Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"The associations between paternal postpartum depressive symptoms and testosterone and cortisol levels in hair over the first two years postpartum","authors":"Lydia Richter ,&nbsp;Luisa Bergunde ,&nbsp;Marlene Karl ,&nbsp;Isabel Jaramillo ,&nbsp;Victoria Weise ,&nbsp;Judith T. Mack ,&nbsp;Kerstin Weidner ,&nbsp;Wei Gao ,&nbsp;Tilmann von Soest ,&nbsp;Susan Garthus-Niegel ,&nbsp;Susann Steudte-Schmiedgen","doi":"10.1016/j.pnpbp.2024.111245","DOIUrl":"10.1016/j.pnpbp.2024.111245","url":null,"abstract":"<div><h3>Background</h3><div>After the birth of a child, also fathers may develop postpartum depression. Altered steroid hormone concentrations are discussed as a possible underlying mechanism, as these have been associated with depressive symptoms in previous studies outside the postpartum period. While higher paternal testosterone levels have been found to protect against paternal postpartum depressive symptoms (PPDS), an association between higher cortisol levels and PPDS has been seen in postpartum mothers, with no comparable studies available on fathers.</div></div><div><h3>Objective</h3><div>This study aimed to investigate cross-sectional and longitudinal associations between testosterone and cortisol levels in hair and PPDS over a period of 2 years postpartum.</div></div><div><h3>Methods</h3><div>Data from <em>N</em> = 226 fathers, who took part in the endocrine sub-study DREAM_HAIR of the longitudinal prospective cohort study DREAM, were used. PPDS were assessed 8 weeks, 14 months, and 24 months after birth using the Edinburgh Postnatal Depression Scale. At the same time, fathers provided 2 cm scalp-near hair samples in which testosterone (HairT) and cortisol (HairF) levels were determined. Cross-sectional and longitudinal associations between HairT, HairF and paternal PPDS were investigated.</div></div><div><h3>Results</h3><div>Correlation analyses showed a negative cross-sectional association between HairF levels and paternal PPDS 14 months after birth. A random intercept cross-lagged panel model revealed prospective relationships between paternal PPDS 8 weeks postpartum and HairF 14 months postpartum, and additionally between 14 months and 2 years postpartum in an exploratory model with similarly good model fit. No further significant associations of HairF with paternal PPDS emerged, and none of the analyses with HairT became significant. The overall pattern of results was confirmed when controlling for the influence of batch and storage time on HairT and HairF levels.</div></div><div><h3>Conclusion</h3><div>No consistent relationships between HairT or HairF and paternal PPDS emerged in this relatively healthy cohort. In HairF analyses with significant results, lower HairF was associated with more severe PPDS. Longitudinal results imply that altered cortisol secretion may rather follow than precede changes in paternal PPDS. Further research on hormonal changes in PPDS in fathers should consider possible covariates and examine fathers with higher depressive burden, which may help to identify fathers at risk and inform future preventive and interventive approaches.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111245"},"PeriodicalIF":5.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967261","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":"Revealing potential drug targets in schizophrenia through proteome-wide Mendelian randomization genetic insights","authors":"Wenhuo Xie ,&nbsp;Jiaping Zheng ,&nbsp;Chenghua Kong ,&nbsp;Wei Luo ,&nbsp;Xiaoxia Lin ,&nbsp;Yu Zhou","doi":"10.1016/j.pnpbp.2024.111208","DOIUrl":"10.1016/j.pnpbp.2024.111208","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia (SCZ) is a severe, chronic mental disorder with no current cure. Identifying novel pharmacological targets is crucial for developing more effective treatments.</div></div><div><h3>Methods</h3><div>We performed two-sample Mendelian randomization (MR) analyses to estimate the associations between cerebrospinal fluid (CSF) containing 154 proteins and plasma containing 734 proteins and risk of SCZ. Bidirectional MR analysis, steiger filtering, bayesian colocalization, phenotypic scanning, and validation analysis were examined to validate the assumptions of MR. For proteins significantly associated with SCZ identified by MR, we explored their potential impact on brain structures, including cortical surface area (SA), thickness (TH), and the volume of subcortical structures.