Comprehensive psychoneuroendocrinology最新文献

{"title":"Frequencies of persistence, activity pacing, fear avoidance and general stress in acute neck pain","authors":"Morf Rita ,&nbsp;Reicherzer Leah ,&nbsp;Degenfellner Jürgen ,&nbsp;Hasenbring Monika ,&nbsp;Erat Anna ,&nbsp;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}

{"title":"Cortisol awakening response in pregnant women with depressive disorders: a potential marker of recovery status from pregnancy to postpartum","authors":"Carlinde W. Broeks ,&nbsp;Babette Bais ,&nbsp;Rien Van ,&nbsp;Hilmar H. Bijma ,&nbsp;Elisabeth F.C. van Rossum ,&nbsp;Witte J.G. Hoogendijk ,&nbsp;Mijke P. Lambregtse-Van den Berg ,&nbsp;Astrid M. Kamperman","doi":"10.1016/j.cpnec.2025.100297","DOIUrl":"10.1016/j.cpnec.2025.100297","url":null,"abstract":"<div><h3>Introduction</h3><div>Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to peripartum depression, potentially contributing to symptom persistence. This study examines the relationship between the cortisol awakening response (CAR) during pregnancy and depressive symptom reduction postpartum.</div></div><div><h3>Methods</h3><div>Pregnant women with a current depressive episode were included in this study, part of a larger RCT on bright light therapy. At baseline (12–32 weeks of pregnancy), participants provided saliva samples at awakening, +30, and +60 min post-awakening. The CAR was assessed using three measures: area under the curve relative to ground (AUCg), area under the curve relative to increase (AUCi), and peak reactivity (difference between awakening and +30 min cortisol levels). Depressive symptoms were measured using the Hamilton Depression Rating Scale (HAM-D) at baseline and two months postpartum. Linear regression models assessed associations between CAR measures and depressive symptom change, adjusting for relevant covariates.</div></div><div><h3>Results</h3><div>The study included 55 pregnant women (mean age: 32.3 years, SD 4.8; mean gestational age: 19.7 weeks). Mean HAM-D scores decreased from 16.7 (SD 5.3) at baseline to 5.7 (SD 5.6) postpartum. Higher AUCi during pregnancy was associated with less symptom reduction postpartum (unadjusted β = 0.36, p = .02; adjusted β = 0.36, p = .02), as was peak cortisol reactivity (unadjusted β = 0.33, p = .03; adjusted β = 0.32, p = .03), while AUCg showed no significant association with symptom change (unadjusted p = .19; adjusted p = .28).</div></div><div><h3>Conclusion</h3><div>Higher AUCi and peak cortisol reactivity of the cortisol awakening response during pregnancy were linked to persistence of depressive symptoms postpartum, suggesting that heightened cortisol reactivity to awakening may indicate persistent stress vulnerability in peripartum depression. Total cortisol output (AUCg) was not predictive of recovery. These findings underscore the potential relevance of stress reactivity over basal cortisol levels in peripartum depression and highlight the need for further research in larger samples to elucidate the usefulness in clinical practice.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100297"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903693","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}

{"title":"Effect of a multidisciplinary lifestyle intervention on stress-related parameters in people with rheumatoid arthritis and osteoarthritis: secondary analysis of the \"Plants for Joints\" randomized controlled trial","authors":"C.A. Wagenaar ,&nbsp;J. Christiaans ,&nbsp;V. Hermans ,&nbsp;W. Walrabenstein ,&nbsp;F.A. Koopman ,&nbsp;H. van Middendorp ,&nbsp;D. van Schaardenburg","doi":"10.1016/j.cpnec.2025.100298","DOIUrl":"10.1016/j.cpnec.2025.100298","url":null,"abstract":"<div><h3>Objective</h3><div>In two randomized controlled trials, the Plants for Joints (PFJ) multidisciplinary lifestyle intervention reduced signs and symptoms of rheumatoid arthritis (RA), or metabolic syndrome-associated hip or knee osteoarthritis (MSOA) compared with usual care. This secondary analysis aimed to evaluate the effect of the PFJ intervention on stress-related parameters.</div></div><div><h3>Methods</h3><div>In two PFJ observer-blind randomized controlled trials (RCT), people with (1) RA with low-moderate disease activity or (2) MSOA were randomized to receive the PFJ lifestyle intervention or usual care. The 16-week PFJ intervention consisted of a whole-food plant-based diet, physical activity, and sleep and stress management. This secondary analysis investigated stress-related outcomes including heart rate, heart rate variability (HRV: root square mean of successive differences (RMSSD) and normalised high frequency (HFnorm), salivary cortisol, perceived stress (Perceived Stress Scale 10; PSS-10), and time spent on stress-reducing activities. An intention-to-treat analysis with a linear regression model (HRV) or linear mixed model (cortisol and PSS-10), adjusted for baseline values, was used to analyse between-group differences.</div></div><div><h3>Results</h3><div>77 people with RA and 64 with MSOA completed the RCT. RA participants following the PFJ intervention showed a significant improvement in HFnorm (between-group difference: 6.6; 95 % CI 0.5, 12.6) and an improving trend in RMSSD (4.3; 95 % CI -1.5, 10.1) alongside non-significant reductions of heart rate (3.1; 95 % CI-3.9, 10.1), salivary cortisol (1.3; 95 % CI -0.6, 3.1) and perceived stress (−2.0; 95 % CI -4.4, 0.3), compared to usual care. In participants with MSOA, there were no differences in heart rate, HRV outcomes, cortisol, or perceived stress between the intervention and control group. Both RA and MSOA participants temporarily increased time spent on stress-reducing activities, yet no change from baseline was observed after 16 weeks. In RA participants increased time spent on stress-reducing activities was associated with increased HFnorm.</div></div><div><h3>Conclusion</h3><div>This secondary analysis suggests the PFJ program may have a positive influence on stress-related parameters in people with RA, but not MSOA, compared to usual care.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100298"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937526","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}

