Comprehensive psychoneuroendocrinology最新文献

{"title":"Metabolic syndromes mediate the association between depression and cardiovascular diseases in the UK Biobank Population Study","authors":"Tingting Lan ,&nbsp;Yanqing Zhu ,&nbsp;Guoqi Cai ,&nbsp;Faming Pan ,&nbsp;Mengmeng Wang","doi":"10.1016/j.cpnec.2026.100340","DOIUrl":"10.1016/j.cpnec.2026.100340","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to assess the potential mediating role of metabolic syndrome (MetS) between depression and cardiovascular disease (CVD).</div></div><div><h3>Methods</h3><div>This population-based prospective cohort study analyzed data collected between March 2006 and December 2010 from 353,610 participants aged 37 to 73 years from the UK Biobank. Depression was assessed using self-reported questionnaires and linked hospital-based clinical depression diagnosis. MetS was defined as the presence of 3 or more of unhealthy waist circumference, dyslipidemia, hypertension, hyperglycemia and hypertriglyceridemia. Incident CVD was identified through linked hospital and death records. Counterfactual-based mediation analysis was conducted to estimate the mediating effect.</div></div><div><h3>Results</h3><div>After an average follow-up of 15 years, 38424 CVD events occurred in 353,610 participants (55% women; mean age at baseline, 56 years). Study findings indicated a significant direct association between depression and CVD (HR = 1.310; 95% CI, 1.277-1.342). A significant indirect association was also observed between depression and CVD (HR = 1.035; 95% CI, 1.031-1.037), indicating that 12.9% of the association of depression with CVD was mediated by MetS. Among the components of MetS, unhealthy waist circumference showed the largest estimated mediated proportion (PM = 10.2%; NIE HR = 1.027). MetS accounted for a higher proportion of the association between depression and CVD in males (PM = 14.2%; NIE HR = 1.026), than females (PM = 11.2%; NIE HR = 1.034). Blood pressure mediated the association only in participants aged ≥55 years (PM = −2.2%).</div></div><div><h3>Conclusion</h3><div>MetS partially mediates the association between depression and CVD during midlife. Unhealthy waist circumference may be the most important potential target for preventive interventions.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100340"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357797","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 mediating roles of diet and physical activity in the association between different obesity phenotypes and risk of depression: A cox survival analysis approach","authors":"Yang Liu ,&nbsp;Yue Zheng ,&nbsp;Mingfang Wang ,&nbsp;Juan Liao ,&nbsp;Lu Long","doi":"10.1016/j.cpnec.2025.100332","DOIUrl":"10.1016/j.cpnec.2025.100332","url":null,"abstract":"<div><div>Although obesity has been linked to an increased risk of depression, the risk associated with different obesity phenotypes remain unclear, as does the role of lifestyle behaviors. Participants from the UK Biobank who were free of depression at the baseline and had complete data on body composition and metabolism-related measures were selected and followed up. Multivariable Cox models were employed to assess the risk of developing depression according to obesity phenotypes. Mediation analyses were conducted to evaluate the potential mediating effects of diet and physical activity in this association. Among 391,781 participants, a total of 20,027 incident depression was recorded after a median follow-up period of 13.39 years. Our study revealed that different obesity phenotypes increased the risk of depression to varying degrees. Compared with healthy non-obese individuals, those with BMI ≥30 kg/m² only had the lowest risk of depression (HR: 1.15, 95 %CI: 1.04, 1.28), and then followed by central obesity (HR: 1.60, 95 %CI: 1.51, 1.70), metabolically unhealthy obesity (HR: 1.63, 95 %CI: 1.56, 1.70). Sarcopenic obesity results in the highest risk of depression among these four phenotypes (HR: 1.86, 95 %CI: 1.40, 2.46). Both physical activity and diet mediated the effect of the four obesity phenotypes on the risk of depression. In the relationship between BMI ≥30 only and depression, physical activity mediated for 2.49 % and diet mediated for 1.60 %. Between metabolically unhealthy obesity and depression, physical activity mediated for 7.08 % and diet mediated for 1.86 %. This set of data was 5.29 % and 1.47 % in the relationship between central obesity and depression, and 6.22 % and 1.25 % in the relationship between sarcopenic obesity and depression. Subgroup analyses revealed that the female with obesity (including four types) had a higher risk of depression compared to the male, whereas individuals aged 60 years or older and those who were former or current smokers with obesity (except sarcopenic obesity) exhibited a lower risk of depression. These findings provide a basis for the prevention of obesity-depression comorbidity in obese patients.