Biological psychiatry global open science最新文献

{"title":"Intrinsic Gene Expression Correlates of the Biophysically Modeled Diffusion Magnetic Resonance Imaging Signal","authors":"Ajay P. Singh ,&nbsp;Michael Fromandi ,&nbsp;Daniel Pimentel-Alarcón ,&nbsp;Donna M. Werling ,&nbsp;Audrey P. Gasch ,&nbsp;John-Paul J. Yu","doi":"10.1016/j.bpsgos.2024.100430","DOIUrl":"10.1016/j.bpsgos.2024.100430","url":null,"abstract":"<div><div>Magnetic resonance imaging (MRI) is a powerful tool to identify the structural and functional correlates of neurological illness but provides limited insight into molecular neurobiology. Using rat genetic models of autism spectrum disorder, we show that image texture–processed neurite orientation dispersion and density imaging (NODDI) diffusion MRI possesses an intrinsic relationship with gene expression that corresponds to the biophysically modeled cellular compartments of the NODDI diffusion signal. Specifically, we demonstrate that neurite density index and orientation dispersion index signals are correlated with intracellular and extracellular gene expression, respectively. Moreover, we further demonstrate that these imaging signals correlate with genes specifically relevant to the etiopathogenesis of autism spectrum disorder. In sum, our data suggest fundamental relationships between gene expression and diffusion MRI, implicating the potential of diffusion MRI to probe causal neurobiological mechanisms in neuroimaging phenotypes in autism spectrum disorder.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100430"},"PeriodicalIF":4.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depressive and Negative Symptoms in the Early and Established Stages of Schizophrenia: Integrating Structural Brain Alterations, Cognitive Performance, and Plasma Interleukin 6 Levels","authors":"Fabiana Corsi-Zuelli ,&nbsp;Gary Donohoe ,&nbsp;Siân Lowri Griffiths ,&nbsp;Cristina M. Del-Ben ,&nbsp;Andrew J. Watson ,&nbsp;Tom Burke ,&nbsp;Paris A. Lalousis ,&nbsp;Declan McKernan ,&nbsp;Derek Morris ,&nbsp;John Kelly ,&nbsp;Colm McDonald ,&nbsp;Saahithh R. Patlola ,&nbsp;Carmine Pariante ,&nbsp;Nicholas M. Barnes ,&nbsp;Golam M. Khandaker ,&nbsp;John Suckling ,&nbsp;Bill Deakin ,&nbsp;Rachel Upthegrove ,&nbsp;Maria R. Dauvermann","doi":"10.1016/j.bpsgos.2024.100429","DOIUrl":"10.1016/j.bpsgos.2024.100429","url":null,"abstract":"<div><h3>Background</h3><div>Depressive and negative symptoms are related to poor functional outcomes in schizophrenia. Cognitive deficits, reduced brain cortical thickness and volumes, and inflammation may contribute to depressive and negative symptoms, but pharmacological treatment and disease progression may confound the associations.</div></div><div><h3>Methods</h3><div>We evaluated whether higher plasma interleukin 6 (IL-6) levels would be associated with more severe negative or depressive symptoms in schizophrenia and explored illness stage utilizing early (BeneMin [Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism], <em>n</em> = 201, 72.8% male) and established (iRELATE [Immune Response &amp; Social Cognition in Schizophrenia], <em>n</em> = 94, 67.3% male) schizophrenia cohorts. Using structural equation modeling in a subsample (iRELATE: <em>n</em> = 42, 69.0% male; BeneMin: <em>n</em> = 102, 76.5% male) with data on structural brain metrics (cortical thickness and volume), general cognitive performance, and plasma IL-6 levels, we assessed the interrelationships between these variables on depressive and negative symptom severity in early and established schizophrenia samples combined and in early schizophrenia only. All analyses were adjusted for sex, age, and chlorpromazine equivalent dose.</div></div><div><h3>Results</h3><div>Higher plasma IL-6 levels were related to more severe depressive symptoms in early schizophrenia (<em>p</em> &lt; .05) and negative symptoms in established schizophrenia (<em>p</em> &lt; .05). Structural equation modeling findings in early and established schizophrenia samples combined and early schizophrenia only showed that the interrelationship between higher plasma IL-6 levels, structural brain metrics, and general cognitive performance did not predict the severity of depressive and negative symptoms (<em>p</em> &gt; .05). Higher plasma IL-6 levels and lower general cognitive performance were associated with reduced brain metrics (<em>p</em> &lt; .05).