Translational Psychiatry最新文献

{"title":"White matter alterations associated with chronic cannabis use disorder: a structural network and fixel-based analysis.","authors":"Suzan Maleki, Joshua Hendrikse, Karyn Richardson, Rebecca A Segrave, Sam Hughes, Edouard Kayayan, Stuart Oldham, Warda Syeda, James P Coxon, Karen Caeyenberghs, Juan F Domínguez D, Nadia Solowij, Dan I Lubman, Chao Suo, Murat Yücel","doi":"10.1038/s41398-024-03150-0","DOIUrl":"10.1038/s41398-024-03150-0","url":null,"abstract":"<p><p>Cannabis use disorder (CUD) is associated with adverse mental health effects, as well as social and cognitive impairment. Given prevalence rates of CUD are increasing, there is considerable efforts, and need, to identify prognostic markers which may aid in minimising any harm associated with this condition. Previous neuroimaging studies have revealed changes in white matter (WM) organization in people with CUD, though, the findings are mixed. In this study, we applied MRI-based analysis techniques that offer complimentary mechanistic insights, i.e., a connectome approach and fixel-based analysis (FBA) to investigate properties of individual WM fibre populations and their microstructure across the entire brain, providing a highly sensitive approach to detect subtle changes and overcome limitations of previous diffusion models. We compared 56 individuals with CUD (median age 25 years) to a sample of 38 healthy individuals (median age 31.5 years). Compared to controls, those with CUD had significantly increased structural connectivity strength (FDR corrected) across 9 edges between the right parietal cortex and several cortical and subcortical regions, including left orbitofrontal, left temporal pole, and left hippocampus and putamen. Utilizing FBA, WM density was significantly higher in those with CUD (FWE-corrected) across the splenium of the corpus callosum, and lower in the bilateral cingulum and right cerebellum. We observed significant correlation between cannabis use over the past month and connectivity strength of the frontoparietal edge, and between age of regular use and WM density of the bilateral cingulum and right cerebellum. Our findings enhance the understanding of WM architecture alterations associated with CUD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401426","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":"Association between social media use and depressive symptoms in middle-aged and older Chinese adults.","authors":"Yanling Qi, Chenghe Zhang, Mei Zhou, Ruiyuan Zhang, Yuxiao Chen, Changwei Li","doi":"10.1038/s41398-024-03142-0","DOIUrl":"10.1038/s41398-024-03142-0","url":null,"abstract":"<p><p>The burden of depressive symptoms among middle-aged and older Chinese during the COVID-19 pandemic is unclear, and the contribution of social media use to depressive symptoms in this population has not been studied. To address the gaps, we analyzed data from the China Health and Retirement Longitudinal Study, nationally representative biannual surveys among adults aged ≥45 years. Social media use and depressive symptoms were measured in the 2018 and 2020 surveys. We tested longitudinal associations between baseline (2018) social media activities and risk of depressive symptoms in two years among 9121 participants without depressive symptoms. We also evaluated whether social media activity could reduce depressive symptoms during this period among 5302 individuals with depressive symptoms at baseline. Depressive symptoms affected 36·0% of this population in 2020. Women, individuals living in rural areas, and residents of western China provinces were particularly affected. Among participants without depressive symptoms, engaging in social media activities at baseline was associated with a 24.0% (95% confidence interval [CI]: 10-36%) lower likelihood of developing depressive symptoms over the next two years. Among depressed participants, compared to individuals not using social media, those initiating three or more social media activities during this period had 1.24 (95% CI: 1.05-1.46) times higher chance of becoming non-depressed, and those using social media all the time were 1·36 (95% CI: 1·09-1·72) times more likely to become non-depressed. In conclusion, middle-aged and older Chinese adults have a substantial burden of depressive symptoms, and social media activities may help to prevent and reduce the symptoms.