Pub Date : 2025-08-01Epub Date: 2025-06-21DOI: 10.1016/j.cpnec.2025.100309
Marina Saskovets , Mykhailo Lohachov , Zilu Liang
Background
Sound is a powerful cue that can influence emotional and physiological states. While musical sounds have been widely studied for their stress-reducing effects, less attention has been given to the role of paralanguage. This study investigates whether a soothing vocal intonation beyond its semantic content can facilitate stress recovery by modulating neurophysiological and biochemical stress markers.
Methods
Thirty-five participants underwent a standardized stress induction task before being exposed to one of three conditions: a soothing voice narration, a robotic voice narration, or silence. Prefrontal cortex (PFC) hemodynamic activity was recorded using functional near-infrared spectroscopy (fNIRS), while stress biomarkers, including salivary cortisol and electrodermal activity (EDA), were measured at multiple time points. The Laterality Index Response (LIR) was computed to assess stress-related cortical asymmetry.
Results
Stress induction significantly increased cortisol levels, EDA, and right-lateralized PFC activation across all groups. During the recovery phase, the soothing voice group demonstrated a significantly faster cortisol reduction compared to both control groups. fNIRS data revealed distinct PFC hemodynamic patterns, with the soothing voice condition shifting activation toward Brodmann areas 45 and 9. However, EDA recovery patterns did not differ significantly across groups.
Conclusion
These findings highlight the potential of paralanguage, specifically soothing voice intonation, in accelerating physiological stress recovery. The observed modulation of cortisol and PFC activity suggests that auditory interventions incorporating emotional prosody could enhance stress regulation strategies. Future research should explore individual differences in response to paralanguage-based interventions and their broader clinical applications.
{"title":"Paralanguage as a tool for shaping stress response in Listeners: Multimodal physiological sensing study","authors":"Marina Saskovets , Mykhailo Lohachov , Zilu Liang","doi":"10.1016/j.cpnec.2025.100309","DOIUrl":"10.1016/j.cpnec.2025.100309","url":null,"abstract":"<div><h3>Background</h3><div>Sound is a powerful cue that can influence emotional and physiological states. While musical sounds have been widely studied for their stress-reducing effects, less attention has been given to the role of paralanguage. This study investigates whether a soothing vocal intonation beyond its semantic content can facilitate stress recovery by modulating neurophysiological and biochemical stress markers.</div></div><div><h3>Methods</h3><div>Thirty-five participants underwent a standardized stress induction task before being exposed to one of three conditions: a soothing voice narration, a robotic voice narration, or silence. Prefrontal cortex (PFC) hemodynamic activity was recorded using functional near-infrared spectroscopy (fNIRS), while stress biomarkers, including salivary cortisol and electrodermal activity (EDA), were measured at multiple time points. The Laterality Index Response (LIR) was computed to assess stress-related cortical asymmetry.</div></div><div><h3>Results</h3><div>Stress induction significantly increased cortisol levels, EDA, and right-lateralized PFC activation across all groups. During the recovery phase, the soothing voice group demonstrated a significantly faster cortisol reduction compared to both control groups. fNIRS data revealed distinct PFC hemodynamic patterns, with the soothing voice condition shifting activation toward Brodmann areas 45 and 9. However, EDA recovery patterns did not differ significantly across groups.</div></div><div><h3>Conclusion</h3><div>These findings highlight the potential of paralanguage, specifically soothing voice intonation, in accelerating physiological stress recovery. The observed modulation of cortisol and PFC activity suggests that auditory interventions incorporating emotional prosody could enhance stress regulation strategies. Future research should explore individual differences in response to paralanguage-based interventions and their broader clinical applications.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100309"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-05-12DOI: 10.1016/j.cpnec.2025.100299
Ruolin Zhu , Lu Wang , Xingqi Wu , Kai Wang
Sleep difficulties are common and often precede depressive disorders. We aimed to explore the associations between systemic inflammatory markers and depression risk in individuals with difficulty sleeping. We utilized data from the National Health and Nutrition Examination Survey (NHANES, 2005–2020), encompassing 7916 participants who reported having difficulty sleeping. The systemic inflammation response index (SIRI) and neutrophil‒platelet ratio (NPR) were calculated using peripheral blood cell counts. Odds ratios (ORs) and 95 % confidence intervals (CIs) of the SIRI/NPR for depression risk were calculated via logistic regression models. Restricted cubic spline (RCS) analysis was used to examine the dose‒response relationships between these indices and depression risk, whereas receiver-operating characteristic (ROC) analysis was used to evaluate their prognostic accuracy for depression risk. Participants in the highest SIRI and NPR quartile groups had significantly greater depression risk than those in the lowest quartile group did (OR (SIRI): 1.50, 95 % CI = 1.10–2.04; OR (NPR): 1.49, 95 % CI = 1.04–2.13). Subgroup analyses revealed consistent associations across different demographics and clinical subgroups. RCS analyses revealed a nonlinear association between depression risk and the SIRI (J-shaped, P nonlinearity <0.001) but not the NPR (P nonlinearity >0.05). ROC analysis revealed moderate discriminative ability for both the SIRI (AUC = 0.66, 95 % CI = 0.64–0.68) and the NPR (AUC = 0.65, 95 % CI = 0.63–0.67) in predicting depression among individuals with difficulty sleeping. These findings suggest that the SIRI and NPR are independently associated with increased depression risk among individuals with difficulty sleeping.
