Kaitlyn LaRocco , Peroushini Villiamma , Justin Hill , Mara A. Russell , Ralph J. DiLeone , Stephanie M. Groman
{"title":"Disruptions in Reward-Guided Decision-Making Functions Are Predictive of Greater Oral Oxycodone Self-Administration in Male and Female Rats","authors":"Kaitlyn LaRocco , Peroushini Villiamma , Justin Hill , Mara A. Russell , Ralph J. DiLeone , Stephanie M. Groman","doi":"10.1016/j.bpsgos.2025.100450","DOIUrl":"10.1016/j.bpsgos.2025.100450","url":null,"abstract":"<div><h3>Background</h3><div>Problematic opioid use that emerges in a subset of individuals may be due to preexisting disruptions in the biobehavioral mechanisms that regulate drug use. The identity of these mechanisms is not known, but emerging evidence suggests that suboptimal decision making that is observable prior to drug use may contribute to the pathology of addiction.</div></div><div><h3>Methods</h3><div>The current study investigated the relationship between decision-making phenotypes and opioid-taking behaviors in male and female Long Evans rats. Adaptive decision-making processes were assessed using a probabilistic reversal learning task and oxycodone- (or vehicle, as a control) taking behaviors assessed daily in 32 sessions using a saccharin fading procedure that promoted dynamic intake of oxycodone. Tests of motivation, extinction, and reinstatement were also performed.</div></div><div><h3>Results</h3><div>Computational analyses of decision-making data identified data-driven metrics that predicted self-administration of oxycodone and addiction-relevant behaviors. Moreover, preexisting impairments in reward-guided decision making observed in female rats were associated with greater addiction-relevant behaviors when compared with males.</div></div><div><h3>Conclusions</h3><div>These results provide new insights into the biobehavioral mechanisms that regulate opiate-taking behaviors and offer a novel phenotypic approach for interrogating sex differences in addiction susceptibility and opioid use disorders.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100450"},"PeriodicalIF":4.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465067","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}
Stuart Matan-Lithwick , Melissa C. Misztal , Mu Yang , Thomas DeLong , Shreejoy Tripathy , Jeffrey T. Dunn , David A. Bennett , Philip L. De Jager , Yanling Wang , Daniel W. Fisher , Hongxin Dong , Daniel Felsky
{"title":"A Transcriptomic Signature of Depressive Symptoms in Late Life","authors":"Stuart Matan-Lithwick , Melissa C. Misztal , Mu Yang , Thomas DeLong , Shreejoy Tripathy , Jeffrey T. Dunn , David A. Bennett , Philip L. De Jager , Yanling Wang , Daniel W. Fisher , Hongxin Dong , Daniel Felsky","doi":"10.1016/j.bpsgos.2025.100448","DOIUrl":"10.1016/j.bpsgos.2025.100448","url":null,"abstract":"<div><h3>Background</h3><div>Depressive symptoms in late life can impair daily function and accompany cognitive decline. However, the molecular mechanisms that underlie these changes in the brain remain poorly understood.</div></div><div><h3>Methods</h3><div>Differential expression analysis was performed on bulk-tissue RNA sequencing data generated from dorsolateral prefrontal cortex samples of elderly participants in ROS/MAP (Religious Orders Study and Memory and Aging Project; <em>N</em> = 998, mean age at death = 89.7 years). Bulk tissue RNA sequencing was analyzed against depressive symptoms measured prior to death, controlling for Alzheimer’s disease neuropathology, medication status, and lifestyle factors. Sex-stratified models were also tested.</div></div><div><h3>Results</h3><div>Increased abundance of the Prader-Willi syndrome–associated gene <em>PWAR1</em> (corrected <em>p</em> = 5.47 × 10<sup>−3</sup>) and <em>CTDSPL2</em> (corrected <em>p</em> = .03) were associated with a higher burden of depressive symptoms in the combined sample. An additional 14 genes showed suggestive associations, including several with known links to neuropsychiatric illness (e.g., <em>ACVR2B-AS1</em>, <em>COL19A1</em>). Functional enrichment analysis revealed downregulation of aerobic metabolism and upregulation of both amino acid catabolism and DNA modification processes. Differential expression signatures were poorly correlated between males and females (Pearson <em>r</em> = 0.12; 95% CI, 0.10 to 0.13), and only the male group showed independently significant differential expression. Little overlap was found with previously published analyses of major depressive disorder.