</div></div><div><h3>Conclusions</h3><div>Our results indicate that higher plasma IL-6 levels may be differently associated with the severity of depressive and negative symptoms dependent on the illness stage. Future work identifying elevated levels of inflammation in larger samples may allow stratification and personalized intervention by subgroups who are at risk of poor outcomes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100429"},"PeriodicalIF":4.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reelin Deficiency and Synaptic Impairment in the Adolescent Prefrontal Cortex Following Initial Synthetic Cannabinoid Exposure","authors":"Thenzing J. Silva-Hurtado ,&nbsp;Gabriele Giua ,&nbsp;Olivier Lassalle ,&nbsp;Leila Makrini-Maleville ,&nbsp;Benjamin Strauss ,&nbsp;Jim Wager-Miller ,&nbsp;Jean-Marc Freyermuth ,&nbsp;Ken Mackie ,&nbsp;Emmanuel Valjent ,&nbsp;Olivier J.J. Manzoni ,&nbsp;Pascale Chavis","doi":"10.1016/j.bpsgos.2024.100426","DOIUrl":"10.1016/j.bpsgos.2024.100426","url":null,"abstract":"<div><h3>Background</h3><div>Adolescent cannabinoid exposure can have long-lasting effects on the brain, particularly in the prefrontal cortex, where the reelin protein plays a crucial role in neural organization. Chronic cannabinoid exposure leads to reelin deficiency and behavioral abnormalities, but the underlying mechanisms remain unclear. With the increasing use of synthetic cannabinoids (SCs) among young people, understanding these effects is crucial.</div></div><div><h3>Methods</h3><div>We examined the cellular and synaptic consequences of initial SC exposure in adolescent male mice 1 day after a single in vivo exposure to WIN 55,212-2. Our approach combined immunohistochemistry, Western blots, conditional CB₁ receptor (CB1R) knockout mouse lines, quantitative polymerase chain reaction, and ex vivo electrophysiology to investigate the effects of SC on reelin expression and synaptic plasticity. Additionally, single-molecule fluorescent in situ hybridization profiling was used to identify cellular coexpression patterns of reelin and CB1Rs.</div></div><div><h3>Results</h3><div>Our findings indicate that a single exposure to SC decreased reelin expression in specific prefrontal cortex layers accompanied by disrupted proteolytic fragmentation but not changes in messenger RNA expression. Single-molecule fluorescent in situ hybridization profiling revealed a strong coexpression of CB1R and reelin. Furthermore, our pharmacological and genetic approaches demonstrated that CB1Rs in GABAergic (gamma-aminobutyric acidergic) neurons mediate the SC-induced decrease in reelin. This decrease in reelin results in a reduction in long-term potentiation, phenocopying reelin haploinsufficient mice. Notably, we restored long-term potentiation by infusing reelin bilaterally, establishing a functional link between reelin depletion and synaptic deficits.</div></div><div><h3>Conclusions</h3><div>These findings provide new insights into the neural consequences of adolescent cannabinoid consumption and highlight the critical role of reelin in the cellular mechanisms associated with SC initiation during adolescence.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100426"},"PeriodicalIF":4.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oscillating Mindfully: Using Machine Learning to Characterize Systems-Level Electrophysiological Activity During Focused Attention Meditation","authors":"Noga Aviad ,&nbsp;Oz Moskovich ,&nbsp;Ophir Orenstein ,&nbsp;Etam Benger ,&nbsp;Arnaud Delorme ,&nbsp;Amit Bernstein","doi":"10.1016/j.bpsgos.2024.100423","DOIUrl":"10.1016/j.bpsgos.2024.100423","url":null,"abstract":"<div><h3>Background</h3><div>There has been rapid growth of neuroelectrophysiological studies that aspire to uncover the “black box” of mindfulness and meditation. Reliance on traditional data analysis methods hinders understanding of the complex, nonlinear, multidimensional, and systemic nature of the functional neuroelectrophysiology of meditation states.