Biological psychiatry global open science最新文献

{"title":"Sex Differences in the Development of an Opioid Addiction–Like Phenotype: A Focus on the Telescoping Effect","authors":"Eleanor Blair Towers ,&nbsp;Kyle A. Hsu ,&nbsp;Emaan I. Qillawala ,&nbsp;Shaniece D. Fraser ,&nbsp;Wendy J. Lynch","doi":"10.1016/j.bpsgos.2024.100373","DOIUrl":"10.1016/j.bpsgos.2024.100373","url":null,"abstract":"<div><h3>Background</h3><p>Women develop addiction and drug-related health consequences after fewer years of drug use than men; this accelerated time course, or telescoping effect, has been observed clinically for multiple drugs, including opioids. Preclinical studies indicate that this is a biologically based phenomenon; however, these studies have focused exclusively on cocaine, and none have considered health effects.</p></div><div><h3>Methods</h3><p>In this study, we used a rat (Sprague Dawley) model to determine sex differences in the time course for the development of an opioid addiction–like phenotype, as defined by the development of physical dependence (withdrawal-induced weight loss) and an increase in motivation for fentanyl (under a progressive-ratio schedule). Effects were determined following either 10 days (optimized, experiment 1) or 3 days (threshold, experiment 2) of extended-access fentanyl self-administration (24 hours/day, fixed ratio 1, 2- to 5-minute trials/hour) or following short-access fentanyl self-administration (subthreshold, experiment 3; fixed ratio 1, up to 40 infusions/day). Opioid-related adverse health effects were also determined (experiment 4).</p></div><div><h3>Results</h3><p>Motivation for fentanyl was similarly increased in males and females following 10 days of extended-access self-administration (experiment 1), was transiently increased in females, but not males, following 3 days of extended-access self-administration (experiment 2) and was not increased in either sex following short-access self-administration (experiment 3). Females developed fentanyl-associated adverse health effects more readily than males (experiment 4), with particularly robust differences during extended-access self-administration and withdrawal.</p></div><div><h3>Conclusions</h3><p>As with findings in humans, female rats developed opioid addiction–like features and adverse health consequences more readily than male rats. These data provide support for a biologically based telescoping effect in females for opioids, particularly for opioid-related adverse health consequences.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100373"},"PeriodicalIF":4.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000867/pdfft?md5=304ca317bd24b38de4a19b893d9b2e7e&pid=1-s2.0-S2667174324000867-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173820","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":"Exploring the Embodied Mind: Functional Connectome Fingerprinting of Meditation Expertise","authors":"Sébastien Czajko ,&nbsp;Jelle Zorn ,&nbsp;Loïc Daumail ,&nbsp;Gael Chetelat ,&nbsp;Daniel S. Margulies ,&nbsp;Antoine Lutz","doi":"10.1016/j.bpsgos.2024.100372","DOIUrl":"10.1016/j.bpsgos.2024.100372","url":null,"abstract":"<div><h3>Background</h3><p>Short mindfulness-based interventions have gained traction in research due to their positive impact on well-being, cognition, and clinical symptoms across various settings. However, these short-term trainings are viewed as preliminary steps within a more extensive transformative path, presumably leading to long-lasting trait changes. Despite this, little is still known about the brain correlates of these meditation traits.</p></div><div><h3>Methods</h3><p>To address this gap, we investigated the neural correlates of meditation expertise in long-term Buddhist practitioners, comparing the large-scale brain functional connectivity of 28 expert meditators with 47 matched novices. Our hypothesis posited that meditation expertise would be associated with specific and enduring patterns of functional connectivity present during both meditative (open monitoring/open presence and loving-kindness and compassion meditations) and nonmeditative resting states, as measured by connectivity gradients.