6) of individuals performed a supervised band-elastic resistance exercise program (2 times a week, for 10 weeks, 6 exercises, 3 sets of 12-15 repetitions, 60 seconds of interval). We verified for acute effects: IL-2 (P=0.0085) and IL-4 (P=0.0253) levels increased, while IL-6 decreased (P=0.0435), and for chronic effects: increased IL-2 and IL-4 levels (significant effect size - Pre vs Post), a decrease in disease symptoms, and an increase in muscular strength. This study adds to what is already known about how resistance exercises affect people with BD and SCH in both short-term (systemic cytokines levels) and long-term (symptoms of disease, muscular strength, and systemic cytokines levels).

Patients suffering from psoriatic arthritis (PsA) often experience depression due to chronic joint pain, which significantly hinders their recovery process. However, the relationship between these two conditions is not well understood. Through a review of existing studies, we revealed that certain neuroendocrine hormones and neurotransmitters are involved in the neuroimmune interactions related to both PsA and depression. These include adrenocorticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH), cortisol, monoamine neurotransmitters, and brain-derived neurotrophic factor (BDNF). Notably, the signalling pathway involving CRH, MCs, and Th17 cells plays a crucial role in linking PsA with depression; thus, this pathway may help clarify their connection. In this review, we outline the inflammatory immune changes associated with PsA and depression. Additionally, we explore how neuroendocrine hormones and neurotransmitters influence inflammatory responses in these two conditions. Finally, our focus will be on potential treatment strategies for patients with PsA and depression through the targeting of the CRH-MC-Th17 pathway. This review aims to provide a theoretical framework as well as new therapeutic targets for managing PsA alongside depression.

Multiple lines of evidence indicate that mood disorders, such as major depressive and bipolar disorder, are associated with abnormalities in neuroglial cells. This chapter discusses the existing literature investigating the potential role of astrocytes, oligodendrocytes, and microglia in mood pathology. We will describe evidence from in vivo imaging, postmortem, animal models based on (stress) paradigms that mimic depressive-like behavior, and biomarker studies in blood and cerebrospinal fluid in patients with mood disorders. The effect of medication used in the treatment of mood disorders, such as antidepressants and lithium, on glial function is discussed. Lastly, we highlight the most relevant findings about potential deficiencies in glia-glia crosstalk in mood disorders. Overall, decreased astrocyte and oligodendrocyte density and expression and microglial changes in homeostatic functions have frequently been put forward in MDD pathology. Studies of BD report similar findings to some extent; however, the evidence is less well established. Together, these findings are suggestive of reduced glial cell function leading to potential white matter abnormalities, glutamate dysregulation, disrupted neuronal functioning, and neurotransmission. However, more research is required to better understand the exact mechanisms underlying glial cell contributions to mood disorder development.

Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society, being mainly represented by major depressive disorder (MDD) and bipolar disorder (BD). The etiopathogenesis of mood disorders is extremely complex, with a wide spectrum of biological, psychological, and sociocultural factors being responsible for their appearance and development. In this sense, immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders, worsening mainly the central nervous system (neuroinflammation) and the periphery of the body (systemic inflammation). However, these alterations cannot be understood separately, but as part of a complex picture in which different factors and systems interact with each other. Psychoneuroimmunoendocrinology (PNIE) is the area responsible for studying the relationship between these elements and the impact of mind-body integration, placing the immune system as part of a whole. Thus, the dysfunction of the immune system is capable of influencing and activating different mechanisms that promote disruption of the psyche, damage to the nervous system, alterations to the endocrine and metabolic systems, and disruption of the microbiota and intestinal ecosystem, as well as of other organs and, in turn, all these mechanisms are responsible for inducing and enhancing the immune dysfunction. Similarly, the clinical approach to these patients is usually multidisciplinary, and the therapeutic arsenal includes different pharmacological (for example, antidepressants, antipsychotics, and lithium) and non-pharmacological (i.e., psychotherapy, lifestyle, and electroconvulsive therapy) treatments. These interventions also modulate the immune system and other elements of the PNIE in these patients, which may be interesting to understand the therapeutic success or failure of these approaches. In this sense, this review aims to delve into the relationship between immune dysfunction and mood disorders and their integration in the complex context of PNIE. Likewise, an attempt will be made to explore the effects on the immune system of different strategies available in the clinical approach to these patients, in order to identify the mechanisms described and their possible uses as biomarkers.

