Molecular Psychiatry最新文献

{"title":"40Hz transcranial alternating current stimulation enhance insomnia treatment efficacy: a pilot study","authors":"Qi Zhou, Xiaoqian Guo, Xiaolin Zheng, Qicheng Tao, Chang Li, Yafang Tang, Zhiwang Liu, Guolin Jin, Dongsheng Zhou","doi":"10.1038/s41380-025-03001-4","DOIUrl":"https://doi.org/10.1038/s41380-025-03001-4","url":null,"abstract":"<p>Insomnia is a prevalent clinical condition characterized by difficulty for patients to initiate and/or stay in sleep along with common comorbidities such as irritability or fatigue during wakefulness [1]. Study found that insomnia patients show declines in cognitive abilities such as working memory and aspects of execution [2]. Currently, pharmacotherapy and cognitive-behavioral therapy for insomnia (CBT-I) are the primary treatment methods in clinical practice, but the effects of drug tolerance, dependence, and side effects, as well as CBT-I in terms of compliance, treatment professionalism, and their efficacy appears to vary among individuals [3]. Therefore, various neuromodulation techniques, such as magnetic stimulation, electrical stimulation, and light stimulation, strive to provide innovative therapeutic alternatives.</p><p>Flickering light stimulation is a non-invasive neuromodulation technique that has promising futures in alleviating pathological changes in insomnia [4]. Current research hypothesized that the therapeutic effect of light flickering stands on the fundamentals of brain entrainment, such as repetitive and regular stimulation of light, sound or other electrical and magnetic signals could prompt the brain to produce brain waves in the matching frequency, and 40 Hz light induce the strongest gamma oscillation [5, 6]. Even though studies conducted specifically on light flickering and insomnia is yet limited, we are going to introduce a new study below that demonstrates the specific neurochemical basis for 40 Hz flickering and how its therapeutic effect on insomnia was achieved [7].</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"54 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MMP-2/9 inhibition modulates sharp wave abundance, inhibitory proteoglycan sulfation, and fear memory in juvenile zebrafish: relevance to affective disorders","authors":"Ismary Blanco, Samantha Deasy, Matthew Amontree, Miranda Gabriel, Adam Caccavano, Stefano Vicini, Eric Glasgow, Katherine Conant","doi":"10.1038/s41380-025-03007-y","DOIUrl":"https://doi.org/10.1038/s41380-025-03007-y","url":null,"abstract":"<p>Sharp wave ripple (SWR) events, present in diverse species, spontaneously occur in the hippocampus during quiescent restfulness and slow-wave sleep. SWRs comprise a negative deflection, the sharp wave (SW) event with an often-superimposed ripple (R) and are the neural correlates of memory consolidation and recall. The Anterodorsolateral lobe (ADL) (zebrafish hippocampal homolog) exhibits SW and SWR events, and since SWs initiate SWRs, their abundance typically shows the same directionality. In previous work, we observed matrix metalloproteinase-9 (MMP-9)-dependent effects on depression-relevant behaviors, perineuronal net (PNN) levels, and SWR abundance in the adult rodent hippocampus. Here, we investigate MMP-2/9-dependent effects on biochemical, behavioral, and neurophysiological endpoints in juvenile zebrafish and zebrafish at the transition from the late juvenile period to early adulthood. With MMP-2/9 inhibition, juvenile zebrafish showed reduced SW amplitude and abundance together with increased fear memory retention and decreased sociability. Juvenile zebrafish also showed an increased percentage of longer-duration SW events. Except for a reduction in SW amplitude, these changes were not observed at the transition from late juvenile to early adulthood. These changes were accompanied by increased levels of chondroitin sulfate (CS) proteoglycan 4-<i>O</i>-sulfation, which modulates PNNs and excitatory-to-inhibitory (E/I) balance. Discontinuation of MMP-2/9 inhibition in juvenile zebrafish normalized deficits in ADL SW abundance and sociability. Together, these findings show that MMP-2/9 significantly influences E/I balance and learning and memory during the highly plastic juvenile period. Findings also have relevance to an emerging appreciation of PNN changes that may contribute to altered neuronal oscillations and mood or cognition.