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Abstract: Background: Over 60% of patients with major depressive disorder (MDD) do not respond fully to therapy. Half of them eventually will not respond at all and will be referred to as treatment resistant depression (TRD) patients. Stressful life events were found to be associated with MDD and were also found to affect the course of the disease. We hypothesize that negative life events might be an independent risk factor for TRD. Methods: One hundred and seven unipolar MDD patients, all treated for at least 4 weeks, were enrolled in the study. Patients were assessed on their psychiatric and medical history, and seven categories of stressful life events. Results: 39.3% of participants were defined as TRD patients and 60.7% as non-TRD. TRD patients had more severe depression, more past suicide attempts, more hospitalizations, longer episodes, and received more benzodiazepines, antipsychotics, and ECT. Job loss and financial stress were more prevalent among the TRD group. Overall, the TRD patients had more negative life events than responders. Limitations: This is a retrospective study. In addition, the definition of TRD was done dichotomically, therefore the association between number of stressful life events and the degree of resistance was not tested. Conclusions: Job loss and financial distress were found to predict TRD. The loss of a parent and severe health conditions were not associated with TRD, suggesting that events affecting the development of MDD, do not necessarily affect the treatment outcome. [Copyright &y& Elsevier]

Background: The "Iron Swords" War beginning in October 2023 led to unprecedented levels of shock and trauma across Israel, significantly impacting the Israeli population and medical personnel. This study aimed to evaluate and compare the perceived personal resilience and sense of danger among physicians in hospitals located in different conflict zone proximities in Israel during this period. Methods: A quantitative, cross-sectional study was conducted from March to August 2024, during an active phase of the war, using a structured anonymous questionnaire. Participants were 161 physicians from three hospitals: one in southern Israel near the Gaza Strip, another in northern Israel near the borders with Lebanon, Syria, and Jordan, and a third in central Israel near Tel Aviv. The survey measured personal resilience using the Connor-Davidson Resilience Scale (CD-RISC-10) and sense of danger using the Solomon & Prager scale. Statistical analyses included Kruskal-Wallis H test, multiple linear regression, two-way analysis of variance (ANOVA), and Sobel test for mediation effects. Results: The final sample included 161 physicians (54 southern, 56 central, 51 northern). The mean resilience score was 31.14 ± 5.77, and the mean sense of danger score was 8.36 ± 4.15 (scales 0–40 and 0–20, respectively). Physicians in the southern hospital reported significantly higher sense of danger scores (p = 0.005). A trend towards lower resilience scores was noted among southern hospital physicians (p = 0.068) (p = 0.068). Two-way ANOVA revealed significant main effects of hospital location and gender on resilience (p = 0.046 and p = 0.003, respectively) and sense of danger (p = 0.005 and p = 0.062, respectively). Multiple regression analysis identified hospital location (β = -0.178, p = 0.023) and gender (β = 0.229, p = 0.004) as significant predictors of resilience. Mediation analysis indicated that personal resilience partially mediated the relationship between hospital location and sense of danger (indirect effect = 0.2896, p < 0.001). Conclusions: Physicians working near conflict zones report higher levels of perceived danger, though their resilience is comparable to peers in less threatened regions. Enhancing personal resilience is crucial to mitigate the heightened sense of danger. This could include regular resilience training, psychological support, and specific programs for single and childless physicians to improve safety perceptions. Additionally, fostering a supportive community with clear communication and robust emergency protocols is essential for enhancing staff resilience and safety in hospitals. [ABSTRACT FROM AUTHOR]

Background: Functional near-infrared spectroscopy (fNIRS) is being increasingly utilized to visualize the brain areas involved in cognitive activity to understand the human brain better. Its portability and easy setup give it an advantage over other functional brain imaging tools. The current study utilizes fNIRS while performing a Stroop test, which is commonly used to assess the impairment of information selection in depression. Aim: To compare cortical activation during the Stroop test in depressed individuals to healthy controls. Methods: This cross-sectional study compared oxyhemoglobin (OxyHb) concentration changes in 39 individuals with depression to 40 healthy individuals. The Stroop test was construed in an event-related design with an intertrial interval of 2 seconds with jitter. A continuous wave fNIRS system was used for recording the cortical activity at 17 locations. Analysis of fNIRS data was done using statistical parametric mapping (SPM) for estimating general linear model (GLM) coefficients. Further analysis of the mean change of OxyHb concentrations during the 2 seconds after the presentation of congruent and incongruent stimuli was done between the groups using Mann--Whitney U test corrected for multiple comparisons with Bonferroni correction. Results: While the number of errors and correct responses were similar between the groups, the reaction time for correct responses was more in the depression group in comparison to healthy individuals (t = -2.39, P = 0.01). For both healthy and depressive individuals in incongruent versus congruent task contrast, deactivation was seen in the region between the left middle frontal sulcus and frontopolar area of the brain (t = 0.41 and t = 0.21, respectively, P < 0.05). The depressed group had a higher mean change in OxyHb concentration following incongruent stimuli in comparison to the HCs (mean rank: HC = 32.63, depression = 47.56). Conclusion: Our findings indicate that individuals with depression exhibited prolonged reaction times and distinct activation patterns of the frontal cortex compared to healthy individuals. The observed pattern of brain activation for congruent and incongruent tasks among both healthy and depressed individuals aligns with the findings of the prior studies, emphasizing the utility of fNIRS as a valuable instrument for assessing brain activity. [ABSTRACT FROM AUTHOR]

Patients with health pathologies may exhibit psychological features in addition to medical symptomatology. A sample of 76 Italian women with an age range between 23 and 78 years old (mean = 50.22 ± 10.47 years) diagnosed with fibromyalgia (a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, cognitive and mood issues) was examined to identify typical characteristics of their psychological profile. All patients were administered a series of questionnaires, to assess avoidance of physical touch by others; anxiety; depression; risk of developing psychotic disorders; self-criticism and perfectionism; acceptance of chronic pain; general impact of the pathology on their lives, and the predisposition to experience positive emotional states. The scores resulting from this assessment were evaluated against the normative data. Patients with fibromyalgia showed psychological dysfunction in most of the scales administered, with a significantly higher disposition to experience compassion towards others (t = 5.94, df = 75, p < 0.001). A higher risk of psychosis was related with higher levels of depression (B = 0.49, t = 0.20, p = 0.015), poor involvement in daily activities (B = 0.41, t = 0.13, p = 0.002), touch avoidance (especially towards strangers, B = −0.20, t = 0.14, p = 0.01), and overall poor quality of life (B = 0.40, t = 0.16, p = 0.01). This study may broaden the possibility to evaluate psychological features in this clinical population; it may contribute to tailoring psychological care and related treatments in the context of health services. [ABSTRACT FROM AUTHOR]