Psychological distress can significantly obstruct the treatment outcomes of patients with psoriasis. This meta-analysis aimed to examine the effects of psychological intervention on the mental health and functional capabilities in patients with psoriasis.

PubMed, EMBASE, and Cochrane Library were searched for relevant studies published up to May 1, 2023. The primary outcome was a change in anxiety, depression, and quality of life (QoL). Standardized mean difference (SMD) was calculated, and 95% confidence interval (CI) was determined for the estimation.

This meta-analysis involved 1048 subjects, including 515 patients who received psychological interventions and 533 patients in control groups who did not receive psychological interventions. The results showed that psychological intervention significantly improved anxiety symptoms (SMD - 0.41; 95%CI - 0.77, - 0.05; I2 = 71.5%; PHeterogeneity = 0 .001). There was no significant improvement in the symptoms of depression (SMD - 0.52; 95%CI - 1.13, 0.10; I2 = 86%; PHeterogeneity < 0 .001) and QoL (SMD - 0.05; 95%CI - 0.22, 0.11; I2 = 39%; PHeterogeneity = 0 .108) in patients who received psychological intervention compared with controls.

Psychological intervention ameliorated anxiety symptoms in patients with psoriasis but had no significant impact on depression or QoL.

Perivascular spaces (PVS) are fluid-filled spaces surrounding the brain parenchymal vasculature. Literature suggests that PVS may play a significant role in aging and neurological disorders, including Alzheimer's disease (AD). The aim of this study is to investigate whether the relationship between MRI-visible PVS and stress is influenced by neuroinflammation in an elderly population with different levels of cognitive impairment.

Using brain MRI scans acquired at 1.5 T, PVS were quantified in a cohort of 461 individuals, consisting of cognitively healthy controls (n = 48), people with mild cognitive impairment (MCI, n = 322) and Alzheimer's disease (AD, n = 91). PVS volume fraction was calculated in the basal ganglia and centrum semiovale using a semi-automated segmentation approach. Stress was quantified with levels of salivary cortisol. Inflammatory biomarkers measured from plasma included cytokines, matrix metalloproteinases and C-reactive protein. General linear models were used to test the relationship between PVS and cortisol, when interacting with inflammatory markers. This was done on the whole cohort and within each clinical cognitive group.

In the centrum semiovale, higher inflammation levels reduced the relationship of cortisol with PVS. In basal ganglia, higher levels of C-reactive protein reduced the negative relationship of cortisol with PVS. All analyses were accounted for age, sex, body mass index (BMI) and total hippocampal volume. There was a significant interaction effect between cortisol and C-reactive protein on PVS volume fraction in the MCI group.

These findings suggest an influence of neuroinflammation on the PVS structure in Alzheimer's disease spectrum, and offer insight for better understanding physiological processes of cognitive impairment onset.

This review article explores the transformative potential of dynamic, real-time biosensing in biorhythm tracking for psychiatric disorders. Psychiatric diseases, characterized by a complex, heterogeneous, and multifactorial pathophysiology, pose challenges in both diagnosis and treatment. Common denominators in the pathophysiology of psychiatric diseases include disruptions in the stress response, sleep-wake cycle, energy metabolism, and immune response: all of these are characterized by a strong biorhythmic regulation (e.g., circadian), leading to dynamic changes in the levels of biomarkers involved. Technological and practical limitations have hindered the analysis of such dynamic processes to date. The integration of biosensors marks a paradigm shift in psychiatric research. These advanced technologies enable multiplex, non-invasive, and near-continuous analysis of biorhythmic biomarkers in real time, overcoming the constraints of conventional approaches. Focusing on the regulation of the stress response, sleep/wake cycle, energy metabolism, and immune response, biosensing allows for a deeper understanding of the heterogeneous and multifactorial pathophysiology of psychiatric diseases. The potential applications of nanobiosensing in biorhythm tracking, however, extend beyond observation. Continuous monitoring of biomarkers can provide a foundation for personalized medicine in Psychiatry, and allow for the transition from syndromal diagnostic entities to pathophysiology-based psychiatric diagnoses. This evolution promises enhanced disease tracking, early relapse prediction, and tailored disease management and treatment strategies. As non-invasive biosensing continues to advance, its integration into biorhythm tracking holds promise not only to unravel the intricate etiology of psychiatric disorders but also for ushering in a new era of precision medicine, ultimately improving the outcomes and quality of life for individuals grappling with these challenging conditions.

