Pub Date : 2025-12-17DOI: 10.1016/j.psyneuen.2025.107729
Kristin M. Davis , Molly A. Wright , Christopher G. Engeland , Kyle W. Murdock
Background
Inflammation contributes to cardiovascular and metabolic disease development. Reducing disease risk by targeting inflammation is therefore desirable in prevention research. However, circulating markers of inflammation are often difficult to detect in younger individuals. Ex vivo stimulated cytokine production offers a promising alternative measure of immune function. Yet, few studies among younger adults have used this measure to date or have assessed its reliability over time.
Methods
First-year university students (N = 110, age 18–19 years) completed two study visits, one each at the beginning and end of their first semester. Circulating cytokines and lipopolysaccharide-stimulated cytokine production were assayed at each visit; composites for each were created using IL-1β, IL-6, and IFN-γ. Analyses excluded participants with CRP ≥ 10 mg/L. Pearson’s correlations were used to examine unadjusted associations between circulating and stimulated cytokine composites, within and across visits. Multiple linear regression was then used to test concurrent associations between the circulating and stimulated cytokine composites, and the within-person stability of each measure across visits, adjusting for sex, body mass index, perceived stress, physical activity, diet quality, and sleep quality.
Results
Study visits occurred 13 weeks ± 8 days apart. The circulating and stimulated cytokine composites were significantly correlated at visit 1 (r= 0.374, p<0.01) and at visit 2 (r=0.246, p = 0.02). This association remained significant in regression analyses at both visit 1 (B [95 % CI] = 0.407 [0.196, 0.617], p < 0.01) and visit 2 (B [95 % CI] = 0.312 [0.041, 0.584], p=0.03). The circulating cytokine composite at visit 1 was not significantly associated with the circulating cytokine composite at visit 2 in either correlation (r=-0.009, p=0.94) or regression (B [95 % CI] = -0.007 [-0.192, 0.179], p = 0.94) analyses. Stimulated cytokine production at visit 1 was significantly associated with stimulated cytokine production at visit 2 in both correlation (r=0.515, p<0.01) and regression analyses (B [95 % CI] = 0.497 [0.293 0.701], p<0.01).
Conclusions
Contrasting with some past research, circulating cytokines were significantly associated with stimulated cytokine production in the present sample concurrently at both visits. Stimulated cytokine production was more stable within-person across visits (∼13 weeks apart) compared to circulating cytokines in these students. Measurement of stimulated cytokines may be informative for understanding between-person differences in inflammation-related disease risk in younger adults, in part because they appear more stable compared to circulating cytokines.
{"title":"Systemic inflammation and ex vivo inflammatory responses in first semester university students","authors":"Kristin M. Davis , Molly A. Wright , Christopher G. Engeland , Kyle W. Murdock","doi":"10.1016/j.psyneuen.2025.107729","DOIUrl":"10.1016/j.psyneuen.2025.107729","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation contributes to cardiovascular and metabolic disease development. Reducing disease risk by targeting inflammation is therefore desirable in prevention research. However, circulating markers of inflammation are often difficult to detect in younger individuals. <em>Ex vivo</em> stimulated cytokine production offers a promising alternative measure of immune function. Yet, few studies among younger adults have used this measure to date or have assessed its reliability over time.</div></div><div><h3>Methods</h3><div>First-year university students (N = 110, age 18–19 years) completed two study visits, one each at the beginning and end of their first semester. Circulating cytokines and lipopolysaccharide-stimulated cytokine production were assayed at each visit; composites for each were created using IL-1β, IL-6, and IFN-γ. Analyses excluded participants with CRP ≥ 10 mg/L. Pearson’s correlations were used to examine unadjusted associations between circulating and stimulated cytokine composites, within and across visits. Multiple linear regression was then used to test concurrent associations between the circulating and stimulated cytokine composites, and the within-person stability of each measure across visits, adjusting for sex, body mass index, perceived stress, physical activity, diet quality, and sleep quality.</div></div><div><h3>Results</h3><div>Study visits occurred 13 weeks ± 8 days apart. The circulating and stimulated cytokine composites were significantly correlated at visit 1 (r= 0.374, p<0.01) and at visit 2 (r=0.246, p = 0.02). This association remained significant in regression analyses at both visit 1 (<em>B</em> [95 % CI] = 0.407 [0.196, 0.617], p < 0.01) and visit 2 (<em>B</em> [95 % CI] = 0.312 [0.041, 0.584], p=0.03). The circulating cytokine composite at visit 1 was not significantly associated with the circulating cytokine composite at visit 2 in either correlation (r=-0.009, p=0.94) o<em>r</em> regression (<em>B</em> [95 % CI] = -0.007 [-0.192, 0.179], p = 0.94) analyses. Stimulated cytokine production at visit 1 was significantly associated with stimulated cytokine production at visit 2 in both correlation (r=0.515, p<0.01) and regression analyses (<em>B</em> [95 % CI] = 0.497 [0.293 0.701], p<0.01).</div></div><div><h3>Conclusions</h3><div>Contrasting with some past research, circulating cytokines were significantly associated with stimulated cytokine production in the present sample concurrently at both visits. Stimulated cytokine production was more stable within-person across visits (∼13 weeks apart) compared to circulating cytokines in these students. Measurement of stimulated cytokines may be informative for understanding between-person differences in inflammation-related disease risk in younger adults, in part because they appear more stable compared to circulating cytokines.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107729"},"PeriodicalIF":3.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.psyneuen.2025.107726
Rafaela Mrdjen-Hodžić , Olga Malev , Natalija Novokmet , Jelena Šarac , Dubravka Havaš Auguštin , Saša Missoni , Sofia Ana Blažević
Background
Maternal psychosocial stress during pregnancy has been associated with long-term developmental and metabolic consequences in offspring. Cortisol, a primary stress hormone, plays a central role in this process, and its levels may be influenced by environmental factors, such as geographic isolation. The aim of this study was to investigate the association between place of residence (islands or mainland) and newborn-sex on maternal cortisol levels (as a physiological indicator of stress) and neonatal anthropometry in the first Croatian Islands’ Birth Cohort Study (CRIBS).
