Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Pharmacogenetics of obsessive-compulsive disorder: Investigations of intragenic and regulatory region genetic variations","authors":"Gwyneth Zai ,&nbsp;Clement C. Zai ,&nbsp;Vanessa F. Gonçalves ,&nbsp;Karen Wigg ,&nbsp;Christine Lochner ,&nbsp;Dan J. Stein ,&nbsp;Carol A. Mathews ,&nbsp;James L. Kennedy ,&nbsp;Margaret A. Richter","doi":"10.1016/j.pnpbp.2025.111315","DOIUrl":"10.1016/j.pnpbp.2025.111315","url":null,"abstract":"<div><div>Few pharmacogenetic studies on the use of genetic variations to predict antidepressant response in obsessive-compulsive disorder (OCD) have been published. This study expanded on the limited literature on single nucleotide polymorphisms (SNPs) across previously identified putative susceptibility genes for OCD, by incorporating known functional regulatory elements for all genes of interest. We investigated 17 SNPs in 12 genes implicated in OCD risk in 206 European ancestry OCD patients with selective serotonin reuptake inhibitor (SSRI) antidepressant response data, examining functional polymorphisms in remote regulatory regions. No association was observed between any regulatory region markers tested and drug response. We observed nominally significant associations between SNPs within the serotonin 1B receptor (<em>5HT1B</em>; SNP rs1778258), SLIT and NTRK-like family member 5 (<em>SLITRK5</em>; SNP rs10450811), and fas apoptotic inhibitory molecule 2 (<em>FAIM2</em>; SNP rs706795), with response to any SSRI, which did not survive multiple comparisons. This study supports a potential role for a number of OCD-associated risk genes in response to antidepressant treatment, warranting further investigation.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111315"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588277","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}

{"title":"Snapshot of disease continuum centered on Alzheimer's disease: Exploring modifiable risk factors","authors":"Ming Zheng MD, PhD","doi":"10.1016/j.pnpbp.2025.111316","DOIUrl":"10.1016/j.pnpbp.2025.111316","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a leading neurodegenerative disorder, characterized by progressive cognitive decline and memory impairment, with a complex etiology involving genetic, environmental, and lifestyle factors. Traditionally, AD has been studied in isolation, but emerging evidence highlights its interconnectedness with various comorbidities across multiple organ systems. This study introduces a Disease-Wide Association Study (DWAS) approach to explore the disease continuum centered around AD. Using the FinnGen cohort, which includes over 392,000 participants, this study systematically analyzed the comorbidities associated with AD, spanning cardiovascular, metabolic, musculoskeletal, digestive, and oncological conditions. These findings reveal that AD is part of a much broader, systemic disease continuum, with shared pathophysiological mechanisms, including chronic inflammation, metabolic dysregulation, and vascular health, which may influence AD onset and progression. Temporal analysis of pre- and post-AD comorbidities identifies modifiable risk factors such as hypertension, atherosclerosis, and type 2 diabetes that may not only precede AD but also exacerbate its progression. The study emphasizes the importance of an integrated care approach for AD patients, addressing both neurological and systemic health to improve outcomes. Furthermore, by identifying modifiable risk factors, this research opens new avenues for early interventions aimed at delaying or preventing AD. These findings challenge the traditional view of AD as an isolated disease and provide insights into the shared etiology of AD and its comorbidities, offering potential targets for personalized therapeutic strategies and public health policies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111316"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580268","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}