{"title":"Is there a female-male self-selection bias in TSST-based reactive stress research?","authors":"Victoria Xu ,&nbsp;Audrey-Ann Journault ,&nbsp;Samuel Alarie ,&nbsp;Charles-Édouard Giguère ,&nbsp;Emy Beaumont ,&nbsp;Sonia Lupien","doi":"10.1016/j.cpnec.2025.100296","DOIUrl":"10.1016/j.cpnec.2025.100296","url":null,"abstract":"<div><div>A selection bias occurs when a given sample of participants only represents a subset of the population under study, which may subsequently limit the generalizability of findings. While previous studies have noticed a potential female-male selection bias in human stress research, with female participants often being over-represented, no prior research has directly addressed this issue in the context of stress reactivity. This exploratory study aimed to systematically examine this observation. A total of 120 scientific articles (N = 10 103) published from 2014 to 2023 on the topic of human stress reactivity retrieved from PUBMED and PsycINFO were examined to compile sex ratios by study location (United States, Germany, China, Canada, Israel, United Kingdom). The meta-analysis and meta-regression results indicated that females participate in reactive stress studies more frequently than males, although the observed difference is small. Moreover, there is no significant discrepancy regarding male and female participation rates between the countries examined. This result supports a higher female representation level in stress research samples. The findings provide leads for future studies aiming to further investigate the underlying antecedents of selection bias in human stress research. A better understanding of the phenomenon could lead researchers to optimize recruitment methods to obtain more representative samples.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100296"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949008","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}

{"title":"Trauma writing reduces conserved transcriptional response to adversity (CTRA) gene expression: A culturally adapted pilot study","authors":"Gail Ironson ,&nbsp;Roger McIntosh ,&nbsp;Maria Di Bello ,&nbsp;Yasmin Shemali ,&nbsp;Salman Ahmad ,&nbsp;Hannah Hoogerwoerd ,&nbsp;Steve Cole","doi":"10.1016/j.cpnec.2025.100310","DOIUrl":"10.1016/j.cpnec.2025.100310","url":null,"abstract":"<div><h3>Introduction</h3><div>Psychosocial interventions to reduce posttraumatic stress disorder (PTSD)-associated distress can improve health of people with PTSD. To identify potential biological mechanisms, we tested whether a PTSD-focused written emotional disclosure (WED) intervention can reduce a stress-associated gene expression profile known as the Conserved Transcriptional Response to Adversity (CTRA).</div></div><div><h3>Methods</h3><div>This pilot RCT compared 4 sessions of WED to a control group writing about daily events among thirteen Hispanic women who were living with or at risk for HIV, and had pre-post intervention gene expression data available (9 WED, 3 control). The PTSD checklist for the DSM-5 (PCL-5) was used to measure trauma symptom severity and CTRA gene expression was assessed by whole blood RNA sequencing.</div></div><div><h3>Results</h3><div>Primary analyses showed a significant Time x Intervention interaction (F_[1,11] = 16.01; p = 0.002), with the Intervention group showing a significant decrease in CTRA gene expression whereas the Control group revealed a significant increase. Effects on trauma symptoms were also significant.</div></div><div><h3>Conclusion</h3><div>PTSD-focused WED can reduce CTRA gene expression and PTSD symptoms in Hispanic women living with or at risk for HIV infection. We believe this is the first study to show that trauma treatment impacts CTRA gene expression in the context of PTSD.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100310"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665993","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}