Methods
A total of N = 337 pregnant women from the CRIBS cohort were included: N = 188 residing on islands and N = 149 residing on the mainland. Maternal plasma cortisol levels were measured during the second trimester using High performance liquid chromatography (HPLC). Anthropometry and cortisol data were analyzed using appropriate parametric and non-parametric tests, two-way ANOVA or ANCOVA for group comparisons, and mixed-effects modeling for repeated measures.
Results
Pre- and post- pregnancy BMI values were elevated in women residing on the islands in comparison to women residing on the mainland. Cortisol levels, birth weight, birth length, and head circumference were influenced by newborn sex. Mothers carrying female offspring had higher cortisol levels and their offspring lower developmental outcomes, with greater differences observed among island residents for birth weight and length.
Conclusion
Fetal sex and environmental context (mainland vs. island) influence maternal HPA axis regulation and early developmental outcomes, suggesting that island residents may experience unique stressors related to their environment. Sex-specific associations in maternal cortisol and neonatal growth highlight the importance of considering fetal sex in studies of prenatal stress biology. Future work should clarify how geographic isolation influences prenatal stress biology and identify actionable risks to improve maternal and child health.
{"title":"Sex-specific associations between second-trimester maternal cortisol and neonatal outcomes in island and mainland populations","authors":"Rafaela Mrdjen-Hodžić , Olga Malev , Natalija Novokmet , Jelena Šarac , Dubravka Havaš Auguštin , Saša Missoni , Sofia Ana Blažević","doi":"10.1016/j.psyneuen.2025.107726","DOIUrl":"10.1016/j.psyneuen.2025.107726","url":null,"abstract":"<div><h3>Background</h3><div>Maternal psychosocial stress during pregnancy has been associated with long-term developmental and metabolic consequences in offspring. Cortisol, a primary stress hormone, plays a central role in this process, and its levels may be influenced by environmental factors, such as geographic isolation. The aim of this study was to investigate the association between place of residence (islands or mainland) and newborn-sex on maternal cortisol levels (as a physiological indicator of stress) and neonatal anthropometry in the first Croatian Islands’ Birth Cohort Study (CRIBS).</div></div><div><h3>Methods</h3><div>A total of N = 337 pregnant women from the CRIBS cohort were included: N = 188 residing on islands and N = 149 residing on the mainland. Maternal plasma cortisol levels were measured during the second trimester using High performance liquid chromatography (HPLC). Anthropometry and cortisol data were analyzed using appropriate parametric and non-parametric tests, two-way ANOVA or ANCOVA for group comparisons, and mixed-effects modeling for repeated measures.</div></div><div><h3>Results</h3><div>Pre- and post- pregnancy BMI values were elevated in women residing on the islands in comparison to women residing on the mainland. Cortisol levels, birth weight, birth length, and head circumference were influenced by newborn sex. Mothers carrying female offspring had higher cortisol levels and their offspring lower developmental outcomes, with greater differences observed among island residents for birth weight and length.</div></div><div><h3>Conclusion</h3><div>Fetal sex and environmental context (mainland vs. island) influence maternal HPA axis regulation and early developmental outcomes, suggesting that island residents may experience unique stressors related to their environment. Sex-specific associations in maternal cortisol and neonatal growth highlight the importance of considering fetal sex in studies of prenatal stress biology. Future work should clarify how geographic isolation influences prenatal stress biology and identify actionable risks to improve maternal and child health.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107726"},"PeriodicalIF":3.6,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-14DOI: 10.1016/j.psyneuen.2025.107728
Anna E. Soerensen , Stijn Vos , Marijke A.K.A. Braeken , Marion I. van den Heuvel , Bea R.H. Van den Bergh , Tim S. Nawrot
Background
Maternal distress has been associated with many offspring behavioural developmental outcomes, potentially through epigenetic modification of the glucocorticoid receptor NR3C1 or the imprinting control region between insulin-like growth factor 2 and H19 (IGF2/H19).
Methods
148 mother-infant pairs from the Prenatal Early Life Stress (PELS) cohort participated in this study. Maternal self-reported psychosocial and work-related factors were determined during pregnancy. NR3C1 and IGF2/H19 methylation levels were measured by bisulfite-pyrosequencing in the buccal cells of the infant (3–5 months). Infant and preschooler (4 years) temperament were assessed by the Infant- and Children’s Behavior Questionnaire (IBQ-R-vsf and CBQ-R-vsf, respectively). Linear mixed effect models, linear regression models and mediation analyses were used to test associations.
Findings
Maternal work-related physical and emotional demands were predictive of infant NR3C1 and IGF2/H19 methylation on several cytosine-phosphate-guanine sites. NR3C1 and IGF2/H19 methylation were associated with infant surgency. NR3C1 was found to mediate the association between maternal work-related physical demands and surgency in infancy.
Conclusions
Occupational stressors during pregnancy were shown to associate with NR3C1 and IGF2/H19 methylation in the infant, which may be linked with temperament.