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100332"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939578","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":"Association between anxiety symptoms on risky e-biking riding behavior among adolescents: based on gut-brain axis","authors":"Liting Zhou ,&nbsp;Jiayu Liu ,&nbsp;Shuyi Li ,&nbsp;Yujun Xiong ,&nbsp;Feifeng Qin ,&nbsp;Zhongyun Luo ,&nbsp;Dongmei Huang ,&nbsp;Huihe Chen ,&nbsp;Xiaomin Wang","doi":"10.1016/j.cpnec.2026.100337","DOIUrl":"10.1016/j.cpnec.2026.100337","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the association between anxiety symptoms and risky e-bike riding behavior (RERB) among adolescents and to explore whether gut microbiota mediates this relationship.</div></div><div><h3>Methods</h3><div>Adolescents using e-bikes were recruited through a combined online and offline recruitment approach. Data collection involved supervised electronic questionnaire completion in face-to-face settings, with biological samples collected independently by participants. Anxiety symptoms were assessed using the Generalized Anxiety Disorder-7 scale. RERB were evaluated via a structured questionnaire, yielding separate scores for aggressive behaviors (ABS), violation behaviors (VBS), and negligent behaviors (NES), along with total behavior scores (TBS). Fecal samples were obtained for metagenomic sequencing to characterize gut microbiota composition. Multiple linear regression was employed to elucidate the associations between anxiety symptoms and RERB. Partial Least Squares Path Modeling (PLS-PM) was applied to evaluate the potential mediating role of gut microbiota in these associations.</div></div><div><h3>Results</h3><div>A total of 71 adolescents were included in this cross-sectional study. Anxiety symptoms were significantly associated with RERB, including TBS and VBS (both <em>P</em> &lt; 0.05). Among the 15 microbial genera identified from fecal samples, 17 species showed significant association with both anxiety symptoms and RERB. PLS-PM modeling revealed a significant mediating effect of specific gut microbiota in the anxiety→behavior pathway, particularly for TBS and VBS. In contrast, for ABS, a reverse pathway—microbiota→anxiety→behavior—was found significant.</div></div><div><h3>Conclusions</h3><div>Anxiety symptoms were significantly associated with RERB among adolescents. Specific gut microbiota may mediate these associations, suggesting a potential microbiota–brain–behavior pathway.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100337"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978541","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":"Reviewer Acknowledgement","authors":"","doi":"10.1016/j.cpnec.2026.100339","DOIUrl":"10.1016/j.cpnec.2026.100339","url":null,"abstract":"","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100339"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147420172","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 correlational study of the 24 solar terms and meteorological factors with the acute exacerbation of bipolar disorder","authors":"Jian Chen ,&nbsp;Tingting Wu ,&nbsp;Hongyu Wu ,&nbsp;Jingying Zhou ,&nbsp;Wenfei Li","doi":"10.1016/j.cpnec.2025.100336","DOIUrl":"10.1016/j.cpnec.2025.100336","url":null,"abstract":"<div><h3>Background</h3><div>Bipolar disorder (BD) is a severe mood disorder, and increasing evidence suggests that acute episodes of BD may exhibit seasonal patterns. However, the relationship between acute BD episodes and meteorological factors remains a contentious issue in academia. This study aims to investigate the distribution of BD acute episodes across 24 solar terms, offering a fresh perspective on the link between BD acute episodes and meteorological factors.