</div></div><div><h3>Results</h3><div>MR analysis identified 13 protein-SCZ pairs at Bonferroni significance (<em>P</em> &lt; 5.63 × 10⁻⁵). Notably, the genetically proxied protein level of neuromedin B (NMB) was associated with an increased risk for SCZ (odds ratio [OR] = 1.41; 95 % CI, 1.27 to 1.58; <em>P</em> = 6.68 × 10⁻¹⁰). Bayesian colocalization suggested that NMB shares genetic variations with SCZ. Further, NMB interacts with target proteins of current SCZ drugs and was validated in the UK Biobank. The genetically proxied NMB was positively associated with an increase in the surface area (SA) of the parahippocampal gyrus (β = 8.93 mm², 95 % CI, 1.58 to 16.3, <em>P</em> = .02). Additionally, an increase in the genetically proxied SA of the parahippocampal gyrus was inversely associated with the risk of SCZ (OR = 0.996, 95 % CI, 0.993 to 0.999, <em>P</em> = .04).</div></div><div><h3>Conclusions</h3><div>The findings suggest that NMB may represent a promising target for pharmacological intervention in SCZ. This warrants further investigation into the specific constituents involved, which could have potential for follow-up studies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111208"},"PeriodicalIF":5.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746688","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":"Medial septal cholinergic neurotransmission is essential for social memory in mice","authors":"Apoorva Bettagere Shivakumar ,&nbsp;Sonam Fathima Mehak ,&nbsp;Amritanshu Gupta ,&nbsp;Gireesh Gangadharan","doi":"10.1016/j.pnpbp.2024.111207","DOIUrl":"10.1016/j.pnpbp.2024.111207","url":null,"abstract":"<div><div>Social memory, a fundamental component of social behavior, is essential for the recognition and recall of familiar and novel animals/humans which is disrupted in several neuropsychiatric disorders. Although hippocampal circuitry is crucial for social memory, the role of extra-hippocampal regions in this behavior remains elusive. Here, we identified the physiological link between medial septal dependent cholinergic theta oscillations in the hippocampus and social memory behavior. We found that selective ablation of cholinergic neurons in the medial septum impaired social memory in mice, while their sociability and social novelty remained intact. Additionally, these mice showed an attenuation of cholinergic theta oscillations (3–7 Hz) in the hippocampal dorsal CA2 (dCA2) region. Furthermore, enhancing dCA2 theta oscillations by elevating cholinergic signaling using acetylcholinesterase inhibitor rescued social memory deficit. Together, these results indicate that 1) medial septal cholinergic neurons are essential for modulating social memory 2) cholinergic hippocampal theta oscillations contribute to social memory processes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111207"},"PeriodicalIF":5.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746689","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":"Measuring the effects of ketogenic diet on neuropsychiatric disorder: A scoping review","authors":"Wali Yousufzai ,&nbsp;Monika Singh ,&nbsp;Leeda Ahmadi ,&nbsp;Shreya Balamurali ,&nbsp;Divyaraj Bavishi ,&nbsp;Sahar Ashraf ,&nbsp;Daniel B. Stuart ,&nbsp;Regina Baronia ,&nbsp;Wail Amor","doi":"10.1016/j.pnpbp.2024.111205","DOIUrl":"10.1016/j.pnpbp.2024.111205","url":null,"abstract":"<div><div>Objective: This scoping review aims to examine the available literature on the ketogenic diet's (KD) efficiency as a potential therapeutic intervention for various neuropsychiatric disorders. Introduction: The KD is a high-fat, low-carbohydrate diet that has been studied for its potential benefits in managing neuropsychiatric disorders. However, the extent of its effectiveness across a spectrum of these conditions remains unclear. Inclusion criteria: The study designs considered eligible encompassed randomized and non-randomized controlled trials, retrospective and prospective observational studies, and comparative effectiveness assessments. The criteria for including each study were