{"title":"NR3C1 and IGF2/H19 methylation patterns predict infant and preschooler temperament: Links to maternal stress in pregnancy","authors":"Anna E. Soerensen , Stijn Vos , Marijke A.K.A. Braeken , Marion I. van den Heuvel , Bea R.H. Van den Bergh , Tim S. Nawrot","doi":"10.1016/j.psyneuen.2025.107728","DOIUrl":"10.1016/j.psyneuen.2025.107728","url":null,"abstract":"<div><h3>Background</h3><div>Maternal distress has been associated with many offspring behavioural developmental outcomes, potentially through epigenetic modification of the glucocorticoid receptor <em>NR3C1</em> or the imprinting control region between insulin-like growth factor 2 and <em>H19</em> (<em>IGF2/H19</em>).</div></div><div><h3>Methods</h3><div>148 mother-infant pairs from the Prenatal Early Life Stress (PELS) cohort participated in this study. Maternal self-reported psychosocial and work-related factors were determined during pregnancy. <em>NR3C1</em> and <em>IGF2/H19</em> methylation levels were measured by bisulfite-pyrosequencing in the buccal cells of the infant (3–5 months). Infant and preschooler (4 years) temperament were assessed by the Infant- and Children’s Behavior Questionnaire (IBQ-R-vsf and CBQ-R-vsf, respectively). Linear mixed effect models, linear regression models and mediation analyses were used to test associations.</div></div><div><h3>Findings</h3><div>Maternal work-related physical and emotional demands were predictive of infant <em>NR3C1</em> and <em>IGF2/H19</em> methylation on several cytosine-phosphate-guanine sites. <em>NR3C1</em> and <em>IGF2/H19</em> methylation were associated with infant surgency. <em>NR3C1</em> was found to mediate the association between maternal work-related physical demands and surgency in infancy.</div></div><div><h3>Conclusions</h3><div>Occupational stressors during pregnancy were shown to associate with <em>NR3C1</em> and <em>IGF2/H19</em> methylation in the infant, which may be linked with temperament.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107728"},"PeriodicalIF":3.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-14DOI: 10.1016/j.psyneuen.2025.107727
D. Cantini , P. Paletta , C. Sexton , C. Schmidt , M. Cha , D. Aspesi , S. McGuinness , K. LaDouceur , M. Kavaliers , E. Choleris
The estrogen, 17β-estradiol (E2), rapidly facilitates social recognition in various regions of the social brain network. The medial amygdala (MeA) is heavily involved in the processing of social cues and expresses the three main estrogen receptors (ER): ERα, ERβ, and G Protein-Coupled ER (GPER).
All ERs, as well as oxytocin and its receptor (OTR) in the MeA are crucial for social recognition in female mice, suggesting an interplay between ERs and OTR in the rapid facilitation of this social behavior. Here, we demonstrate an interplay between E2 and the three ERs (ERα, ERβ, GPER) with OTR in the MeA underlying the rapid facilitation of social recognition. Ovariectomized female mice were bilaterally infused with a sub-effective dose of OTR antagonist (i.e. the highest dose that does not prevent social recognition) into the MeA via indwelling cannulae, prior to an infusion of either E2 or one of the three ER agonists: ERα agonist PPT, ERβ agonist DPN, GPER agonist G1. A social recognition paradigm designed to measure rapid effects of treatment was employed. In all conditions, the sub-effective dose of OTR antagonist prevented the rapid facilitation of social recognition by E2 and each of the three ER agonists. The results show that E2 and the three main ERs require OTRs to rapidly facilitate social recognition in the MeA of female mice, thus demonstrating a rapid, likely non-genomic, interplay between the estrogen and oxytocin systems in social cognitive processing within a key region of the social brain.
{"title":"Estrogen and oxytocin receptors interplay in the medial amygdala to rapidly facilitate social recognition","authors":"D. Cantini , P. Paletta , C. Sexton , C. Schmidt , M. Cha , D. Aspesi , S. McGuinness , K. LaDouceur , M. Kavaliers , E. Choleris","doi":"10.1016/j.psyneuen.2025.107727","DOIUrl":"10.1016/j.psyneuen.2025.107727","url":null,"abstract":"<div><div>The estrogen, 17β-estradiol (E2), rapidly facilitates social recognition in various regions of the social brain network. The medial amygdala (MeA) is heavily involved in the processing of social cues and expresses the three main estrogen receptors (ER): ERα, ERβ, and G Protein-Coupled ER (GPER).</div><div>All ERs, as well as oxytocin and its receptor (OTR) in the MeA are crucial for social recognition in female mice, suggesting an interplay between ERs and OTR in the rapid facilitation of this social behavior. Here, we demonstrate an interplay between E2 and the three ERs (ERα, ERβ, GPER) with OTR in the MeA underlying the rapid facilitation of social recognition. Ovariectomized female mice were bilaterally infused with a sub-effective dose of OTR antagonist (i.e. the highest dose that does not prevent social recognition) into the MeA via indwelling cannulae, prior to an infusion of either E2 or one of the three ER agonists: ERα agonist PPT, ERβ agonist DPN, GPER agonist G1. A social recognition paradigm designed to measure rapid effects of treatment was employed. In all conditions, the sub-effective dose of OTR antagonist prevented the rapid facilitation of social recognition by E2 and each of the three ER agonists. The results show that E2 and the three main ERs require OTRs to rapidly facilitate social recognition in the MeA of female mice, thus demonstrating a rapid, likely non-genomic, interplay between the estrogen and oxytocin systems in social cognitive processing within a key region of the social brain.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107727"},"PeriodicalIF":3.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.psyneuen.2025.107722
Kendra L. Wilson , Bethany L. Boettner , Christopher R. Browning , Jodi L. Ford , Baldwin M. Way
Exposure to areas high in violent crime is a potent stressor that influences health outcomes by chronically undermining safety and upregulating biological stress responses. We tested the hypothesis that the association between cortisol, as measured in head hair, and inflammation, as measured by C-Reactive Protein (CRP) in capillary blood, is dependent on the degree of violent crime within adolescents’ everyday activity spaces. Because structural inequities cause Black adolescents to spend more time in areas with higher rates of violent crime, we tested this hypothesis in Black and White youth separately. 137 adolescents (Mage = 15.55, 57 % female, 52 % Black, 48 % White) participated in the study. We obtained continuous GPS-tracked data for one week to assess the average violent crime rate across the areas where participants spent time; biosamples were collected at the end of the week. Among Black adolescents, there was an interaction such that higher GPS-tracked activity space violent crime levels were associated with a positive and significant association between CRP and cortisol, consistent with models suggesting that stress can dysregulate immune-endocrine functioning. Conversely, for Black adolescents with low rates of exposure, cortisol had a negative association with CRP, consistent with a normative effect of glucocorticoid inhibition of inflammation. For White adolescents, cortisol and violence levels were significantly lower than for Black adolescents, and in this context, there was a weak main effect of violence exposure on CRP but no significant interaction. Results suggest the association between cortisol and inflammation varies across violent crime levels within the areas adolescents spend time and emphasize the importance of studying how an adolescent’s environment shapes biological responses to chronic stressors.