</p></div><div><h3>Results</h3><p>Applying a support vector classifier to states not included in training, we successfully decoded expertise as a trait, demonstrating its non–state-dependent nature. The signature of expertise was further characterized by an increased integration of large-scale brain networks, including the dorsal and ventral attention, limbic, frontoparietal, and somatomotor networks. The latter correlated with a higher ability to create psychological distance from thoughts and emotions.</p></div><div><h3>Conclusions</h3><p>Such heightened integration of bodily maps with affective and attentional networks in meditation experts could point toward a signature of the embodied cognition cultivated in these contemplative practices.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100372"},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000855/pdfft?md5=40f89fc9138b1916dc32744913bee376&pid=1-s2.0-S2667174324000855-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163644","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":"Electroencephalographic Microstates During Sleep and Wake in Schizophrenia","authors":"Michael Murphy ,&nbsp;Chenguang Jiang ,&nbsp;Lei A. Wang ,&nbsp;Nataliia Kozhemiako ,&nbsp;Yining Wang","doi":"10.1016/j.bpsgos.2024.100371","DOIUrl":"10.1016/j.bpsgos.2024.100371","url":null,"abstract":"<div><h3>Background</h3><p>Aberrant functional connectivity is a hallmark of schizophrenia. The precise nature and mechanism of dysconnectivity in schizophrenia remains unclear, but evidence suggests that dysconnectivity is different in wake versus sleep. Microstate analysis uses electroencephalography (EEG) to investigate large-scale patterns of coordinated brain activity by clustering EEG data into a small set of recurring spatial patterns, or microstates. We hypothesized that this technique would allow us to probe connectivity between brain networks at a fine temporal resolution and uncover previously unknown sleep-specific dysconnectivity.</p></div><div><h3>Methods</h3><p>We studied microstates during sleep in patients with schizophrenia by analyzing high-density EEG sleep data from 114 patients with schizophrenia and 79 control participants. We used a polarity-insensitive <em>k</em>-means analysis to extract a set of 6 microstate topographies.</p></div><div><h3>Results</h3><p>These 6 states included 4 widely reported canonical microstates. In patients and control participants, falling asleep was characterized by a shift from microstates A, B, and C to microstates D, E, and F. Microstate F was decreased in patients during wake, and microstate E was decreased in patients during sleep. The complexity of microstate transitions was greater in patients than control participants during wake, but this reversed during sleep.</p></div><div><h3>Conclusions</h3><p>Our findings reveal behavioral state–dependent patterns of cortical dysconnectivity in schizophrenia. Furthermore, these findings are largely unrelated to previous sleep-related EEG markers of schizophrenia such as decreased sleep spindles. Therefore, these findings are driven by previously undescribed sleep-related pathology in schizophrenia.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100371"},"PeriodicalIF":4.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000843/pdfft?md5=f54af03c03108f894b1911814da26a63&pid=1-s2.0-S2667174324000843-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142149437","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":"Precision Functional Mapping to Advance Developmental Psychiatry Research","authors":"Alyssa K. Labonte BS ,&nbsp;M. Catalina Camacho ,&nbsp;Julia Moser ,&nbsp;Sanju Koirala ,&nbsp;Timothy O. Laumann ,&nbsp;Scott Marek ,&nbsp;Damien Fair ,&nbsp;Chad M. Sylvester","doi":"10.1016/j.bpsgos.2024.100370","DOIUrl":"10.1016/j.bpsgos.2024.100370","url":null,"abstract":"<div><p>Many psychiatric conditions have their roots in early development. Individual differences in prenatal brain function (which is influenced by a combination of genetic risk and the prenatal environment) likely interact with individual differences in postnatal experience, resulting in substantial variation in brain functional organization and development in infancy. Neuroimaging has been a powerful tool for understanding typical and atypical brain function and holds promise for uncovering the neurodevelopmental basis of psychiatric illness; however, its clinical utility has