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation. [ABSTRACT FROM AUTHOR]

Although youth and adults with obsessive-compulsive disorder (OCD) endorse elevated incidence of exposure to traumatic life events during childhood, the existing literature on adverse childhood experiences (ACEs) and OCD is mixed and studies focusing on pediatric OCD are limited. The present study examines the relationship between ACEs and OCD onset, symptom severity, negative cognitive patterns, comorbidity, and cognitive-behavioral therapy (CBT) response in 142 children and adolescents with OCD. ACEs were ascertained from parent reports. Most parents reported child exposure to ACEs. Out of the parents who reported ACEs, 50% reported ACE exposure prior to OCD diagnosis and 50% reported ACE exposure after OCD diagnosis. No significant associations between ACEs and comorbidity or CBT response were found, suggesting that CBT for pediatric OCD is effective regardless of ACE exposure. Family financial problems were associated with increased obsessive-compulsive symptom severity and negative thinking. Implications for research and practice are discussed. [ABSTRACT FROM AUTHOR]

Background: Physiotherapy plays a key role in managing fibromyalgia, a multifaceted disorder, through a combination of active and passive treatments. The purpose of this review is to compare the efficacy of "hands-off" treatments alone versus the combination of "hands-off" and "hands-on" therapies. Methods: MEDLINE (PubMed), CENTRAL, and Embase were searched. English-language randomized controlled trials involving adults with fibromyalgia were included. The included studies were divided into subgroups to reduce the possible heterogeneity. We calculated the standardized mean difference or mean difference with 95% confidence intervals for the continuous data according to the outcome measures. We used the risk ratio for dichotomous data of the drop-out rate of the studies. Results: We included and analyzed seven RCTs. The meta-analysis showed no significant results in the outcomes, pain, QoL, health status, and drop-out rate. We found significant results (p < 0.001) in favor of combining "hands-off" and "hands-on" treatments for the rest quality (SMD 0.72, 95% CI 0.35 to 1.09). Conclusions: This review increases the treatment options available for clinicians. Up to now, the main guidelines on managing fibromyalgia suggest only approaches based on "hands-off" treatments. These findings suggest that other approaches based on mixed interventions combining "hands-off" and "hands-on" treatments did not reduce the patient outcomes. Moreover, the mixed intervention led to better results for the patients' sleep quality than the "hands-off" treatments alone. [ABSTRACT FROM AUTHOR]

Aims: To investigate the relationships between depression symptoms, perceived stigma, disease severity, patient‐provider communication and medication adherence in fibromyalgia patients. The objectives were to explore how these factors influence treatment adherence and to develop a comprehensive model illustrating their interconnections. Background: Fibromyalgia is a chronic pain syndrome with fatigue, sleep issues and idiopathic pain. Medication adherence is limited by insufficient symptom relief, side effects and costs. Stigma further complicates fibromyalgia. Disease severity affects patient‐provider communication. Associations between depression, stigma, severity, communication and adherence in fibromyalgia are unclear. Design: A cross‐sectional, correlational study. Methods: The STROBE guidelines for cross‐sectional studies were followed. Participants included Hebrew‐speaking participants who were members of two Facebook groups: 'Shades of Purple' and 'Fibromyalgia‐ Get to Know!' Between February and April 2022. They undertook evaluations using The Patient Health Questionnaire‐9 to gauge depression symptoms, assessed perceived stigma, utilised The Revised Fibromyalgia Impact Questionnaire to determine disease severity, employed The Patient Reaction Assessment questionnaire for patient‐provider communication, and used the 8‐item Morisky Medication Adherence Scale (MMAS‐8). Associations between the variables were explored using Pearson's correlations and path analyses. Results: The study included 141 women with fibromyalgia, aged 22 to 76 years. Most reported having a stable partner (69.5%) and 75.2% had children. The treatment adherence levels were as follows: 53.2% (N = 75)—low, 33.3% (N = 47)—medium and 13.5% (N = 19)—high. Depression positively correlated with stigma. Stigma negatively correlated with patient‐provider communication. Patient‐provider communication positively correlated with treatment adherence. A significant negative indirect effect of depression on treatment adherence through stigma and patient‐provider communication was found. Conclusions: Perceived stigma and patient‐provider communication played a mediating role in the relationships between depression and treatment adherence among women with fibromyalgia. Relevance to Clinical Practice: Addressing stigma related to fibromyalgia and effective patient‐provider communication can positively influence treatment adherence. Patient or Public Contribution: No patient or public contribution. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a core feature of schizophrenia, playing a pivotal role in the pathogenesis and prognosis of this disorder. Cognitive impairment in schizophrenia encompasses a wide range of domains, including processing speed, episodic memory, working memory, and executive function. These deficits persist throughout the course of the illness and significantly impact functional outcomes and quality of life. Therefore, it is imperative to identify the biological basis of cognitive deficits in schizophrenia and develop effective treatments. The role of N-methyl-D-aspartate (NMDA) receptors in synaptic transmission and plasticity has long been recognized, making them potential targets for schizophrenia treatment. This review will focus on emerging pharmacology targeting NMDA receptors, offering strategies for the prevention and treatment of cognitive deficits in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: We carried out a systematic review of the medical literature on potential effects of caregiving on the health and well being of spouses of Fibromyalgia (FM) patients and pooled the results in a meta-analysis. Methods: The review is comprised of original studies that examined the mood states and well-being of husbands/wives, or long-term intimate partners, of FM patients. The authors searched the PubMed, Scopus, APA PsycNet and Web of Science databases using the key words "fibromyalgia and spouses," "fibromyalgia and partners," and "fibromyalgia and husbands." Of 570 papers that were initially identified using the search words, 18 papers were considered eligible. We used the Joanna Briggs Institute Critical Appraisal Checklist (JBICAC) and Critical Appraisal Skills Program (CASP) tools to assess the risk of bias in the analytical cross-sectional and qualitative studies, respectively. Results: The overall score in mood states was significantly higher among spouses of FM patients than among spouses of individuals without FM (SMD [95% CI] = 0.52 [0.30; 0.74]). The strongest evidence was found for depression, SMD [95% CI] = 0.68 [0.33; 1.03]. The overall standardized score of quality of life was significantly lower among spouses of FM patients, SMD [95% CI] = -0.59 [-0.79; -0.38], with significant differences in physical function and role, emotional role, and mental health subscales. Limitation: Limitation of this review is the scant number of studies that addressed several health domains, which made it impossible to carry out meta-analyses in these domains. Conclusion: Spouses of FM patients show the emotional and physical consequences of caregiving, and impaired quality of life. Addressing these problems can prevent deterioration of their health and improve their quality of life. [ABSTRACT FROM AUTHOR]