{"title":"The association between levels of GPS-tracked activity space violent crime and the relationship between cortisol and a biomarker of inflammation amongst Black and White adolescents","authors":"Kendra L. Wilson , Bethany L. Boettner , Christopher R. Browning , Jodi L. Ford , Baldwin M. Way","doi":"10.1016/j.psyneuen.2025.107722","DOIUrl":"10.1016/j.psyneuen.2025.107722","url":null,"abstract":"<div><div>Exposure to areas high in violent crime is a potent stressor that influences health outcomes by chronically undermining safety and upregulating biological stress responses. We tested the hypothesis that the association between cortisol, as measured in head hair, and inflammation, as measured by C-Reactive Protein (CRP) in capillary blood, is dependent on the degree of violent crime within adolescents’ everyday activity spaces. Because structural inequities cause Black adolescents to spend more time in areas with higher rates of violent crime, we tested this hypothesis in Black and White youth separately. 137 adolescents (M<sub>age</sub> = 15.55, 57 % female, 52 % Black, 48 % White) participated in the study. We obtained continuous GPS-tracked data for one week to assess the average violent crime rate across the areas where participants spent time; biosamples were collected at the end of the week. Among Black adolescents, there was an interaction such that higher GPS-tracked activity space violent crime levels were associated with a positive and significant association between CRP and cortisol, consistent with models suggesting that stress can dysregulate immune-endocrine functioning. Conversely, for Black adolescents with low rates of exposure, cortisol had a negative association with CRP, consistent with a normative effect of glucocorticoid inhibition of inflammation. For White adolescents, cortisol and violence levels were significantly lower than for Black adolescents, and in this context, there was a weak main effect of violence exposure on CRP but no significant interaction. Results suggest the association between cortisol and inflammation varies across violent crime levels within the areas adolescents spend time and emphasize the importance of studying how an adolescent’s environment shapes biological responses to chronic stressors.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107722"},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-11DOI: 10.1016/j.psyneuen.2025.107723
Ana Paula Toselli , Franco Baretta , Agustina Villegas , Oriana Micaela Casado , Franco Rafael Mir , María Angélica Rivarola
The perinatal environment critically shapes neurodevelopmental trajectories. Early life stress (ELS), particularly when associated with disrupted maternal care, has been linked to long-lasting neurobiological and behavioral alterations. This study explored the potential of gestational environmental enrichment (EE) to modulate these effects in a rodent model. Pregnant Wistar rats were housed under either EE or standard conditions (SC); offspring were subsequently exposed to stress paradigms, including maternal separation (MS), intruder male (IM) or no stress (NS) during lactation. In adolescence, males and females were evaluated for anxiety-like and social behaviors using elevated plus maze, open field, and social preference tests. A composite Z-score was calculated to provide a comprehensive measure of anxiety-related behaviors by integrating the parameters from the elevated plus maze and open field tests. Additionally, neuronal activity in regions associated with emotional and social regulation was analyzed. Our findings revealed significant sex-dependent differences in behavioral outcomes. Females exhibited reduced anxiety-like behaviors and greater exploratory activity than males, regardless of ELS exposure or gestational housing. Gestational EE mitigated anxiety-like behaviors, as indicated by reduced Z-scores and modulated social interaction patterns in both sexes, although specific effects varied according to stress condition. At the neural level, EE enhanced ΔFosB expression in the basolateral amygdala of MS offspring, while ELS reduced hippocampal ΔFosB, particularly in the dentate gyrus and CA2 regions. Moreover, sex-dependent patterns of ΔFosB activity emerged across amygdalar and hippocampal circuits, aligning with the behavioral differences observed. These results suggest that EE buffers ELS effects by differentially recruiting amygdalo-hippocampal circuits, highlighting sex-specific vulnerability and resilience mechanisms relevant to neurodevelopment.
