Acta Neuropsychiatrica最新文献

{"title":"Analysis of 470,000 exome-sequenced cases and controls fails to identify any genes impacting risk of developing affective disorder.","authors":"David Curtis","doi":"10.1017/neu.2025.10025","DOIUrl":"10.1017/neu.2025.10025","url":null,"abstract":"<p><strong>Objective: </strong>A previous analysis of 200,000 exome-sequenced UK Biobank participants using weighted burden analysis of rare, damaging variants failed to identify any genes associated with risk of affective disorder requiring specialist treatment. Exome-sequence data has now been made available for the remaining 270,000 participants and a two-stage process was applied in order to test for association in this second sample using only genes showing suggestive evidence for association in the first sample.</p><p><strong>Methods: </strong>Cases were defined as participants who reported having seen a psychiatrist for 'nerves, anxiety, tension or depression'. Exhaustive testing of the first sample was carried out using rare variant analyses informed by 45 different predictors of impact of nonsynonymous variants. The 100 genes showing the strongest evidence for association were then analysed in the second sample using the same predictor as had been most statistically significant in the first sample.</p><p><strong>Results: </strong>The results for the 100 nominated genes conformed closely with the null hypothesis, with none approaching statistical significance after correction for multiple testing.</p><p><strong>Conclusion: </strong>Risk of common affective disorder, even if severe enough to warrant specialist referral, is not sufficiently impacted by effects of rare variants in a small enough number of genes that effects can be detected even with large sample sizes. Actionable results might be obtained with a more extreme phenotype but very significant resources would be required to achieve adequate power. This research has been conducted using the UK Biobank Resource.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e69"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychosocial wellbeing of people with dementia: systematic review and construct analysis.","authors":"Lena M Hofbauer, Francisca S Rodriguez","doi":"10.1017/neu.2025.10021","DOIUrl":"10.1017/neu.2025.10021","url":null,"abstract":"<p><strong>Objective: </strong>Psychosocial wellbeing is increasingly recognised as a key outcome in dementia research and care, reflecting a shift towards person-centred care and patient-reported outcome measures. However, progress is hindered by a lack of a clear and consistent definition. The present systematic review aimed to establish how previous dementia research has defined the term and how existing definitions may be unified.</p><p><strong>Methods: </strong>A systematic literature review was conducted in <i>PubMed</i>, <i>Embase</i>, and <i>Web of Science</i> using only the term 'psychosocial' as well as terms related to dementia in the search string. Two blinded reviewers independently conducted the abstract screening and full-text screening. Definitions used in included records were extracted and their content grouped into categories and domains. For papers presenting empirical findings, quality screening was performed using <i>Critical Appraisal Skills Programme</i> (CASP) checklists and findings were narratively summarised.</p><p><strong>Results: </strong>A total of <i>n</i> = 36 records were identified that provided a definition for psychosocial wellbeing. Conceptualizations most commonly (86 %) included emotional wellbeing, social health (64%), behavioural symptoms (44%), and subjective lived wellbeing (42%). A total of <i>n</i> = 23 records also contained empirical data, which indicated that psychosocial wellbeing may be improved by several interventions such as tailored activities and validation group therapies, among others.</p><p><strong>Discussion: </strong>The construct of 'psychosocial wellbeing' as currently used in dementia research predominantly incorporates emotional and subjective lived wellbeing, social health, and behavioural symptoms. This indicates an emerging consensus. To progress dementia research and care practice, it is essential that future studies use a common operationalisation.