睡眠困难是常见的,通常先于抑郁症。我们的目的是探索全身性炎症标志物与睡眠困难个体抑郁风险之间的关系。我们使用了国家健康和营养检查调查(NHANES, 2005-2020)的数据,其中包括7916名报告睡眠困难的参与者。利用外周血细胞计数计算全身炎症反应指数(SIRI)和中性粒细胞-血小板比率(NPR)。通过logistic回归模型计算抑郁风险的SIRI/NPR的比值比(ORs)和95%置信区间(CIs)。使用限制性三次样条(RCS)分析来检验这些指标与抑郁风险之间的剂量-反应关系,而使用受试者工作特征(ROC)分析来评估它们对抑郁风险的预后准确性。最高SIRI和NPR四分位数组的参与者抑郁风险显著高于最低四分位数组(OR (SIRI): 1.50, 95% CI = 1.10-2.04;Or (npr): 1.49, 95% ci = 1.04-2.13)。亚组分析揭示了不同人口统计学和临床亚组之间的一致关联。RCS分析显示抑郁风险与SIRI呈非线性相关(j形,P非线性>; 0.001),而与NPR无非线性相关(P非线性>;0.05)。ROC分析显示,SIRI (AUC = 0.66, 95% CI = 0.64-0.68)和NPR (AUC = 0.65, 95% CI = 0.63-0.67)在预测睡眠困难个体抑郁方面具有中等判别能力。这些发现表明,在睡眠困难的个体中,SIRI和NPR与抑郁风险增加独立相关。
{"title":"Systemic inflammatory indices and the risk of depression in individuals with sleep difficulties: A cohort study based on NHANES 2005–2020","authors":"Ruolin Zhu , Lu Wang , Xingqi Wu , Kai Wang","doi":"10.1016/j.cpnec.2025.100299","DOIUrl":"10.1016/j.cpnec.2025.100299","url":null,"abstract":"<div><div>Sleep difficulties are common and often precede depressive disorders. We aimed to explore the associations between systemic inflammatory markers and depression risk in individuals with difficulty sleeping. We utilized data from the National Health and Nutrition Examination Survey (NHANES, 2005–2020), encompassing 7916 participants who reported having difficulty sleeping. The systemic inflammation response index (SIRI) and neutrophil‒platelet ratio (NPR) were calculated using peripheral blood cell counts. Odds ratios (ORs) and 95 % confidence intervals (CIs) of the SIRI/NPR for depression risk were calculated via logistic regression models. Restricted cubic spline (RCS) analysis was used to examine the dose‒response relationships between these indices and depression risk, whereas receiver-operating characteristic (ROC) analysis was used to evaluate their prognostic accuracy for depression risk. Participants in the highest SIRI and NPR quartile groups had significantly greater depression risk than those in the lowest quartile group did (OR (SIRI): 1.50, 95 % CI = 1.10–2.04; OR (NPR): 1.49, 95 % CI = 1.04–2.13). Subgroup analyses revealed consistent associations across different demographics and clinical subgroups. RCS analyses revealed a nonlinear association between depression risk and the SIRI (J-shaped, P nonlinearity <0.001) but not the NPR (P nonlinearity >0.05). ROC analysis revealed moderate discriminative ability for both the SIRI (AUC = 0.66, 95 % CI = 0.64–0.68) and the NPR (AUC = 0.65, 95 % CI = 0.63–0.67) in predicting depression among individuals with difficulty sleeping. These findings suggest that the SIRI and NPR are independently associated with increased depression risk among individuals with difficulty sleeping.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100299"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-07-08DOI: 10.1016/j.cpnec.2025.100311
Yasmine Zerroug , Marie-France Marin , Mara Brendgen , Miriam Beauchamp , Jean R. Séguin , Sylvana M. Côté , Catherine M. Herba
From adolescence onwards, internalizing symptoms, such as depressive and anxiety symptoms, are twice as prevalent in adolescent girls than boys. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which controls production and regulation of glucocorticoids (cortisol and cortisone), is linked to depressive and anxiety symptoms. Findings on hair cortisol, cortisone and the cortisol/cortisone ratio in relation to these symptoms have been inconsistent, particularly in adolescent community samples. The ratio provides an indication of the active versus inactive balance of cortisol concentrations, as a proxy of 11-beta-hydroxysteroid dehydrogenase enzymes. In addition, few studies have investigated whether these associations are the same for adolescent girls and boys. Hair samples of 64 adolescent girls and 59 adolescent boys (aged between 14 and 15 years old) were analyzed using the liquid chromatography-mass spectrometry (LC-MS) extraction method. Internalizing symptoms were measured via validated self-reported online questionnaires. For adolescent boys, no associations between hair glucocorticoids and depressive or anxiety symptoms were found. For adolescent girls, the analyses revealed a positive association between hair cortisone concentrations and depressive symptoms. Our findings highlight significant sex differences in the mechanisms that might operate between glucocorticoid concentrations and internalizing symptoms. Future longitudinal studies could test the predictive, sex-dependent effect of hair glucocorticoids concentrations during adolescence on the development of internalizing disorders in adulthood. Gaining a deeper understanding of HPA axis functioning could help to identify youth who are at greater risk of developing stress-related psychopathologies.