been relatively limited thus far. A substantial challenge in this endeavor is the traditional approach of averaging brain data across groups despite individuals varying in their brain organization, which likely obscures important clinically relevant individual variation. Precision functional mapping (PFM) is a neuroimaging technique that allows the capture of individual-specific and highly reliable functional brain properties. Here, we discuss how PFM, through its focus on individuals, has provided novel insights for understanding brain organization across the life span and its promise in elucidating the neural basis of psychiatric disorders. We first summarize the extant literature on PFM in normative populations, followed by its limited utilization in studying psychiatric conditions in adults. We conclude by discussing the potential for infant PFM in advancing developmental precision psychiatry applications, given that many psychiatric disorders start during early infancy and are associated with changes in individual-specific functional neuroanatomy. By exploring the intersection of PFM, development, and psychiatric research, this article underscores the importance of individualized approaches in unraveling the complexities of brain function and improving clinical outcomes across development.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100370"},"PeriodicalIF":4.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000831/pdfft?md5=46c0d9937bd209ed7118e5bf4dfbb509&pid=1-s2.0-S2667174324000831-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168182","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":"Daily Social Isolation Maps Onto Distinctive Features of Anhedonic Behavior: A Combined Ecological and Computational Investigation","authors":"Valeria Gigli ,&nbsp;Paola Castellano ,&nbsp;Valerio Ghezzi ,&nbsp;Yuen-Siang Ang ,&nbsp;Martino Schettino ,&nbsp;Diego A. Pizzagalli ,&nbsp;Cristina Ottaviani","doi":"10.1016/j.bpsgos.2024.100369","DOIUrl":"10.1016/j.bpsgos.2024.100369","url":null,"abstract":"<div><h3>Background</h3><p>Loneliness and social isolation have detrimental consequences for mental health and act as vulnerability factors for the development of depressive symptoms, such as anhedonia. The mitigation strategies used to contain COVID-19, such as social distancing and lockdowns, allowed us to investigate putative associations between daily objective and perceived social isolation and anhedonic-like behavior.</p></div><div><h3>Methods</h3><p>Reward-related functioning was objectively assessed using the Probabilistic Reward Task. A total of 114 unselected healthy individuals (71% female) underwent both a laboratory and an ecological momentary assessment. Computational modeling was applied to performance on the Probabilistic Reward Task to disentangle reward sensitivity and learning rate.</p></div><div><h3>Results</h3><p>Findings revealed that objective, but not subjective, daily social interactions were associated with motivational behavior. Specifically, higher social isolation (less time spent with others) was associated with higher responsivity to rewarding stimuli and a reduced influence of a given reward on successive behavioral choices.</p></div><div><h3>Conclusions</h3><p>Overall, the current results broaden our knowledge of the potential pathways that link (COVID-19–related) social isolation to altered motivational functioning.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100369"},"PeriodicalIF":4.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266717432400082X/pdfft?md5=a814b502df144b7f7875b3cc48222b45&pid=1-s2.0-S266717432400082X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142075862","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":"The Predictive Value of Plasma Bioactive Lipids on Craving in Human Volunteers With Alcohol Use Disorder","authors":"Cristina Miliano ,&nbsp;Luis A. Natividad ,&nbsp;Susan Quello ,&nbsp;Mike Stoolmiller ,&nbsp;Ann M. Gregus ,&nbsp;Matthew W. Buczynski ,&nbsp;Barbara J. Mason","doi":"10.1016/j.bpsgos.2024.100368","DOIUrl":"10.1016/j.bpsgos.2024.100368","url":null,"abstract":"<div><h3>Background</h3><p>Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by alcohol seeking and consumption despite negative consequences. Despite the availability of multiple treatments, patients continue to exhibit high relapse rates. Thus, biomarkers that can identify patients at risk for heightened craving are urgently needed. Mounting preclinical and clinical evidence implicates perturbations in bioactive lipid signaling in the neurobiology of craving in AUD. We hypothesize that these lipids are potential biomarkers for predicting alcohol craving in patients with AUD.