</div></div><div><h3>Methods</h3><div>This analysis was based on retrospectively collected hospitalization records from patients with acute BD episodes at Anhui Mental Health Center (2020–2022), and contemporaneous meteorological data.</div></div><div><h3>Results</h3><div>The two peaks of BD manic episodes occurred during Rainwater and Grain in Ear solar terms, whereas the peak of depressive episodes was observed during Rainwater and Summer Solstice solar terms. BD manic episodes were significantly correlated with temperature differences, interday temperature differences and interday wind speed differences. Depressive episodes were significantly correlated with the temperature difference, interday wind speed difference and atmospheric pressure. Linear regression analysis revealed that the interday atmospheric pressure difference and interday temperature difference were significantly associated with acute BD episodes.</div></div><div><h3>Conclusion</h3><div>This study conducted a large-scale survey on the distribution of acute BD episodes across 24 solar terms in the Chinese population and their correlations with meteorological factors and sociodemographic characteristics. The findings indicate that the distribution of BD acute episodes varies across the 24 solar terms and that there is a correlation between BD acute episodes and certain meteorological factors, particularly drastic changes in temperature and atmospheric pressure, which may account for the differences in the number of BD acute episodes across the solar terms.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100336"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978540","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 effect of gender-affirming hormonal treatment on personality traits - a NEO-PI-R study","authors":"Mats Holmberg ,&nbsp;Alex Wallen ,&nbsp;Ivanka Savic","doi":"10.1016/j.cpnec.2026.100338","DOIUrl":"10.1016/j.cpnec.2026.100338","url":null,"abstract":"<div><h3>Introduction</h3><div>Gender-affirming hormone therapy is a crucial component of the medical transition for many transgender individuals. While there are well-established differences in personality traits between cisgender men and women, the effects of gender-affirming hormone therapy on these traits in transgender individuals remain largely unexplored.</div></div><div><h3>Aims</h3><div>The primary aim of this study was to investigate whether gender-affirming hormone therapy affects personality traits in transgender individuals.</div></div><div><h3>Materials and methods</h3><div>Adult transgender persons referred for gender-affirming hormone therapy to ANOVA, Center for Andrology, Sexual Medicine, and Trans Medicine at Karolinska University Hospital, Stockholm, Sweden, completed the NEO-PI-R inventory once before starting hormone therapy and once after a minimum of six months of either anti-androgen and estradiol treatment or testosterone therapy. Changes in scores were analyzed using the Wilcoxon Signed-Ranks Test. Patients who had any known hormonal, chromosomal, psychiatric, neurological, or other major medical disorders were excluded from the study.</div></div><div><h3>Results</h3><div>At baseline, the assigned female at birth (AFAB) had significantly higher NEO-PI-R scores in the dimension ”Agreeableness” and the facets E5 “Excitement seeking” and A2 ”Straightforwardness” compared to the assigned male at birth (AMAB). With treatment, the AMAB showed an increase in O3 “Feelings” (md = 2.00; IQR = 0.00−11.50; <em>p</em> = 1.5E-02) and the AFAB showed a decrease in “Neuroticism” (md = −2.00; IQR = −5.50−1.00; <em>p</em> = 3.8E-02), N3 “Depression” (md = −3.00; IQR = −8.25−3.00; <em>p</em> = 2.8E-02), and N6 “Vulnerability” (md = −4.50; IQR = −9.00−2.00; <em>p</em> = 90E-03), as well as an increase in “Actions” (median = 4.00; IQR = −2.50−8.00; <em>p</em> = 1.7E-02). After treatment, the greatest difference between the groups was seen in N6 “Vulnerabiliy”. In AMAB, significant negative correlations between the change in NEO-PI-R score and the change in estradiol were found in 2 dimensions and 6 facets.</div></div><div><h3>Conclusions</h3><div>Few changes in personality traits were observed, but they aligned with expectations based on established sex differences in personality traits. In general, more changes were observed in the testosterone treated group. The reduction in “Neuroticism” and “Vulnerability” in the AFAB with treatment, but a worsening or no change in the AMAB may be concerning. Further studies are needed to solidify these results and explore the underlying causes.