This paper advocates for considering disgust as a primary emotional system within Panksepp's Affective Neuroscience framework, which has the potential to improve the efficacy of psychotherapy with obsessive-compulsive disorder, hypochondriasis, and emetophobia. In 2007, Toronchuk and Ellis provided comprehensive evidence that DISGUST system, as they defined it, matched all Panksepp's criteria for a primary emotional system. A debate ensued and was not unambiguously resolved. This paper is an attempt to resume this discussion and supplement it with the data that accumulated since then on DISGUST's relationship with the immune system and the role of DISGUST dysregulation in psychopathology. We hope that renewed research interest in DISGUST has the potential to improve clinical efficacy with hard-to-treat conditions. [ABSTRACT FROM AUTHOR]

New-onset chronic musculoskeletal (MSK) pain (>3 months duration) is a common symptom of post-COVID-19 syndrome (PCS). This study aimed to characterise new-onset chronic MSK pain in patients with PCS and its overlap with Fibromyalgia Syndrome (FMS). We enrolled patients with new-onset chronic MSK pain post-COVID-19 and assessed the nature of the pain and associated symptoms using the C19-YRS (Yorkshire Rehabilitation Scale). The FMS assessment was conducted as part of a standard clinical examination using the American College of Rheumatology (ACR) 2010 criteria: (1) Widespread Pain Index (WPI) ≥ 7 and symptoms severity (SS) score ≥ 5, or WPI between 3 and 6 and SS score ≥ 9, (2) symptoms consistent for at least 3 months, and (3) no alternative diagnosis. Of the eighteen patients (average age 49.6 (SD 11.8) years; BMI 31.7 (SD 8.6)), twelve were female. The average symptom duration was 27.9 (SD 6.97) months post-infection. Thirteen patients (72.2%) met the FMS criteria, with an average WPI score of 8.8 and an average SS score of 8.2, indicating a high level of pain and significant quality of life impacts. These findings support the hypothesis that FMS may develop as a long-term sequela of a viral infection, underscoring the need for further research into post-viral long-term conditions. [ABSTRACT FROM AUTHOR]

For several decades, the dopamine hypothesis contributed to the discovery of numerous typical and atypical antipsychotics and was the sole hypothesis for the pathophysiology of schizophrenia. However, neither typical nor atypical antipsychotics, other than clozapine, have been effective in addressing negative symptoms and cognitive impairments, which are indices for the prognostic and disability outcomes of schizophrenia. Following the development of atypical antipsychotics, the therapeutic targets for antipsychotics expanded beyond the blockade of dopamine D2 and serotonin 5-HT2A receptors to explore the partial agonism of the D2 receptor and the modulation of new targets, such as D3, 5-HT1A, 5-HT7, and metabotropic glutamate receptors. Despite these efforts, to date, psychiatry has not successfully developed antipsychotics with antipsychotic properties proven to be superior to those of clozapine. The glutamate hypothesis, another hypothesis regarding the pathophysiology/pathomechanism of schizophrenia, was proposed based on clinical findings that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists, such as phencyclidine and ketamine, induce schizophrenia-like psychotic episodes. Large-scale genome-wide association studies (GWASs) revealed that approximately 30% of the risk genes for schizophrenia (the total number was over one hundred) encode proteins associated with glutamatergic transmission. These findings supported the validation of the glutamate hypothesis, which was inspired by the clinical findings regarding NMDAR antagonists. Additionally, these clinical and genetic findings suggest that schizophrenia is possibly a syndrome with complicated pathomechanisms that are affected by multiple biological and genetic vulnerabilities. The glutamate hypothesis has been the most extensively investigated pathophysiology/pathomechanism hypothesis, other than the dopamine hypothesis. Studies have revealed the possibility that functional abnormalities of the NMDAR play important roles in the pathophysiology/pathomechanism of schizophrenia. However, no antipsychotics derived from the glutamatergic hypothesis have yet been approved for the treatment of schizophrenia or treatment-resistant schizophrenia. Considering the increasing evidence supporting the potential pro-cognitive effects of glutamatergic agents and the lack of sufficient medications to treat the cognitive impairments associated with schizophrenia, these previous setbacks cannot preclude research into potential novel glutamate modulators. Given this background, to emphasize the importance of the dysfunction of the NMDAR in the pathomechanism and/or pathophysiology of schizophrenia, this review introduces the increasing findings on the functional abnormalities in glutamatergic transmission associated with the NMDAR. [ABSTRACT FROM AUTHOR]