</div></div><div><h3>Methods</h3><div>Thus, to reveal the complex systemic neuroelectrophysiology of meditation, we applied a machine learning extreme gradient boosting classification algorithm and 4 complementary feature importance methods to extract systemic electroencephalography features characterizing mindful states from electroencephalography recorded during a focused attention meditation and a control mind-wandering state among 26 experienced meditators.</div></div><div><h3>Results</h3><div>The algorithm classified meditation versus mind-wandering states with 83% accuracy, with an area under the receiver operating characteristic curve of 79% and F1 score of 74%. Feature importance techniques identified 10 electroencephalography features associated with increased power and coherence of high-frequency oscillations during focused attention meditation relative to an instructed mind-wandering state.</div></div><div><h3>Conclusions</h3><div>The findings help delineate the complex systemic oscillatory activity that characterizes meditation.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100423"},"PeriodicalIF":4.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Rate of Unique Mitochondrial DNA Deletion Breakpoints in Young Adults With Early-Life Stress","authors":"Teresa E. Daniels ,&nbsp;Brooke E. Hjelm ,&nbsp;William W. Lewis-de los Angeles ,&nbsp;Eric Smith ,&nbsp;Audrey A. Omidsalar ,&nbsp;Brandi L. Rollins ,&nbsp;Anna Sherman ,&nbsp;Stephanie Parade ,&nbsp;Marquis P. Vawter ,&nbsp;Audrey R. Tyrka","doi":"10.1016/j.bpsgos.2024.100422","DOIUrl":"10.1016/j.bpsgos.2024.100422","url":null,"abstract":"<div><h3>Background</h3><div>Mounting evidence suggests that mitochondria respond to psychosocial stress. Recent studies suggest mitochondrial DNA (mtDNA) deletions may be increased in some psychiatric disorders, but no studies have examined early-life stress (ELS) and mtDNA deletions. In this study, we assessed mtDNA deletions in peripheral blood mononuclear cells of medically healthy young adults with and without ELS.</div></div><div><h3>Methods</h3><div>Participants (<em>n</em> = 181; 69% female), ages 18 to 40 years, were recruited from the community. Participants with ELS (<em>n</em> = 108) had moderate to severe childhood maltreatment; 83 also had parental loss, and 59 had psychiatric disorders. Participants in the control group (<em>n</em> = 73) had no maltreatment, parental loss, or psychiatric disorders. Standardized interviews and self-report measures assessed demographic variables, stress, and mental health. mtDNA from peripheral blood mononuclear cells was amplified via long-range polymerase chain reaction; mtDNA deletions were quantified via Seq-Well, next-generation sequencing, and the Splice-Break pipeline. Linear regression models were used to assess relationships of mtDNA deletion metrics with ELS, adult stressors, psychiatric disorders, and demographics.</div></div><div><h3>Results</h3><div>Participants with ELS had significantly greater rates of unique mtDNA deletion breakpoints per 10,000 coverage than participants without ELS (<em>p</em> &lt; .001), correcting for age, sex, and sequencing depth. Cumulative mtDNA deletion read percentage was not significantly different between groups. Psychiatric disorders and adult stressors were associated with greater unique mtDNA deletion breakpoints (<em>p</em>s &lt; .05) but did not account for associations of ELS with mtDNA deletions.</div></div><div><h3>Conclusions</h3><div>The increased number of unique mtDNA deletion breakpoints in participants with ELS suggests that mitochondrial genomes undergo observable alterations in the context of early stress. Future studies will examine mtDNA deletions with metabolic health measures.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100422"},"PeriodicalIF":4.