{"title":"Sex differences in associations between hair glucocorticoids and internalizing symptoms in adolescents","authors":"Yasmine Zerroug , Marie-France Marin , Mara Brendgen , Miriam Beauchamp , Jean R. Séguin , Sylvana M. Côté , Catherine M. Herba","doi":"10.1016/j.cpnec.2025.100311","DOIUrl":"10.1016/j.cpnec.2025.100311","url":null,"abstract":"<div><div>From adolescence onwards, internalizing symptoms, such as depressive and anxiety symptoms, are twice as prevalent in adolescent girls than boys. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which controls production and regulation of glucocorticoids (cortisol and cortisone), is linked to depressive and anxiety symptoms. Findings on hair cortisol, cortisone and the cortisol/cortisone ratio in relation to these symptoms have been inconsistent, particularly in adolescent community samples. The ratio provides an indication of the active versus inactive balance of cortisol concentrations, as a proxy of 11-beta-hydroxysteroid dehydrogenase enzymes. In addition, few studies have investigated whether these associations are the same for adolescent girls and boys. Hair samples of 64 adolescent girls and 59 adolescent boys (aged between 14 and 15 years old) were analyzed using the liquid chromatography-mass spectrometry (LC-MS) extraction method. Internalizing symptoms were measured via validated self-reported online questionnaires. For adolescent boys, no associations between hair glucocorticoids and depressive or anxiety symptoms were found. For adolescent girls, the analyses revealed a positive association between hair cortisone concentrations and depressive symptoms. Our findings highlight significant sex differences in the mechanisms that might operate between glucocorticoid concentrations and internalizing symptoms. Future longitudinal studies could test the predictive, sex-dependent effect of hair glucocorticoids concentrations during adolescence on the development of internalizing disorders in adulthood. Gaining a deeper understanding of HPA axis functioning could help to identify youth who are at greater risk of developing stress-related psychopathologies.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100311"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-05-15DOI: 10.1016/j.cpnec.2025.100300
Andrew El Alam , Mohamad Fleifel , Hicham Baba , Souha Bayda , Bertha Maria Nassani , Jocelyne Azar , Arnaud Monier
<div><h3>Background</h3><div>Obesity is one of the most significant global health concerns. As per the World Health Organization (WHO), obesity currently affects nearly 1.9 billion individuals around the world. Patients suffering from such a metabolic disease exhibit multiple medical conjoint medical conditions, and are predisposed to future high-morbidity and mortality complications. In addition, such patients might suffer from psychiatric compromises, at any time during their lives, that might have contributed to obesity. For many of these patients, bariatric surgery remains one of the leading methodologies in facilitating weight loss.</div></div><div><h3>Aim</h3><div>To study the prevalence of selected mental health disorders history, including depression, childhood trauma, and eating disorders, plus abnormal eating behaviors in patients with obesity undergoing pre-bariatric surgery evaluation. In addition, we intended to find any inter-associations between different mental health disorders and demographics in such patients.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, conducted at the Nutrition and Obesity Department at Louis Pasteur Hospital, France, we enrolled 234 patients with obesity undertaking pre-bariatric surgery evaluation.</div></div><div><h3>Results</h3><div>Around 31.2 % of participants had a history of depression, with 46.5 % receiving treatment. Childhood trauma was identified in 22.6 % of patients, and 12.8 % exhibited eating disorders, subclassified into binge eating disorder (6.4 %), bulimia (3.2 %), and night eating syndrome (3.4 %). Abnormal eating behaviors was also prominent in such patients, with 66.2 % engaging in activities such as snacking, hyperphagia, emotional eating, and compulsive eating. Sociodemographic associations showed that females were more likely to be diagnosed with depression, binge eating disorder, and compulsive eating, while males were more prone to hyperphagia. Childhood trauma was significantly associated with depression, binge eating disorder, bulimia, and abnormal eating behaviors. Multinomial logistic regression analysis revealed various predictors for depression, eating disorders, and abnormal eating behaviors across different categories. Notably, depression was associated with unemployment, trauma, and compulsions. Binge eating disorder showed significant associations with trauma and the female sex, while bulimia was notably associated with trauma. Night eating syndrome was inversely related to marriage status. Subgroup analysis further highlighted associations between depression, eating disorders, and abnormal eating behaviors in specific demographic groups.</div></div><div><h3>Conclusion</h3><div>There is a complex link between mental health disorders and eating patterns in individuals with obesity undergoing pre-bariatric surgery evaluation. Understanding this association is important for developing comprehensive preoperative care strategies that address both physica