Depression has emerged as a significant global health concern, exerting a profound impact on individuals, as evidenced by its high prevalence and associated suicide rates. Considering its pervasive nature, the absence of optimal treatment modalities remains a challenge. Acupuncture has garnered substantial clinical and experimental validation for its efficacy in addressing diverse forms of depression, including postpartum, post-stroke, and adolescent depression. This article endeavors to elucidate the distinctive attributes and underlying mechanisms of acupuncture in the contemporary treatment of depression. Research has demonstrated that acupuncture exerts diverse physiological effects in animal models of depression, encompassing modulation of the brain, serum, and brain-gut axis. These effects are attributed to various mechanisms, including anti-inflammatory and anti-oxidative actions, promotion of neuronal plasticity, neuroprotection, neurotrophic effects, modulation of neurotransmitters, regulation of endocrine and immune functions, and modulation of cell signal pathways. Currently, the therapeutic mechanism of acupuncture involves the engagement of multiple targets, pathways, and bidirectional regulation. Hence, acupuncture emerges as a promising alternative medical modality, exhibiting substantial research prospects and meriting comprehensive worth further study and dissemination.

To investigate the relationship between cognitive complaints, systemic inflammatory biomarkers, and psychological general well-being (PGWB) after mild/asymptomatic SARS-CoV-2 infection, according to the presence of long COVID and work tasks.

University employees and metal workers were recruited in a cross-sectional study 4 months after SARS-CoV-2 infection to assess cognitive impairment, individual PGWB index, inflammatory biomarkers, namely platelet-lymphocyte, neutrophil-lymphocyte, and lymphocyte-monocyte ratios, and the presence of long COVID symptoms.

A significant increase in the levels of inflammatory biomarkers was observed in subjects with long COVID. Furthermore, the PGWB index was influenced by long COVID symptoms and subjective cognitive and depressive symptoms, but not by work activity.

In occupational settings, it is crucial to detect the presence of long COVID symptoms and systemic inflammation early, as they may be associated with lower PGWB.

Psoriasis and psoriatic arthritis are associated with an increased risk of mental health conditions such as depression and anxiety. People with psoriatic disease (PsD) are also more likely to die by suicide than those without. Mood disorders affect people with PsD in a multitude of ways, such as in effectiveness of care, response to treatment, remission rates, and quality of life. Although the links between PsD and mental health conditions have not been fully elucidated, this review will highlight recent studies investigating shared biologic mechanisms between depression and PsD. Since mental health disorders can be assessed and treated effectively, dermatologists and rheumatologists should be aware of the mental health burden in individuals with PsD to accomplish the following: (1) educate their patients with PsD about this association, (2) screen for mental health conditions on an ongoing basis in their clinical practice, (3) refer their patients with PsD to a mental health professional when needed, and (4) ensure selection of a safe PsD treatment in the setting of comorbid mental health disease. Finally, important treatment considerations for individuals with PsD and depression are reviewed. This topic was presented at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting.

Vitiligo is an acquired autoimmune skin disease characterized by patchy depigmentation of the skin, often accompanied by white hair. The aetiology of vitiligo is complex and difficult to cure, and its disfiguring appearance significantly impacts patients' mental and physical health. Psychological stress is a major factor in inducing and exacerbating vitiligo, as well as affecting its treatment efficacy, though the specific mechanisms remain unclear. Increasing research on the brain-skin axis in skin immunity suggests that psychological stress can influence local skin immunity through this axis, which may play a crucial role in the pathogenesis of vitiligo. This review focuses on the role of brain-skin axis in the pathogenesis of vitiligo, and explores the possible mechanism of brain-skin axis mediating the pathogenesis of vitiligo from the aspects of sympathetic nervous system, hypothalamic-pituitary-adrenal (HPA) axis and hormones and neuropeptides, aiming to provide the necessary theoretical basis for psychological intervention in the prevention and treatment of vitiligo.