{"title":"Noradrenergic modulation of stress induced catecholamine release: Opposing influence of FG7142 and yohimbine","authors":"Vladimir Visocky,&nbsp;Carleigh J. Turner,&nbsp;Matthew H. Lowrie,&nbsp;Anthony Alibro,&nbsp;Fany Messanvi,&nbsp;Yogita Chudasama","doi":"10.1016/j.pnpbp.2025.111314","DOIUrl":"10.1016/j.pnpbp.2025.111314","url":null,"abstract":"<div><div>Life stress modulates decision making, particularly in the face of risk, in some cases prompting vulnerable populations to make suboptimal, life-altering choices. In the brain, stress is known to alter the extracellular release of catecholamines in structures such as basolateral amygdala (BLA) and nucleus accumbens (NAc), but the relationship between catecholamines and decision-making behavior under stress has not been systemically explored. We developed an operant touchscreen decision-making task for rats comprising elements of loss aversion and risk seeking behavior. Rats were first injected systemically with an adrenergic α_2A-receptor agonist (guanfacine) and antagonist (yohimbine), as well as a partial inverse GABA_A agonist, FG 7142, known to induce anxiety and stress related physiological responses in a variety of species, including humans. We then used fiber photometry to monitor NE in the basolateral amygdala (BLA), and DA activity in the nucleus accumbens (NAc) while animals engaged in decision-making and following systemic injections of FG 7142 and yohimbine. We found that neither yohimbine nor guanfacine had any impact on decision making strategy but altered motivational state with yohimbine making the animal almost insensitive to the reward outcome. The pharmacological induction of stress with FG 7142 biased the rats' decisions towards safety, but this bias shifted towards risk when co-treated with yohimbine. In the BLA and NAc, FG 7142 altered catecholamine release with systemic yohimbine producing opposing effects on NE and DA release. These findings highlight the catecholamine basis of loss aversion and neuromodulation of critical brain structures during stress through α2_A adrenoreceptors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111314"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588255","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}

{"title":"Improved recognition memory and reduced inflammation following β-caryophyllene treatment in the Wistar-Kyoto rodent model of treatment-resistant depression","authors":"Helen Clunas ,&nbsp;Samara Walpole ,&nbsp;Ilijana Babic ,&nbsp;Mayank Nair ,&nbsp;Naomi May ,&nbsp;Xu-Feng Huang ,&nbsp;Nadia Solowij ,&nbsp;Kelly A. Newell ,&nbsp;Katrina Weston-Green","doi":"10.1016/j.pnpbp.2025.111312","DOIUrl":"10.1016/j.pnpbp.2025.111312","url":null,"abstract":"<div><div>Persistent low mood, anxiety and cognitive deficits are common symptoms of depression and highly efficacious treatments that address symptoms including cognitive dysfunction are still required. β-caryophyllene (BCP) is a terpene with anti-inflammatory and pro-cognitive properties; however, its efficacy on cognition in depression remains unclear. This study aimed to investigate acute and chronic BCP treatment effects on cognitive, depressive- and anxiety-like behaviours, and inflammation in male and female Wistar-Kyoto (WKY) rats, a rodent model of treatment-resistant depression. Rats were administered either BCP (50 mg/kg) or vehicle (control). Open field (OFT), social interaction, sucrose preference, novel object recognition (NOR) and elevated plus maze (EPM) tests were conducted after acute (1 h) and chronic (2 weeks) treatment. Peripheral plasma inflammatory cytokine levels were examined. BCP acutely increased locomotor activity in the OFT but did not improve social interaction, whereas chronic BCP prevented increased latency to first interaction in females (not males). BCP did not improve sucrose preference or prevent anxiety-like behaviours in the EPM. BCP significantly increased novel object discrimination in the NOR test in male and female WKY rats and reduced cytokine levels after chronic treatment. This study shows for the first time that chronic BCP treatment improved recognition memory and exerted anti-inflammatory properties in a rodent model of depressive-like behaviours. BCP did not significantly improve anxiety-like behaviours, social interaction or anhedonia in WKY rats of either sex. These findings demonstrate the pro-cognitive effects of BCP in a rodent model of treatment-resistant depression worthy of further investigation.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111312"},"PeriodicalIF":5.