Fibromyalgia is characterized by chronic widespread pain, fatigue, and sleep disturbances. Recent theories attribute fibromyalgia to central sensitization syndromes, suggesting altered nociceptive processing leads to hyperalgesia and allodynia. Standardized effective treatments are currently lacking. Palmitoylethanolamide and melatonin have shown pain-relieving effects in chronic pain conditions, including fibromyalgia, with excellent safety. Our open-label study assessed the impact of a daily combination of 1200 mg of palmitoylethanolamide and 0.2 mg of melatonin on pain, sleep, and quality of life in fibromyalgia patients. Between June 2023 and March 2024, 50 patients (2016 ACR criteria) were treated and evaluated at baseline, 1 month, 3 months, and 4 months (1 month discontinuation). The assessments included VAS for pain, ISI for insomnia, HAQ for health assessments, and a tender points evaluation. The patients, averaging 54.12 years old with a 3:1 female-to-male ratio, showed significant improvements in VAS, ISI, and HAQ scores relative to their own baselines and a reduction in tender points at 1 and 3 months, which was maintained at 4 months. No adverse events were reported. This study is the first to demonstrate the efficacy of a palmitoylethanolamide and melatonin combination as an adjunct therapy in fibromyalgia, highlighting its potential to reduce pain and improve sleep and quality of life. [ABSTRACT FROM AUTHOR]

Objective: Objective: The aim of this study was to investigate if psychache and hopelessness may serve as reliable predictors of suicidal ideation among female fibromyalgia (FM) patients. Method: This was a cross-sectional study of 50 women with FM, examining the relationship between psychological pain, hopelessness, depressive symptoms, and suicidal ideation. FM diagnosis was confirmed by the American College of Rheumatology (ACR) criteria. Demographic data, the Mini International Neuropsychiatric Interview (MINI 7.0.2), the Beck Depression Inventory-II (BDI-II), the Beck Hopelessness Scale (BHS), the Pittsburgh Sleep Quality Index (PSQI) and the Psychache Scale were utilized to assess these relationships and their predictive value for suicidality. Results: The mean age of the participants was 50.2 years (±8.7). Thirty-two (64%) patients had current major depression, 11 (22%) had bipolar disorder, 20 (40%) presented passive suicidal ideation and 14 (28%) presented active suicidal ideation. Psychological pain correlated with both depressive symptoms (p<0.01; r= 0.648) and hopelessness (p=0.029; r=0.312) but did not predict suicidal ideation. Logistic regression analyses revealed depressive symptom severity as a predictor of passive suicidal ideation (odds ratio = 1.486; 95% CI: 1.017 - 2.170), while hopelessness predicted active suicidal ideation (odd ratio = 1.356; 95% CI, 1.049 - 1.753). Conclusions: FM female patients showed increased prevalence of suicidal ideation. Hopelessness predicts active suicidal ideation but psychological pain did not serve as predictive factor for suicide ideation among female FM patients. [ABSTRACT FROM AUTHOR]

Although the pathophysiology of fibromyalgia syndrome has been better understood in recent decades, a unified model of its pathogenesis and an effective therapeutic approach are still far from being realized. The main aim of this article will be to delve into the fundamental mechanisms of the pathophysiology of fibromyalgia conceptualized as stress intolerance syndrome. Using the biopsychosocial model of chronic pain syndromes, we will describe the potential role of the attachment system, C-tactile fibers, and oxytocinergic system dysfunction in the pathophysiology of fibromyalgia syndrome and other central sensitivity syndromes. At the end of the article, the therapeutic implications of this new global and translational pathophysiological model will be briefly discussed. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) imposes a significant burden on patients and their families because of its high prevalence rate and disabling nature. Given the lack of definitive conclusions regarding its pathogenesis, physicians heavily rely on patients' subjective symptom descriptions for diagnosis because reliable diagnostic biomarkers are currently unavailable. The role of the inflammatory response in the pathogenesis of SCZ has been supported by some studies. The findings of these studies showed abnormal changes in the levels of inflammatory factors, such as cytokines (CKs), in both peripheral blood and cerebrospinal fluid (CSF) among individuals affected by SCZ. The findings imply that inflammatory factors could potentially function as risk indicators for the onset of SCZ. Consequently, researchers have directed their attention towards investigating the potential utility of CKs as viable biomarkers for diagnosing SCZ. Extracellular vesicles (EVs) containing disease-specific components exhibit remarkable stability and abundance, making them promising candidates for biomarker discovery across various diseases. CKs encapsulated within EVs secreted by immune cells offer valuable insights into disease progression. This review presents a comprehensive analysis summarizing the relationship between CKs and SCZ and emphasizes the vital role of CKs encapsulated within EVs in the pathogenesis and development of SCZ. [ABSTRACT FROM AUTHOR]

Background: Depression acts as a noteworthy worldwide public health challenge. Identifying accessible biomarkers is crucial for early diagnosis and intervention. The relationship between depression in adult Americans and the neutrophil to high-density lipoprotein cholesterol ratio (NHR) was investigated in this research. Methods: The relationship between NHR and depressive symptoms was analyzed utilizing National Health and Nutrition Examination Survey data from 2005 to 2018 and the Patient Health Questionnaire-9. The study included 33,871 participants with complete NHR and depression data. Adjusted multivariable logistic regression models were used to account for possible confounders, and subgroup analyses were conducted to investigate effect changes. Results: Elevated NHR levels were positively correlated with a heightened risk of depression (OR = 1.03, 95% CI: 1.01–1.05, P < 0.0005). After the NHR was divided into tertiles, those in the top tertile had an 18% higher chance of developing depression than those in the bottom tertile (OR = 1.18; 95% CI: 1.05–1.32; P for trend = 0.0041). Subgroup analyses revealed variations in this association based on race and marital status. Additionally, the relationship between NHR and depression demonstrated a U-shaped pattern, with a significant breakpoint identified at an NHR of 6.97. Conclusion: These results imply that the NHR may be a potential biomarker for depression risk, with implications for early detection and personalized treatment. Further research is needed to elucidate the mechanisms underlying the NHR-depression link and establish causality. [ABSTRACT FROM AUTHOR]

Background: Chronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI). Methods: Twenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity – plus event-related potential functional plasticity markers, captured via EEG. Discussion: The results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic action of psychedelic-therapy more broadly. It will also deliver essential data to inform the design of a potential subsequent RCT. [ABSTRACT FROM AUTHOR]