Depression is a common mental disorder, the effective treatment of which remains a challenging issue worldwide. The clinical pathogenesis of depression has been deeply explored, leading to the formulation of various pathogenic hypotheses. Among these, the monoamine neurotransmitter hypothesis holds a prominent position, yet it has significant limitations as more than one-third of patients do not respond to conventional treatments targeting monoamine transmission disturbances. Over the past few decades, a growing body of research has highlighted the link between inflammation and depression as a potential key factor in the pathophysiology of depression. In this review, we first summarize the relationship between inflammation and depression, with a focus on the pathophysiological changes mediated by inflammation in depression. The mechanisms linking inflammation to depression as well as multiple anti-inflammatory strategies are also discussed, and their efficacy and safety are assessed. This review broadens the perspective on specific aspects of using anti-inflammatory strategies for treating depression, laying the groundwork for advancing precision medicine for individuals suffering from "inflamed" depression.

Previous studies have demonstrated a bidirectional relationship between inflammation and depression. Activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes is closely related to the pathogenesis of various neurological diseases. In patients with major depressive disorder, NLRP3 inflammasome levels are significantly elevated. Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies. In this review, we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome. Moreover, we outlined various therapeutic strategies that target the NLRP3 inflammasome, including NLRP3 inflammatory pathway inhibitors, natural compounds, and other therapeutic compounds that have been shown to be effective in treating depression. Additionally, we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression. Currently, there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment. The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression. Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.

PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.

Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.

Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.

Despite the frequent diagnostic delays of rare neurologic diseases (RND), it remains difficult to study RNDs and their comorbidities due to their rarity and hence the statistical underpowering. Affecting one to two in a million annually, stiff person syndrome (SPS) is an RND characterized by painful muscle spasms and rigidity. Leveraging underutilized electronic health records (EHR), this study showcased a machine-learning-based framework to identify clinical features that optimally characterize the diagnosis of SPS.

A machine-learning-based feature selection approach was employed on 319 items from the past medical histories of 48 individuals (23 with a diagnosis of SPS and 25 controls) with elevated serum autoantibodies against glutamic-acid-decarboxylase-65 (anti-GAD65) in Dartmouth Health's EHR to determine features with the highest discriminatory power. Each iteration of the algorithm implemented a Support Vector Machine (SVM) model, generating importance scores-SHapley Additive exPlanation (SHAP) values-for each feature and removing one with the least salient. Evaluation metrics were calculated through repeated stratified cross-validation.

Depression, hypothyroidism, GERD, and joint pain were the most characteristic features of SPS. Utilizing these features, the SVM model attained precision of 0.817 (95% CI 0.795-0.840), sensitivity of 0.766 (95% CI 0.743-0.790), F-score of 0.761 (95% CI 0.744-0.778), AUC of 0.808 (95% CI 0.791-0.825), and accuracy of 0.775 (95% CI 0.759-0.790).

This framework discerned features that, with further research, may help fully characterize the pathologic mechanism of SPS: depression, hypothyroidism, and GERD may respectively represent comorbidities through common inflammatory, genetic, and dysautonomic links. This methodology could address diagnostic challenges in neurology by uncovering latent associations and generating hypotheses for RNDs.

The coexistence of childhood asthma and mental health (MH) conditions can impact management and health outcomes but we need to better understand the etiology of multimorbidity. We investigated the association between childhood asthma and MH conditions as well as the determinants of their coexistence.

We used data from the Canadian Health Survey of Children and Youth 2019 (3-17 years; n = 47,871), a cross-sectional, nationally representative Statistics Canada dataset. Our primary outcome was condition status (no asthma or MH condition; asthma only; MH condition only; both asthma, and a MH condition (AMHM)). Predictors of condition status were assessed using multiple multinomial logistic regression. Sensitivity analyses considered individual MH conditions.

MH condition prevalence was almost two-fold higher among those with asthma than those without asthma (21.1% vs. 11.6%, respectively). There were increased risks of each condition category associated with having allergies, other chronic conditions, and family members smoking in the home while there were protective associations with each condition status category for being female and born outside of Canada. Four additional variables were associated with AMHM and MH condition presence with one additional variable associated with both AMHM and asthma. In sensitivity analyses, the associations tended to be similar for most characteristics, although there was some variability.