{"title":"A safe path to bariatric surgery: Mental health disorders in pre-operative patients","authors":"Andrew El Alam , Mohamad Fleifel , Hicham Baba , Souha Bayda , Bertha Maria Nassani , Jocelyne Azar , Arnaud Monier","doi":"10.1016/j.cpnec.2025.100300","DOIUrl":"10.1016/j.cpnec.2025.100300","url":null,"abstract":"<div><h3>Background</h3><div>Obesity is one of the most significant global health concerns. As per the World Health Organization (WHO), obesity currently affects nearly 1.9 billion individuals around the world. Patients suffering from such a metabolic disease exhibit multiple medical conjoint medical conditions, and are predisposed to future high-morbidity and mortality complications. In addition, such patients might suffer from psychiatric compromises, at any time during their lives, that might have contributed to obesity. For many of these patients, bariatric surgery remains one of the leading methodologies in facilitating weight loss.</div></div><div><h3>Aim</h3><div>To study the prevalence of selected mental health disorders history, including depression, childhood trauma, and eating disorders, plus abnormal eating behaviors in patients with obesity undergoing pre-bariatric surgery evaluation. In addition, we intended to find any inter-associations between different mental health disorders and demographics in such patients.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, conducted at the Nutrition and Obesity Department at Louis Pasteur Hospital, France, we enrolled 234 patients with obesity undertaking pre-bariatric surgery evaluation.</div></div><div><h3>Results</h3><div>Around 31.2 % of participants had a history of depression, with 46.5 % receiving treatment. Childhood trauma was identified in 22.6 % of patients, and 12.8 % exhibited eating disorders, subclassified into binge eating disorder (6.4 %), bulimia (3.2 %), and night eating syndrome (3.4 %). Abnormal eating behaviors was also prominent in such patients, with 66.2 % engaging in activities such as snacking, hyperphagia, emotional eating, and compulsive eating. Sociodemographic associations showed that females were more likely to be diagnosed with depression, binge eating disorder, and compulsive eating, while males were more prone to hyperphagia. Childhood trauma was significantly associated with depression, binge eating disorder, bulimia, and abnormal eating behaviors. Multinomial logistic regression analysis revealed various predictors for depression, eating disorders, and abnormal eating behaviors across different categories. Notably, depression was associated with unemployment, trauma, and compulsions. Binge eating disorder showed significant associations with trauma and the female sex, while bulimia was notably associated with trauma. Night eating syndrome was inversely related to marriage status. Subgroup analysis further highlighted associations between depression, eating disorders, and abnormal eating behaviors in specific demographic groups.</div></div><div><h3>Conclusion</h3><div>There is a complex link between mental health disorders and eating patterns in individuals with obesity undergoing pre-bariatric surgery evaluation. Understanding this association is important for developing comprehensive preoperative care strategies that address both physica","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100300"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-02DOI: 10.1016/j.cpnec.2025.100303
C. Sue Carter
The purpose of this narrative review is to examine the hypothesis that two neuropeptides, vasopressin (VP) and oxytocin (OT) and their receptors have central roles in the behavioral and physiological consequences of psychedelic interventions. Transient consequences of psychedelics can include anxiety and in some cases sickness responses such as nausea and vomiting, which may involve VP and other components of the hypothalamic-pituitary-adrenal axis. Stressful experiences are often followed by a pulsatile release of OT. The effects of OT depend on interactions with VP and may be more apparent following stressful experiences including those associated with psychedelic drugs. Effects of both the VP-OT system and psychedelics also are mediated through interactions with the autonomic nervous system and the immune system, contributing to a process called “stress response hormesis.” The hypotheses arising from a hormetic perspective could guide novel approaches to understanding dose- and time-dependent psychedelic functions and to the treatment of emotional and physical disorders.