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population","authors":"Taena Hanson ,&nbsp;Sophia Spencer ,&nbsp;Samantha A. Harker ,&nbsp;Fatoumata Barry ,&nbsp;Phoebe Burton ,&nbsp;Jennifer Beauchemin ,&nbsp;Sarah E. Mennenga ,&nbsp;B. Blair Braden ,&nbsp;Viren D'Sa ,&nbsp;Daphne Koinis-Mitchell ,&nbsp;Sean C.L. Deoni ,&nbsp;Candace R. Lewis","doi":"10.1016/j.bpsgos.2024.100421","DOIUrl":"10.1016/j.bpsgos.2024.100421","url":null,"abstract":"<div><h3>Background</h3><div>Hippocampal volume increases throughout early development and is an important indicator of cognitive abilities and mental health. However, hippocampal development is highly vulnerable to exposures during development, as seen by smaller hippocampal volume and differential epigenetic programming in genes implicated in mental health. However, few studies have investigated hippocampal volume in relation to the peripheral epigenome across development, and even less is known about potential genetic moderators. Therefore, in this study, we explored relationships between hippocampal volume and peripheral DNA methylation of mental health–related genes, specifically <em>NR3C1</em>, <em>FKBP5</em>, and <em>SLC6A4</em>, throughout early development and whether these associations were moderated by age or genotype.</div></div><div><h3>Methods</h3><div>Bilateral hippocampal volume was computed from T2-weighted images through FreeSurfer, and DNA methylation was measured from saliva using the Illumina MethylationEPIC microarray in a pediatric population (<em>N</em> = 248, females = 112, mean_age = 5.13 years, SD_age = 3.60 years).</div></div><div><h3>Results</h3><div>Multiple linear regression and bootstrapping analyses revealed that DNA methylation of <em>NR3C1</em>, <em>FKBP5</em>, and <em>SLC6A4</em> was associated with hippocampal volume and that these relationships were moderated by age and gene-specific variants.</div></div><div><h3>Conclusions</h3><div>These findings support the validity of peripheral DNA methylation profiles for indirectly assessing hippocampal volume and development and underscore the importance of genotype and age considerations in research. Therefore, peripheral epigenetic profiles may be a promising avenue for investigating the impacts of early-life stress on brain structure and subsequent mental health outcomes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100421"},"PeriodicalIF":4.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Correlates of Irritability and Potential Moderating Effects of Inhibitory Control","authors":"Mariah DeSerisy ,&nbsp;Jacob W. Cohen ,&nbsp;Huiyu Yang ,&nbsp;Bruce Ramphal ,&nbsp;Paige Greenwood ,&nbsp;Kahini Mehta ,&nbsp;Michael P. Milham ,&nbsp;Theodore D. Satterthwaite ,&nbsp;David Pagliaccio ,&nbsp;Amy E. Margolis","doi":"10.1016/j.bpsgos.2024.100420","DOIUrl":"10.1016/j.bpsgos.2024.100420","url":null,"abstract":"<div><h3>Background</h3><div>Irritability affects up to 20% of youth and is a primary reason for referral to pediatric mental health clinics. Irritability is thought to be associated with disruptions in processing of reward, threat, and cognitive control; however, empirical study of these associations at both the behavioral and neural level have yielded equivocal findings that may be driven by small sample sizes and differences in study design. Associations between irritability and brain connectivity between cognitive control and reward- or threat-processing circuits remain understudied. Furthermore, better inhibitory control has been linked to lower irritability and differential neural functioning among irritable youth, suggesting that good inhibitory control may serve as a protective factor.</div></div><div><h3>Methods</h3><div>We hypothesized that higher irritability scores would be associated with less positive (or negative) connectivity between cognitive control and threat-processing circuits and between cognitive control and reward-processing circuits in the Healthy Brain Network dataset (release 10.0; <em>N</em> = 4135). We also hypothesized that these associations would be moderated by inhibitory control such that weaker associations between irritability and connectivity would be detected in youths with better than with worse inhibitory control. Regression models were used to test whether associations between irritability and between-network connectivity were moderated by inhibitory control.</div></div><div><h3>Results</h3><div>Counter to our hypothesis, we detected higher irritability associated with reduced connectivity between threat- and reward-processing and cognitive control networks only in 5- to 9-year-old boys. Inhibitory control did not moderate associations of irritability with between-network connectivity.