There are common risk factors of asthma and MH conditions along with their multimorbidity with a tendency for MH risk factors to be associated with multimorbidity. MH condition presence is common and important to assess among children with asthma.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

Generalized anxiety disorder (GAD) is marked by prolonged and excessive worry, physical signs of anxiety, and associated neuroinflammation. Traditional treatments, like pharmacotherapy and cognitive-behavioral therapy (CBT), often leave residual symptoms and have high relapse rates. This study aimed to explore the efficacy of algorithm-based modular psychotherapy (MoBa), a combination of CBT and mindfulness meditation as validated by the research domain criteria (RDoC), in reducing anxiety and neuroinflammation in GAD. A longitudinal design was used, with 50 patients with GAD undergoing a 12-week MoBa treatment. The patients were investigated pre- and post-treatment using MRI to measure neuroinflammatory markers (DBSI-RF, diffusion-basis spectral imaging-based restricted fraction) in the hippocampus, amygdala, and neocortex. Clinical symptoms were assessed using the Hamilton Anxiety Rating Scale (HAM-A) and the Generalized Anxiety Disorder 7-item scale (GAD-7). Results indicated significant reductions in both anxiety symptoms and MRI RF values in the amygdala, suggesting decreased neuroinflammation. A reduction in anxiety was associated with the amelioration of neuroinflammation in the amygdala. These results suggest that MoBa is effective in alleviating both the psychological and neuroinflammatory aspects of GAD, offering a promising personalized treatment approach. Future research should focus on long-term effects and the mechanisms through which MoBa impacts neuroinflammation and anxiety.

Osteoporosis and major depressive disorder (MDD) represent two significant health challenges globally, particularly among perimenopausal women. This study utilizes NHANES data and Mendelian randomization (MR) analysis to explore the link between them, aiming to provide a basis for intervention strategies for this group.

The study analyzed NHANES 2007-2018 data using weighted logistic regression in R software to evaluate the link between MDD and osteoporosis risk. Then, a two-sample MR analysis with GWAS summary statistics was performed, mainly using the IVW method. Additional validation included MR Egger, Weighted Median, Mode, and MR-PRESSO methods.

The research analysis indicated a significant link between MDD and the risk of osteopenia/osteoporosis. Our analysis revealed a significant positive relationship between MDD and both femoral neck osteoporosis (OR = 6.942 [95 % CI, 1.692-28.485]) and trochanteric osteoporosis (OR = 4.140 [95 % CI, 1.699-10.089]). In analyses related to osteopenia, a significant positive correlation was observed between MDD and both total femoral osteopenia (OR = 3.309 [95 % CI, 1.577-6.942]) and trochanteric osteopenia (OR = 2.467 [95 % CI, 1.004-6.062]). Furthermore, in the MR analysis, genetically predicted MDD was causally associated with an increased risk of osteoporosis via the IVW method (P = 0.013).

Our study was limited by potential selection bias due to excluding subjects with missing data, and its applicability was primarily to European and American populations.

Integrating NHANES and MR analyses, a robust correlation between MDD and osteoporosis was identified, emphasizing the significance of addressing this comorbidity within clinical practice and meriting further investigation.