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"35 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving","authors":"Eun-Kyung Hwang, Amanda M. Wunsch, Marina E. Wolf","doi":"10.1038/s41380-025-03026-9","DOIUrl":"https://doi.org/10.1038/s41380-025-03026-9","url":null,"abstract":"<p>Incubation of cocaine craving, a translationally relevant model for the persistence of drug craving during abstinence, ultimately depends on strengthening of nucleus accumbens core (NAcc) synapses through synaptic insertion of homomeric GluA1 Ca²⁺-permeable AMPA receptors (CP-AMPARs). Here we tested the hypothesis that CP-AMPAR upregulation results from a form of homeostatic plasticity, previously characterized in vitro and in other brain regions, that depends on retinoic acid (RA) signaling in dendrites. Under normal conditions, ongoing synaptic transmission maintains intracellular Ca²⁺ at levels sufficient to suppress RA synthesis. Prolonged blockade of neuronal activity results in disinhibition of RA synthesis, leading to increased GluA1 translation and synaptic insertion of homomeric GluA1 CP-AMPARs. Using slice recordings, we found that increasing RA signaling in NAcc medium spiny neurons (MSN) from drug-naïve rats rapidly upregulates CP-AMPARs. This is observed only in MSN expressing the D1 dopamine receptor. In MSN recorded from rats that have undergone incubation of craving, we observe CP-AMPAR upregulation in D1 MSN (but not D2 MSN) and the effect of exogenous RA application is occluded in these D1 MSN. Instead, interruption of RA signaling in the slice normalizes the incubation-associated elevation of synaptic CP-AMPARs. Paralleling this in vitro finding, interruption of RA signaling in the NAcc of ‘incubated rats’ normalizes elevated cue-induced cocaine seeking back to non-incubated levels. These results suggest that RA signaling becomes tonically active in the NAcc during cocaine withdrawal and, by maintaining elevated CP-AMPAR levels, contributes to the incubation of cocaine craving.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"44 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emergence of chronic diseases of adulthood and middle age in the young: the COIDS (chronic inflammation, obesity, insulin resistance/type 2 diabetes, and depressive syndromes) noxious quartet of pro-inflammatory stress outcomes","authors":"Julio Licinio, Alice W. Licinio, João Vicente Busnello, Luciana Ribeiro, Philip W. Gold, Stefan R. Bornstein, Ma-Li Wong","doi":"10.1038/s41380-025-03034-9","DOIUrl":"https://doi.org/10.1038/s41380-025-03034-9","url":null,"abstract":"<p>Major depression, type 2 diabetes, and essential (primary) hypertension are chronic medical and psychiatric disorders that have traditionally affected primarily adults and middle-aged individuals. However, recent decades have witnessed an increasing prevalence of these conditions among children and adolescents. For diseases that typically require prolonged exposure to risk factors to emerge in childhood and adolescence, the amount of exposure to a single risk factor would have to be exceptionally high. We advance the alternative hypothesis of multiple factors acting synergistically. Biological mechanisms underlying the response to ongoing (chronic) stress are logical candidates for being a shared pathway. In the context of persistent and synergistic psychological, social, and economic pressures, unremitting stress can lead to such disease outcomes, exerting a direct influence on the emergence of chronic disorders, and it can also contribute to obesity. Depression follows the same trajectory; therefore, we should examine it as an entity whose consequences are directly reflected in behavioral outcomes, including (over-) eating. Other contributing pathways include chronic sleep deprivation, epigenetic modifications, telomere shortening, the physical environment, pathogens, and the microbiome. We introduce here the concept of the Chronic inflammation, Obesity, Insulin resistance/type 2 diabetes, and Depressive Syndromes (COIDS) noxious quartet of pro-inflammatory stress outcomes, as an increasingly common pathophysiologic state, representing a distinct presentation of type 2 allostatic overload, with direct implications for the current chronic disease epidemic. The compounded effects of a pro-inflammatory state that is fueled by four different and co-existing sources may contribute to explain the emergence of chronic diseases of adulthood and middle age in the young. PPARγ might represent a potential translational therapeutic target for those with COIDS. We propose that highly adverse environments sustain sufficient chronic stress to bring about in the young diseases that had been previously confined to adults.