</p></div><div><h3>Methods</h3><p>This study used archival deidentified clinical data and corresponding plasma specimens from 157 participants in 3 clinical studies of AUD. We evaluated plasma levels of 8 lipid species as predictors of craving in response to in vivo alcohol and affective cues during abstinence.</p></div><div><h3>Results</h3><p>Participants were 109 men and 48 women who met DSM-5 criteria for severe AUD. We found that plasma levels of 12- and 15-HETE, 12/15-lipoxygenase–produced proinflammatory lipids, and palmitoylethanolamide, an anti-inflammatory fatty acid amide hydrolase–regulated lipid metabolite, were differentially correlated with alcohol craving during abstinence, predicting higher craving independent of demographics, alcohol use history, and multiple therapeutic treatments.</p></div><div><h3>Conclusions</h3><p>Our findings highlight the promise of these lipid metabolites as biomarkers of heightened alcohol craving. The results open a novel opportunity for further research and clinical evaluation of these biomarkers to optimize existing treatments and develop new therapeutics for AUD.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100368"},"PeriodicalIF":4.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000818/pdfft?md5=6ecccc79410719a00d3bc468dadc1ded&pid=1-s2.0-S2667174324000818-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141850808","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":"Dynamic Functional Connectivity Correlates of Trait Mindfulness in Early Adolescence","authors":"Isaac N. Treves ,&nbsp;Hilary A. Marusak ,&nbsp;Alexandra Decker ,&nbsp;Aaron Kucyi ,&nbsp;Nicholas A. Hubbard ,&nbsp;Clemens C.C. Bauer ,&nbsp;Julia Leonard ,&nbsp;Hannah Grotzinger ,&nbsp;Melissa A. Giebler ,&nbsp;Yesi Camacho Torres ,&nbsp;Andrea Imhof ,&nbsp;Rachel Romeo ,&nbsp;Vince D. Calhoun ,&nbsp;John D.E. Gabrieli","doi":"10.1016/j.bpsgos.2024.100367","DOIUrl":"10.1016/j.bpsgos.2024.100367","url":null,"abstract":"<div><h3>Background</h3><p>Trait mindfulness—the tendency to attend to present-moment experiences without judgment—is negatively correlated with adolescent anxiety and depression. Understanding the neural mechanisms that underlie trait mindfulness may inform the neural basis of psychiatric disorders. However, few studies have identified brain connectivity states that are correlated with trait mindfulness in adolescence, and they have not assessed the reliability of such states.</p></div><div><h3>Methods</h3><p>To address this gap in knowledge, we rigorously assessed the reliability of brain states across 2 functional magnetic resonance imaging scans from 106 adolescents ages 12 to 15 (50% female). We performed both static and dynamic functional connectivity analyses and evaluated the test-retest reliability of how much time adolescents spent in each state. For the reliable states, we assessed associations with self-reported trait mindfulness.</p></div><div><h3>Results</h3><p>Higher trait mindfulness correlated with lower anxiety and depression symptoms. Static functional connectivity (intraclass correlation coefficients 0.31–0.53) was unrelated to trait mindfulness. Among the dynamic brains states that we identified, most were unreliable within individuals across scans. However, one state, a hyperconnected state of elevated positive connectivity between networks, showed good reliability (intraclass correlation coefficient = 0.65). We found that the amount of time that adolescents spent in this hyperconnected state positively correlated with trait mindfulness.</p></div><div><h3>Conclusions</h3><p>By applying dynamic functional connectivity analysis on over 100 resting-state functional magnetic resonance imaging scans, we identified a highly reliable brain state that correlated with trait mindfulness. This brain state may reflect a state of mindfulness, or awareness and arousal more generally, which may be more pronounced in people who are higher in trait mindfulness.