specifically related to neuropsychiatric disorders, referring to the DSM-5 coding guidelines. Methods: A systemic search was performed by an experienced reference librarian across multiple databases to pinpoint studies relevant to the influence of the ketogenic diet on neuropsychiatric disorders. All relevant articles were included that ranged over the last thirteen years. All relevant records identified were compiled into the Covidence systematic review software. Results: A total of 30 studies were reviewed, which reported effects of the KD on neuropsychiatric disorders, including improvements in Global Developmental Delay, Childhood Autism, Attention Deficit/Hyperactivity Disorder (ADHD) symptoms, psychotic symptoms, Bipolar and Related Disorders, Depressive Disorder symptoms, anxiety symptoms, eating disorders, Substance-Related and Addictive Disorders, Major and Mild Neurocognitive Disorders, and Seizure Disorders. Conclusion: The KD may serve as a promising therapeutic intervention for various neuropsychiatric disorders. However, the evidence is heterogeneous, and further rigorous research is needed to establish the KD as a standard treatment for these disorders and to understand the underlying mechanisms of its effects. Implications for Practice: This review underscores the need for healthcare professionals to consider the potential benefits and limitations of the KD when managing patients with neuropsychiatric disorders. It also highlights the importance of individualized treatment plans based on the specific needs and responses of each patient.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111205"},"PeriodicalIF":5.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734740","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":"How dopamine shapes trust beliefs","authors":"Bianca A. Schuster,&nbsp;Claus Lamm","doi":"10.1016/j.pnpbp.2024.111206","DOIUrl":"10.1016/j.pnpbp.2024.111206","url":null,"abstract":"<div><div>Learning whom to trust is integral for healthy relationships and social cohesion, and atypicalities in trust learning are common across a range of clinical conditions, including schizophrenia spectrum disorders, Parkinson's disease, and depression. Persecutory delusions – rigid, unfounded beliefs that others are intending to harm oneself – significantly impact affected individuals' lives as they are associated with a range of negative health outcomes, including suicidal behaviour and relapse. Recent advances in computational modelling and psychopharmacology have significantly extended our understanding of the brain bases of dynamic trust learning, and the neuromodulator dopamine has been suggested to play a key role in this. However, the specifics of this role on a computational and neurobiological level remain to be fully established. The current review article provides a comprehensive summary of novel conceptual developments and empirical findings regarding the computational role of dopamine in social learning processes. Research findings strongly suggest a conceptual shift, from dopamine as a reward mechanism to a teaching signal indicating which information is relevant for learning, and shed light on the neurocomputational mechanisms via which antipsychotics may alleviate symptoms of aberrant social learning processes such as persecutory delusions. Knowledge gaps and inconsistencies in the extant literature are examined and the most pressing issues highlighted, laying the foundation for future research that will further advance our understanding of the neuromodulation of social belief updating processes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111206"},"PeriodicalIF":5.