</div></div><div><h3>Conclusions</h3><div>Exploratory findings indicate that reduced between-network connectivity may underlie difficulty regulating negative emotions, leading to greater irritability.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100420"},"PeriodicalIF":4.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Male Mice","authors":"Wei-li Chang ,&nbsp;Karly Tegang ,&nbsp;Benjamin A. Samuels ,&nbsp;Michael Saxe ,&nbsp;Juergen Wichmann ,&nbsp;Denis J. David ,&nbsp;Indira Mendez David ,&nbsp;Angélique Augustin ,&nbsp;Holger Fischer ,&nbsp;Sabrina Golling ,&nbsp;Jens Lamerz ,&nbsp;Doris Roth ,&nbsp;Martin Graf ,&nbsp;Sannah Zoffmann ,&nbsp;Luca Santarelli ,&nbsp;Ravi Jagasia ,&nbsp;René Hen","doi":"10.1016/j.bpsgos.2024.100419","DOIUrl":"10.1016/j.bpsgos.2024.100419","url":null,"abstract":"<div><h3>Background</h3><div>Impairments in behavioral pattern separation (BPS)—the ability to distinguish between similar contexts or experiences—contribute to memory interference and overgeneralization seen in many neuropsychiatric conditions, including depression, anxiety, posttraumatic stress disorder, dementia, and age-related cognitive decline. Although BPS relies on the dentate gyrus and is sensitive to changes in adult hippocampal neurogenesis, its significance as a pharmacological target has not been tested.</div></div><div><h3>Methods</h3><div>In this study, we applied a human neural stem cell high-throughput screening cascade to identify compounds that increase human neurogenesis. One compound with a favorable profile, RO6871135, was then tested in young and aged mice for effects on BPS and anxiety-related behaviors.</div></div><div><h3>Results</h3><div>Chronic treatment with RO6871135 (7.5 mg/kg) increased adult hippocampal neurogenesis and improved BPS in a fear discrimination task in both young and aged mice. RO6871135 treatment also lowered innate anxiety-like behavior, which was more apparent in mice exposed to chronic corticosterone. Ablation of adult hippocampal neurogenesis by hippocampal irradiation supported a neurogenesis-dependent mechanism for RO6871135-induced improvements in BPS. To identify possible mechanisms of action, in vitro and in vivo kinase inhibition and chemical proteomics assays were performed. These tests indicated that RO6871135 inhibited CDK8, CDK11, CaMKIIa, CaMKIIb, MAP2K6, and GSK-3β. An analog compound also demonstrated high affinity for CDK8, CaMKIIa, and GSK-3β.</div></div><div><h3>Conclusions</h3><div>These studies demonstrate a method for empirical identification and preclinical testing of novel neurogenic compounds that can improve BPS and point to possible novel mechanisms that can be interrogated for the development of new therapies to improve specific endophenotypes such as impaired BPS.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100419"},"PeriodicalIF":4.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERK2 Signaling in the Nucleus Accumbens Facilitates Stress Susceptibility and Cocaine Reinstatement","authors":"Lyonna F. Parise ,&nbsp;Sergio D. Iñiguez ,&nbsp;Brandon L. Warren ,&nbsp;Eric M. Parise ,&nbsp;Ryan K. Bachtell ,&nbsp;David M. Dietz ,&nbsp;Eric J. Nestler ,&nbsp;Carlos A. Bolaños-Guzmán","doi":"10.1016/j.bpsgos.2024.100416","DOIUrl":"10.1016/j.bpsgos.2024.100416","url":null,"abstract":"<div><h3>Background</h3><div>Second-messenger signaling within the mesolimbic reward circuit plays a key role in the negative effects of stress and the underlying mechanisms that promote drug abuse. Because the nucleus accumbens (NAc) integrates reward valence, we investigated how ERK2 (extracellular signal-regulated protein kinase-2) signaling affects the development of stress-related comorbidities, including negative affect and drug sensitivity.</div></div><div><h3>Methods</h3><div>We assessed how chronic unpredictable stress influenced the phosphorylation of ERK2-signaling proteins within the NAc of male Sprague Dawley rats. Using a herpes simplex virus, we either upregulated or downregulated NAc ERK2 activation and evaluated behavioral responses to stress-eliciting stimuli (elevated plus maze, open field, forced swim test) and cocaine-seeking behavior (conditioned place preference, self-administration). We also examined ERK2-mediated modifications in spine morphology of medium spiny neurons within the NAc.