Background and Objectives: Fibromyalgia syndrome (FMS) is defined as a chronic pain syndrome that is characterized by widespread pain, tenderness, and diffuse stiffness. In addition, neuropsychological symptoms such as fatigue, sleep disorders, poor mood, cognitive impairment, and headaches are often reported. Many reports have addressed the coexistence of affective disorders and anxiety with FMS, yet few have focused on its association with obsessive compulsive disorder (OCD). We investigated the occurrence of classical patterns of OCD in participants with FMS and assessed their effect on pain perception and functional impairment. Material and Methods: The research population included 37 patients diagnosed with FMS, treated at the Rheumatology Clinic in the Sheba Medical Center, Tel-Hashomer, Israel. We used validated questionnaires including a demographic questionnaire, a questionnaire on average and maximal pain intensity, the Eysenck Personality Questionnaire-Revised (EPQ-R), the Perceived Stress Scale, the Pain Catastrophizing Scale, the Pain Obsessive questionnaire, and the Yale–Brown Obsessive Compulsive Scale (Y-BOCS). Results: Patients with FMS were found to have intrusive and obsessive thoughts regarding pain for several hours every day, causing a high degree of anxiety and high levels of pain, catastrophizing, and magnification, leading to helplessness and functional impairment. In total, 27% of the patients reported severe malfunction due to pain and pain ideation, and 49% demonstrated mild obsessive compulsive symptoms that were strongly correlated with pain intensity and functional impairment. Conclusions: Obsessive compulsive thinking patterns contribute to pain magnification and to the cognitive aspects of fibromyalgia syndrome. [ABSTRACT FROM AUTHOR]

Trace elements are essential for several physiological processes. To date, various data have suggested that inadequate levels of trace elements may be involved in the pathogenesis of different chronic diseases, including immune-mediated ones, or may develop during their course. Systemic sclerosis (SSc) is a complex autoimmune multisystemic disease, primarily characterized by microvascular dysregulation, the widespread activation of the immune system and tissue fibrosis. According to the latest reports regarding the pathogenesis of SSc, the main pathophysiological processes—inflammation, vasculopathy and fibrosis—may include various trace element derangements. The present literature review aims to update the available data regarding iron, zinc, copper and selenium status in SSc as well as to underline the possible implications of these trace elements in the complexity of the pathogenic process of the disease. We observe that the status of trace elements in SSc plays a crucial role in numerous pathogenic processes, emphasizing the necessity for proper monitoring and supplementation. The reported data are heterogenous and scarce, and future studies are needed in order to draw clearer conclusions about their complete spectrum. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to estimate fibromyalgia Syndrome (FMS) prevalence in diabetes mellitus (DM) patients and explore associated factors. Methods: A cross-sectional study was conducted from June 2023 to February 2024 at King Khalid University Hospital in Riyadh, Saudi Arabia, targeting DM patients aged 18 years and above. A non-probability sampling technique was utilized. Participants were screened for FMS using the Arabic fibromyalgia rapid screening tool. Results: A total of 224 participants were included. The prevalence of FMS was 12.5%. A significant gender disparity was observed to be greater in females (OR = 4.32, 95% CI: 1.63-13.2, p = 0.005). No significant correlation was found between FMS prevalence and HbA1c levels (p = 0.215). Moreover, the presence of diabetic complications, namely diabetic foot, was significantly associated with FMS (OR = 5.68, 95% CI: 1.57-20.5, p = 0.007). Noteworthy, a prior diagnosis with psychiatric illness showed higher odds of fibromyalgia (OR= 7.42, 95% CI: 1.88-31.1, p = 0.004) Conclusion: The study revealed a significant prevalence of FMS among DM patients in Riyadh, underscoring the need for healthcare professionals to incorporate FMS screening into routine diabetic care, particularly for females and those with diabetic complications. This approach would ensure a holistic management strategy for DM patients, potentially improving their quality of life. Further research is warranted to explore the mechanisms linking DM and FMS. [ABSTRACT FROM AUTHOR]

Fibromyalgia is a syndrome characterized by chronic widespread musculoskeletal pain, which may or may not be associated with muscle or joint stiffness, accompanied by other symptoms such as fatigue, sleep disturbances, anxiety, and depression. It is a highly prevalent condition globally, being considered the third most common musculoskeletal disorder, following lower back pain and osteoarthritis. It is more prevalent in women than in men, and although it can occur at any age, it is more common between the ages of thirty and thirty-five. Although the pathophysiology and etiopathogenesis remain largely unknown, three underlying processes in fibromyalgia have been investigated. These include central sensitization, associated with an increase in the release of both excitatory and inhibitory neurotransmitters; peripheral sensitization, involving alterations in peripheral nociceptor signaling; and inflammatory and immune mechanisms that develop concurrently with the aforementioned processes. Furthermore, it has been determined that genetic, endocrine, psychological, and sleep disorders may influence the development of this pathology. The accurate diagnosis of fibromyalgia remains challenging as it lacks specific diagnostic biomarkers, which are still under investigation. Nonetheless, diagnostic approaches to the condition have evolved based on the use of scales and questionnaires for pain identification. The complexity associated with this pathology makes it difficult to establish a single effective treatment. Therefore, treatment is multidisciplinary, involving both pharmacological and non-pharmacological interventions aimed at alleviating symptoms. The non-pharmacological treatments outlined in this review are primarily related to physiotherapy interventions. The effectiveness of physical exercise, both on land and in water, as well as the application of electrotherapy combined with transcranial therapy and manual therapy has been highlighted. All of these interventions aim to improve the quality of life of patients highly affected by fibromyalgia. [ABSTRACT FROM AUTHOR]