{"title":"Gestational environmental enrichment modulates neurophysiological and behavioral outcomes in adolescent rats after early-life stress: Sex differences in emotional and social behavior","authors":"Ana Paula Toselli , Franco Baretta , Agustina Villegas , Oriana Micaela Casado , Franco Rafael Mir , María Angélica Rivarola","doi":"10.1016/j.psyneuen.2025.107723","DOIUrl":"10.1016/j.psyneuen.2025.107723","url":null,"abstract":"<div><div>The perinatal environment critically shapes neurodevelopmental trajectories. Early life stress (ELS), particularly when associated with disrupted maternal care, has been linked to long-lasting neurobiological and behavioral alterations. This study explored the potential of gestational environmental enrichment (EE) to modulate these effects in a rodent model. Pregnant Wistar rats were housed under either EE or standard conditions (SC); offspring were subsequently exposed to stress paradigms, including maternal separation (MS), intruder male (IM) or no stress (NS) during lactation. In adolescence, males and females were evaluated for anxiety-like and social behaviors using elevated plus maze, open field, and social preference tests. A composite Z-score was calculated to provide a comprehensive measure of anxiety-related behaviors by integrating the parameters from the elevated plus maze and open field tests. Additionally, neuronal activity in regions associated with emotional and social regulation was analyzed. Our findings revealed significant sex-dependent differences in behavioral outcomes. Females exhibited reduced anxiety-like behaviors and greater exploratory activity than males, regardless of ELS exposure or gestational housing. Gestational EE mitigated anxiety-like behaviors, as indicated by reduced Z-scores and modulated social interaction patterns in both sexes, although specific effects varied according to stress condition. At the neural level, EE enhanced ΔFosB expression in the basolateral amygdala of MS offspring, while ELS reduced hippocampal ΔFosB, particularly in the dentate gyrus and CA2 regions. Moreover, sex-dependent patterns of ΔFosB activity emerged across amygdalar and hippocampal circuits, aligning with the behavioral differences observed. These results suggest that EE buffers ELS effects by differentially recruiting amygdalo-hippocampal circuits, highlighting sex-specific vulnerability and resilience mechanisms relevant to neurodevelopment.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107723"},"PeriodicalIF":3.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-10DOI: 10.1016/j.psyneuen.2025.107724
Frederike Adammek , David Walzik , Alexander Schenk , Tobias Esser , Sina Trebing , Sarah Valder , Dennis Dreiskämper , Philipp Zimmer , Niklas Joisten
<div><h3>Background</h3><div>The biological foundation of changes in mental state after acute exercise is not yet understood, but it may be related to immunological alterations. The study investigated the hypothesis that the exercise-induced mobilization in circulating immune cells and cellular inflammation markers are associated with changes in the subjective mental state. As a secondary aim, the study investigated, wether the effects of the circulating immune cells are sex-dependent.</div></div><div><h3>Methods</h3><div>In a randomized cross-over trial, 24 young healthy adults (eight female; age 25.75 ± 4.35 years) completed a single exercise bout until exhaustion on a cycle ergometer and a passive control session. Outcomes were assessed immediately before, after the session, and 1 h, 3 h, 24 h, and 48 h after the session and comprise cell counts of leukocytes, lymphocytes, neutrophils and platelets, and the inflammation markers neutrophil-to-lymphocyte-ratio, platelet-to-lymphocyte-ratio and systemic-immune-inflammation-index as blood-based parameters, and subjective mental state measured using the Multidimensional-Mood-Questionnaire (MDMQ, subdomains <em>mood</em>, <em>energetic arousal</em>, <em>calmness</em>).</div></div><div><h3>Results</h3><div>There were significant time*group effects for all blood-based parameters (p < 0.001) and significant main effects of time for the MDMQ <em>mood</em> (p < 0.001) and <em>energetic arousal</em> (p = 0.008). No significant sex-dependent differences were obeserved. Within the intervention group, MDMQ <em>energetic arousal</em> showed significant correlations with lymphocytes (r<sub>rm</sub>=-0.41, p < 0.001), platelets (r<sub>rm</sub>=-0.28, p = 0.002), NLR (r<sub>rm</sub>=0.28, p = 0.002), PLR (r<sub>rm</sub>=0.33, p < 0.001), SII (r<sub>rm</sub>=0.269, p = 0.003) and MDMQ <em>calmness</em> showed significant correlations with leukocytes (r<sub>rm</sub>=-0.29, p = 0.002), lymphocytes (r<sub>rm</sub>=-0.36, p < 0.001), platelets (r<sub>rm</sub>=-0.30, p = 0.001), and PLR (r<sub>rm</sub>=0.25, p = 0.007). Within the control group, MDMQ <em>mood</em> showed significant correlations with lymphocytes (r<sub>rm</sub>=0.20, p = 0.031, NLR (r<sub>rm</sub>=-0.28, p = 0.002), PLR (r<sub>rm</sub>=-0.19, p = 0.033), SII (r<sub>rm</sub>=-0.24, p = 0.008) and MDMQ <em>calmness</em> showed significant correlations with PLR (r<sub>rm</sub>=-0.23, p = 0.011), SII (r<sub>rm</sub>=-0.20, p = 0.029). Fisher´s z-test revealed no significant difference between the correlations of the groups.</div></div><div><h3>Conclusion</h3><div>Acute exhaustive exercise affects immune cells, inflammation markers, and the subjective mental state regardless of sex. The correlation between blood-based parameters and the MDMQ appears to be robust and indicates relevant psychoneuroimmune associations in the human body. However, the acute exercise intervention used in this study does not influence this association.</div></div><