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e71"},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the network structures of depressive symptom profiles in Asian patients with depressive disorders: findings from the Research on Asian Psychotropic Patterns for Antidepressants, Phase 3.","authors":"Han Seul Kim, Seonjae Lee, Jeongha Lee, Tae Young Choi, Sung-Won Jung, Hyung-Jun Yoon, Hyun Soo Kim, Yangsik Kim, Hyun-Ju Yang, Narae Jeong, Eunsoo Moon, Daeho Kim, Tian-Mei Si, Roy Abraham Kallivayalil, Andi J Tanra, Amir Hossein Jalali Nadoushan, Kok Yoon Chee, Afzal Javed, Kang Sim, Pornjira Pariwatcharakul, Mian-Yoon Chong, Toshiya Inada, Shih-Ku Lin, Norman Sartorius, Naotaka Shinfuku, Takahiro A Kato, Jae-Hon Lee, Seon-Cheol Park","doi":"10.1017/neu.2025.10020","DOIUrl":"10.1017/neu.2025.10020","url":null,"abstract":"<p><strong>Background: </strong>Depression is a complex mental health disorder with highly heterogeneous symptoms that vary significantly across individuals, influenced by various factors, including sex and regional contexts. Network analysis is an analytical method that provides a robust framework for evaluating the heterogeneity of depressive symptoms and identifying their potential clinical implications.</p><p><strong>Objective: </strong>To investigate sex-specific differences in the network structures of depressive symptoms in Asian patients diagnosed with depressive disorders, using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3, which was conducted in 2023.</p><p><strong>Methods: </strong>A network analysis of 10 depressive symptoms defined according to the National Institute for Health and Care Excellence guidelines was performed. The sex-specific differences in the network structures of the depressive symptoms were examined using the Network Comparison Test. Subgroup analysis of the sex-specific differences in the network structures was performed according to geographical region classifications, including East Asia, Southeast Asia, and South or West Asia.</p><p><strong>Results: </strong>A total of 998 men and 1,915 women with depression were analysed in this study. The analyses showed that all 10 depressive symptoms were grouped into a single cluster. Low self-confidence and loss of interest emerged as the most central nodes for men and women, respectively. In addition, a significant difference in global strength invariance was observed between the networks. In the regional subgroup analysis, only East Asian men showed two distinct clustering patterns. In addition, significant differences in global strength and network structure were observed only between East Asian men and women.</p><p><strong>Conclusion: </strong>The study highlights the sex-specific differences in depressive symptom networks across Asian countries. The results revealed that low self-confidence and loss of interest are the main symptoms of depression in Asian men and women, respectively. The network connections were more localised in men, whereas women showed a more diverse network. Among the Asian subgroups analysed, only East Asians exhibited significant differences in network structure. The considerable effects of neurovegetative symptoms in men may indicate potential neurobiological underpinnings of depression in the East Asian population.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e70"},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopsychiatry of late life depression: role of ageing-related immune/inflammatory processes in the development and progression of depression.","authors":"Antonio L Teixeira, Izabela G Barbosa, Moises E Bauer, Aline S de Miranda","doi":"10.1017/neu.2025.10019","DOIUrl":"10.1017/neu.2025.10019","url":null,"abstract":"<p><strong>Background: </strong>Late-life depression (LLD) arises from a complex interplay among biological, psychological, and social factors. Biologically, three main hypotheses have been proposed to explain the distinct clinical features of LLD. The vascular hypothesis supports vascular-related white matter changes in the development of LLD, while the neurodegenerative hypothesis suggests that LLD might be a prodrome of neurodegenerative diseases. The inflammatory hypothesis, which is the main focus of this review, posits that heightened inflammation underlies LLD directly or indirectly through neurodegenerative and microvascular alterations.</p><p><strong>Methods: </strong>This is a non-systematic review on the role played by inflammation in the pathophysiology of LLD and the related opportunities to define biomarkers and therapeutic targets. We searched PubMed from January 2010 through March 2025 for relevant English-language studies.