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406919","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":"Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder.","authors":"Eric Zillich, Hanna Belschner, Diana Avetyan, Diego Andrade-Brito, José Jaime Martínez-Magaña, Josef Frank, Naguib Mechawar, Gustavo Turecki, Judit Cabana-Domínguez, Noèlia Fernàndez-Castillo, Bru Cormand, Janitza L Montalvo-Ortiz, Markus M Nöthen, Anita C Hansson, Marcella Rietschel, Rainer Spanagel, Stephanie H Witt, Lea Zillich","doi":"10.1038/s41398-024-03139-9","DOIUrl":"10.1038/s41398-024-03139-9","url":null,"abstract":"<p><p>Structural and functional changes of the brain are assumed to contribute to excessive cocaine intake, craving, and relapse in cocaine use disorder (CUD). Epigenetic and transcriptional changes were hypothesized as a molecular basis for CUD-associated brain alterations. Here we performed a multi-omics study of CUD by integrating epigenome-wide methylomic (N = 42) and transcriptomic (N = 25) data from the same individuals using postmortem brain tissue of Brodmann Area 9 (BA9). Of the N = 1 057 differentially expressed genes (p < 0.05), one gene, ZFAND2A, was significantly upregulated in CUD at transcriptome-wide significance (q < 0.05). Differential alternative splicing (AS) analysis revealed N = 98 alternatively spliced transcripts enriched in axon and dendrite extension pathways. Strong convergent overlap in CUD-associated expression deregulation was found between our BA9 cohort and independent replication datasets. Epigenomic, transcriptomic, and AS changes in BA9 converged at two genes, ZBTB4 and INPP5E. In pathway analyses, synaptic signaling, neuron morphogenesis, and fatty acid metabolism emerged as the most prominently deregulated biological processes. Drug repositioning analysis revealed glucocorticoid receptor targeting drugs as most potent in reversing the CUD expression profile. Our study highlights the value of multi-omics approaches for an in-depth molecular characterization and provides insights into the relationship between CUD-associated epigenomic and transcriptomic signatures in the human prefrontal cortex.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393585","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":"Effects of depression and cognitive impairment on increased risks of incident dementia: a prospective study from three elderly cohorts.","authors":"Yushun Yan, Hailin Xiang, Min Wang, Jinxue Wei, Huanhuan Fan, Yue Du, Yuanmei Tao, Yikai Dou, Yangrui Ma, Xiao Yang, Xiaohong Ma","doi":"10.1038/s41398-024-03125-1","DOIUrl":"10.1038/s41398-024-03125-1","url":null,"abstract":"<p><p>Depression is usually accompanied with cognitive impairment and increases risk of incident dementia. However, evidence has been limited on the effect size of depression with cognitive impairment and their synergistic effect on future dementia. To explore this, we examined three large cross-country population-based prospective cohorts. Depressive symptoms were assessed by epidemiologic scale, while cognitive impairment was defined by subjective cognitive tests. Dementia was ascertained by self-reported physician-diagnosed conditions. Cox proportional hazard models were employed to determine the hazard ratio (HR) and 95% confidence interval (95% CI), with adjustments of potential confounding variables. Addictive and multiplicative interactions were calculated to evaluate the synergistic effect. A total of 64,706 participants were included at baseline (mean age: 63.9, female: 55.2%), where 4197 (6.5%) individuals had depressive symptoms only, 28,175 (43.5%) individuals had cognitive impairment only, 11,564 (17.9%) individuals had both, and 20,770 (32.1%) individuals had neither. Compared with the neither group, all the other three groups had higher risks of subsequent dementia (depression only: HR 1.65, 95% CI 1.26-2.17; cognitive impairment only: HR 2.71, 95% CI 2.33-3.14; depression with cognitive impairment: HR 3.51, 95% CI 2.95-4.17). There was insignificant additive (RERI, 0.15, 95% CI -0.45-0.75; AP, 0.042, 95% CI -0.13-0.21; SI, 1.06, 95% CI 0.83-1.37) and multiplicative (0.78, 95% CI 0.58-1.06) interaction between depression and cognitive impairment on subsequent dementia. We found depression with cognitive impairment has higher risks of dementia than either condition alone and no significant synergistic effect exists between these two factors.