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717822","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":"Increased structural covariance of cortical measures in individuals with an at-risk mental state","authors":"Daiki Sasabayashi ,&nbsp;Sakiko Tsugawa ,&nbsp;Shinichiro Nakajima ,&nbsp;Tsutomu Takahashi ,&nbsp;Yoichiro Takayanagi ,&nbsp;Shinsuke Koike ,&nbsp;Naoyuki Katagiri ,&nbsp;Masahiro Katsura ,&nbsp;Atsushi Furuichi ,&nbsp;Yuko Mizukami ,&nbsp;Shimako Nishiyama ,&nbsp;Haruko Kobayashi ,&nbsp;Yusuke Yuasa ,&nbsp;Naohisa Tsujino ,&nbsp;Atsushi Sakuma ,&nbsp;Noriyuki Ohmuro ,&nbsp;Yutaro Sato ,&nbsp;Kazuho Tomimoto ,&nbsp;Naohiro Okada ,&nbsp;Mariko Tada ,&nbsp;Michio Suzuki","doi":"10.1016/j.pnpbp.2024.111197","DOIUrl":"10.1016/j.pnpbp.2024.111197","url":null,"abstract":"<div><div>An anomalous pattern of structural covariance has been reported in schizophrenia, which has been suggested to represent connectome changes during brain maturation and neuroprogressive processes. It remains unclear whether similar differences exist in a clinical high-risk state for psychosis, and if they are associated with a prodromal phenotype and/or later psychosis onset. This multicenter magnetic resonance imaging study cross-sectionally examined structural covariance in a large at-risk mental state (ARMS) sample with different outcomes. The whole-brain structural covariance of four cortical measures (thickness, area, volume, and gyrification) was assessed in 155 individuals with ARMS, who were subclassified into 26 (16.8 %) with a later psychosis onset (ARMS-P), 44 with persistent subthreshold psychotic symptoms, and 53 with the remission of psychotic symptoms (ARMS-R) during the clinical follow-up, and 191 healthy controls. The relationships of changes in structural covariance with clinical symptoms and cognitive impairments were also investigated in the ARMS subsample. Structural covariance was significantly higher in widespread cortical regions in the ARMS group than in the controls, with each cortical measure having a different pattern in affected cortical regions. The higher structural covariance of the cortical area was partly related to severe suspiciousness–persecutory ideation. Structural covariance was significantly higher, mainly in fronto-parietal gyrification, in the ARMS-P group than in the ARMS-R group. The present results suggest that changes in structural covariance result in psychosis vulnerability and the excessive structural covariance of brain gyrification in ARMS subjects may contribute to their later clinical course.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111197"},"PeriodicalIF":5.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696235","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":"Mendelian randomization and genetic pleiotropy analysis for the connection between inflammatory bowel disease and Alzheimer's disease","authors":"Yuxuan Wu ,&nbsp;Yu Yan ,&nbsp;Jike Qi ,&nbsp;Yuxin Liu ,&nbsp;Ting Wang ,&nbsp;Hao Chen ,&nbsp;Xinying Guan ,&nbsp;Chu Zheng ,&nbsp;Ping Zeng","doi":"10.1016/j.pnpbp.2024.111203","DOIUrl":"10.1016/j.pnpbp.2024.111203","url":null,"abstract":"<div><h3>Background</h3><div>The gut-microbiome-brain axis (GMBA) implies the connection between inflammatory bowel disease (IBD) and Alzheimer's disease (AD). We aimed to comprehensively explore the relation between IBD (and its subtypes) and AD, early-onset AD (EOAD) and late-onset AD (LOAD) from a genetic pleiotropy perspective.</div></div><div><h3>Methods</h3><div>Relying on summary statistics (<em>N</em> = 472,868 for AD, 185,204 for EOAD, 191,061 for LOAD, 59,957 for IBD, 45,975 for CD, and 40,266 for UC), we first performed Mendelian Randomization to examine the causal association between IBD and AD by leveraging vertical pleiotropy. Then, we estimated global and local genetic correlations, followed by cross-trait association analysis to identify SNPs and genes with horizontal pleiotropy. Particularly, we utilized multi-trait colocalization analysis to assess the role of microbes in the common genetic etiology underlying the two types of diseases. Finally, we conducted functional enrichment analysis for pleiotropic genes.</div></div><div><h3>Results</h3><div>We discovered suggestively causal relations between IBD (and its subtypes) and EOAD (OR_IBD = 1.06 [1.01–1.11], OR_CD = 1.05 [1.01–1.10], OR_UC = 1.08 [1.01–1.15]) as well as between UC and LOAD (OR = 1.04 [1.01–1.08]), and discovered 44 local regions showing suggestively significant genetic correlations between IBD (and its subtypes) and AD (and EODA and LOAD). We further detected substantial genetic overlap, as characterized by 182  AD-associated, 3 EOAD-associated and 51 LOAD-associated pleiotropic SNPs as well as 291 pleiotropic genes. Pleiotropic genes more likely enriched in the GMBA-relevant tissues such as brain, intestine and esophagus. Moreover, we identified three microorganisms related to these disease pairs, including the <em>Catenibacterium</em>, <em>Clostridia</em>, and <em>Prevotella</em> species.