</p><p><strong>Results: </strong>Patients with LLD have elevated circulating levels of inflammatory biomarkers (e.g., C-reactive protein and interleukin-6) as well as evidence of neuroinflammation. Although the exact origin of this inflammatory profile remains unclear, it is thought to be exacerbated by immune cell senescence and the presence of physical comorbidities, including cardiovascular and metabolic diseases. Pharmacological (e.g., selective serotonin receptor inhibitors) and non-pharmacological (e.g., diet, physical interventions) approaches for LLD seem to exert their therapeutic effect, at least in part, through inflammation-related mechanisms.</p><p><strong>Conclusion: </strong>Recognizing the unique features of LLD compared to depression in other periods of life is an important step toward its proper management. More specifically, understanding the role of inflammation in LLD holds both theoretical and practical implications, including anti-inflammatory or immune-based strategies as potential therapeutic interventions.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e67"},"PeriodicalIF":2.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender-Affirming Hormone Therapy, Quality of Life, and the Role of Oestradiol and Testosterone in Transgender Individuals.","authors":"E E S Petersen, F Kiy, U S Kesmodel, M L Pop, G Kjaersdam Telléus, A Stensballe, J Dal, A Højgaard, M Winterdahl","doi":"10.1017/neu.2025.10018","DOIUrl":"https://doi.org/10.1017/neu.2025.10018","url":null,"abstract":"<p><strong>Objectives: </strong>The present study examines the quality of life (QoL) of transgender and gender-diverse individuals receiving versus not receiving gender-affirming hormone therapy (GAHT) in those assigned male at birth (AMAB) and assigned female at birth (AFAB). It also explores the relationship between QoL and concentrations of oestradiol and testosterone.</p><p><strong>Methods: </strong>This cross-sectional study used the WHOQOL-BREF questionnaire to assess QoL. Participants were categorised into four groups based on assigned sex at birth (AMAB or AFAB) and GAHT status, with non-GAHT participants serving as controls. MANOVA and t-tests were used to compare QoL between groups, and linear regression analyses examined associations between QoL and oestradiol/testosterone concentrations in AMAB and AFAB participants.</p><p><strong>Results: </strong>The study included 360 participants: 169 AMAB (143 GAHT, 26 controls) and 191 AFAB (141 GAHT, 50 controls). GAHT recipients had significantly higher QoL than controls in both AMAB (p < 0.01) and AFAB (p = 0.02) groups, particularly in the psychological health domain (D2). AFAB participants reported higher overall QoL than AMAB in both GAHT (p = 0.01) and control (p = 0.04) groups, with significance in the social domain among GAHT participants. No significant relationship was found between oestradiol concentrations and QoL for participants AMAB. However, a significant relationship between testosterone concentrations and QoL was observed only in the social relationship domain (D3) for participant AFAB.</p><p><strong>Conclusion: </strong>This study highlights the benefits of GAHT for QoL and differences in QoL between AMAB and AFAB individuals.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"1-29"},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement system dysfunction in autism spectrum disorder: evidence for altered C1q and C3 levels (complement system dysfunction in ASD).","authors":"Meltem Gunaydin, Ozlem Dogan, Fatih Gunay, Merve Cikili-Uytun, Özge Celik-Buyukceran, Didem Behice Oztop","doi":"10.1017/neu.2025.10017","DOIUrl":"10.1017/neu.2025.10017","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by impairments in social communication, repetitive behaviours, and restricted interests. Emerging evidence suggests that immune system dysregulation, particularly alterations in the complement system, may contribute to ASD pathophysiology. This study aimed to compare the serum levels of complement proteins (C1q, C2, C3, C4, MBL, L-ficolin, and hsCRP) between children with ASD and non-ASD controls. A total of 88 children (44 with ASD and 44 age- and sex-matched healthy controls) participated in this study. Complement protein levels were measured using enzyme-linked immunosorbent assay (from serum samples. The severity of ASD symptoms was assessed using standardised diagnostic tools, including the Childhood Autism Rating Scale, the Autism Behaviour Checklist, and the Repetitive Behaviour Scale-Revised. Serum C1q levels were significantly lower in the ASD group (<i>p</i> < 0.001). C3 levels were lower (<i>p</i> = 0.033), while C2 levels were slightly higher (<i>p</i> = 0.015) in the ASD group. There are no significant differences in C4, MBL, or L-ficolin levels. Logistic regression analysis identified reduced C1q levels as a significant predictor of ASD (<i>p</i> = 0.001). However, this study found no significant correlations between complement levels and ASD symptom severity scores. The findings suggest that alterations in complement system proteins, particularly reduced serum C1q levels, may be associated with ASD. Given C1q’s critical role in synaptic pruning and neuroimmune regulation, these results support the hypothesis that complement system dysfunction may contribute to the pathophysiology of ASD.