急性运动后精神状态变化的生物学基础尚不清楚，但可能与免疫改变有关。本研究探讨了运动诱导的循环免疫细胞动员和细胞炎症标志物与主观精神状态变化相关的假设。作为次要目的，该研究调查了循环免疫细胞的作用是否具有性别依赖性。方法在一项随机交叉试验中，24名年轻健康成人（8名女性，年龄25.75 ± 4.35岁）在自行车计力器和被动对照上完成一次运动，直到精疲力竭。结果在治疗前、治疗后以及治疗后1 h、3 h、24 h和48 h进行评估，包括白细胞、淋巴细胞、中性粒细胞和血小板的细胞计数，炎症标志物中性粒细胞与淋巴细胞比率、血小板与淋巴细胞比率和系统免疫炎症指数作为血液参数，以及使用多维情绪问卷（MDMQ、情绪子域、能量觉醒、平静）测量的主观精神状态。结果所有血液参数均存在显著的时间*组效应（p <； 0.001），MDMQ情绪（p <； 0.001）和能量觉醒（p = 0.008）均存在显著的时间主效应。未观察到显著的性别依赖性差异。在干预组,MDMQ能量唤醒显示显著的相关性淋巴细胞(rrm = -0.41, p & lt; 0.001)、血小板(rrm = -0.28, p = 0.002),NLR (rrm = 0.28, p = 0.002),PLR (rrm = 0.33, p & lt; 0.001),他们(rrm = 0.269, p = 0.003)和白细胞MDMQ冷静显示显著的相关性(rrm = -0.29, p = 0.002),淋巴细胞(rrm = -0.36, p & lt; 0.001)、血小板(rrm = -0.30, p = 0.001),和PLR (rrm = 0.25, p = 0.007)。在对照组,MDMQ情绪显示与淋巴细胞显著相关性(rrm = 0.20, p = 0.031,NLR (rrm = -0.28, p = 0.002),PLR (rrm = -0.19, p = 0.033),他们(rrm = -0.24, p = 0.008)和PLR MDMQ冷静显示显著的相关性(rrm = -0.23, p = 0.011),他们(rrm = -0.20, p = 0.029)。Fisher’s z检验显示组间相关性无显著差异。结论急性力竭运动对免疫细胞、炎症指标及主观精神状态均有影响。基于血液的参数和MDMQ之间的相关性似乎是强大的，并表明在人体内相关的精神神经免疫关联。然而，本研究中使用的急性运动干预并不影响这种关联。临床试验注册号drks00028792
{"title":"Immune cell mobilization after exhaustive exercise and its association with subjective mental state in young healthy adults: A randomized cross-over study","authors":"Frederike Adammek , David Walzik , Alexander Schenk , Tobias Esser , Sina Trebing , Sarah Valder , Dennis Dreiskämper , Philipp Zimmer , Niklas Joisten","doi":"10.1016/j.psyneuen.2025.107724","DOIUrl":"10.1016/j.psyneuen.2025.107724","url":null,"abstract":"<div><h3>Background</h3><div>The biological foundation of changes in mental state after acute exercise is not yet understood, but it may be related to immunological alterations. The study investigated the hypothesis that the exercise-induced mobilization in circulating immune cells and cellular inflammation markers are associated with changes in the subjective mental state. As a secondary aim, the study investigated, wether the effects of the circulating immune cells are sex-dependent.</div></div><div><h3>Methods</h3><div>In a randomized cross-over trial, 24 young healthy adults (eight female; age 25.75 ± 4.35 years) completed a single exercise bout until exhaustion on a cycle ergometer and a passive control session. Outcomes were assessed immediately before, after the session, and 1 h, 3 h, 24 h, and 48 h after the session and comprise cell counts of leukocytes, lymphocytes, neutrophils and platelets, and the inflammation markers neutrophil-to-lymphocyte-ratio, platelet-to-lymphocyte-ratio and systemic-immune-inflammation-index as blood-based parameters, and subjective mental state measured using the Multidimensional-Mood-Questionnaire (MDMQ, subdomains <em>mood</em>, <em>energetic arousal</em>, <em>calmness</em>).</div></div><div><h3>Results</h3><div>There were significant time*group effects for all blood-based parameters (p < 0.001) and significant main effects of time for the MDMQ <em>mood</em> (p < 0.001) and <em>energetic arousal</em> (p = 0.008). No significant sex-dependent differences were obeserved. Within the intervention group, MDMQ <em>energetic arousal</em> showed significant correlations with lymphocytes (r<sub>rm</sub>=-0.41, p < 0.001), platelets (r<sub>rm</sub>=-0.28, p = 0.002), NLR (r<sub>rm</sub>=0.28, p = 0.002), PLR (r<sub>rm</sub>=0.33, p < 0.001), SII (r<sub>rm</sub>=0.269, p = 0.003) and MDMQ <em>calmness</em> showed significant correlations with leukocytes (r<sub>rm</sub>=-0.29, p = 0.002), lymphocytes (r<sub>rm</sub>=-0.36, p < 0.001), platelets (r<sub>rm</sub>=-0.30, p = 0.001), and PLR (r<sub>rm</sub>=0.25, p = 0.007). Within the control group, MDMQ <em>mood</em> showed significant correlations with lymphocytes (r<sub>rm</sub>=0.20, p = 0.031, NLR (r<sub>rm</sub>=-0.28, p = 0.002), PLR (r<sub>rm</sub>=-0.19, p = 0.033), SII (r<sub>rm</sub>=-0.24, p = 0.008) and MDMQ <em>calmness</em> showed significant correlations with PLR (r<sub>rm</sub>=-0.23, p = 0.011), SII (r<sub>rm</sub>=-0.20, p = 0.029). Fisher´s z-test revealed no significant difference between the correlations of the groups.</div></div><div><h3>Conclusion</h3><div>Acute exhaustive exercise affects immune cells, inflammation markers, and the subjective mental state regardless of sex. The correlation between blood-based parameters and the MDMQ appears to be robust and indicates relevant psychoneuroimmune associations in the human body. However, the acute exercise intervention used in this study does not influence this association.</div></div><","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107724"},"PeriodicalIF":3.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1016/j.psyneuen.2025.107725
Maija Korpisaari , Anna-Maiju Leinonen , Tiina Ikäheimo , Mikko Tulppo , Marjo Seppänen , Sirkka Keinänen-Kiukaanniemi , Raija Korpelainen , Vahid Farrahi , Tiina Lankila
Purpose
It is known that physical activity (PA) helps improve physical and mental health; however, the association between longitudinal changes in PA and cumulative stress at midlife remains ill-defined. This study examined the association between leisure-time physical activity (LTPA) and chronic stress, quantified as allostatic load at midlife, in a population-based sample of Finnish adults.
