Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Increased structural covariance of cortical measures in individuals with an at-risk mental state.","authors":"Daiki Sasabayashi, Sakiko Tsugawa, Shinichiro Nakajima, Tsutomu Takahashi, Yoichiro Takayanagi, Shinsuke Koike, Naoyuki Katagiri, Masahiro Katsura, Atsushi Furuichi, Yuko Mizukami, Shimako Nishiyama, Haruko Kobayashi, Yusuke Yuasa, Naohisa Tsujino, Atsushi Sakuma, Noriyuki Ohmuro, Yutaro Sato, Kazuho Tomimoto, Naohiro Okada, Mariko Tada, Motomu Suga, Norihide Maikusa, Eric Plitman, Cassandra M J Wannan, Andrew Zalesky, Mallar Chakravarty, Kyo Noguchi, Hidenori Yamasue, Kazunori Matsumoto, Takahiro Nemoto, Hiroaki Tomita, Masafumi Mizuno, Kiyoto Kasai, Michio Suzuki","doi":"10.1016/j.pnpbp.2024.111197","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2024.111197","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111197"},"PeriodicalIF":5.3,"publicationDate":"2024-11-21","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, Yu Yan, Jike Qi, Yuxin Liu, Ting Wang, Hao Chen, Xinying Guan, Chu Zheng, Ping Zeng","doi":"10.1016/j.pnpbp.2024.111203","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2024.111203","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Relying on summary statistics (N = 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.</p><p><strong>Results: </strong>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 CE-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 Catenibacterium, Clostridia, and Prevotella species.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111203"},"PeriodicalIF":5.3,"publicationDate":"2024-11-21","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, Shaobing Li, Nannan Liu, Tongxin Li, Yanzhe Li, Xinxu Wang, Shen Li, Jie Li, Xiang Yang Zhang","doi":"10.1016/j.pnpbp.2024.111202","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2024.111202","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (p = 0.027, p = 0.020). Compared to healthy controls, FEAN-SZ patients exhibited longer latencies and lower amplitudes in the P3 components (all p_s < 0.001). Significant differences in the P3 components were observed among three groups of DUP (< 8 months, 8 to 48 months, and ≥ 48 months) (all p_s < 0.001). In the 8 ≤ DUP < 48 months group, the N1 amplitude and P3a latency predicted positive symptom scores and general psychopathology scores, respectively (β = -0.165, p = 0.037; β = 0.541, p < 0.001); P3b latency predicted negative symptom scores in the DUP < 8 months group (β = 0.391, p < 0.001). N1 amplitude predicted general psychopathology scores only in the DUP > 48 months group (β = -0.228, p = 0.040). Multiple linear regression analysis indicated that the latency and amplitude of P3a were independently associated with DUP (B = 0.124, p < 0.001; B = -1.161, p = 0.012).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111202"},"PeriodicalIF":5.3,"publicationDate":"2024-11-21","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, Marta Barrera-Conde, Elk Kossatz, Emma Veza, Rafael de la Torre, Arnau Busquets-Garcia, Patricia Robledo, Nieves Pizarro","doi":"10.1016/j.pnpbp.2024.111200","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2024.111200","url":null,"abstract":"<p><p>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 Bacilli and Clostridia. Administering the SYN effectively counteracts hypersociability in females, and normalizes the overall abundance of Bacilli, specifically by increasing Lactobacillaceae. On the contrary, it rescues emotional recognition deficits in male TS mice and increases the relative abundance of the families Lactobacillaceae, Streptococcaceae and Atopobiaceae. 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.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111200"},"PeriodicalIF":5.3,"publicationDate":"2024-11-19","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, Osamu Nakagawasai, Kohei Takahashi, Ryotaro Ono, Miharu Wako, Wataru Nemoto, Koichi Tan-No","doi":"10.1016/j.pnpbp.2024.111198","DOIUrl":"10.1016/j.pnpbp.2024.111198","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"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}

{"title":"Relationships between clinical symptoms, cognitive functioning, and TMS-evoked potential features in patients with major depressive disorder.","authors":"Jiaxin Li, Xingxing Li, Junyao Liu, Shuochi Wei, Dongsheng Zhou, Dongmei Wang, Xiangyang Zhang","doi":"10.1016/j.pnpbp.2024.111184","DOIUrl":"10.1016/j.pnpbp.2024.111184","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment is a common clinical symptom of patients with major depressive disorder (MDD). Transcranial magnetic stimulation-evoked potentials (TEPs) detect cortical excitability and connectivity and provide potential biomarkers for MDD patients and their cognitive impairment. This study aimed to investigate the interrelationships between clinical symptoms, cognitive function, and electrophysiological marker TEPs in patients with MDD.