</div></div><div><h3>Conclusion</h3><div>The suggestively causal associations and shared genetic basis between IBD and its subtypes with AD, EOAD and LOAD may commonly drive their co-occurrence, and gut microbes might partly explain the shared genetic etiology. Further studies are warranted to elaborate the possibly biological mechanisms underlying the two types of diseases.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111203"},"PeriodicalIF":5.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696238","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":"Duration of untreated psychosis and cognitive function in first-episode antipsychotic-naïve schizophrenia: Evidence from auditory P300","authors":"Chenghao Lu ,&nbsp;Shaobing Li ,&nbsp;Nannan Liu ,&nbsp;Tongxin Li ,&nbsp;Yanzhe Li ,&nbsp;Xinxu Wang ,&nbsp;Shen Li ,&nbsp;Jie Li ,&nbsp;Xiang Yang Zhang","doi":"10.1016/j.pnpbp.2024.111202","DOIUrl":"10.1016/j.pnpbp.2024.111202","url":null,"abstract":"<div><h3>Objective</h3><div>The relationship between the duration of untreated psychosis (DUP) and cognitive function in schizophrenia (SZ) patients remains debated, with no empirical evidence from event-related potential (ERP) studies supporting their association. This study aims to investigate the relationship between DUP and cognitive functions, as well as psychiatric symptoms, in first-episode antipsychotic-naïve SZ (FEAN-SZ) patients using ERP.</div></div><div><h3>Methods</h3><div>The study included 321 Chinese FEAN-SZ patients and 146 healthy controls. The DUP and sociodemographic characteristics of all participants were collected, and psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale. The P300 (P3) components, including P3a, P3b and N100, were recorded from all participants using auditory oddball paradigm.</div></div><div><h3>Results</h3><div>25.5 % of patients did not receive timely treatment for over four years, and those with lower educational levels or more severe negative symptoms had longer DUP (<em>p</em> = 0.027, <em>p</em> = 0.020). Compared to healthy controls, FEAN-SZ patients exhibited longer latencies and lower amplitudes in the P3 components (all <em>p</em>_<em>s</em> &lt; 0.001). Significant differences in the P3 components were observed among three groups of DUP (&lt; 8 months, 8 to 48 months, and ≥ 48 months) (all <em>p</em>_<em>s</em> &lt; 0.001). In the 8 ≤ DUP &lt; 48 months group, the N1 amplitude and P3a latency predicted positive symptom scores and general psychopathology scores, respectively (β = −0.165, <em>p</em> = 0.037; β = 0.541, <em>p</em> &lt; 0.001); P3b latency predicted negative symptom scores in the DUP &lt; 8 months group (β = 0.391, <em>p</em> &lt; 0.001). N1 amplitude predicted general psychopathology scores only in the DUP &gt; 48 months group (β = −0.228, <em>p</em> = 0.040). Multiple linear regression analysis indicated that the latency and amplitude of P3a were independently associated with DUP (B = 0.124, <em>p</em> &lt; 0.001; B = −1.161, <em>p</em> = 0.012).</div></div><div><h3>Conclusions</h3><div>SZ patients who have a longer DUP exhibit more severe P3 deficits, and the P3 components may be indicative of different psychiatric symptom severity in DUPs of different lengths, as well as the P3a component may serve as an electrophysiologic marker to assess the length of DUP.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111202"},"PeriodicalIF":5.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696230","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":"Microbiota and social behavior alterations in a mouse model of down syndrome: Modulation by a synbiotic treatment","authors":"Jose Antonio González-Parra ,&nbsp;Marta Barrera-Conde ,&nbsp;Elk Kossatz ,&nbsp;Emma Veza ,&nbsp;Rafael de la Torre ,&nbsp;Arnau Busquets-Garcia ,&nbsp;Patricia Robledo ,&nbsp;Nieves Pizarro","doi":"10.1016/j.pnpbp.2024.111200","DOIUrl":"10.1016/j.pnpbp.2024.111200","url":null,"abstract":"<div><div>Sex differences in the composition and functionality of gut microbiota are an emerging field of interest in neurodevelopmental disorders, as they may help in understanding the