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in behavioral and neural responses induced by witnessing social defeat stress during adolescence or adulthood in mice","authors":"Lucas Canto-de-Souza ,&nbsp;Daniela Baptista-de-Souza ,&nbsp;Mariana Thiele ,&nbsp;Vitor Gonçalves Garcia ,&nbsp;Katellyn Costa Silva ,&nbsp;Fernanda Victorino de Souza ,&nbsp;Carlos C. Crestani ,&nbsp;Ricardo Luiz Nunes-de-Souza","doi":"10.1016/j.pnpbp.2025.111313","DOIUrl":"10.1016/j.pnpbp.2025.111313","url":null,"abstract":"<div><div>Psychosocial stress can lead to emotional disorders and memory-related cognitive impairments. Evidence suggests that stress effects vary with age and sex, involving brain structures such as the medial prefrontal cortex (mPFC), amygdala, and hippocampus. This study hypothesized that witnessing social defeat stress (WSDS) during adolescence or adulthood would produce anxiety- and depression-like behaviors and cognitive deficits in adulthood, with outcomes affected by sex. We examined WSDS effects on male and female mice exposed during adolescence or adulthood, assessing: (i) social avoidance in the social interaction test, (ii) anxiety in the elevated plus-maze (EPM) and open field tests, (iii) cognition in the object recognition test, (iv) depression-like behaviors in the sucrose splash test, and (v) ΔFosB expression in neurons within the mPFC, basolateral amygdala (BLA) and dorsal hippocampus (DH). WSDS during adolescence resulted in reduced EPM open-arm exploration in both sexes and impaired novel object discrimination in males. In adulthood, WSDS reduced open-arm entries only in females and impaired novel object discrimination in both sexes. Female mice showed higher mPFC ΔFosB labeling than males, while control males exhibited higher labeling in the BLA and DH, which was not observed in WSDS mice. In conclusion, this study shows that WSDS during adolescence or adulthood induces anxiety-like behavior in both sexes, cognitive impairments in males, and sex-specific patterns of neuronal activation.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111313"},"PeriodicalIF":5.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574468","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}

{"title":"Genetic causal effects of multi-site chronic pain on post-traumatic stress disorder: Evidence from a two-sample, two-step Mendelian randomization study","authors":"Zuxing Wang ,&nbsp;Qiao Lu ,&nbsp;Shuyu Hou ,&nbsp;Hongru Zhu","doi":"10.1016/j.pnpbp.2025.111307","DOIUrl":"10.1016/j.pnpbp.2025.111307","url":null,"abstract":"<div><h3>Background</h3><div>Existing evidence supports a correlation between multi-site chronic pain and post-traumatic stress disorder (PTSD), but it is yet to be determined if this correlation is causal and in what direction the causation works.</div></div><div><h3>Methods</h3><div>Applying two-sample Mendelian randomization (MR) analysis to data from available genome-wide association studies in populations of European ancestry, we estimated the causal association between multi-site chronic pain and no pain versus PTSD. Moreover, we used multivariable and mediation MR analysis to assess the mediating effects of 13 lifestyle factors or diseases on the causal relationship between multi-site chronic pain and PTSD. The MR analyses were mainly conducted with the inverse variance weighted (IVW) method, followed by various sensitivity and validation analyses.</div></div><div><h3>Results</h3><div>Multi-site chronic pain dramatically increases the risk of developing PTSD (odds ratio [OR]_IVW = 2.39, 95 % confidence interval [CI] = 1.72–3.31, <em>p</em> = 2.10 × 10⁻⁷), and no pain significantly reduces the risk of developing PTSD (OR_IVW = 0.12, 95 % CI = 0.05–0.30, <em>p</em> = 3.14 × 10⁻⁶). Multivariable MR found that 13 potential confounding factors do not influence the causal effect of multi-site chronic pain on PTSD. Moreover, body mass index (BMI) (6.98 %), educational attainment (8.79 %), major depressive disorder (MDD) (36.98 %) and insomnia (27.25 %) mediate the causal connection between multi-site chronic pain and PTSD.</div></div><div><h3>Conclusion</h3><div>Overall, individuals with multi-site chronic pain may be at a higher risk of developing PTSD, and this risk is partially influenced by the pathways involving BMI, educational attainment, MDD, and insomnia. These factors offer potential targets for therapeutic interventions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111307"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552886","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}