</p><p><strong>Methods: </strong>A total of 117 participants were recruited, including 59 MDD patients and 58 healthy controls. Clinical symptoms were assessed by the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, and cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). TEPs were recorded by transcranial magnetic stimulation combined with electroencephalography (TMS-EEG).</p><p><strong>Results: </strong>MDD patients exhibited lower RBANS total (P < 0.001), immediate memory (P = 0.001), language (P = 0.003), attention (P < 0.001), and delayed memory (P = 0.008) scores than HCs. Patients with MDD had larger amplitudes for N100 (P = 0.040) and N280 (P = 0.037), compared to HCs. Correlation analysis indicated significant correlations between the following RBANS scores and TEPs: language and N45 amplitude (r = 0.222, P = 0.024), language and P60 amplitude (r = 0.278, P = 0.004), attention and P180 amplitude (r = 0.213, P = 0.030), RBANS total score and P30 amplitude (r = 0.198, P = 0.044), visuospatial/constructional index and N100 amplitude (r = -0.272, P = 0.005).</p><p><strong>Conclusion: </strong>The results of this study indicate that cortical dysfunction and cognitive impairment are present in patients with MDD and that there is a strong correlation between them, suggesting that TEPs detected by the TMS-EEG may be used as a biomarker for MDD patients and their cognitive impairment.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111184"},"PeriodicalIF":5.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645214","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":"The immune regulatory mechanism of ketamine-induced psychiatric disorders: A new perspective on drug-induced psychiatric symptoms","authors":"Peipei Wang ,&nbsp;Junmei Hu ,&nbsp;Congliang Chen ,&nbsp;Zihan Jiang ,&nbsp;Yu Zhang ,&nbsp;Kexin Lin ,&nbsp;Linchuan Liao ,&nbsp;Xia Wang","doi":"10.1016/j.pnpbp.2024.111194","DOIUrl":"10.1016/j.pnpbp.2024.111194","url":null,"abstract":"<div><div>Ketamine, a psychoactive substance strictly regulated by international drug conventions, is classified as a “new type drug” due to its excitatory, hallucinogenic, or inhibitory effects. The etiology of ketamine-induced psychiatric symptoms is multifaceted, with the immune regulatory mechanism being the most prominent among several explanatory theories. In recent years, the interaction between the immune system and nervous system have garnered significant attention in neuropsychiatric disorder research. Notably, the infiltration of peripheral lymphocytes into the central nervous system has emerged as an early hallmark of certain neuropsychiatric disorders. However, a notable gap exists in the current literature, regarding the immune regulatory mechanisms, specifically the peripheral immune alterations, associated with ketamine-induced psychiatric symptoms. To address this void, this article endeavors to provide a comprehensive overview of the pathophysiological processes implicated in psychiatric disorders or symptoms, encompassing those elicited by ketamine. This analysis delves into aspects such as nerve damage, alterations within the central immune system, and the regulation of the peripheral immune system. By emphasizing the intricate crosstalk between the peripheral immune system and the central nervous system, this study sheds light on their collaborative role in the onset and progression of psychiatric diseases or symptoms. This insight offers fresh perspectives on the underlying mechanisms, diagnosis and therapeutic strategies for mental disorders stemming from drug abuse.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111194"},"PeriodicalIF":5.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632833","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":"Transcriptional signatures of gray matter volume changes in mild traumatic brain injury","authors":"Lu Wang ,&nbsp;He Wang ,&nbsp;Yijing Zhang ,&nbsp;Mengjing Cai ,&nbsp;Zhihui Zhang ,&nbsp;Minghuan Lei ,&nbsp;Yujie Zhang ,&nbsp;Jiaxuan Zhao ,&nbsp;Ying Wang ,&nbsp;Jinglei Xu ,&nbsp;Ying Zhai ,&nbsp;Jinghan Sun ,&nbsp;Qi An ,&nbsp;Wenjie Cai ,&nbsp;Yifan Jiang ,&nbsp;Feng Liu ,&nbsp;Yanmin Peng ,&nbsp;Lining Guo","doi":"10.1016/j.pnpbp.2024.111195","DOIUrl":"10.1016/j.pnpbp.2024.111195","url":null,"abstract":"<div><h3>Background</h3><div>Neuroimaging studies have shown that patients with mild traumatic brain injury (mTBI) often exhibit changes in gray matter volume (GMV) in the brain. However, the results regarding these changes are inconsistent, and the underlying molecular mechanisms remain unclear. This study aimed to investigate GMV changes in mTBI patients and uncover the molecular mechanisms driving these alterations.</div></div><div><h3>Methods</h3><div>We conducted a neuroimaging meta-analysis on nine studies, involving 396 mTBI patients and 338 healthy controls, to identify consistent patterns of GMV changes. Additionally, we utilized the Allen Human Brain Atlas database to explore transcriptome-neuroimaging spatial correlations, identifying genes whose expression profiles are linked to GMV changes in mTBI patients. Enrichment analyses were also performed to determine the biological significance of the altered GMV-related genes.