</div></div><div><h3>Results</h3><div>Chronic unpredictable stress increased the phosphorylation of ERK2-signaling proteins within the NAc. Viral-mediated activation of NAc ERK2 enhanced susceptibility to both depression- and anxiety-related stimuli and increased cocaine-seeking behavior (conditioned place preference and reinstatement). These behavioral changes were associated with an increase in stubby and mushroom spines of NAc medium spiny neurons. Conversely, downregulation of ERK2 activation attenuated affect-related behavioral responses in the forced swim test and blunted cocaine’s rewarding effects without influencing NAc spine morphology.</div></div><div><h3>Conclusions</h3><div>NAc ERK2 contributes to stress-induced behavioral deficits, including anxiety- and depression-like phenotypes, while promoting cocaine-seeking behavior. These findings suggest that ERK2 signaling in the NAc plays a role in the comorbidity of these related syndromes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100416"},"PeriodicalIF":4.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum BDNF Increase After 9-Month Contemplative Mental Training Is Associated With Decreased Cortisol Secretion and Increased Dentate Gyrus Volume: Evidence From a Randomized Clinical Trial","authors":"Lara M.C. Puhlmann ,&nbsp;Pascal Vrtička ,&nbsp;Roman Linz ,&nbsp;Sofie L. Valk ,&nbsp;Ioannis Papassotiriou ,&nbsp;George P. Chrousos ,&nbsp;Veronika Engert ,&nbsp;Tania Singer","doi":"10.1016/j.bpsgos.2024.100414","DOIUrl":"10.1016/j.bpsgos.2024.100414","url":null,"abstract":"<div><h3>Background</h3><div>In this study, we investigated whether mindfulness- and meditation-based mental training that improves stress regulation can upregulate BDNF (brain-derived neurotrophic factor), an important promoter of hippocampal neuroplasticity, and examined cortisol reduction as a mediating pathway.</div></div><div><h3>Methods</h3><div>In a randomized clinical trial, 332 healthy adults were randomly assigned to one of the 3 training cohorts or a passive control cohort. Training participants completed up to three 3-month-long modules targeting attention-based mindfulness, socio-affective skills, or socio-cognitive skills. We examined change in serum BDNF levels after each 3-month training interval; evaluated whether training effects were linked to reduced cortisol release in the long-term, diurnally, and when acutely stress-induced; and explored associations with hippocampal volume changes.</div></div><div><h3>Results</h3><div>In the combined training cohorts, BDNF increased significantly and cumulatively after 3-, 6-, and 9-month training relative to the pretraining baseline (3 month: <em>t</em>₅₁₆ = 3.57 [estimated increase: 1353 pg/mL], 6 month: <em>t</em>₅₁₆ = 3.45 [1557 pg/mL], 9 month: <em>t</em>₅₁₆ = 3.45 [2276 pg/mL]; all <em>p</em>s &lt; .001). After 9 months, training cohort BDNF was not higher than control cohort BDNF, which displayed unexplained variance. However, moderated mediation analysis showed that only training effects, and not control cohort BDNF change, were partially mediated by simultaneously reduced long-term cortisol release (3-month averages) measured in hair (15.1% mediation, <em>p</em> = .021). Individually greater BDNF increase after training correlated with more reduced long-term and stress-induced cortisol release. Moreover, greater BDNF increase after 9 months of training correlated with dentate gyrus volume increase (<em>t</em>₁₀₈ = 2.09, <em>p</em> = .039).</div></div><div><h3>Conclusions</h3><div>Longitudinal contemplative training may promote a neurobiological pathway from stress reduction to increased BDNF levels to enhanced hippocampal volume. However, single serum BDNF measurements can be unreliable for assessing long-term neurotrophic effects in healthy adults. Future studies should investigate nonspecific BDNF measurement effects before considering application in preventive health care.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100414"},"PeriodicalIF":4.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}