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e64"},"PeriodicalIF":2.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroencephalogram activity related to psychopathological and neuropsychological symptoms in institutionalised minors: a systematic review.","authors":"Carlos Barbosa-Torres, Natalia Bueso-Izquierdo, Alejandro Arévalo-Martínez, Juan Manuel Moreno-Manso","doi":"10.1017/neu.2025.19","DOIUrl":"https://doi.org/10.1017/neu.2025.19","url":null,"abstract":"<p><strong>Objective: </strong>This systematic review aims to update the current evidence on the effects of institutionalisation in minors living in residential care homes, specifically focusing on alterations in neuronal systems and their association with psychopathological and neuropsychological outcomes.</p><p><strong>Methods: </strong>Searches were conducted in the Web of Science, Scopus, PubMed, and Google Scholar databases, following PRISMA methodology for peer-reviewed empirical articles. The final selection comprised 10 studies that met the inclusion criteria: (1) published articles with quantitative data, (2) aimed at observing the relationship between psychological and neuropsychological symptoms and the electroencephalogram (EEG) activity in institutionalised children, (3) published between 2016 and 2023, and (4) examining institutionalised minors in residential care homes.</p><p><strong>Results: </strong>The articles show that these children exhibit general immaturity in EEG patterns, with a predominance of slow waves (primarily in the theta band). They also demonstrate poorer performance in executive functions (e.g. working memory, inhibition, and processing speed) and cognitive processes, along with a higher risk of externalising problems. However, current evidence does not allow definitive conclusions on whether early EEG abnormalities predict long-term neuropsychological deficits, despite data showing associations between EEG changes and certain cognitive dysfunctions at the time of evaluation.</p><p><strong>Conclusion: </strong>The reviewed evidence suggests that EEG alterations in institutionalised minors are linked to executive dysfunction and increased psychopathological risk. These findings highlight the value of EEG in identifying at-risk children and inform the design of preventive interventions. Longitudinal studies are needed to clarify causal relationships.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":"37 ","pages":"e62"},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of acceptance and commitment therapy for suicidality: a systematic review and meta-analysis.","authors":"Ju Hyun Tak, Seo-Eun Cho, Seong-Jin Cho, Seung-Gul Kang, Seung Min Bae, Kyoung-Sae Na","doi":"10.1017/neu.2025.18","DOIUrl":"10.1017/neu.2025.18","url":null,"abstract":"<p><p>Acceptance and commitment therapy (ACT) is recognised as an effective treatment for a variety of mental illnesses. Several meta-analyses have reported the efficacy of ACT in various mental and physical conditions, including depression, anxiety, and pain, but not for suicidality. This study aimed to determine the therapeutic effectiveness of ACT on suicidality through a systematic review and meta-analysis. Electronic databases such as PubMed, Embase, Scopus, and the Cochrane Library were searched for studies. The primary outcome measure was the effectiveness of ACT for suicidality which includes suicidal ideations and attempts. This systematic review and meta-analysis included eight studies, all of which were judged to have a high risk of bias. In the meta-analysis, the pooled standardised mean difference for suicidal ideations was 1.122 (95% confidence interval (CI) = 0.261 to 1.982). This meta-analysis suggests that ACT is effective for reducing suicidal ideation, but the high risk of bias across studies should be considered as a major limitation. Further well-designed studies are needed to confirm these findings.