Introduction: Post-traumatic stress disorder (PTSD) is a psychiatric disorder triggered by exposure to a life-threatening or sexually violent traumatic event, and is characterized by symptoms involving intrusive re-experiencing, persistent avoidance of associated stimuli, emotional and cognitive disturbances, and hyperarousal for long periods after the trauma has occurred. These debilitating symptoms induce occupational and social impairments that contribute to a significant clinical burden for PTSD patients, and substantial socioeconomic costs, reaching approximately $20,000 dollars per individual with PTSD each year in the US. Despite increased translational research focus in the field of PTSD, the development of novel, effective pharmacotherapies for its treatment remains an important unmet clinical need. Observations: In this review, we summarize the evidence implicating dysfunctional activity of the amygdala in the pathophysiology of PTSD. We identify the transient receptor potential canonical (TRPC) ion channels as promising drug targets given their distribution in the amygdala, and evidence from animal studies demonstrating their role in fear response modulation. We discuss the evidence-based pharmacotherapy and psychotherapy treatment approaches for PTSD. Discussion: In view of the prevalence and economic burden associated with PTSD, further investigation is warranted into novel treatment approaches based on our knowledge of the involvement of brain circuitry and the role of the amygdala in PTSD, as well as the potential added value of combined pharmacotherapy and psychotherapy to better manage PTSD symptoms. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to examine the potential influence of RS4680 (COMT), RS16965628 (SLC6A4), and RS1019385 (GRIN2B) polymorphisms on the therapeutic response to repetitive transcranial magnetic stimulation (rTMS) and selective serotonin reuptake inhibitors (SSRIs) in individuals with obsessivecompulsive disorder (OCD). Patients and methods: Thirty-six untreated outpatients diagnosed with OCD were recruited and allocated to active or sham rTMS groups for two weeks. The mean age of the participants was 31.61, with 17 males (47.22%) and 19 females (52.78%). Peripheral blood samples (5 mL) were collected from each participant using ethylenediaminetetraacetic acid (EDTA) vacuum tubes for genotyping purposes, clinical evaluation was taken place at baseline and second week. Results: The A allele of RS4680, C allele of RS16965628, and GG allele of RS1019385 were identified as potential bio-markers for predicting treatment response to OCD treatments (rTMS & SSRIs). Conclusion: Those genes may serve as bio-markers for the combined treatment of rTMS and SSRIs in OCD. The finding hold promise for further research and the potential implementation of precision treatment of OCD. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR1900023641. [ABSTRACT FROM AUTHOR]

Fibromyalgia and osteoarthritis are among the most prevalent rheumatic conditions worldwide. Nonpharmacological interventions have gained scientific endorsements as the preferred initial treatments before resorting to pharmacological modalities. Repetitive transcranial magnetic stimulation (rTMS) is among the most widely researched neuromodulation techniques, though it has not yet been officially recommended for fibromyalgia. This review aims to summarize the current evidence supporting rTMS for treating various fibromyalgia symptoms. Recent findings: High-frequency rTMS directed at the primary motor cortex (M1) has the strongest support in the literature for reducing pain intensity, with new research examining its long-term effectiveness. Nonetheless, some individuals may not respond to M1-targeted rTMS, and symptoms beyond pain can be prominent. Ongoing research aims to improve the efficacy of rTMS by exploring new brain targets, using innovative stimulation parameters, incorporating neuronavigation, and better identifying patients likely to benefit from this treatment. Summary: Noninvasive brain stimulation with rTMS over M1 is a well-tolerated treatment that can improve chronic pain and overall quality of life in fibromyalgia patients. However, the data are highly heterogeneous, with a limited level of evidence, posing a significant challenge to the inclusion of rTMS in official treatment guidelines. Research is ongoing to enhance its effectiveness, with future perspectives exploring its impact by targeting additional areas of the brain such as the medial prefrontal cortex, anterior cingulate cortex, and inferior parietal lobe, as well as selecting the right patients who could benefit from this treatment. [ABSTRACT FROM AUTHOR]

Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune diseases seem to be particularly correlated with depressive comorbidity, raising the question of their possible common pathomechanism. The PubMed database was searched, focusing on results published after 2016. A particular reciprocal correlation of depressive disorders with psoriasis, atopic dermatitis, alopecia areata, impetigo, lupus and systemic scleroderma was found. One possible explanation for the co-occurrence of the above diseases is that the inflammatory theory may be applicable to depression, the various elements of which also apply to autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular level. We aimed to examine the effects of typical and atypical antipsychotics on human iPSC-derived neural progenitor cells (NPCs). Methods: Proliferation and neurite outgrowth were measured by live cell imaging, and gene expression levels related to neuronal identity were analyzed by RT-QPCR and immunocytochemistry during differentiation into hippocampal dentate gyrus granule cells following treatment of low- and high-dose antipsychotics (haloperidol, olanzapine, and risperidone). Results: Antipsychotics did not modify the growth properties of NPCs after 3 days of treatment. However, the characteristics of neurite outgrowth changed significantly in response to haloperidol and olanzapine. After three weeks of differentiation, mRNA expression levels of the selected neuronal markers increased (except for MAP2), while antipsychotics caused only subtle changes. Additionally, we found no changes in MAP2 or GFAP protein expression levels as a result of antipsychotic treatment. Conclusions: Altogether, antipsychotic medications promoted neurogenesis in vitro by influencing neurite outgrowth rather than changing cell survival or gene expression. This study provides insights into the effects of antipsychotics on neuronal differentiation and highlights the importance of considering neurite outgrowth as a potential target of action. [ABSTRACT FROM AUTHOR]

To investigate the association between three selected pain polymorphisms and clinical, functional, sensory-related, psychophysical, psychological or cognitive variables in a sample of women with fibromyalgia (FMS). One hundred twenty-three (n = 123) women with FMS completed demographic (age, height, weight), clinical (years with pain, intensity of pain at rest and during daily living activities), functional (quality of life, physical function), sensory-related (sensitization-associated and neuropathic-associated symptoms), psychophysical (pressure pain thresholds), psychological (sleep quality, depressive and anxiety level) and cognitive (pain catastrophizing, kinesiophobia) variables. Those three genotypes of the OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 single nucleotide polymorphisms were obtained by polymerase chain reactions from no-stimulated whole saliva collection. No significant differences in demographic, clinical, functional, sensory-related, psychophysical, psychological and cognitive variables according to OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680 genotype were identified in our sample of women with FMS. A multilevel analysis did not either reveal any significant gene-to-gene interaction between OPRM1 rs1799971 x HTR1B rs6296, OPRM1 rs1799971 x COMT rs4680 and HTR1B rs6296 x COMT rs4680 for any of the investigated outcomes. This study revealed that three single nucleotide polymorphisms, OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680, mostly associated with chronic pain were not involved in phenotyping features of FMS. Potential gene-to-gene interaction and their association with clinical phenotype in women with FMS should be further investigated in future studies including large sample sizes. [ABSTRACT FROM AUTHOR]