{"title":"Evaluating the causal effects of circulating metabolic biomarkers on Alzheimer's disease","authors":"Jianbin Du ,&nbsp;Ancha Baranova ,&nbsp;Hongbao Cao ,&nbsp;Fuquan Zhang","doi":"10.1016/j.pnpbp.2025.111309","DOIUrl":"10.1016/j.pnpbp.2025.111309","url":null,"abstract":"<div><h3>Background</h3><div>The diagnosis and treatment of Alzheimer's disease (AD) is challenging due to the complexity of its pathogenesis. Although research suggests a link between circulating metabolites and AD, their causal relationship is not fully understood.</div></div><div><h3>Methods</h3><div>Based on publicly available genome-wide association study data, we investigated the causative relationship between AD (7759 cases and 334,740 controls) and 233 traits describing circulating metabolites (136,016 participants) using a two-sample Mendelian randomization (MR) method. We adopted the inverse variance weighted approach as the priority and performed sensitivity analyses with MR-Egger intercept method and Cochran's Q test.</div></div><div><h3>Results</h3><div>The overall causal effect of circulating metabolic traits on AD was significantly higher than the inverse effect (beta: 0.15 ± 0.42 <em>vs.</em> 0.04 ± 0.07; <em>p</em> &lt; 0.05). A total of 72 circulating metabolic traits (odd ratio (OR): 1.16–2.48) had a significant positive causal effect on AD, while a total of 16 circulating metabolic traits with significant negative causal effects on AD were detected (OR: 0.38–0.88). AD had a significant positive causal effect (OR: 1.02–1.17) on 142 circulating metabolic traits and a negative causal effect (OR: 0.87–0.99) on 43 circulating metabolic traits. Circulating metabolites that have a bi-directional causative relationship with AD mainly include apolipoprotein B levels, total cholesterol levels, total triglycerides levels, and omega-6 fatty acids levels.</div></div><div><h3>Conclusion</h3><div>The causative relationship between AD and the circulating metabolic traits is complex and bidirectional. Analyzing metabolites causally involved in the development of AD may provide clues for identifying preventive and therapeutic targets for this disorder.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111309"},"PeriodicalIF":5.3,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558876","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}

{"title":"Prediction of relapse in a French cohort of outpatients with schizophrenia (FACE-SZ): Prediction, not association.","authors":"Susana Barbosa ,&nbsp;Ryad Tamouza ,&nbsp;Marion Leboyer ,&nbsp;Bruno Aouizerate ,&nbsp;Christelle Andrieu ,&nbsp;Myrtille Andre ,&nbsp;Wahid Boukouaci ,&nbsp;Delphine Capdevielle ,&nbsp;Isabelle Chereau ,&nbsp;Julie Clauss Kobayashi ,&nbsp;Nathalie Coulon ,&nbsp;Jean-Michel Dorey ,&nbsp;Laetitia Davidovic ,&nbsp;Caroline Dubertret ,&nbsp;Eric Fakra ,&nbsp;Guillaume Fond ,&nbsp;Tudi Goze ,&nbsp;Olfa Khalfallah ,&nbsp;Sylvain Leignier ,&nbsp;Pierre Michel Llorca ,&nbsp;Ophélia Godin","doi":"10.1016/j.pnpbp.2025.111304","DOIUrl":"10.1016/j.pnpbp.2025.111304","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia (SZ) commonly manifests through multiple relapses, each impeding the path to recovery and incurring personal and societal costs. Despite the identification of various risk factors associated to the risk of relapse, the development of accurate algorithms predictive of relapse has been limited, partly due to inadequate statistical methods. Additionally, despite the wealth of data showing strong associations between inflammation and schizophrenia, the two existing studies failed to demonstrate whether inflammatory parameters could predict relapse. Our goal is then to identify clinical and inflammatory parameters associated with relapse in schizophrenia and to develop model to predict relapse in each patient.</div></div><div><h3>Methods</h3><div>We have used classical Cox regression, survival penalized regression, as well as survival random forests to analyze clinical and inflammatory biological data collected in the network of the Schizophrenia Expert Centers in France in which individuals with SZ are clinically assessed and followed up annually for 3 years.</div></div><div><h3>Results</h3><div>Among 247 individuals with SZ, 71 (29 %) experienced a psychotic relapse during the 3-year follow-up period. The variables most consistently associated with relapses were smoking status, severity of positive symptoms and low global functioning. From a panel of inflammatory parameters, only IL-8 serum levels were associated with time to relapse. The predictive performance, assessed using C-index, was 0.54 using both penalized regression and random forests.</div></div><div><h3>Conclusions</h3><div>We found several clinical and biological variables consistently associated with relapses across three distinct statistical methods. However, despite these associations, the predictive capacity of these models remained low, highlighting that association does not necessarily mean prediction.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111304"},"PeriodicalIF":5.