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"34 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer’s disease patient brain extracts induce multiple pathologies in novel vascularized neuroimmune organoids for disease modeling and drug discovery","authors":"Yanru Ji, Xiaoling Chen, Zhen Wang, Connor Joseph Meek, Jenna Lillie McLean, Yang Yang, Chongli Yuan, Jean-Christophe Rochet, Fei Liu, Ranjie Xu","doi":"10.1038/s41380-025-03041-w","DOIUrl":"https://doi.org/10.1038/s41380-025-03041-w","url":null,"abstract":"<p>Alzheimer’s Disease (AD) is the most common cause of dementia, afflicting 55 million individuals worldwide, with limited treatment available. Current AD models mainly focus on familial AD (fAD), which is due to genetic mutations. However, models for studying sporadic AD (sAD), which represents over 95% of AD cases without specific genetic mutations, are severely limited. Moreover, the fundamental species differences between humans and animals might significantly contribute to clinical failures for AD therapeutics that have shown success in animal models, highlighting the urgency to develop more translational human models for studying AD, particularly sAD. In this study, we developed a complex human pluripotent stem cell (hPSC)-based vascularized neuroimmune organoid model, which contains multiple cell types affected in human AD brains, including human neurons, microglia, astrocytes, and blood vessels. Importantly, we demonstrated that brain extracts from individuals with sAD can effectively induce multiple AD pathologies in organoids four weeks post-exposure, including amyloid beta (Aβ) plaque-like aggregates, tau tangle-like aggregates, neuroinflammation, elevated microglial synaptic pruning, synapse/neuronal loss, and impaired neural network activity. Proteomics analysis also revealed disrupted AD-related pathways in our vascularized AD neuroimmune organoids. Furthermore, after treatment with Lecanemab, an FDA-approved antibody drug targeting Aβ, AD brain extracts exposed organoids showed a significant reduction of amyloid burden, along with an elevated vascular inflammation response. Thus, the vascularized neuroimmune organoid model provides a unique opportunity to study AD, particularly sAD, under a pathophysiological relevant three-dimensional (3D) human cell environment. It also holds great promise to facilitate AD drug development, particularly for immunotherapies.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"15 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic and epigenomic consequences of heterozygous loss-of-function mutations in AKAP11, a shared risk gene for bipolar disorder and schizophrenia","authors":"Nargess Farhangdoost, Calwing Liao, Yumin Liu, Daniel Rochefort, Farah Aboasali, Alessia Pietrantonio, Martin Alda, Patrick A. Dion, Boris Chaumette, Anouar Khayachi, Guy A. Rouleau","doi":"10.1038/s41380-025-03040-x","DOIUrl":"https://doi.org/10.1038/s41380-025-03040-x","url":null,"abstract":"<p>The gene A-kinase anchoring protein 11 (<i>AKAP11</i>) recently emerged as a shared risk factor between bipolar disorder and schizophrenia, driven by large-effect loss-of-function (LoF) variants. Recent research has uncovered the neurophysiological characteristics and synapse proteomics profile of <i>Akap11</i>-mutant mouse models. Considering the role of AKAP11 in binding cAMP-dependent protein kinase A (PKA) and mediating phosphorylation of numerous substrates, such as transcription factors and epigenetic regulators, and given that chromatin alterations have been implicated in the brains of patients with bipolar disorder and schizophrenia, it is crucial to uncover the transcriptomic and chromatin dysregulations following the heterozygous knockout of <i>AKAP11</i>, particularly in human neurons. This study uses genome-wide approaches to investigate such aberrations in human induced pluripotent stem cell (iPSC)-derived neurons. We show the impact of heterozygous <i>AKAP11</i> LoF mutations on the gene expression landscape and profile the DNA methylation and histone acetylation modifications. Altogether we highlight the involvement of aberrant activity of intergenic and intronic enhancers, which are enriched in PBX homeobox 2 (PBX2) and Nuclear Factor-1 (NF1) known binding motifs, respectively, in transcription dysregulations of genes mainly involved in DNA-binding transcription factor activity, actin binding and cytoskeleton regulation, and cytokine receptor binding. We also show significant downregulation of pathways related to ribosome structure and function, a pathway also altered in BD and SCZ post-mortem brain tissues and heterozygous <i>Akap11</i>-KO mice synapse proteomics. A better understanding of the dysregulations resulting from haploinsufficiency in <i>AKAP11</i> improves our knowledge of the biological roots and pathophysiology of BD and SCZ, paving the way for better therapeutic approaches.