Background. Primary Sjögren's syndrome (pSS) is recognized for its autoimmune origin. Its hallmark symptoms, dry eyes and mouth, result from glandular inflammation. Prior literature indicates that pSS not only affects the peripheral system but also involves the central nervous system (CNS), giving rise to various neuropsychiatric symptoms. However, there is limited published research on the psychiatric comorbidities in individuals with pSS. Methods. A comprehensive search was conducted on PubMed and Google Scholar for this narrative review. The search spanned from inception until August 2023. Its aim was to locate studies focusing on the psychiatric manifestations of pSS and the potential underlying mechanisms. Results. The most commonly reported psychiatric complications among these individuals are depression and cognitive dysfunction. Other psychiatric manifestations that have been reported in pSS individuals include anxiety, sleep disorders, psychosis, catatonia, bipolar disorder, and obsessive‐compulsive disorder. Conclusion. In conclusion, patients with pSS often display multiple psychiatric symptoms. These symptoms can significantly impair functioning and reduce quality of life. Hence, prompt diagnosis and management are crucial. [ABSTRACT FROM AUTHOR]

Background/Aim: Fibromyalgia (FM) is a complex and debilitating condition that significantly impacts patients' daily lives. The continuous assessment of the impact and severity of FM is essential to manage the condition effectively. Assessment tools in Arabic are lacking for use in Saudi Arabia, which might lead to ineffective management. This study aimed to translate and cross-culturally adapt and validate the Arabic version of the Revised Fibromyalgia Impact Questionnaire (FIQR). Methods: Following translation guidelines, 2 Arabic translators and 2 English-certified translators performed forward and backward translations of the FIQR. In a cross-sectional study design, the questionnaire was piloted with 5 participants and then subjected to cognitive interviews and psychometric analysis. Participants were FM patients recruited from a University Hospital in Riyadh and FM support groups in Saudi Arabia. The internal consistency, and reliability using the Cronbach α and interclass correlation coefficient (ICC) of 2-week test–retest, and criterion validity were evaluated. Results: The results included a total of 42 participants with FM. Six minor modifications were made during the stepwise translation of the questionnaire. The Arabic version of the FIQR had good internal consistency and test–retest reliability, with a Cronbach α of 0.855 for the physical functioning domain, 0.663 for overall well-being, 0.803 for symptoms, and 0.895 for the total FIQR, and the Pearson correlation coefficient of the ICC for physical functioning was 0.769 (95% confidence interval (CI), 0.541– 0.884) for the overall well-being domain, 0.555 (95% CI, 0.129– 0.772) for the symptoms domain, and 0.720 (95% CI, 0.370– 0.868) and 0.794 (95% CI, 0.579– 0.899) for the total FIQR score (p < 0.001), respectively. Conclusion: The Arabic version of the FIQR is a valid, reliable, and practical tool for assessing the impact of FM on Arabic-speaking patients and potentially contributing to the improvement of FM outcomes. [ABSTRACT FROM AUTHOR]

Background: Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms. Methods: In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006–2010, age = 55.0 ± 7.5 [40–70] years; second visit: 2014–2019; age = 62.7 ± 7.5 [44–80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and depressive symptoms on the second visit among 138 multimodal imaging phenotypes. Results: Longitudinal data were consistent with significant bidirectional causal relationship between SLEs and depressive symptoms. In cross-sectional analyses, SLEs were significantly associated with lower bilateral nucleus accumbal volume and lower fractional anisotropy of the forceps major. Depressive symptoms were significantly associated with extensive white matter hyperintensities, thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures. Lower bilateral nucleus accumbal volume were the only imaging phenotypes with overlapping effects of depressive symptoms and SLEs (B = −0.032 to −0.023, p = 0.006–0.034). Depressive symptoms and SLEs significantly partially mediated the effects of each other on left and right nucleus accumbens volume (proportion of effects mediated = 12.7–14.3%, p < 0.001− p = 0.008). For the left nucleus accumbens, post-hoc seed-based analysis showed lower resting-state functional connectivity with the left orbitofrontal cortex (cluster size = 83 voxels, p = 5.4 × 10−5) in participants with high v. no SLEs. Conclusions: The nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Both genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA. Methods: A total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions. Results: Four tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071–2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515–3.379, P < 0.001), and negative cognition (OR = 2.252, 95%CI: 1.264–4.013, P = 0.006) were all independently associated with SA in patients with MDD. Furthermore, GMDR analysis indicated a significant interaction between HTR2A rs3125 and negative life events. Negative life events in conjunction with the HTR2A rs3125 CG + GG genotype were associated with a higher SA risk in patients with MDD when compared to the absence of negative life events in conjunction with the CC genotype (OR = 2.547, 95% CI: 1.264–5.131, P = 0.009). Conclusion: Several risk factors and a potential interaction between HTR2A rs3125 and negative life events were identified in patients with SA and MDD. The observed interaction likely modulates the risk of MDD and SA, shedding light on the pathogenesis of SA in patients with MDD. [ABSTRACT FROM AUTHOR]

Studies investigating the association between IL-6/IL-6R axis and schizophrenia (SZ) susceptibility found inconsistent data. To reconcile the results, a systematic review followed by a meta-analysis was performed to assess the associations. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in July 2022 using electronic databases PubMed, EBSCO, Science Direct, PsychInfo, and Scopus. Study quality was assessed by the Newcastle–Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Fifty-eight studies were identified, including 4,200 SZ patients and 4,531 controls. Our meta-analysis results showed an increase of IL-6 levels in plasma, serum, or CSF and decreased IL-6R levels in serum in patients under treatment. Further studies are needed to better elucidate the correlation between the IL-6/IL-6R axis and the schizophrenia. [ABSTRACT FROM AUTHOR]