{"title":"The psychedelic-peptide paradox: a hormetic hypothesis","authors":"C. Sue Carter","doi":"10.1016/j.cpnec.2025.100303","DOIUrl":"10.1016/j.cpnec.2025.100303","url":null,"abstract":"<div><div>The purpose of this narrative review is to examine the hypothesis that two neuropeptides, vasopressin (VP) and oxytocin (OT) and their receptors have central roles in the behavioral and physiological consequences of psychedelic interventions. Transient consequences of psychedelics can include anxiety and in some cases sickness responses such as nausea and vomiting, which may involve VP and other components of the hypothalamic-pituitary-adrenal axis. Stressful experiences are often followed by a pulsatile release of OT. The effects of OT depend on interactions with VP and may be more apparent following stressful experiences including those associated with psychedelic drugs. Effects of both the VP-OT system and psychedelics also are mediated through interactions with the autonomic nervous system and the immune system, contributing to a process called “stress response hormesis.” The hypotheses arising from a hormetic perspective could guide novel approaches to understanding dose- and time-dependent psychedelic functions and to the treatment of emotional and physical disorders.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100303"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-03DOI: 10.1016/j.cpnec.2025.100304
Yunchang Yang, Yaofeng Wang, Yunqin Sun
<div><h3>Background</h3><div>Multiple clinical studies have observed a close relationship between metals in plasma and serum, immunocytes, and schizophrenia; however, it remains unclear whether there is a genetic causal effect between metals in plasma and serum,immunocytes, and schizophrenia.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the causal effects of metals in the plasma and serum on schizophrenia and the mediating role of immunocytes using Mendelian randomization methods in an East Asian population.</div></div><div><h3>Methods</h3><div>Summary results for 21 metals in plasma and serum,731 immunocytes and schizophrenia were acquired from publicly available genome-wide association studies (GWASs). GWAS data for metals, immunocytes, and schizophrenia were accessed between 2024 and 11–26 and 2024-12-02,Authors had no access to identifiable individual participant data. This study utilized two-sample Mendelian randomization (MR) analysis to establish causal relationships, which was achieved by employing various statistical methods, including inverse variance-weighted, simple mode, MR–Egger, weighted median, and weighted mode. Multiple sensitivity analyses, including heterogeneity tests, horizontal pleiotropy tests, MR-PRESSO tests, and leave-one-out analyses, were performed to confirm the reliability of the MR data. Finally, mediation analysis was employed to ascertain the immunocyte pathway that leads to schizophrenia from the metals in the plasma and serum. The study used anonymized summary-level GWAS data from public databases (e.g., GWAS Catalog, iEU Open GWAS), which do not contain personally identifiable information.</div></div><div><h3>Results</h3><div>The data of the East Asian population were analyzed by Mendelian randomization and two serum metallic traits that may reduce the risk of schizophrenia were identified: Serum iron (odds ratio (OR):0.54, 95 % confidence interval (CI):0.30–0.96, p = 0.036) and serum molybdenum levels (odds ratio (OR):0.54, 95 % confidence interval (CI):0.34–0.87, p = 0.011) corresponds to a 46 % reduction in schizophrenia risk. A baseline lifetime risk of 1 % in the general population, this translates to an absolute risk reduction of 0.46 %, with a number needed to treat (NNT) of approximately 217 individuals to prevent one case. They exhibited a negative causal relationship with the risk of Schizophrenia. Through mediation analysis, we identified a specific immunocyte subtype, CD33dim HLA DR + CD11b- Absolute Count, that not only correlates with serum iron levels but also shows a strong association with schizophrenia risk, suggesting a potential pathway through which serum iron may influence schizophrenia development. Serum iron levels showed a negative causal relationship in schizophrenia through the mediation of immunocytes with CD33dim HLA DR + CD11b- Absolute Count (mediation proportion:21 %).</div></div><div><h3>Conclusions</h3><div>This study identified a causal relationship
多项临床研究发现,血浆和血清中的金属、免疫细胞和精神分裂症之间存在密切关系;然而,目前尚不清楚血浆和血清中的金属、免疫细胞和精神分裂症之间是否存在遗传因果关系。目的采用孟德尔随机化方法,研究东亚人群血浆和血清中金属对精神分裂症的因果关系及免疫细胞的介导作用。方法从公开的全基因组关联研究(GWASs)中获得血浆和血清中21种金属、731种免疫细胞与精神分裂症的综合结果。在2024- 11-26和2024-12-02期间访问了金属、免疫细胞和精神分裂症的GWAS数据,作者无法获得可识别的个体参与者数据。本研究采用双样本孟德尔随机化(MR)分析建立因果关系,采用方差加权逆、简单模式、MR - egger、加权中位数、加权模式等多种统计方法。进行多重敏感性分析,包括异质性检验、水平多效性检验、MR- presso检验和留一分析,以确认MR数据的可靠性。最后,采用中介分析从血浆和血清中的金属确定导致精神分裂症的免疫细胞途径。该研究使用了来自公共数据库(例如,GWAS Catalog, iEU Open GWAS)的匿名汇总级GWAS数据,这些数据不包含个人身份信息。结果对东亚人群的数据进行孟德尔随机化分析,确定了两种可能降低精神分裂症风险的血清金属特征:血清铁(优势比(OR):0.54, 95%可信区间(CI): 0.30-0.96, p = 0.036)和血清钼水平(优势比(OR):0.54, 95%可信区间(CI): 0.34-0.87, p = 0.011)对应于精神分裂症风险降低46%。在一般人群中,基线终身风险为1%,这意味着绝对风险降低0.46%,需要治疗的人数(NNT)约为217人才能预防1例病例。它们与患精神分裂症的风险呈负相关。通过中介分析,我们确定了一种特定的免疫细胞亚型CD33dim HLA DR + CD11b- Absolute Count,它不仅与血清铁水平相关,而且与精神分裂症风险有很强的相关性,提示血清铁可能通过一种潜在的途径影响精神分裂症的发展。血清铁水平通过CD33dim HLA DR + CD11b- Absolute Count免疫细胞介导(介导比例21%),与精神分裂症患者血清铁水平呈负相关。结论本研究通过孟德尔随机化分析确定了东亚人群血浆和血清金属、免疫细胞与精神分裂症之间的因果关系,为精神分裂症的早期发现、诊断和治疗提供了新的理论依据。