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"112 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term clinical outcome of a novel bilateral capsulotomy with focused ultrasound in refractory obsessive-compulsive disorder treatment.","authors":"Kyung Won Chang, Jhin Goo Chang, Hyun Ho Jung, Chan-Hyung Kim, Jin Woo Chang, Se Joo Kim","doi":"10.1038/s41380-024-02799-9","DOIUrl":"10.1038/s41380-024-02799-9","url":null,"abstract":"<p><p>Magnetic resonance-guided focused ultrasound (MRgFUS) capsulotomy is a promising treatment for refractory obsessive-compulsive disorder (OCD); however, long-term clinical outcome studies are lacking. We aimed to investigate the long-term efficacy and safety of MRgFUS capsulotomy in patients with refractory OCD. Ten of the eleven patients who underwent MRgFUS capsulotomy for treatment-resistant OCD between 2013 and 2014 were included in this study. Clinical outcomes were assessed after 10 years of follow-up post-MRgFUS capsulotomy using tools such as neuropsychological test, the Frontal Systems Behavior Scale (FrSBe), and a locally developed MRgFUS-patient-centered outcomes questionnaire. After 10 years of follow-up, there was a mean improvement of 52.3% in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score. Seven out of the ten participants responded fully (Y-BOCS reduction ≥35% + CGI-I 1 or 2) to the procedure, two of whom achieved remission (Y-BOCS score ≤12 and CGI-S 1 or 2). Obsessive-compulsive symptoms and overall functioning significantly reduced and improved, respectively (Y-BOCS = 20.7 after 2 years vs. 16.4 after 10 years, p = 0.012; Global Assessment of Functioning = 57.4 after 2 years vs. 69.0 after 10 years, p = 0.011). The patients experienced significantly improved frontal lobe-related functions (FrSBe Sum before 91.0 ± 17.6 vs. after 78.6 ± 17.7, p < 0.05). No adverse effects, including cases of suicide and neurological deficits, were reported. The majority of the respondents were generally satisfied with MRgFUS capsulotomy. MRgFUS capsulotomy is an effective and safe treatment option for the treatment of severe refractory OCD with sustained efficacy even after 10 years.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":"1897-1905"},"PeriodicalIF":9.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and risk factors of antidepressant withdrawal symptoms: a meta-analysis and systematic review.","authors":"Mi-Mi Zhang, Xuan Tan, Yong-Bo Zheng, Na Zeng, Zhe Li, Mark Abie Horowitz, Xue-Zhu Feng, Ke Wang, Zi-Yi Li, Wei-Li Zhu, Xinyu Zhou, Peng Xie, Xiujun Zhang, Yumei Wang, Jie Shi, Yan-Ping Bao, Lin Lu, Su-Xia Li","doi":"10.1038/s41380-024-02782-4","DOIUrl":"10.1038/s41380-024-02782-4","url":null,"abstract":"<p><p>Antidepressants are among the most extensively prescribed psychotropic drugs worldwide. Discontinuation induced withdrawal symptoms have been reported for almost all antidepressants. The incidence of antidepressant withdrawal syndrome (AWS) and other characteristics remain unknown. We searched the PubMed, Embase, PsycINFO, MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials databases from inception to December 31, 2023. Randomized double-blinded trials, longitudinal or cross-sectional studies that reported the incidence and other characteristics of antidepressant withdrawal symptoms were included. The pooled incidence of AWS was calculated by a random effects model. We included 35 studies, of which 2 studies just provided incidence of specific withdrawal symptoms, and 4 studies only described other characteristics. The pooled incidence of AWS from all available studies was 42.9%, from 11 RCTs was 44.4%, in studies in which the treatment duration was mostly 8-12 weeks, which usually appear within 2 weeks, and were generally measured for <4 weeks. The incidence in selective serotonin-norepinephrine reuptake inhibitors was the lowest (29.7%), followed by selective serotonin reuptake inhibitors (45.6%) and tricyclic antidepressants (59.7%), without significant differences (p = 0.221). Treatment duration showed a dose-response to the incidence of AWS (6-12 W: 35.1%, 12-24 W: 42.7%, >24 W: 51.4%). The half-life did not show such a simple dose-dependent relationship. The pooled estimate was robust regardless whether withdrawal symptoms were measured in RCTs or observational studies (including face-to-face and online survey studies). Tapering the dose reduced the incidence of AWS compared with abrupt stoppage (34.5% vs 42.5%), without a significant difference (p = 0.484). Risk factors for withdrawal symptoms included being female, younger, experiencing adverse effects early in treatment, taking higher doses or longer duration of medication, abrupt cessation of drugs, and those with a lower clearance of drugs or with serotonin 1A receptor gene variation. The findings suggest the incidence of AWS are common and some clinical characteristics and risk factors which can help clinicians identify who is at greater risk of experiencing AWS. Discontinuation studies on long-term antidepressant users with long follow-up periods are required in the future.