</div></div><div><h3>Results</h3><div>We observed consistent GMV increases in the bilateral middle cingulate/paracingulate gyri, right striatum, and right dorsolateral superior frontal gyrus, along with GMV decreases in the right insula and left lingual gyrus. Moreover, we found spatial associations between mTBI-related GMV changes and the expression of 977 genes, which were primarily enriched in specific biological processes, body tissues, and developmental time windows of the cerebral cortex.</div></div><div><h3>Conclusion</h3><div>Our findings improve the understanding of GMV abnormalities in mTBI patients and provide insights into the molecular mechanisms underlying these changes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111195"},"PeriodicalIF":5.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632835","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":"Social isolation intensifies adgrl3.1-related externalizing and internalizing behaviors in zebrafish","authors":"Barbara D. Fontana ,&nbsp;Nancy Alnassar ,&nbsp;William H.J. Norton ,&nbsp;Matthew O. Parker","doi":"10.1016/j.pnpbp.2024.111193","DOIUrl":"10.1016/j.pnpbp.2024.111193","url":null,"abstract":"<div><div>Externalizing disorders (EDs) are characterized by outward-directed behaviors such as aggression and hyperactivity. They are influenced by gene-environment interactions, yet our understanding of the genetic predispositions and environmental contexts that give rise to them is incomplete. Additionally, people with EDs often exhibit comorbid internalizing symptoms, which can complicate the clinical presentation and treatment strategies. Following on from our previous studies, we examined genes x environment interaction as a risk factor for EDs by looking at internalizing and externalizing behaviors after social isolation. Specifically, we subjected <em>adgrl3.1</em> knockout zebrafish — characterized by hyperactivity and impulsivity — to a 2-week social isolation protocol. We subsequently assessed the impact on anxiety-like behavior, abnormal repetitive behaviors, working memory, and social interactions. Genotype-specific additive effects emerged, with socially isolated <em>adgrl3.1</em> knockout fish exhibiting intensified comorbid phenotypes, including increased anxiety, abnormal repetitive behaviors, reduced working memory, and altered shoaling, when compared to WT fish. The findings demonstrate that genetic predispositions interact with environmental stressors, such as social isolation, to exacerbate both externalizing and internalizing symptoms. This underlines the necessity for comprehensive diagnostic and intervention strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111193"},"PeriodicalIF":5.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632831","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":"A new pharmacological strategy against treatment-resistant depression","authors":"Juan Pedro Pineda-Gómez ,&nbsp;Carmelo Millón ,&nbsp;Noelia Cantero-García ,&nbsp;Marta Flores-Gómez ,&nbsp;David Ladrón de Guevara-Miranda ,&nbsp;Antonio Flores-Burgess ,&nbsp;Zaida Díaz-Cabiale","doi":"10.1016/j.pnpbp.2024.111191","DOIUrl":"10.1016/j.pnpbp.2024.111191","url":null,"abstract":"<div><div>Major depressive disorder affects more than 50 million people in the world. However, 50% of patients don't respond to two or more drugs or psychotherapeutic treatments, named treatment-resistant depression (TRD). In this work, we propose a new augmentation treatment against TRD based on combining Fluoxetine (FLX) and the N-terminal fragment Galanin, GAL(1–15). In Wistar Kyoto (WKY) rats, akin to endogenous depression genetically, we evaluate GAL(1–15)’s impact on FLX-induced behaviours on tests measuring despair and anhedonia. We explored GALR2 involvement using the antagonist M871 and an in vivo model with siRNA 5-HT1A knockdown. Also, the 5-HT1AR was analyzed by autoradiography binding in several brain regions. We analyze the corticosterone levels and a dexamethasone-suppressed corticotropin-releasing hormone stimulation to study the HPA axis regulation. Our results shows that only the combination of FLX + GAL(1–15) induced antidepressant effects in the WKY animals in Behavioural tests related to despair. This combination also reduced corticosterone levels in the WKY animals and modulated the functional characteristics of the serotoninergic receptor 5-HT1A in the prefrontal cortex. These novel results suggest combining GAL(1–15) with FLX is a new potentiation strategy in TRD cases. It shows the innovative potential of the interactions between the galaninergic and serotonergic systems to find new strategies and drugs against resistant depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111191"},"PeriodicalIF":5.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632837","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}