{"title":"Causality effect of 21 metals in plasma and serum, 731 immunocytes, and schizophrenia: an intermediary Mendelian randomization study in East Asian populations","authors":"Yunchang Yang, Yaofeng Wang, Yunqin Sun","doi":"10.1016/j.cpnec.2025.100304","DOIUrl":"10.1016/j.cpnec.2025.100304","url":null,"abstract":"<div><h3>Background</h3><div>Multiple clinical studies have observed a close relationship between metals in plasma and serum, immunocytes, and schizophrenia; however, it remains unclear whether there is a genetic causal effect between metals in plasma and serum,immunocytes, and schizophrenia.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the causal effects of metals in the plasma and serum on schizophrenia and the mediating role of immunocytes using Mendelian randomization methods in an East Asian population.</div></div><div><h3>Methods</h3><div>Summary results for 21 metals in plasma and serum,731 immunocytes and schizophrenia were acquired from publicly available genome-wide association studies (GWASs). GWAS data for metals, immunocytes, and schizophrenia were accessed between 2024 and 11–26 and 2024-12-02,Authors had no access to identifiable individual participant data. This study utilized two-sample Mendelian randomization (MR) analysis to establish causal relationships, which was achieved by employing various statistical methods, including inverse variance-weighted, simple mode, MR–Egger, weighted median, and weighted mode. Multiple sensitivity analyses, including heterogeneity tests, horizontal pleiotropy tests, MR-PRESSO tests, and leave-one-out analyses, were performed to confirm the reliability of the MR data. Finally, mediation analysis was employed to ascertain the immunocyte pathway that leads to schizophrenia from the metals in the plasma and serum. The study used anonymized summary-level GWAS data from public databases (e.g., GWAS Catalog, iEU Open GWAS), which do not contain personally identifiable information.</div></div><div><h3>Results</h3><div>The data of the East Asian population were analyzed by Mendelian randomization and two serum metallic traits that may reduce the risk of schizophrenia were identified: Serum iron (odds ratio (OR):0.54, 95 % confidence interval (CI):0.30–0.96, p = 0.036) and serum molybdenum levels (odds ratio (OR):0.54, 95 % confidence interval (CI):0.34–0.87, p = 0.011) corresponds to a 46 % reduction in schizophrenia risk. A baseline lifetime risk of 1 % in the general population, this translates to an absolute risk reduction of 0.46 %, with a number needed to treat (NNT) of approximately 217 individuals to prevent one case. They exhibited a negative causal relationship with the risk of Schizophrenia. Through mediation analysis, we identified a specific immunocyte subtype, CD33dim HLA DR + CD11b- Absolute Count, that not only correlates with serum iron levels but also shows a strong association with schizophrenia risk, suggesting a potential pathway through which serum iron may influence schizophrenia development. Serum iron levels showed a negative causal relationship in schizophrenia through the mediation of immunocytes with CD33dim HLA DR + CD11b- Absolute Count (mediation proportion:21 %).</div></div><div><h3>Conclusions</h3><div>This study identified a causal relationship ","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100304"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-06DOI: 10.1016/j.cpnec.2025.100307
Ana Vanessa Costa Rodrigues da Silva , Sérgio Reis Soares , Rui Filipe Oliveira Miguelote
Introduction
Polycystic Ovary Syndrome (PCOS) and Functional Hypothalamic Amenorrhea (FHA) are two prevalent causes of secondary oligo/amenorrhea (OA) in women. Women with polycystic ovarian morphology (PCOM) frequently exhibit features of both PCOS and FHA, creating diagnostic challenges in clinical practice. This exploratory study explores how psychological and metabolic stress markers, combined with hormonal profiling, can distinguish FHA-PCOM from PCOS-PCOM.
Methods
In this prospective observational exploratory study, ninety-one women with OA were recruited from the general population. They were classified into PCOM and non-PCOM groups using transvaginal ultrasonography (antral follicle number per ovary ≥20 or ovarian volume ≥10 cm3). Psychological stress was assessed using Perceived Stress Scale (PSS-10), Hospital Anxiety and Depression Scale (HADS), and State-Trait Anxiety Inventory (STAI). Clinical evaluations included physical examinations, transvaginal ultrasonography, and comprehensive biochemical analyses. Cluster analysis was performed to identify distinct phenotypic profiles.
Results
All women in the PCOM group met the Rotterdam Criteria for PCOS and two-thirds of them exhibited overlapping features of both FHA and PCOS. The cluster analysis identified three PCOM subgroups: PCOM–CL1 displayed classic PCOS traits, including elevated androgens and insulin resistance; PCOM–CL2 exhibited psychological stress with FHA-like features; PCOM–CL3 showed metabolic stress with higher engagement in physical activity (both in duration and intensity), low leptin, and reduced insulin resistance. Additionally, PCOM-CL3 exhibited the lowest levels of psychological stress compared to the other two clusters. Non-PCOM women formed two clusters, one dominated by psychological stress and the other by metabolic stress. STAI-Trait and HADS were validated as reliable tools for assessing psychological stress in OA-PCOM cases.