Growing evidence implicates systemic inflammation in the loss of structural brain integrity in natural ageing and disorder development. Chronic stress and glucocorticoid exposure can potentiate inflammatory processes and may also be linked to neuronal atrophy, particularly in the hippocampus and the human neocortex. To improve understanding of emerging maladaptive interactions between stress and inflammation, this study examined evidence for glucocorticoid- and inflammation-mediated neurodegeneration in healthy mid-aged adults. N = 169 healthy adults (mean age = 39.4, 64.5% female) were sampled from the general population in the context of the ReSource Project. Stress, inflammation and neuronal atrophy were quantified using physiological indices of chronic stress (hair cortisol (HCC) and cortisone (HEC) concentration), systemic inflammation (interleukin-6 (IL-6), high-sensitive C-reactive protein (hs-CRP)), the systemic inflammation index (SII), hippocampal volume (HCV) and cortical thickness (CT) in regions of interest. Structural equation models were used to examine evidence for pathways from stress and inflammation to neuronal atrophy. Model fit indices indicated good representation of stress, inflammation, and neurological data through the constructed models (CT model: robust RMSEA = 0.041, robust χ2 = 910.90; HCV model: robust RMSEA <0.001, robust χ2 = 40.95). Among inflammatory indices, only the SII was positively associated with hair cortisol as one indicator of chronic stress (β = 0.18, p < 0.05). Direct and indirect pathways from chronic stress and systemic inflammation to cortical thickness or hippocampal volume were non-significant. In exploratory analysis, the SII was inversely related to mean cortical thickness. Our results emphasize the importance of considering the multidimensionality of systemic inflammation and chronic stress, with various indicators that may represent different aspects of the systemic reaction. We conclude that inflammation and glucocorticoid-mediated neurodegeneration indicated by IL-6 and hs-CRP and HCC and HEC may only emerge during advanced ageing and disorder processes, still the SII could be a promising candidate for detecting associations between inflammation and neurodegeneration in younger and healthy samples. Future work should examine these pathways in prospective longitudinal designs, for which the present investigation serves as a baseline.

Anxiety and depression are major side effects induced by currently available antiepileptic drugs; apart from this, they also diminish intelligence and language skills which cause hepatic failure, anemia, etc. Hence, in this study, we assessed antiepileptic effect of a phytochemical mangiferin. Epilepsy, a prevalent non communicable neurological disorder, affects infants and older population throughout the world. Epilepsy-induced comorbidities are more severe and if not treated cautiously lead to disability and even worse cases, mortality. The onset and duration of convulsion were observed. Seizure severity score was assessed by provoking kindling with 35 mg/kg PTZ. Prooxidants and antioxidants were measured to assess the antioxidant effect of mangiferin. Inflammatory markers were measured to determine the anti-inflammatory effect of mangiferin. The levels of neurotransmitters and ATPases were quantified to evaluate the neuroprotective effect of mangiferin. Mangiferin significantly decreased the onset and duration convulsion. It also decreased the seizure severity score, locomotor activity, and immobilization effectively. The excitatory neurotransmitter was reduced, and inhibitory neurotransmitter was increased in mice treated with mangiferin. Overall, our results confirm that mangiferin efficiently protects mice from PTZ-induced seizures. It can be subjected to further research to be prescribed as a potent antiepileptic drug.

Investigation on specific biomarkers for diagnostic or prognostic usage in mental diseases and especially bipolar disorder BD seems to be one outstanding field in current research. Serum neurofilament light (sNfL), a marker for neuro-axonal injury, is increased in various acute and chronic neurological disorders, but also neuro-psychiatric conditions, including affective disorders. The aim of our study was to determine a potential relation between a neuron-specific marker like sNfL and different clinical states of BD.

In the current investigation, 51 patients with BD and 35 HC were included. Mood ratings with the Hamilton depression scale (HAMD) and the Young mania rating scale (YMRS) have been included. Illness duration was defined as the period from the time of diagnosis out of self-report and medical records. sNFL was quantified by a commercial ultrasensitive single molecule array (Simoa).

There was a significant positive correlation between the number of manic episodes in the past and sNfL, controlled for age and duration of illness. (R = 0.49, p = 0.03) Depressive episodes were not associated to sNfL values. (R = 0.311, p = n.s.) Patients with >3 years of illness duration showed significantly higher levels of sNfL (M18.59; SD 11.89) than patients with shorter illness duration (M = 12.38, p = 0.03) and HC (M = 11.35, p = 0.02). Patients with <3 years of illness and HC did not differ significantly in sNfL levels.

Interestingly, individuals with BD and HC did not differ in sNFL levels in general. Nevertheless, looking at the BD cohort more specifically, we found that individuals with BD with longer duration of illness (>3 years) had higher levels of sNfL than those with an illness duration below 3 years. Our results confirm previous reports on the relation of neuro-axonal injury as evidenced by sNfL and illness specific variables in bipolar disorder. Further studies are needed to clarify if sNfL may predict the disease course and/or indicated response to treatment regimes.

: To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT).

: This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA.

: There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects.

: Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications.