{"title":"The impact of a multimodal intervention on physical health factors and lifestyle in patients with affective disorders – results from a randomized controlled trial","authors":"Ida Schou Ipsen ,&nbsp;Rasmus Schwarz ,&nbsp;Lars Vedel Kessing ,&nbsp;Kamilla W. Miskowiak ,&nbsp;Maj Vinberg","doi":"10.1016/j.cpnec.2025.100295","DOIUrl":"10.1016/j.cpnec.2025.100295","url":null,"abstract":"<div><h3>Background</h3><div>Traditional treatment for affective disorders primarily focuses on symptom management through pharmacotherapy and psychotherapy and rarely addresses co-existing physical impairments.</div></div><div><h3>Methods</h3><div>This randomized controlled trial assessed the impact of a six-month multimodal intervention (AWARE) on physical health in patients with bipolar and unipolar depressive disorders. A total of 103 patients, median age 40.75 years (65 % female), were randomized into the AWARE group (n = 50) or treatment as usual (TAU) group (n = 53). The AWARE intervention included five modules focused on activities of daily living, mood management, social relations, physical health, and cognition, with participants receiving approximately 12 sessions. TAU involved standard psychiatric care, Health outcomes were evaluated on sleep, metabolic markers, substance use, medication side effects, and perceived physical health. Statistical analyses used logistic regression for group comparisons and analysis of covariance for continuous outcomes.</div></div><div><h3>Results</h3><div>The AWARE group had significant improvements in sleep onset latency and reported reduced physical pain affecting daily work compared to TAU. However, no statistically significant differences were found in other physical health outcomes, such as metabolic markers, substance use, medication side effects, or perceived physical health. Study limitations include a modest sample size and a relatively short intervention duration.</div></div><div><h3>Conclusion</h3><div>While the AWARE intervention improved sleep and pain management, it did not significantly affect other health markers. Future research should involve longer intervention periods, larger sample sizes, and a comprehensive approach to both mental and physical health.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100295"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902027","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}

{"title":"The systemic immune-inflammation index (SII) as a biomarker for depression in a community sample of adolescents","authors":"Anett Schumacher ,&nbsp;Eric Tu ,&nbsp;Carly Albaum ,&nbsp;Daphne J. Korczak","doi":"10.1016/j.cpnec.2025.100302","DOIUrl":"10.1016/j.cpnec.2025.100302","url":null,"abstract":"<div><h3>Background</h3><div>Depression is associated with increased levels of pro-inflammatory biomarkers in children and adolescents. As research to date has primarily focused on inflammatory cytokines, the potential role of white blood cells (WBCs) and platelets in the inflammatory response is not well understood. This study examines the association of blood cell based inflammatory indices, including the systemic immune-inflammation index (SII), and depressive symptoms in participants in the Adolescent Brain Cognitive Development Study.</div></div><div><h3>Methods</h3><div>Adolescents were recruited from community settings and completed self-report measures of depression symptoms and semi-structured psychiatric interview to determine depression diagnosis. Participants provided blood samples to obtain absolute counts of neutrophil, lymphocyte, monocyte, and platelet levels for calculation of inflammatory indices. The association between depression and inflammatory markers was examined while accounting for participant age, sex, ethnicity, comorbid psychiatric disorder, parental education and annual household income.</div></div><div><h3>Results</h3><div>Of 858 participants (mean age: 12.4 ± 1.1 years; 45 % female), 101 received a diagnosis of a depressive disorder. Greater depressive symptoms were significantly associated with higher neutrophil and platelet levels (<em>β</em> = 0.013 and <em>β</em> = 0.018, respectively) and higher SII (<em>β</em> = 0.012), after adjusting for covariates. Diagnosis of depression was not associated with WBC levels or indices.</div></div><div><h3>Conclusions</h3><div>In this community-based sample of adolescents, greater depressive symptoms were associated with elevated SII and individual white blood cell levels. Future studies using larger, longitudinal clinical samples are needed to confirm the potential role of the SII in adolescent depression, and the involvement of inflammation in early-onset depression.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"23 ","pages":"Article 100302"},"PeriodicalIF":2.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115949","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}