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100367"},"PeriodicalIF":4.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000806/pdfft?md5=cdd0fcdcfe4c44cbd938645681cdc57a&pid=1-s2.0-S2667174324000806-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098287","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":"Integrated Long Noncoding RNA and Messenger RNA Expression Analysis Identifies Molecules Specifically Associated With Resiliency and Susceptibility to Depression and Antidepressant Response","authors":"Qingzhong Wang ,&nbsp;Huizhen Wang ,&nbsp;Yogesh Dwivedi","doi":"10.1016/j.bpsgos.2024.100365","DOIUrl":"10.1016/j.bpsgos.2024.100365","url":null,"abstract":"<div><h3>Background</h3><p>Depression involves maladaptive processes impairing an individual’s ability to interface with the environment appropriately. Long noncoding RNAs (lncRNAs) are gaining traction for their role in higher-order brain functioning. Recently, we reported that lncRNA coexpression modules may underlie abnormal responses to stress in rats showing depression-like behavior. The current study explored the global expression regulation of lncRNAs and messenger RNAs (mRNAs) in the hippocampus of rats showing susceptibility (learned helplessness [LH]) or resiliency (non-LH) to depression and fluoxetine response to LH (LH+FLX).</p></div><div><h3>Methods</h3><p>Multiple comparison analysis was performed with an analysis of variance via the <em>aov</em> and <em>summary</em> function in the R platform to identify the differential expression of mRNAs and lncRNAs among LH, non-LH, tested control, and LH+FLX groups. Weighted gene coexpression network analysis was used to identify distinctive modules and pathways associated with each phenotype. A machine learning analysis was conducted to screen the critical target genes. Based on the combined analysis, the regulatory effects of lncRNAs on mRNA expression were explored.</p></div><div><h3>Results</h3><p>Multiple comparison analyses revealed differentially expressed mRNAs and lncRNAs with each phenotype. Integrated bioinformatics analysis identified novel transcripts, specific modules, and regulatory pairs of mRNA-lncRNA in each phenotype. In addition, the machine learning approach predicted lncRNA-regulated <em>Spp2</em> and <em>Olr25</em> genes in developing LH behavior, whereas joint analysis of mRNA-lncRNA pairs identified <em>Mboat7</em>, <em>Lmod1</em>, <em>I</em><em>l</em><em>18</em>, and <em>Rfx5</em> genes in depression-like behavior and <em>Adam6</em> and <em>Tpra1</em> in antidepressant response.</p></div><div><h3>Conclusions</h3><p>The study shows a novel role for lncRNAs in the development of specific depression phenotypes and in identifying newer targets for therapeutic development.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100365"},"PeriodicalIF":4.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000788/pdfft?md5=c0a81ece017ac96029a09d5a6606085e&pid=1-s2.0-S2667174324000788-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845873","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":"The Impacts of Adolescent Cannabinoid Exposure on Striatal Anxiety- and Depressive-Like Pathophysiology Are Prevented by the Antioxidant N-Acetylcysteine","authors":"Marta De Felice ,&nbsp;Hanna J. Szkudlarek ,&nbsp;Taygun C. Uzuneser ,&nbsp;Mar Rodríguez-Ruiz ,&nbsp;Mohammed H. Sarikahya ,&nbsp;Mathusha Pusparajah ,&nbsp;Juan Pablo Galindo Lazo ,&nbsp;Shawn N. Whitehead ,&nbsp;Ken K.-C. Yeung ,&nbsp;Walter J. Rushlow ,&nbsp;Steven R. Laviolette","doi":"10.1016/j.bpsgos.2024.100361","DOIUrl":"10.1016/j.bpsgos.2024.100361","url":null,"abstract":"<div><h3>Background</h3><p>Exposure to Δ⁹-tetrahydrocannabinol (THC) is an established risk factor for later-life neuropsychiatric vulnerability, including mood- and anxiety-related symptoms. The psychotropic effects of THC on affect and anxiogenic behavioral phenomena are known to target the striatal network, particularly the nucleus accumbens, a neural region linked to mood and anxiety disorder pathophysiology. THC may increase neuroinflammatory responses via the redox system and dysregulate inhibitory and excitatory neural balance in various brain circuits, including the striatum. Thus, interventions that can induce antioxidant effects may counteract the neurodevelopmental impacts of THC exposure.