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":"1758-1769"},"PeriodicalIF":9.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder.","authors":"Gitte Bundgaard Christiansen, Liselotte Vogdrup Petersen, Hannah Chatwin, Zeynep Yilmaz, Diana Schendel, Cynthia M Bulik, Jakob Grove, Isabell Brikell, Birgitte Dige Semark, Katrine Holde, Mohamed Abdulkadir, Christopher Hübel, Clara Albiñana, Bjarni Jóhann Vilhjálmsson, Anders D Børglum, Ditte Demontis, Preben Bo Mortensen, Janne Tidselbak Larsen","doi":"10.1038/s41380-024-02825-w","DOIUrl":"10.1038/s41380-024-02825-w","url":null,"abstract":"<p><p>Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins. Cox regression was used to estimate associations between EDs and ADHD or ASD, and mediation analysis was used to assess the effects of intermediate mood or anxiety disorders. Polygenic scores (PGSs) were used to investigate the genetic association between anorexia nervosa (AN) and ADHD or ASD. Significantly increased risk for any ED was observed following an ADHD or ASD diagnosis. Mediation analysis suggested that intermediate mood or anxiety disorders could account for 44%-100% of the association between ADHD or ASD and ED. Individuals with a full sibling or maternal half sibling with ASD had increased risk of AN compared to those with siblings without ASD. A positive association was found between ASD-PGS and AN risk whereas a negative association was found between AN-PGS and ADHD. In this study, positive phenotypic associations between EDs and ADHD or ASD, mediation by mood or anxiety disorder, and genetic associations between ASD-PGS and AN and between AN-PGS and ADHD were observed. These findings could guide future research in the development of new treatments that can mitigate the development of EDs among individuals with ADHD or ASD.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":"2127-2136"},"PeriodicalIF":9.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment.","authors":"Rachel A Hill, Andrew Gibbons, Wittaya Suwakulsiri, Angela Taseska, Hayley Darke, Atul Malhotra, Hnin Yee, Michael Fahey, Rod W Hunt, Izaak Lim, Kirsten Palmer, Suresh Sundram","doi":"10.1038/s41380-024-02808-x","DOIUrl":"10.1038/s41380-024-02808-x","url":null,"abstract":"<p><p>Maternal infections during pregnancy can increase the risk to offspring of developing a neurodevelopmental disorder. Given the global prevalence and severity of infection with Severe Acute Respiratory Syndrome related Coronavirus 2 (SARS-CoV-2), the objective of this study was to determine if in utero exposure to severe maternal SARS-CoV-2 infection alters infant neurodevelopmental outcomes at 12 months and to identify potential biological markers of adverse infant outcomes. Mother-infant dyads exposed to severe SARS-CoV-2 infection (requiring hospitalization) during pregnancy and age and sociodemographic matched control dyads were recruited from Monash Medical Centre, Australia in 2021/22 and prospectively assessed over 12 months. Maternal serum cytokine levels and Edinburgh Postnatal Depression Scale (EPDS) scores were assessed at birth. DNA methylation was assessed from infant buccal swabs at birth (Illumina EPIC BeadChip). Infant neurodevelopmental outcomes at 12 months were assessed using the Ages and Stages Questionnaire (ASQ-3). Mothers exposed to severe SARS-CoV-2 exhibited elevated serum IL-6 and IL-17A and higher EPDS scores than controls at birth. Infants exposed to severe SARS-CoV-2 in utero demonstrated over 3000 significant differentially methylated sites within their genomes compared to non-exposed (adjusted p-value < 0.05), including genes highly relevant to ASD and synaptic pathways. At 12 months, severe SARS-CoV-2 exposed infants scored lower on the ASQ-3 than non-exposed infants, and communication and problem-solving scores negatively correlated with maternal IL-6 levels at birth. DNA methylation changes therefore unveil potential mechanisms linking infection exposure to delayed neurodevelopment and maternal serum IL-6 levels may be a potential biomarker of child developmental delay. Mothers exposed to severe SARS-CoV-2 infections show elevated pro-inflammatory cytokines. Infants exposed in utero to severe SARS-CoV-2 infection show altered DNA methylation at birth and delayed development at 12 months of age. Created in Biorender.com.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":"1976-1984"},"PeriodicalIF":9.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}