The encounter between torture victims and the legal system is mostly dismissive. Thus, victims have repeatedly submitted complaints regarding alleged torture to the relevant authorities, but these cases are often rejected. A common reason for rejection is the inconsistency within and between testimonies, which can give the impression that the victim is fabricating the story and then undermines the legal case. This paper reviews the reasons that could explain the disparities in the testimonies of torture survivors. It relates to six facets that, taken together, increase the likelihood of inconsistency: (a) detention and interrogation, (b) flaws in normal memory, (c) psychological processes, (d) physical/medical aspects, (e) sociocultural factors, and (f) interview barriers. Examples are provided for each of these reasons for the discrepancy in testimonies. A discussion of the relevance in the field of psychological injury follows this. The study provides recommendations for legal and medical experts working with torture and other traumatized victims regarding the use of the Istanbul Protocol, collaboration, and education to enhance understanding, clarify inconsistencies in testimonies, and support cases in court. [ABSTRACT FROM AUTHOR]

Background: Following exposure to traumatic stress, women are twice as likely as men to develop mood disorders. Yet, individual responses to such stress vary, with some people developing stress-induced psychopathologies while others exhibit resilience. The factors influencing sex-related disparities in affective disorders as well as variations in resilience remain unclear; however, emerging evidence suggests differences in the gut microbiota play a role. In this study, using the single prolonged stress (SPS) model of post-traumatic stress disorder, we investigated pre- and post-existing differences in microbial composition, functionality, and metabolites that affect stress susceptibility or resilience in each sex. Methods: Male and female Sprague–Dawley rats were randomly assigned to control or SPS groups. Two weeks following SPS, the animals were exposed to a battery of behavioral tests and decapitated a day later. Based on their anxiety index, they were further categorized as SPS-resilient (SPS-R) or SPS-susceptible (SPS-S). On the day of dissection, cecum, and selected brain tissues were isolated. Stool samples were collected before and after SPS, whereas urine samples were taken before and 30 min into the SPS. Results: Before SPS exposure, the sympathoadrenal axis exhibited alterations within male subgroups only. Expression of tight junction protein claudin-5 was lower in brain of SPS-S males, but higher in SPS-R females following SPS. Across the study, alpha diversity remained consistently lower in males compared to females. Beta diversity revealed distinct separations between male and female susceptible groups before SPS, with this separation becoming evident in the resilient groups following SPS. At the genus level, Lactobacillus, Lachnospiraceae_Incertae_Sedis, and Barnesiella exhibited sex-specific alterations, displaying opposing abundances in each sex. Additionally, sex-specific changes were observed in microbial predictive functionality and targeted functional modules both before and after SPS. Alterations in the microbial short-chain fatty acids (SCFAs), were also observed, with major and minor SCFAs being lower in SPS-susceptible males whereas branched-chain SCFAs being higher in SPS-susceptible females. Conclusion: This study highlights distinct pre- and post-trauma differences in microbial composition, functionality, and metabolites, associated with stress resilience in male and female rats. The findings underscore the importance of developing sex-specific therapeutic strategies to effectively address stress-related disorders. Highlights SPS model induces divergent anxiety and social behavioral responses to traumatic stress in both male and female rodents. SPS-resilient females displayed less anxiety-like behavior and initiated more interactions towards a juvenile rat than SPS-resilient males. Sex-specific pre-existing and SPS-induced differences in the gut microbial composition and predictive functionality were observed in susceptible and resilient rats. SPS-resilient males displayed elevated cecal acetate levels, whereas SPS-susceptible females exhibited heightened branched-chain SCFAs. Plain language summary: After experiencing traumatic stress, women are more likely than men to develop mood disorders like anxiety and depression. However, people's responses to trauma vary—some develop mental health issues while others remain resilient. Recent research suggests that the bacteria in the gut might play a role in these differences. In this study, using a rat model of post-traumatic stress disorder (PTSD), we investigated whether there are differences in gut bacteria between male and female rats before and after stress exposure. The study involved two groups of rats—one not exposed to stress (control) and the other exposed to a traumatic event (stressed). The rats' behavior was evaluated using different tests to determine who among the males and females were vulnerable to stress and who were resilient. We found that even before the stress, there were differences in the types of bacteria and their functions in the guts of male and female rats. These differences were also linked to how they responded to stress. Interestingly, the bacteria that were more abundant in resilient males were found to be more abundant in vulnerable females. Additionally, the traumatic stress affected these bacteria and the substances they produce differently in males and females. In essence, our study demonstrates that the types of gut bacteria, their functions, and their products contribute to stress resilience in different ways for male and female rats. This insight suggests that tailored treatments specifically targeting these differences could be specially effective in treating stress-related issues. [ABSTRACT FROM AUTHOR]

Background: Premenstrual Syndrome (PMS) is a common public health issue affecting many women of reproductive age worldwide. This study has been designed to investigate of computer-based stress inoculation training (SIT) counseling approach on anxiety, depression, and stress of university students with PMS. Methods: A randomized trial study with two parallel arms was done from 30 October 2022 to 21 June 2023 on 100 university students aged 18 to 38 at Babol University of Medical Sciences. The participants were randomly divided into two groups intervention and control. The data collection tools included questionnaires on demographic-fertility characteristics, the Premenstrual Symptoms Screening Tool (PSST), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale (PSS-14), the Sheehan Disability Scale (SDS) and Riff’s Psychological Well-being Scale (RPWS). The data were assessed using chi-square, t-student, ANOVA repeated measure, and linear regression tests. A significance level of P < 0.05 was considered for the analysis. Results: The results of the study showed that the SIT interventions decreased the PMS severity and most psychological factors so in the intervention group, SIT was able to significantly reduce anxiety, depression, perceived stress, and Sheehan’s disability after intervention (P < 0.001). Based on multiple linear regression analysis, the most predictors of HADS were the PSS and SDS (β = 0.285, p = 0.009 and β = 0.236, p = 0.024, respectively). Conclusion: The computer-based SIT counseling approach could reduce the severity of symptoms and psychological factors in students. Therefore, SIT intervention is recommended to manage their PMS. Trial registration: IRCT20230130057274N2. [ABSTRACT FROM AUTHOR]