{"title":"Depression and the prefrontal-hippocampal pathway - A multimodal neuroimaging study in transgender women","authors":"Setthanan Jarukasemkit ,&nbsp;Karen M. Tam ,&nbsp;Seksan Yoadsanit ,&nbsp;Ty Easley ,&nbsp;Hailey Modi ,&nbsp;Lyn Stahl ,&nbsp;Adun Kampaengtip ,&nbsp;Thanissara Chansakul ,&nbsp;Rena Janamnuaysook ,&nbsp;Akarin Hiransuthikul ,&nbsp;Chaipat Chunharas ,&nbsp;Janine D. Bijsterbosch","doi":"10.1016/j.cpnec.2025.100288","DOIUrl":"10.1016/j.cpnec.2025.100288","url":null,"abstract":"<div><div>This study aims to investigate functional and neurotransmitter signaling in the prefrontal-hippocampal pathway in relation to depression in a cohort of Thai transgender women. Twenty participants completed mental health surveys and imaging between January and March 2024. Depression severity was measured by Patient Health Questionnaire-9 (PHQ-9) scores. Higher PHQ-9 scores were associated with lower GABA levels in the hippocampus, and with lower fractional amplitude of low-frequency fluctuations (fALFF) in the dorsolateral prefrontal cortex. However, removal of the hippocampal GABA outlier resulted in a non-significant relationship with PHQ-9. Therefore, future studies with larger datasets should further investigate the association between GABA and depression in a transgender cohort. These findings revealed interactions between neurotransmitter signaling and functional brain activity of the hippocampal-prefrontal circuit in depression.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"22 ","pages":"Article 100288"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical language lateralization in positive schizotypy and modulating effects of the menstrual cycle","authors":"Helene Hjelmervik ,&nbsp;Josef J. Bless ,&nbsp;Julien Laloyaux ,&nbsp;Kenneth Hugdahl ,&nbsp;Markus Hausmann","doi":"10.1016/j.cpnec.2025.100291","DOIUrl":"10.1016/j.cpnec.2025.100291","url":null,"abstract":"<div><div>Previous studies have shown atypical language asymmetry in male participants with high schizotypy traits, but in female participants the pattern is less clear. Such sex differences could suggest a role of sex hormones, especially since hemispheric asymmetries have been shown to change across the menstrual cycle. By modulating attention in a consonant-vowel dichotic listening test, the current study aimed to investigate language lateralization (ear advantage of non-forced condition) in high vs low positive-schizotypy and the role of the menstrual cycle. In addition, we aimed to replicate menstrual cycle effects on the left attention condition. Thirty-nine female participants were tested in the menstrual (low estradiol) or follicular (high estradiol) cycle phase. Women tested in the follicular phase were found to perform better on the left attention condition, indicating enhanced cognitive control. In the non-forced condition, the high positive-schizotypy group showed increased right hemispheric involvement during the follicular phase relative to the menstrual phase; whereas an increase in left hemispheric dominance was seen in the low positive-schizotypy group during this cycle phase. The results suggest an underlying difference in lateralization between low and high positive-schizotypy that is enhanced by gonadal hormones, perhaps through altered interhemispheric inhibition. Overall, the study suggests that the atypical language lateralization in high schizotypy individuals is highly flexible and dependent on the hormonal milieu, and could potentially be related to neuroprotective effects of estradiol.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"22 ","pages":"Article 100291"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824170","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}

{"title":"Exploring the metabolic signature of intermittent explosive disorder: Preliminary evidence and potential mechanisms for altered bilirubin metabolism","authors":"Jeffrey B. Schwimmer ,&nbsp;Murray B. Stein ,&nbsp;Emil F. Coccaro ,&nbsp;Alejandro D. Meruelo","doi":"10.1016/j.cpnec.2025.100294","DOIUrl":"10.1016/j.cpnec.2025.100294","url":null,"abstract":"<div><div>Intermittent Explosive Disorder (IED) is characterized by impulsive aggression and emotional dysregulation, yet its systemic biological underpinnings remain poorly understood. This study examined bilirubin metabolism and systemic biomarkers as indicators of metabolic vulnerability in individuals with IED. Laboratory data for total and indirect bilirubin and white blood cell (WBC) count were analyzed in individuals with IED and a demographically and clinically matched general population (GP) control group. A 10:1 nearest-neighbor propensity score matching procedure was used to balance covariates including age, sex, race, ethnicity, body mass index (BMI), and alcohol and tobacco use. Participants with hepatobiliary or inflammatory conditions were excluded to reduce heterogeneity and confounding. Group comparisons used unique individuals with biomarker values averaged across timepoints.</div><div>Individuals with IED showed lower total and indirect bilirubin levels compared to matched controls, with a moderate effect size for indirect bilirubin (d = −0.37) and a small effect for total bilirubin (d = −0.10). WBC differences were minimal (d = −0.12). Linear mixed-effects models incorporating repeated measures yielded consistent results, though none of the group differences reached statistical significance, likely due to limited sample size in the IED group. Sensitivity analyses suggested bilirubin findings were more robust to unmeasured confounding than WBC.</div><div>These results highlight a potential hepatobiliary or metabolic signature in IED, rather than a primary inflammatory process. Given the preliminary nature of the findings, absence of cytokine data, and limited statistical power, results should be interpreted cautiously and warrant replication in larger samples with broader inflammatory and lifestyle profiling.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"22 ","pages":"Article 100294"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869657","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}