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393583","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":"Importin α4 deficiency induces psychiatric disorder-related behavioral deficits and neuroinflammation in mice.","authors":"Koki Sakurai, Makiko Morita, Yoshiatsu Aomine, Mitsunobu Matsumoto, Tetsuji Moriyama, Emiko Kasahara, Atsuo Sekiyama, Mayumi Otani, Rieko Oshima, Kate L Loveland, Masami Yamada, Yoshihiro Yoneda, Masahiro Oka, Takatoshi Hikida, Yoichi Miyamoto","doi":"10.1038/s41398-024-03138-w","DOIUrl":"10.1038/s41398-024-03138-w","url":null,"abstract":"<p><p>Importin α4, which is encoded by the Kpna4 gene, is a well-characterized nuclear-cytoplasmic transport factor known to mediate transport of transcription factors including NF-κB. Here, we report that Kpna4 knock-out (KO) mice exhibit psychiatric disorder-related behavioral abnormalities such as anxiety-related behaviors, decreased social interaction, and sensorimotor gating deficits. Contrary to a previous study predicting attenuated NF-κB activity as a result of Kpna4 deficiency, we observed a significant increase in expression levels of NF-κB genes and proinflammatory cytokines such as TNFα, Il-1β or Il-6 in the prefrontal cortex or basolateral amygdala of the KO mice. Moreover, examination of inflammatory responses in primary cells revealed that Kpna4 deficient cells have an increased inflammatory response, which was rescued by addition of not only full length, but also a nuclear transport-deficient truncation mutant of importin α4, suggesting contribution of its non-transport functions. Furthermore, RNAseq of sorted adult microglia and astrocytes and subsequent transcription factor analysis suggested increases in polycomb repressor complex 2 (PRC2) activity in Kpna4 KO cells. Taken together, importin α4 deficiency induces psychiatric disorder-related behavioral deficits in mice, along with an increased inflammatory response and possible alteration of PRC2 activity in glial cells.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393584","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":"The association between patterns of exposure to adverse life events and the risk of chronic kidney disease: a prospective cohort study of 140,997 individuals.","authors":"Chunyang Li, Jie Chen, Yilong Chen, Chao Zhang, Huazhen Yang, Shaobin Yu, Huan Song, Ping Fu, Xiaoxi Zeng","doi":"10.1038/s41398-024-03114-4","DOIUrl":"https://doi.org/10.1038/s41398-024-03114-4","url":null,"abstract":"<p><p>Exposure to adverse life events is linked to somatic disorders. The study aims to evaluate the association between adverse events at varying life stages and the risk of chronic kidney disease (CKD), a condition affecting about 10% population worldwide. This prospective cohort study included 140,997 participants from the UK Biobank. Using survey items related to childhood maltreatment, adulthood adversity and catastrophic trauma, we performed latent class analysis to summarize five distinct patterns of exposure to adverse life events, namely \"low-level exposure\", \"childhood exposure\", \"adulthood exposure\", \"sexual abuse\" and \"child-to-adulthood exposure\". We used Cox proportional hazard regression to evaluate the association of patterns of exposure to adverse life events with CKD, regression-based mediation analysis to decompose the total effect, and gene-environment-wide interaction study (GEWIS) to identify interactions between genetic loci and adverse life events. During a median follow-up of 5.98 years, 2734 cases of incident CKD were identified. Compared with the \"low-level exposure\" pattern, \"child-to-adulthood exposure\" was associated with increased risk of CKD (hazard ratio 1.37, 95% CI 1.14 to 1.65). BMI, smoking and hypertension mediated 11.45%, 9.79%, and 4.50% of this total effect, respectively. Other patterns did not show significant results. GEWIS and subsequent analyses indicated that the magnitude of the association between adverse life events and CKD differed according to genetic polymorphisms, and identified potential underlying pathways (e.g., interleukin 1 receptor activity). These findings underscore the importance of incorporating an individual's psychological encounters and genetic profiles into the precision prevention of