Conclusions
This study highlights the significant overlap between PCOS and FHA phenotypes in women with PCOM and emphasizes the utility of psychological assessments, physical activity metrics, and leptin levels in differential diagnosis. Integrating these diagnostic tools into clinical practice may enhance personalized management strategies for OA-PCOM women, addressing both hormonal and stress-related dimensions.
{"title":"Beyond ovarian Morphology: Integrative stress profiling for distinguishing polycystic ovary syndrome from functional hypothalamic amenorrhea","authors":"Ana Vanessa Costa Rodrigues da Silva , Sérgio Reis Soares , Rui Filipe Oliveira Miguelote","doi":"10.1016/j.cpnec.2025.100307","DOIUrl":"10.1016/j.cpnec.2025.100307","url":null,"abstract":"<div><h3>Introduction</h3><div>Polycystic Ovary Syndrome (PCOS) and Functional Hypothalamic Amenorrhea (FHA) are two prevalent causes of secondary oligo/amenorrhea (OA) in women. Women with polycystic ovarian morphology (PCOM) frequently exhibit features of both PCOS and FHA, creating diagnostic challenges in clinical practice. This exploratory study explores how psychological and metabolic stress markers, combined with hormonal profiling, can distinguish FHA-PCOM from PCOS-PCOM.</div></div><div><h3>Methods</h3><div>In this prospective observational exploratory study, ninety-one women with OA were recruited from the general population. They were classified into PCOM and non-PCOM groups using transvaginal ultrasonography (antral follicle number per ovary ≥20 or ovarian volume ≥10 cm<sup>3</sup>). Psychological stress was assessed using Perceived Stress Scale (PSS-10), Hospital Anxiety and Depression Scale (HADS), and State-Trait Anxiety Inventory (STAI). Clinical evaluations included physical examinations, transvaginal ultrasonography, and comprehensive biochemical analyses<strong>.</strong> Cluster analysis was performed to identify distinct phenotypic profiles.</div></div><div><h3>Results</h3><div>All women in the PCOM group met the Rotterdam Criteria for PCOS and two-thirds of them exhibited overlapping features of both FHA and PCOS. The cluster analysis identified three PCOM subgroups: PCOM–CL1 displayed classic PCOS traits, including elevated androgens and insulin resistance; PCOM–CL2 exhibited psychological stress with FHA-like features; PCOM–CL3 showed metabolic stress with higher engagement in physical activity (both in duration and intensity), low leptin, and reduced insulin resistance. Additionally, PCOM-CL3 exhibited the lowest levels of psychological stress compared to the other two clusters. Non-PCOM women formed two clusters, one dominated by psychological stress and the other by metabolic stress. STAI-Trait and HADS were validated as reliable tools for assessing psychological stress in OA-PCOM cases.</div></div><div><h3>Conclusions</h3><div>This study highlights the significant overlap between PCOS and FHA phenotypes in women with PCOM and emphasizes the utility of psychological assessments, physical activity metrics, and leptin levels in differential diagnosis. Integrating these diagnostic tools into clinical practice may enhance personalized management strategies for OA-PCOM women, addressing both hormonal and stress-related dimensions.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100307"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-04DOI: 10.1016/j.cpnec.2025.100305
Bob Weng , Reid Morrissey , Jenna Lehn , Mustafa Beidas , Tauseef Abubakar , Mohsin Mirza
Background
Polycystic ovarian syndrome (PCOS) is a dysregulated metabolic disorder causing hyperandrogenism, oligomenorrhea/anovulation, and ovarian cysts. The effects of PCOS extend beyond the reproductive detriments, notably an association with mood disorders. Existing literature is limited but suggests comorbid mood derangements increase the severity of PCOS symptoms and comprise a significant portion of healthcare costs in the U.S. Our study aims to further examine the impact of PCOS on the hospitalization course and costs.
Methods
Using data for females ages 18–50 from the National Inpatient Sample (NIS) between 2016 and 2020, a PCOS group was compared to a non-PCOS group for women hospitalized with mood disorders. Length of stay (LOS), hospital costs, and demographic characteristics were analyzed.
Results
PCOS patients accumulated significantly higher LOS and hospital cost. They also were significantly younger, predominantly Caucasian, covered by private insurance, and earned more income. There was a disproportionate use of Medicare for both groups given the younger sample.
Conclusion
Further investigation of demographic nuances and a multidisciplinary approach to PCOS, including policy changes and patient education starting at a young age, should be taken to better understand disease impact on different communities and address the broad scope of the disease (i.e. psychosocial) to reduce its healthcare burden.