</p></div><div><h3>Methods</h3><p>In the current study, we used an established preclinical adolescent rat model to examine the impacts of adolescent THC exposure on various behavioral, molecular, and neuronal biomarkers associated with increased mood and anxiety disorder vulnerability. Moreover, we investigated the protective properties of the antioxidant <em>N</em>-acetylcysteine against THC-related pathology.</p></div><div><h3>Results</h3><p>We demonstrated that adolescent THC exposure induced long-lasting anxiety- and depressive-like phenotypes concomitant with differential neuronal and molecular abnormalities in the two subregions of the nucleus accumbens, the shell and the core. In addition, we report for the first time that <em>N</em>-acetylcysteine can prevent THC-induced accumbal pathophysiology and associated behavioral abnormalities.</p></div><div><h3>Conclusions</h3><p>The preventive effects of this antioxidant intervention highlight the critical role of redox mechanisms underlying cannabinoid-induced neurodevelopmental pathology and identify a potential intervention strategy for the prevention and/or reversal of these pathophysiological sequelae.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100361"},"PeriodicalIF":4.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000740/pdfft?md5=c52d3f439f1ac7a8664a0488832d511b&pid=1-s2.0-S2667174324000740-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843331","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":"Computational Modeling Differentiates Learning Rate From Reward Sensitivity Deficits Produced by Early-Life Adversity in a Rodent Touchscreen Probabilistic Reward Task","authors":"Brian D. Kangas ,&nbsp;Yuen-Siang Ang ,&nbsp;Annabel K. Short ,&nbsp;Tallie Z. Baram ,&nbsp;Diego A. Pizzagalli","doi":"10.1016/j.bpsgos.2024.100362","DOIUrl":"10.1016/j.bpsgos.2024.100362","url":null,"abstract":"<div><h3>Background</h3><p>Exposure to adversity, including unpredictable environments, during early life is associated with neuropsychiatric illness in adulthood. One common factor in this sequela is anhedonia, the loss of responsivity to previously reinforcing stimuli. To accelerate the development of new treatment strategies for anhedonic disorders induced by early-life adversity, animal models have been developed to capture critical features of early-life stress and the behavioral deficits that such stressors induce. We have previously shown that rats exposed to the limited bedding and nesting protocol exhibited blunted reward responsivity in the probabilistic reward task, a touchscreen-based task reverse translated from human studies.</p></div><div><h3>Methods</h3><p>To test the quantitative limits of this translational platform, we examined the ability of Bayesian computational modeling and probability analyses identical to those optimized in previous human studies to quantify the putative mechanisms that underlie these deficits with precision. Specifically, 2 parameters that have been shown to independently contribute to probabilistic reward task outcomes in patient populations, reward sensitivity and learning rate, were extracted, as were trial-by-trial probability analyses of choices as a function of the preceding trial.</p></div><div><h3>Results</h3><p>Significant deficits in reward sensitivity, but not learning rate, contributed to the anhedonic phenotypes in rats exposed to early-life adversity.</p></div><div><h3>Conclusions</h3><p>The current findings confirm and extend the translational value of these rodent models by verifying the effectiveness of computational modeling in distinguishing independent features of reward sensitivity and learning rate that complement the probabilistic reward task’s signal detection end points. Together, these metrics serve to objectively quantify reinforcement learning deficits associated with anhedonic phenotypes.</p></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"4 6","pages":"Article 100362"},"PeriodicalIF":4.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667174324000752/pdfft?md5=be3381784221195868f89bf20c2b213a&pid=1-s2.0-S2667174324000752-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845350","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}