CKD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393587","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":"Circadian clock dysregulation: a potential mechanism of depression in obstructive sleep apnea patients.","authors":"Agata Gabryelska, Szymon Turkiewicz, Piotr Kaczmarski, Adrian Gajewski, Piotr Białasiewicz, Dominik Strzelecki, Maciej Chałubiński, Marcin Sochal","doi":"10.1038/s41398-024-03134-0","DOIUrl":"https://doi.org/10.1038/s41398-024-03134-0","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) is characterized by co-occurrence with affective disorders. Our study aims to investigate the association of circadian clock gene expressions, and the presence and severity of depressive symptoms in OSA patients. The study included 184 individuals, who underwent polysomnography (PSG) and had their peripheral blood collected in the evening before and the morning after the PSG. Patients were divided into two groups: the OSA (apnea-hypopnea index (AHI) > 5) and the control group (AHI < 5). RNA was extracted from peripheral blood leukocytes. Expression levels of the selected genes (BMAL1, CLOCK, PER1, CRY1, NPAS2, and NR1D1) were assessed by qRT-PCR. Questionnaire data was collected in the morning (including the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Chronotype Questionnaire (CQ), and Montgomery-Åsberg Depression Rating Scale (MADRS)). The expression of all examined circadian clock genes in OSA patients was upregulated in the morning compared to the evening (except NPAS2). No differences were observed between OSA and control groups at either time point. Additionally, there was a positive correlation between the severity of depressive symptoms (assessed with MADRS) and morning expression of circadian genes in the group of OSA patients. Finally, in multivariable linear regression, ISI score (B = 0.750, p < 0.001), AM score of CQ (B = 0.416, p = 0.007), and morning PER1 gene expression (B = 4.310, p = 0.042) were found to be predictive factors for greater severity of depression symptoms in OSA patients. Dysregulated circadian clock gene expression in OSA patients is linked to depressive symptom severity, suggesting circadian disruption may underlie affective symptoms in OSA.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393582","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":"Restoring social deficits in IRSp53-deleted mice: chemogenetic inhibition of ventral dentate gyrus Emx1-expressing cells.","authors":"Su Hyun Kim, Bomee Lee, Seong Mi Lee, Yangsik Kim","doi":"10.1038/s41398-024-03104-6","DOIUrl":"https://doi.org/10.1038/s41398-024-03104-6","url":null,"abstract":"<p><p>IRSp53 is a synaptic scaffold protein reported to be involved in schizophrenia, autism spectrum disorders, and social deficits in knockout mice. Identifying critical brain regions and cells related to IRSp53 deletion is expected to be of great help in the treatment of psychiatric problems. In this study, we performed chemogenetic inhibition within the ventral dentate gyrus (vDG) of mice with IRSp53 deletion in Emx1-expressing cells (Emx1-Cre;IRSp53 flox/flox). We observed the recovery of social deficits after chemogenetic inhibition within vDG of Emx1-Cre;IRSp53 flox/flox mice. Additionally, chemogenetic activation induced social deficits in Emx1-Cre mice. CRHR1 expression increased in the hippocampus of Emx1-Cre;IRSp53 flox/flox mice, and CRHR1 was reduced by chemogenetic inhibition. Htd2, Ccn1, and Atp61l were decreased in bulk RNA sequencing, and Eya1 and Ecrg4 were decreased in single-cell RNA sequencing of the hippocampus in Emx1-Cre;IRSp53 flox/flox mice compared to control mice. This study determined that the vDG is a critical brain region for social deficits caused by IRSp53 deletion. Social deficits in Emx1-Cre;IRSp53 flox/flox mice were recovered through chemogenetic inhibition, providing clues for new treatment methods for psychiatric disorders accompanied by social deficits.