</div></div><div><h3>Conclusions</h3><div>Building on recently published single-nucleus profiling, we present the largest-ever study of transcriptomic correlates of depressive symptoms in late life, revealing new insights into sex-specific regulators. <em>PWAR1</em> and <em>CTDSPL2</em> were identified as putative markers of late-life depression in the dorsolateral prefrontal cortex and warrant further study.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100448"},"PeriodicalIF":4.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487437","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}
Douglas W. Barrett, Christopher G. Beevers, F. Gonzalez-Lima
{"title":"Augmenting Internet-Based Cognitive Behavioral Therapy for Major Depressive Disorder With Transcranial Infrared Laser Stimulation","authors":"Douglas W. Barrett, Christopher G. Beevers, F. Gonzalez-Lima","doi":"10.1016/j.bpsgos.2025.100449","DOIUrl":"10.1016/j.bpsgos.2025.100449","url":null,"abstract":"<div><h3>Background</h3><div>Transcranial infrared laser stimulation (TILS) is a noninvasive form of photobiomodulation that facilitates prefrontal energy metabolism and oxygenation, resulting in cognitive-enhancing effects. Cognitive behavioral therapy is a mainstream treatment for major depressive disorder. This is the first study to investigate whether TILS would augment the antidepressant effects of internet-based cognitive behavioral therapy.</div></div><div><h3>Methods</h3><div>Sixty participants with major depressive disorder were given access to Deprexis, a form of internet-based cognitive behavioral therapy, for 12 weeks. After the first 2 weeks, the 40 participants who had improved at least 10% in depressive symptoms from baseline as measured by the Quick Inventory of Depressive Symptomatology–Self-Report were randomly assigned to Deprexis in combination with TILS or sham/placebo. There were no significant group differences in demographics or initial depression data.</div></div><div><h3>Results</h3><div>There was a 43% reduction in Quick Inventory of Depressive Symptomatology–Self-Report scores in the sham group from the initial score to the week 12 score, while adding TILS as an adjunct therapy resulted in a reduction of 56%. Therefore, TILS resulted in an additional 30% reduction in Quick Inventory of Depressive Symptomatology–Self-Report scores ([56−43]/43 = 30%). Participants who received TILS to the right forehead once a week for 4 weeks showed a significantly greater reduction of depressive symptoms than participants who received sham/placebo. Participants reported no adverse effects.</div></div><div><h3>Conclusions</h3><div>While Deprexis alone significantly reduced depression scores in the placebo control group, this beneficial effect was augmented with the addition of TILS as an adjunct therapy. Additional research that pairs neuroenhancement methods such as TILS with cognitive interventions may reveal the potential to improve treatment outcomes in depression and other psychiatric disorders.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 2","pages":"Article 100449"},"PeriodicalIF":4.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134689","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":"Brain-Scale Electroencephalography Patterns of Sleep and Wake in Schizophrenia","authors":"Alena Damborská","doi":"10.1016/j.bpsgos.2024.100428","DOIUrl":"10.1016/j.bpsgos.2024.100428","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100428"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096834","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}
Kleanthi Chalkiadaki , Elpida Statoulla , Maria Zafeiri , Georgia Voudouri , Theoklitos Amvrosiadis , Alexandra Typou , Niki Theodoridou , Dimitrios Moschovas , Apostolos Avgeropoulos , Martina Samiotaki , John O. Mason , Christos G. Gkogkas