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100338"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189134","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":"Corrigendum to \"Systemic inflammatory indices and the risk of depression in individuals with sleep difficulties: A cohort study based on NHANES 2005–2020\" [Compr. Psychoneuroendocrinology 23 (2025) 100299]","authors":"Ruolin Zhu ,&nbsp;Lu Wang ,&nbsp;Xingqi Wu ,&nbsp;Kai Wang","doi":"10.1016/j.cpnec.2025.100335","DOIUrl":"10.1016/j.cpnec.2025.100335","url":null,"abstract":"","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100335"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147420173","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-to-DHEAS awakening response ratio in people with dementia and family caregivers: Associations with age, dementia severity and agitation","authors":"Wanrui Wei ,&nbsp;Töres Theorell ,&nbsp;Gabriella Engstrom ,&nbsp;Azita Emami","doi":"10.1016/j.cpnec.2025.100334","DOIUrl":"10.1016/j.cpnec.2025.100334","url":null,"abstract":"<div><h3>Background</h3><div>The ratio of cortisol to dehydroepiandrosterone sulfate (DHEAS) in the awakening response has emerged as a potential biomarker of stress-related dysregulation in neurodegenerative conditions. Whether this ratio differs between people with dementia (PWD) and family caregivers, and how it varies with age, sex, dementia severity and agitation, remains unclear.</div></div><div><h3>Methods</h3><div>We analyzed 1093 day-level saliva samples from 58 participants (PWD = 28; caregivers = 30). The primary outcome was the log-transformed awakening response ratio of cortisol to DHEAS. Linear mixed-effects models with a participant random intercept and natural splines for age estimated group contrasts as geometric mean ratios (GMRs) from estimated marginal means. Fixed-effect predictors included age, sex, dementia severity (Global Deterioration Scale, GDS), and agitation (Brief Agitation Rating Scale, BARS). Model comparisons were conducted. Within PWD, mean-centered models tested one interaction at a time (Sex × GDS, Sex × BARS, Age × GDS, Age × BARS).</div></div><div><h3>Results</h3><div>There was no between-group difference in the ratio after accounting for within-participant clustering and age (GMR = 0.97, 95 % CI 0.64–1.46; <em>p</em> = 0.87). Within PWD, interaction models indicated that the association between age and the ratio strengthened with higher dementia severity (<em>β</em> = 0.043, <em>p</em> = 0.04) and greater agitation (<em>β</em> = 0.011, <em>p</em> = 0.006). Marginal R² ranged 0.114–0.141; conditional R² 0.358–0.376.</div></div><div><h3>Conclusions</h3><div>Although average ratio did not differ between PWD and caregivers, it increased more steeply with age at higher dementia severity and agitation. These findings highlight the cortisol-to-DHEA(S) awakening response ratio as a non-invasive and clinically relevant biomarker reflecting symptom-linked neuroendocrine heterogeneity in dementia.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100334"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939579","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":"Longitudinal trajectories of cancer-related cognitive impairment and influential factors among patients with lung cancer","authors":"Xiaoju Zhu ,&nbsp;Yalan Huang ,&nbsp;Haiwei Fu ,&nbsp;Sixiong Luo ,&nbsp;Yuanjing Jiang ,&nbsp;Zonghua Wang","doi":"10.1016/j.cpnec.2025.100330","DOIUrl":"10.1016/j.cpnec.2025.100330","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate longitudinal cognitive changes and identify factors associated with cancer-related cognitive impairment (CRCI) among lung cancer survivors.</div></div><div><h3>Methods</h3><div>Cognitive function was assessed using the FACT-Cog (subjective) and TICS-M (objective). The baseline assessment was completed before the use of chemotherapy drugs and recorded as T0. After completing the first cycle of chemotherapy, it was recorded as T1; after the second cycle, as T2; after the third cycle, as T3; after the fourth cycle, as T4; and after the fifth cycle, as T5. Linear mixed-effect models evaluated associations between clinical/sociodemographic factors and cognitive outcomes.