{"title":"Influence of mood disorders on outcomes of polycystic ovarian syndrome - A national inpatient sample study - 2016–2020","authors":"Bob Weng , Reid Morrissey , Jenna Lehn , Mustafa Beidas , Tauseef Abubakar , Mohsin Mirza","doi":"10.1016/j.cpnec.2025.100305","DOIUrl":"10.1016/j.cpnec.2025.100305","url":null,"abstract":"<div><h3>Background</h3><div>Polycystic ovarian syndrome (PCOS) is a dysregulated metabolic disorder causing hyperandrogenism, oligomenorrhea/anovulation, and ovarian cysts. The effects of PCOS extend beyond the reproductive detriments, notably an association with mood disorders. Existing literature is limited but suggests comorbid mood derangements increase the severity of PCOS symptoms and comprise a significant portion of healthcare costs in the U.S. Our study aims to further examine the impact of PCOS on the hospitalization course and costs.</div></div><div><h3>Methods</h3><div>Using data for females ages 18–50 from the National Inpatient Sample (NIS) between 2016 and 2020, a PCOS group was compared to a non-PCOS group for women hospitalized with mood disorders. Length of stay (LOS), hospital costs, and demographic characteristics were analyzed.</div></div><div><h3>Results</h3><div>PCOS patients accumulated significantly higher LOS and hospital cost. They also were significantly younger, predominantly Caucasian, covered by private insurance, and earned more income. There was a disproportionate use of Medicare for both groups given the younger sample.</div></div><div><h3>Conclusion</h3><div>Further investigation of demographic nuances and a multidisciplinary approach to PCOS, including policy changes and patient education starting at a young age, should be taken to better understand disease impact on different communities and address the broad scope of the disease (i.e. psychosocial) to reduce its healthcare burden.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100305"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-06-18DOI: 10.1016/j.cpnec.2025.100308
Morf Rita , Reicherzer Leah , Degenfellner Jürgen , Hasenbring Monika , Erat Anna , Hotz-Boendermaker Sabina
Background
Neck pain (NP) is a common musculoskeletal health problem, persisting in 47 % of cases. A person's engagement in daily activities is defined as activity patterns (eustress persistence, distress persistence, activity pacing, and fear avoidance) that influence the development and continuation of pain. These behaviors may be linked to heightened stress levels, further negatively impacting pain perception. Understanding these relationships is vital, given the intricate interplay between stress, pain, and activity patterns. This study aims to assess the frequency of activity patterns and identify their impact on stress levels in participants with acute NP.
Methods
125 individuals aged 18–65 with acute NP were recruited. Activity patterns were identified using the Avoidance-Endurance Fast Screen, which calculated the frequencies of activity patterns. Furthermore, subjective stress was evaluated using the Stress and Coping Inventory and objective stress using hair cortisol concentration to determine which activity pattern group experienced the highest stress.
Results
Most participants were classified in the eustress persistence group (52 %), followed by activity pacing (22.8 %), distress persistence (19.5 %), and fear avoidance (5.7 %). Subjective and objective stress levels consistently remained below established reference values. Analysis of activity pattern groups showed that distress persistence had the highest subjective stress levels, followed by fear avoidance, while activity pacing had the lowest. No relevant differences between the activity pattern groups were observed in the objective stress measurements.
Discussion
To the best of our knowledge, this study represents the first investigation of frequencies of activity patterns and subjective and objective stress in acute NP.
{"title":"Frequencies of persistence, activity pacing, fear avoidance and general stress in acute neck pain","authors":"Morf Rita , Reicherzer Leah , Degenfellner Jürgen , Hasenbring Monika , Erat Anna , Hotz-Boendermaker Sabina","doi":"10.1016/j.cpnec.2025.100308","DOIUrl":"10.1016/j.cpnec.2025.100308","url":null,"abstract":"<div><h3>Background</h3><div>Neck pain (NP) is a common musculoskeletal health problem, persisting in 47 % of cases. A person's engagement in daily activities is defined as activity patterns (eustress persistence, distress persistence, activity pacing, and fear avoidance) that influence the development and continuation of pain. These behaviors may be linked to heightened stress levels, further negatively impacting pain perception. Understanding these relationships is vital, given the intricate interplay between stress, pain, and activity patterns. This study aims to assess the frequency of activity patterns and identify their impact on stress levels in participants with acute NP.</div></div><div><h3>Methods</h3><div>125 individuals aged 18–65 with acute NP were recruited. Activity patterns were identified using the Avoidance-Endurance Fast Screen, which calculated the frequencies of activity patterns. Furthermore, subjective stress was evaluated using the Stress and Coping Inventory and objective stress using hair cortisol concentration to determine which activity pattern group experienced the highest stress.</div></div><div><h3>Results</h3><div>Most participants were classified in the eustress persistence group (52 %), followed by activity pacing (22.8 %), distress persistence (19.5 %), and fear avoidance (5.7 %). Subjective and objective stress levels consistently remained below established reference values. Analysis of activity pattern groups showed that distress persistence had the highest subjective stress levels, followed by fear avoidance, while activity pacing had the lowest. No relevant differences between the activity pattern groups were observed in the objective stress measurements.</div></div><div><h3>Discussion</h3><div>To the best of our knowledge, this study represents the first investigation of frequencies of activity patterns and subjective and objective stress in acute NP.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100308"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}