{"title":"GABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2−/− Cerebral Organoids","authors":"Kleanthi Chalkiadaki , Elpida Statoulla , Maria Zafeiri , Georgia Voudouri , Theoklitos Amvrosiadis , Alexandra Typou , Niki Theodoridou , Dimitrios Moschovas , Apostolos Avgeropoulos , Martina Samiotaki , John O. Mason , Christos G. Gkogkas","doi":"10.1016/j.bpsgos.2024.100413","DOIUrl":"10.1016/j.bpsgos.2024.100413","url":null,"abstract":"<div><h3>Background</h3><div>The polygenic nature of autism spectrum disorder (ASD) requires the identification of converging genetic pathways during early development to elucidate its complexity and varied manifestations.</div></div><div><h3>Methods</h3><div>We developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the <em>CNTNAP2</em> ASD risk gene.</div></div><div><h3>Results</h3><div>CNTNAP2<sup>−/−</sup> cerebral organoids displayed accelerated cell cycle, ventricular zone disorganization, and increased cortical folding. Proteomic analysis revealed disruptions in glutamatergic/GABAergic (gamma-aminobutyric acidergic) synaptic pathways and neurodevelopment, and transcriptomic analysis revealed differentially expressed genes belonging to inhibitory neuron–related gene networks. Interestingly, there was a weak correlation between the 2 datasets, suggesting nuanced translational control mechanisms. Along these lines, we found upregulated AKT/mTOR (mechanistic target of rapamycin) signaling in CNTNAP2<sup>−/−</sup> organoids. Spatial transcriptomic analysis of CNTNAP2<sup>−/−</sup> ventricular-like zones demonstrated pervasive changes in gene expression, implicating upregulation of cell cycle regulation, synaptic, and glutamatergic/GABAergic pathways. We noted significant overlap of all day-30 organoid omics datasets differentially expressed genes from idiopathic ASD (macrocephaly) induced pluripotent stem cell–derived telencephalic organoids, where FOXG1 was upregulated. Moreover, we detected increased GAD1-expressing and decreased TBR1-expressing cells, suggesting altered GABAergic/glutamatergic neuron development.</div></div><div><h3>Conclusions</h3><div>These findings potentially highlight a shared mechanism in the early cortical development of various forms of ASD, further elucidate the role of CNTNAP2 in ASD pathophysiology and cortical development, and pave the way for targeted therapies that use cerebral organoids as preclinical models.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100413"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933949","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":"Guide for Authors","authors":"","doi":"10.1016/S2667-1743(24)00155-1","DOIUrl":"10.1016/S2667-1743(24)00155-1","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100442"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143092551","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":"Individually Specific Topography Maps Derived From Resting-State Functional Magnetic Resonance Imaging to Understand the Neurobiology of Psychosis","authors":"Philip R. Szeszko","doi":"10.1016/j.bpsgos.2024.100417","DOIUrl":"10.1016/j.bpsgos.2024.100417","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100417"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143092554","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":"Emotional Impairments in Animal Models of Traumatic Neuropathic Pain: Where Do We Stand?","authors":"Filipa Pinto-Ribeiro","doi":"10.1016/j.bpsgos.2024.100424","DOIUrl":"10.1016/j.bpsgos.2024.100424","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100424"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143092107","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":"Subscribers Page","authors":"","doi":"10.1016/S2667-1743(24)00153-8","DOIUrl":"10.1016/S2667-1743(24)00153-8","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100440"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143092552","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":"If Mismatch Negativity Is the Answer, What Is the Question? On the Nature of Predictive Coding Abnormalities in Psychosis","authors":"Valentina Mancini , Matthew M. Nour","doi":"10.1016/j.bpsgos.2024.100412","DOIUrl":"10.1016/j.bpsgos.2024.100412","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 1","pages":"Article 100412"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096836","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}