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393586","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":"Trajectories and predictors of suicidal ideation in clinical characteristics and pharmacological treatments for major depressive disorder: a study based on a national multi-centered prospective cohort.","authors":"Ruoxi Ding, Xuequan Zhu, Lei Feng, Le Xiao, Ling Zhang, Ping He, Gang Wang","doi":"10.1038/s41398-024-03115-3","DOIUrl":"10.1038/s41398-024-03115-3","url":null,"abstract":"<p><p>Suicidal ideation (SI) is a significant precursor and risk marker for suicide behaviors in major depressive disorder (MDD). Exploration of SI trajectory from a longitudinal framework are essential for treatment guidelines and clinical management of suicide risk. This study sought to explore SI trajectories and its associated clinical, sociodemographic characteristics, and initial treatment among patients with MDD. We used data from a non-interventional, national multi-centered prospective cohort study. 1 461 patients with MDD were included in the growth mixture modeling using SI at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and 6 months, 9 months, and 12 months as the indicator. A multinomial regression was employed with SI trajectory as the outcome and anhedonia, depressive symptoms, atypical depressive symptoms, pharmacological treatments, and other covariates as the predictors. Four distinct SI trajectories were identified: a consistently low SI trajectory(50.7%), a persistently mild SI trajectory(20.6%), a fast declined SI trajectory(8.9%), and a slowly declined trajectory(19.8%). Compared to those with a consistently low SI trajectory, a higher score of anhedonia was associated with an increased risk of experiencing persistently mild (RRR = 1.20, 95%CI: 1.05, 1.38) and slowly declined SI (1.54, 95%CI: 1.32, 1.80). Severity of depressive symptom was also positively associated with the risk of experiencing persistently mild (1.15, 95%CI: 1.13, 1.18) and slowly declined SI (1.17, 95%CI: 1.14, 1.21). And the risk of experiencing slowly declined SI was higher for those use SSRI(1.49, 95%CI: 1.02, 2.31), and for those use antidepressant and antipsychotic/mood stabilizer combined therapy (3.78, 95%CI: 1.48, 9.61). The findings of this study are potentially useful for clinical practice as critical indicators of profiles and interventions for prognosis among patients with MDD. Further research is warranted to explore potential modifiable factors and the association between SI trajectories and suicide behavior.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381717","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":"Cacna1c deficiency in forebrain glutamatergic neurons alters behavior and hippocampal plasticity in female mice.","authors":"Srivaishnavi Loganathan, Danusa Menegaz, Jan Philipp Delling, Matthias Eder, Jan M Deussing","doi":"10.1038/s41398-024-03140-2","DOIUrl":"10.1038/s41398-024-03140-2","url":null,"abstract":"<p><p>CACNA1C, coding for the α1 subunit of L-type voltage-gated calcium channel (LTCC) Ca_v1.2, has been associated with multiple psychiatric disorders. Clinical studies have revealed alterations in behavior as well as in brain structure and function in CACNA1C risk allele carriers. These findings are supported by rodent models of Ca_v1.2 deficiency, which showed increased anxiety, cognitive and social impairments as well as a shift towards active stress-coping strategies. These behavioral alterations were accompanied by functional deficits, such as reduced long-term potentiation (LTP) and an excitation/inhibition (E/I) imbalance. However, these preclinical studies are largely limited to male rodents, with few studies exploring sex-specific effects. Here, we investigated the effects of Ca_v1.2 deficiency in forebrain glutamatergic neurons in female conditional knockout (CKO) mice. CKO mice exhibited hyperlocomotion in a novel environment, increased anxiety-related behavior, cognitive deficits, and increased active stress-coping behavior. These behavioral alterations were neither influenced by the stage of the estrous cycle nor by the Nex/Neurod6 haploinsufficiency or Cre expression, which are intrinsically tied to the utilization of the Nex-Cre driver line for conditional inactivation of Cacna1c. In the hippocampus, Ca_v1.2 inactivation enhanced presynaptic paired-pulse facilitation without altering postsynaptic LTP at CA3-CA1 synapses. In addition, CA1 pyramidal neurons of female CKO mice displayed a reduction in dendritic complexity and spine density. Taken together, our findings extend the existing knowledge suggesting Ca_v1.2-dependent structural and functional alterations as possible mechanisms for the behavioral alterations observed in female Ca_v1.2-Nex mice.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381716","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}