Post-COVID-19 syndrome involves a variety of symptoms that last more than 12 weeks after COVID diagnosis. This study aimed to analyze post-COVID-19 syndrome among hospitalized COVID-19 patients 6 and 12 months after hospital discharge. This is an ambidirectional cohort study conducted with individuals who were discharged from three main hospitals in the capital of Mato Grosso State, Brazil, between October and December 2021 and January and March 2022. After data collection from medical records, the individuals were interviewed by telephone 6 and 12 months after hospital discharge, when they were asked about the presence of ongoing or new symptoms and when symptom frequency was evaluated according to sociodemographic and economic characteristics hospitalization, and health conditions. Of all 277 medical records evaluated, 259 patients were eligible to participate in the study, 190 patients six months after discharge and 160 patients 12 months after hospital discharge. At six months, 59% were female patients, 40% were aged 60 years or older, and 87.4% reported at least one symptom. At 12 months, 58.7% were female patients, 37.5% were aged 30 to 49 years, and 67.5% reported at least one symptom. Fatigue was the most common symptom 6 and 12 months after hospital discharge (55.3% and 40.6%, respectively), followed by memory problems (36.8%; 20%), and hair loss (26.8%; 11.2%). The prevalence of post-COVID-19 syndrome was higher among patients of older age, lower income, with hypertension, diabetes, and more severe infection during hospitalization. The risk factors for post-COVID-19 syndrome help understand the long-term effects and the importance of monitoring after the acute phase of the disease.

Persistent stress increases the probability for developing depression significantly thereafter. Repeated social defeat stress is a widely used model to investigate depressive-like behavior in preclinical models. Hence, the repeated social defeat stress model provided an ideal animal model, through which the hypotheses of prevention and treatment can be investigated. We have successfully induced depressive-like behavior for male C57BL/6J mice with this model. Here, we reported that certain level of during-stress social interactions with single female or multiple male peer(s) exerted a positive role in preventing the development of depressive-like behavior induced by repeated social defeat stress. Our data suggested that the stress-susceptible mice may benefit from positive social interaction, which reduces the chance for depressive-like behavior development. Since numerous studies indicate that the metabotropic glutamate receptor 5 (mGluR5) plays an important role in various cognitive functions, we further investigate the treatment effect of 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) on the depressive-like behavior induced by repeated social defeat stress. Most importantly, robust anti-depressant effects have been achieved through modulating the mGluR5 function. We found that single oral dose administration of CDPPB (20 mg/kg), to some extent, alleviated the social avoidance behaviors for the stress-susceptible mice. Our data implies that the CDPPB, a positive allosteric modulator of mGluR5, is a promising anti-depressant candidate with limited side effect.

This study evaluated clinical features of individuals with long COVID (5-8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P < 0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P < 0.001); anxiety-Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P = 0.0013); and "post-COVID sadness" (82.3% vs. 40.4%; P < 0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) (P < 0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination.

Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.

The global incidence of autoimmune diseases is on the rise, and many healthcare professionals believe that chronic stress plays a prominent role in both the aggravation and remission of these conditions. It is believed that prolonged exposure to stress is associated with neuroimmune axis malfunction, which eventually dysregulates multiple immunological factors as well as deregulates autoimmune responses that play a central role in various autoimmune diseases, including rheumatoid arthritis and psoriasis. Herein, we performed validation of an 8-week long rat model of chronic unpredictable stress (CUS) which consisted of exposing groups of rats to random stressors daily for 8 weeks. Additionally, we developed a novel rat model combining 8-week long random stressor-induced CUS with CIA-triggered arthritis and IMQ-triggered psoriasis and have successfully used both these models to assess the role of chronic stress in the aggravation of arthritis and psoriasis, respectively. Notably, the 8-week CUS protocol extensively aggravated and prolonged both arthritis and psoriasis condition in the rat model by upregulating the release of different pro-inflammatory cytokines, dysregulation of immune cell responses and oxidative stress system, which were all related to severe inflammation. Further, CUS aggravated macroscopic features and the increase in destruction of joint tissue and epidermal thickness induced by CIA and IMQ, respectively, in rats. In conclusion, this study suggests that exposure to an 8-week long CUS paradigm aggravates the distinctive characteristics of rheumatoid arthritis and psoriasis in rats via amplifying the inflammatory circuits and immune cell responses linked to these autoimmune diseases.