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e66"},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioural impairments in a mouse model of Kabuki syndrome associated with dopaminergic and neuroinflammatory modulations.","authors":"Thalles F Biondi, Silvia M G Massironi, Eduardo F Bondan, Thiago B Kirsten","doi":"10.1017/neu.2025.17","DOIUrl":"https://doi.org/10.1017/neu.2025.17","url":null,"abstract":"<p><strong>Objective: </strong>Kabuki syndrome is a rare multisystem congenital disorder characterised by specific facial malformations and several other symptoms, including motor impairments, increased susceptibility to infections, immune mediators' deficits, anxiety, and stereotyped behaviours. Considering the reports of motor impairments in Kabuki syndrome patients, the first hypothesis of the present study was that this motor dysfunction was a consequence of striatal dopaminergic modulation. The second hypothesis was that the peripheral immune system dysfunctions were a consequence of neuroinflammatory processes. To study these hypotheses, the mutant <i>bapa</i> mouse was used as it is a validated experimental model of Kabuki syndrome.</p><p><strong>Methods: </strong>Exploratory behaviour, anxiety-like behaviour (light-dark test), repetitive/stereotyped behaviour (spontaneous and induced self-grooming), and tyrosine hydroxylase (TH), astrocyte glial fibrillary acidic protein (GFAP), and ionised calcium-binding adaptor molecule 1 (Iba1) striatal expressions were evaluated in female adult <i>bapa</i> and control mice.</p><p><strong>Results: </strong>Female <i>bapa</i> mice did not present anxiety-like behaviour, but exploratory hyperactivity and stereotyped behaviour both on the spontaneous and induced self-grooming tests. Striatal TH, GFAP, and Iba1 expressions were also increased in <i>bapa</i> mice.</p><p><strong>Conclusion: </strong>The exploratory hyperactivity and the stereotyped behaviour occurred in detriment of the striatal dopaminergic system hyperactivity and a permanent neuroinflammatory process.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":"37 ","pages":"e63"},"PeriodicalIF":2.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escitalopram alters tryptophan metabolism, plasma lipopolysaccharide, and the inferred functional potential of the gut microbiome in deer mice showing compulsive-like rigidity.","authors":"Larissa Karsten, Brian H Harvey, Dan J Stein, Benjamín Valderrama, Thomaz F S Bastiaanssen, Gerard Clarke, John F Cryan, Rencia van der Sluis, Heather Jaspan, Anna-Ursula Happel, De Wet Wolmarans","doi":"10.1017/neu.2025.16","DOIUrl":"10.1017/neu.2025.16","url":null,"abstract":"<p><strong>Objective: </strong>Compulsive-like rigidity may be associated with hyposerotonergia and increased kynurenine (KYN) pathway activity. Conversion of tryptophan (TRP) to KYN, which may contribute to hyposerotonergia, is bolstered by inflammation and could be related to altered gut microbiota composition. Here, we studied these mechanisms in a naturalistic animal model of compulsive-like behavioural rigidity, that is, large nest building (LNB) in deer mice (<i>Peromyscus</i> sp.).</p><p><strong>Methods: </strong>Twenty-four (24) normal nest building (NNB) and 24 LNB mice (both sexes) were chronically administered either escitalopram (a selective serotonin reuptake inhibitor; 50 mg/kg/day) or a control solution, with nesting behaviour analysed before and after intervention. After endpoint euthanising, frontal cortices and striata were analysed for TRP and its metabolites, plasma for microbiota-derived lipopolysaccharide (LPS) and its binding protein (lipopolysaccharide binding protein), and stool samples for microbial DNA.</p><p><strong>Results: </strong>LNB, but not NNB, decreased after escitalopram exposure. At baseline, LNB was associated with reduced frontal cortical TRP concentrations and hyposerotonergia that was unrelated to altered KYN pathway activity. In LNB mice, escitalopram significantly increased frontal-cortical and striatal TRP without altering serotonin concentrations. Treated LNB, compared to untreated LNB and treated NNB mice, had significantly reduced plasma LPS as well as a microbiome showing a decreased inferred potential to synthesise short-chain fatty acids and degrade TRP.</p><p><strong>Conclusions: </strong>These findings support the role of altered serotonergic mechanisms, inflammatory processes, and gut microbiome involvement in compulsive-like behavioural rigidity. Our results also highlight the importance of gut-brain crosstalk mechanisms at the level of TRP metabolism in the spontaneous development of such behaviour.</p>","PeriodicalId":48964,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"e60"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}