Methods
We included members of the Northern Finland Birth Cohort 1966 (NFBC1966) who participated in follow-ups conducted at 31 and 46 years of age (n = 3358). Self-reported leisure-time moderate to vigorous physical activity (MVPA) levels were used to classify participants into two dichotomous groups based on World Health Organization recommendations for PA. According to changes in LTPA from 31 years to 46 years of age, participants were categorized into stable inactive, increased, decreased, and stable active groups. To ensure statistical robustness and enable comparison, two separate allostatic load indices (a 13-item index and a 5-item index) were used, based on biological markers collected in clinical examinations conducted at the 46-years-of-age follow-up. Poisson regression was used to analyze the strength of associations.
Results
From early adulthood to midlife, participants with stable inactivity (rate ratio, RR = 1.18, 95 % confidence interval, CI: 1.11–1.25) or decreasing LTPA (RR = 1.10, 95 % CI: 1.02–1.19) were at a higher risk of allostatic load with the 13-item index compared to those with stable active PA. With the 5-item allostatic load index, only stable inactivity was significantly associated with allostatic load (RR=1.17, 95 % CI: 1.07–1.28). Increased LTPA did not significantly differ from stable activity in terms of risk of allostatic load with the 13-item index (RR = 1.01, 95 % CI: 0.94–1.09) or the 5-item index (RR=1.04, 95 % CI: 0.93–1.15).
Conclusions
Both lower-than-recommended and decreasing LTPA levels through adulthood are associated with the accumulation of chronic stress when transitioning from early adulthood to midlife.
{"title":"Association of longitudinal changes in physical activity with allostatic load in midlife","authors":"Maija Korpisaari , Anna-Maiju Leinonen , Tiina Ikäheimo , Mikko Tulppo , Marjo Seppänen , Sirkka Keinänen-Kiukaanniemi , Raija Korpelainen , Vahid Farrahi , Tiina Lankila","doi":"10.1016/j.psyneuen.2025.107725","DOIUrl":"10.1016/j.psyneuen.2025.107725","url":null,"abstract":"<div><h3>Purpose</h3><div>It is known that physical activity (PA) helps improve physical and mental health; however, the association between longitudinal changes in PA and cumulative stress at midlife remains ill-defined. This study examined the association between leisure-time physical activity (LTPA) and chronic stress, quantified as allostatic load at midlife, in a population-based sample of Finnish adults.</div></div><div><h3>Methods</h3><div>We included members of the Northern Finland Birth Cohort 1966 (NFBC1966) who participated in follow-ups conducted at 31 and 46 years of age (n = 3358). Self-reported leisure-time moderate to vigorous physical activity (MVPA) levels were used to classify participants into two dichotomous groups based on World Health Organization recommendations for PA. According to changes in LTPA from 31 years to 46 years of age, participants were categorized into stable inactive, increased, decreased, and stable active groups. To ensure statistical robustness and enable comparison, two separate allostatic load indices (a 13-item index and a 5-item index) were used, based on biological markers collected in clinical examinations conducted at the 46-years-of-age follow-up. Poisson regression was used to analyze the strength of associations.</div></div><div><h3>Results</h3><div>From early adulthood to midlife, participants with stable inactivity (rate ratio, RR = 1.18, 95 % confidence interval, CI: 1.11–1.25) or decreasing LTPA (RR = 1.10, 95 % CI: 1.02–1.19) were at a higher risk of allostatic load with the 13-item index compared to those with stable active PA. With the 5-item allostatic load index, only stable inactivity was significantly associated with allostatic load (RR=1.17, 95 % CI: 1.07–1.28). Increased LTPA did not significantly differ from stable activity in terms of risk of allostatic load with the 13-item index (RR = 1.01, 95 % CI: 0.94–1.09) or the 5-item index (RR=1.04, 95 % CI: 0.93–1.15).</div></div><div><h3>Conclusions</h3><div>Both lower-than-recommended and decreasing LTPA levels through adulthood are associated with the accumulation of chronic stress when transitioning from early adulthood to midlife.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"184 ","pages":"Article 107725"},"PeriodicalIF":3.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fear conditioning protocols are widely used to investigate fear learning and regulation, with clinical implications for post-traumatic stress and anxiety disorders. In real-world settings, fear learning often occurs under stress, affecting memory strength and regulation. However, laboratory findings on stress effects remain inconsistent, possibly due to the lack of consideration for sex and menstrual-cycle groups, given sex hormones receptors' abundance in fear- and stress-related brain regions. This study examined the impact of 1) pre-acquisition stress and 2) cortisol reactivity on fear processes across sex and menstrual-cycle groups (hormonal data unavailable). A total of 208 participants were exposed to a stressor (men (n = 24), women using oral contraceptives (OCs; n = 25), and women with a menstrual cycle in the early follicular (EF; n = 24) or late follicular phase (LF; n = 26)) or control condition (men (n = 29), OCs (n = 23), EF (n = 26), LF (n = 31)) before undergoing fear acquisition (Context A), where two colors were paired with shock (CS+) and another was not (CS−). On Day 2, one CS+ and the CS− were presented without shock (Context B) for fear extinction learning. On Day 3, extinction recall (Context B) and renewal (Context A) were tested, with all stimuli presented without shock. Fear responses were assessed by skin conductance responses (SCR) and self-reported shock anticipation. Stress-exposed participants showed lower SCR during fear acquisition than controls. During extinction learning, control men exhibited greater SCR reduction than stressed men, whereas LF women showed the opposite pattern. No group differences emerged during extinction recall. During renewal, stressed LF women had lower SCR to the CS+ than their control counterparts. Additional analyses suggested that stressed men with lower cortisol reactivity had higher SCR during fear acquisition and renewal than those with higher cortisol reactivity. These findings indicate that stress exposure and cortisol reactivity differentially influence fear learning and regulation across sex and menstrual-cycle groups, in a context-dependent manner.