</div></div><div><h3>Results</h3><div>Higher education level and later treatment progression were correlated with increased TICS-M scores. In contrast, Rural residence (β = −1.89, p = 0.021) and more comorbidities (β = −2.15, p = 0.033) were associated with reduced FACT-Cog scores. Treatment progression correlated with improved TICS-M scores (β = 0.716, p = 0.001). No significant differences were observed between the chemotherapy and chemoimmunotherapy groups (p &gt; 0.05). A key finding was the observed discordance between stable subjective reports and modestly improving objective scores over time. There was a discrepancy between subjective and objective cognitive evaluations, as FACT-Cog scores remained consistent over time (mean 129.8 ± 20.2), while TICS-M scores showed a slight improvement (from 23.4 ± 4.9 to 24.4 ± 3.7).</div></div><div><h3>Discussion</h3><div>The influence of education, residence, and comorbidities on CRCI trajectories in lung cancer patients highlights the need for integrated evaluation tools. This longitudinal analysis not only identifies distinct risk profiles for CRCI but also underscores the critical need for proactive screening and tailored supportive care programs. These priorities provide a guide for improving cognitive health outcomes in lung cancer survivorship care.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100330"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754166","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":"Maternal thyroid function in the first half of pregnancy and neurodevelopmental outcomes in early adolescence in the Amsterdam Born Children and their Development (ABCD) cohort","authors":"Sarai M. Keestra ,&nbsp;Susanne R. de Rooij ,&nbsp;Tessa J. Roseboom ,&nbsp;Marsh Königs ,&nbsp;Tanja GM. Vrijkotte ,&nbsp;Martijn J.J. Finken","doi":"10.1016/j.cpnec.2025.100333","DOIUrl":"10.1016/j.cpnec.2025.100333","url":null,"abstract":"<div><div>Maternal thyroid hormone levels in pregnancy have been implicated to play a role in brain development, but few observational studies have examined their relationship with neurodevelopmental outcomes beyond early childhood. We investigated associations between maternal thyroid function during the first 20 weeks of pregnancy and neurodevelopmental outcomes in 1824 children aged 10–13 years from the Amsterdam Born Children and their Development (ABCD) cohort. Outcomes included neurocognition (non-verbal intelligence [Raven's Progressive Matrices], executive working memory [SOPT]), behavioural organisation (behaviour regulation and metacognition [BRIEF], and internalizing behaviour and risk-seeking [SURPS]), and emotional, social, and behavioural problems (mother-, teacher-, and self-reported SDQ internalizing and externalizing problems). We fitted linear and quadratic multivariable regression models, as well as restricted cubic splines with three knots for the 10th, 50th and 90th percentiles, choosing the best model to assess associations across the continuous range of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) on the outcomes, both in pregnancies without overt thyroid disease and in the full cohort. Secondary analyses examined potential threshold effects (10th and 90th percentiles of TSH and FT4), and impact of clinical thyroid dysfunction based on cohort-specific reference ranges, anti-TPO positivity, and sex differences. We found a small but significant positive linear association between maternal log-transformed TSH in pregnancies free of overt thyroid disease and non-verbal intelligence in girls (estimate: 0.05, 95 % CI: 0.01 to 0.09, p = 0.02; SMD: 0.015), but not in boys, after correction for multiple testing. No other neurodevelopmental outcomes were associated with maternal thyroid function. These findings suggest that maternal thyroid function in early pregnancy, in the absence of overt thyroid disease, shows no consistent associations with child neurodevelopmental outcomes in adolescence, apart from a small association with non-verbal intelligence in girls that may not be clinically relevant.</div></div>","PeriodicalId":72656,"journal":{"name":"Comprehensive psychoneuroendocrinology","volume":"25 ","pages":"Article 100333"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939590","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}