phenotypic disparities between males and females. This study aimed to characterize sex-related specific alterations in gut microbiota composition in a mouse model of Down syndrome (Ts65Dn mice, TS mice) through the sequencing of the PCR-amplified 16S ribosomal DNA fraction. Moreover, it intended to examine whether the modulation of gut microbiota by the administration of a synbiotic (SYN) treatment would be beneficial for the behavioral alterations observed in male and female TS mice. Our results show that male, but not female, TS mice exhibit alterations in beta diversity compared to their wild-type (WT) littermates. Sex-dependent differences are also observed in the relative abundance of the classes <em>Bacilli</em> and <em>Clostridia</em>. Administering the SYN effectively counteracts hypersociability in females, and normalizes the overall abundance of <em>Bacilli</em>, specifically by increasing <em>Lactobacillaceae</em>. On the contrary, it rescues emotional recognition deficits in male TS mice and increases the relative abundance of the families <em>Lactobacillaceae</em>, <em>Streptococcaceae</em> and <em>Atopobiaceae</em>. In addition, a metagenome KEGG analysis of differentially enriched pathways shows relevant changes in the cofactor biosynthesis and the amino acid synthesis categories. Finally, following SYN treatment, both male and female TS mice exhibit a robust increase in propionic acid levels compared to WT littermates. These findings suggest sex-specific mechanisms that could link gut microbiota composition with behavior in TS mice, and underscore the potential of targeted gut microbiota interventions to modulate social abnormalities in neurodevelopmental disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111200"},"PeriodicalIF":5.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689739","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":"Captopril prevents depressive-like behavior in an animal model of depression by enhancing hippocampal neurogenesis via activation of the ACE2/Ang (1–7)/Mas receptor/AMPK/BDNF pathway","authors":"Takayo Odaira-Satoh ,&nbsp;Osamu Nakagawasai ,&nbsp;Kohei Takahashi ,&nbsp;Ryotaro Ono ,&nbsp;Miharu Wako ,&nbsp;Wataru Nemoto ,&nbsp;Koichi Tan-No","doi":"10.1016/j.pnpbp.2024.111198","DOIUrl":"10.1016/j.pnpbp.2024.111198","url":null,"abstract":"<div><div>The brain's Renin-Angiotensin System plays an important role in the modulation of mental state. Previously we demonstrated that activated angiotensin (Ang) converting enzyme (ACE) 2, which converts Ang II into Ang (1–7), or the intracerebroventricular administration of Ang (1–7) produced an antidepressant-like effect in mice via Mas receptors (MasR). Since the ACE inhibitor Captopril (Cap) increases Ang (1–7) in the brain, it remains unknown whether Cap affects the depressive-like behavior of olfactory bulbectomized (OBX) mice, an animal model of depression. We tested the effect of Cap on the depressive-like behavior of these mice in the tail-suspension test, quantified ACE2, p-AMP activated protein kinase (AMPK), and brain-derived neurotrophic factor (BDNF) using western blots, and examined the changes in Ang (1–7) level, neurogenesis, and in the expression of ACE2 and MasR on various cell types in the hippocampus using immunohistochemistry. While OBX mice exhibited a depressive-like behavior in the tail-suspension test, as well as a reduction in ACE2, Ang (1–7), p-AMPK, BDNF, and hippocampal neurogenesis, these changes were prevented by Cap administration. The intracerebroventricular administration of Ang (1–7) improved the OBX-induced depressive-like behavior. Except for the changes in ACE2 and Ang (1–7), the effects of Cap were inhibited by the coadministration of A779 (MasR inhibitor) or Compound-C (AMPK inhibitor). ACE2 localized to all cell types, while MasR localized to microglia and neurons. Our results suggest that Cap may act on ACE2-positive cells in the hippocampus to increase ACE2 expression level, thereby enhancing signaling in the ACE2/Ang (1–7)/MasR/AMPK/BDNF pathway and producing antidepressant-like effects.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111198"},"PeriodicalIF":5.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677827","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}