{"title":"Influence of pre-acquisition stress on fear learning and regulation as a function of sex and menstrual-cycle groups","authors":"Jessie Provencher , Clémence Peyrot , Marie-Charlotte Beaulieu , Marie-France Marin","doi":"10.1016/j.psyneuen.2025.107719","DOIUrl":"10.1016/j.psyneuen.2025.107719","url":null,"abstract":"<div><div>Fear conditioning protocols are widely used to investigate fear learning and regulation, with clinical implications for post-traumatic stress and anxiety disorders. In real-world settings, fear learning often occurs under stress, affecting memory strength and regulation. However, laboratory findings on stress effects remain inconsistent, possibly due to the lack of consideration for sex and menstrual-cycle groups, given sex hormones receptors' abundance in fear- and stress-related brain regions. This study examined the impact of 1) pre-acquisition stress and 2) cortisol reactivity on fear processes across sex and menstrual-cycle groups (hormonal data unavailable). A total of 208 participants were exposed to a stressor (men (n = 24), women using oral contraceptives (OCs; n = 25), and women with a menstrual cycle in the early follicular (EF; n = 24) or late follicular phase (LF; n = 26)) or control condition (men (n = 29), OCs (n = 23), EF (n = 26), LF (n = 31)) before undergoing fear acquisition (Context A), where two colors were paired with shock (CS+) and another was not (CS−). On Day 2, one CS+ and the CS− were presented without shock (Context B) for fear extinction learning. On Day 3, extinction recall (Context B) and renewal (Context A) were tested, with all stimuli presented without shock. Fear responses were assessed by skin conductance responses (SCR) and self-reported shock anticipation. Stress-exposed participants showed lower SCR during fear acquisition than controls. During extinction learning, control men exhibited greater SCR reduction than stressed men, whereas LF women showed the opposite pattern. No group differences emerged during extinction recall. During renewal, stressed LF women had lower SCR to the CS+ than their control counterparts. Additional analyses suggested that stressed men with lower cortisol reactivity had higher SCR during fear acquisition and renewal than those with higher cortisol reactivity. These findings indicate that stress exposure and cortisol reactivity differentially influence fear learning and regulation across sex and menstrual-cycle groups, in a context-dependent manner.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107719"},"PeriodicalIF":3.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In older adults with Type 2 Diabetes (T2D), hypothalamic-pituitary-adrenal (HPA) axis dysregulation accompanied by cognitive impairment has been reported. While the impact of HPA function on declarative memory (DM), working memory (WM), and executive function (EF) has received increased attention in aging research, its role in T2D remains largely unexplored. This study compared diurnal cortisol patterns and cognitive performance between 51 patients with T2D treated with oral antidiabetic medications, injectable therapies, or a combination of both, and 51 healthy controls matched for age, sex, educational level and, body mass index. Participants completed a battery of neuropsychological tests and the Beck Depression Inventory (BDI-II). Additionally, they provided four saliva samples per day across two weekdays to assess the cortisol awakening response (CAR) and the diurnal cortisol slope (DCS). Group comparisons (T2D vs. controls) and moderation analyses were conducted to assess group differences and the associations between cortisol indices and cognitive performance, with group or depression included as moderators. T2D patients showed poorer performance than healthy controls, particularly on DM and WM, but no significant differences in CAR or DCS. In controls, a higher CAR was related to lower Stroop interference, although no significant relationships were found in T2D patients. Across the entire sample, CAR was negatively associated with Stroop interference at low and moderate depression levels, while DCS was positively associated with RAVLT delayed recall at low levels of depression. Our results indicate that medically treated T2D patients show poorer cognitive performance than healthy controls; however, cortisol does not seem to contribute to these cognitive deficits. These findings add to the limited literature on the impact of the HPA on cognitive function in T2D older adults, and they encourage future studies to delve into the mechanisms that could influence cognitive performance in this population, as well the relevance of depression in these cognitive deficits.
{"title":"Diurnal cortisol cycle and cognitive performance in older people with Type 2 diabetes","authors":"Lorena Vallejo , Mariola Zapater-Fajarí , Teresa Montoliu , Vanesa Hidalgo , Alicia Salvador","doi":"10.1016/j.psyneuen.2025.107718","DOIUrl":"10.1016/j.psyneuen.2025.107718","url":null,"abstract":"<div><div>In older adults with Type 2 Diabetes (T2D), hypothalamic-pituitary-adrenal (HPA) axis dysregulation accompanied by cognitive impairment has been reported. While the impact of HPA function on declarative memory (DM), working memory (WM), and executive function (EF) has received increased attention in aging research, its role in T2D remains largely unexplored. This study compared diurnal cortisol patterns and cognitive performance between 51 patients with T2D treated with oral antidiabetic medications, injectable therapies, or a combination of both, and 51 healthy controls matched for age, sex, educational level and, body mass index. Participants completed a battery of neuropsychological tests and the Beck Depression Inventory (BDI-II). Additionally, they provided four saliva samples per day across two weekdays to assess the cortisol awakening response (CAR) and the diurnal cortisol slope (DCS). Group comparisons (T2D vs. controls) and moderation analyses were conducted to assess group differences and the associations between cortisol indices and cognitive performance, with group or depression included as moderators. T2D patients showed poorer performance than healthy controls, particularly on DM and WM, but no significant differences in CAR or DCS. In controls, a higher CAR was related to lower Stroop interference, although no significant relationships were found in T2D patients. Across the entire sample, CAR was negatively associated with Stroop interference at low and moderate depression levels, while DCS was positively associated with RAVLT delayed recall at low levels of depression. Our results indicate that medically treated T2D patients show poorer cognitive performance than healthy controls; however, cortisol does not seem to contribute to these cognitive deficits. These findings add to the limited literature on the impact of the HPA on cognitive function in T2D older adults, and they encourage future studies to delve into the mechanisms that could influence cognitive performance in this population, as well the relevance of depression in these cognitive deficits.</div></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":"185 ","pages":"Article 107718"},"PeriodicalIF":3.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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