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validating skin electrodes: Paving the way for non-invasive ERG use in psychiatry","authors":"Marc-André Dubois ,&nbsp;Charles-Antoine Pelletier ,&nbsp;Valérie Jomphe ,&nbsp;Richard E. Bélanger ,&nbsp;Simon Grondin ,&nbsp;Marc Hébert","doi":"10.1016/j.pnpbp.2025.111305","DOIUrl":"10.1016/j.pnpbp.2025.111305","url":null,"abstract":"<div><h3>Background</h3><div>Electroretinography (ERG) shows promise for identifying psychiatric biomarkers. The gold-standard approach relies on Dawson-Trick-Litzkow (DTL) electrodes and desktop equipment, but high costs and the expertise required for reliable electrode placement limit its implementation. This study evaluates a cost-effective alternative: a handheld ERG device paired with less invasive self-adhesive skin electrodes, which require minimal training.</div></div><div><h3>Methods</h3><div>ERG responses to cone and rod luminance stimuli were recorded from 49 participants: 15 controls (8 women, 7 men), 18 with bipolar disorder (12 women, 6 men), and 16 with schizophrenia (4 women, 12 men). Each participant underwent ERG testing with both electrode types.</div></div><div><h3>Results</h3><div>Skin electrodes produced significantly smaller amplitudes and shorter latencies than DTL electrodes, except for longer scotopic b-wave latency. Women showed higher amplitudes and shorter latencies than men for both electrode types, with the photopic a-wave amplitude relative difference doubling when using skin electrodes. Reproducibility between eyes was high for both electrode types, though slightly lower for photopic a-wave with skin electrodes (ICC 0.76 vs. 0.86 for DTL).</div></div><div><h3>Conclusion</h3><div>Skin electrodes paired with handheld ERG devices offer a viable, accessible alternative to traditional DTL electrodes paired with desktop equipment. This approach has the potential to expand the applicability of ERG in clinical settings by addressing barriers like cost, complexity, and invasiveness, while highlighting the need to consider sex differences in ERG assessments, particularly with skin electrodes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111305"},"PeriodicalIF":5.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryonic exposure of estrogen and BPA in zebrafish leads to ADHD-like and ASD-like phenotypes, respectively","authors":"Qiaosen Shen ,&nbsp;Feng Zhao ,&nbsp;Na Zhang ,&nbsp;Ling Zheng ,&nbsp;Dongmei Su ,&nbsp;Yongyi Qian ,&nbsp;Liu Xin ,&nbsp;Sun Mingxia ,&nbsp;Zhang Hongxu ,&nbsp;Fangyi Chen ,&nbsp;Wenhui Qiu ,&nbsp;Dong Liu","doi":"10.1016/j.pnpbp.2025.111293","DOIUrl":"10.1016/j.pnpbp.2025.111293","url":null,"abstract":"<div><div>Exposure to the estrogenic pollutant bisphenol A (BPA) during pregnancy and early childhood is a risk factor for numerous neurodevelopmental and psychiatric disorders in humans. To understand why early BPA exposure is associated with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we have analyzed a series of zebrafish behaviors, neurodevelopmental process, and gene expression profiles, after a moderate level of estrogen (17β-estradiol, E₂, as a positive control) and BPA treatments during embryogenesis (2–48 h post fertilization). E₂ exposure-caused hyperactivity was likely due to elevated expression of <em>cyp19a1b</em> since blocking aromatase activity rescued the defect. Furthermore, E₂ exposure resulted in impulsive behaviors, perhaps due to a reduced expression of brain <em>th</em> (crucial for dopamine synthesis), resembling the ADHD phenotypes. However, the hyperactivity upon BPA exposure was due to a reduction of GABAergic neurons, particularly in the midbrain. BPA-exposed fish were less-social, with increased repetitive behaviors and escape rate (during strobe light stimulation), like the ASD phenotypes. Taking advantage of published single-cell and bulk RNA-sequencing data related to zebrafish BPA exposure, we uncovered that embryonic midbrain GABAergic neurons express less <em>stmn1a</em> upon BPA exposure. When <em>stmn1a</em> function was partially lost, 14-day post-fertilization larvae became less social, further stressing the ASD phenotype after BPA exposure. Upon embryonic E₂ and BPA exposure, we have unexpectedly unveiled zebrafish ADHD-like and ASD-like phenotypes, respectively, suggesting that women of childbearing age should be cautious to use BPA and estrogen related products.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111293"},"PeriodicalIF":5.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532190","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}