Biological Psychiatry最新文献

{"title":"Refining Criteria for a Neurodevelopmental Subphenotype of Bipolar Disorders: A FondaMental Advanced Centers of Expertise for Bipolar Disorders Study.","authors":"Antoine Lefrere, Ophélia Godin, Stéphane Jamain, Yecodji Dansou, Ludovic Samalin, Martin Alda, Bruno Aouizerate, Valérie Aubin, Romain Rey, Martina Contu, Philippe Courtet, Caroline Dubertret, Emmanuel Haffen, Dominique Januel, Marion Leboyer, Pierre-Michel Llorca, Emeline Marlinge, Mirko Manchia, Samantha Neilson, Emilie Olié, Pasquale Paribello, Marco Pinna, Mircea Polosan, Paul Roux, Raymund Schwan, Leonardo Tondo, Michel Walter, Eleni Tzavara, Guillaume Auzias, Christine Deruelle, Bruno Etain, Raoul Belzeaux","doi":"10.1016/j.biopsych.2024.09.025","DOIUrl":"10.1016/j.biopsych.2024.09.025","url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses.</p><p><strong>Methods: </strong>We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications.</p><p><strong>Results: </strong>Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder.</p><p><strong>Conclusions: </strong>The proposed NDP constitutes a promising clinical tool for patient stratification in BD.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrogliosis Marker [¹¹C]SL25.1188 After COVID-19 With Ongoing Depressive and Cognitive Symptoms.","authors":"Joeffre Braga, Emily J Y Kuik, Mariel Lepra, Pablo M Rusjan, Stephen J Kish, Erica L Vieira, Zahra Nasser, Natasha Verhoeff, Neil Vasdev, Thomas Chao, Michael Bagby, Isabelle Boileau, Stefan Kloiber, M Ishrat Husain, Nathan Kolla, Yuko Koshimori, Khunsa Faiz, Wei Wang, Jeffrey H Meyer","doi":"10.1016/j.biopsych.2024.09.027","DOIUrl":"10.1016/j.biopsych.2024.09.027","url":null,"abstract":"<p><strong>Background: </strong>After acute COVID-19, 5% of people experience persistent depressive symptoms and reduced cognitive function (COVID-DC). Theoretical models propose that astrogliosis is important in long COVID, but measures primarily indicative of astrogliosis have not been studied in the brain of long COVID or COVID-DC. The objective of the current study was to measure [¹¹C]SL25.1188 total distribution volume ([¹¹C]SL25.1188 V_T), an index of monoamine oxidase B density and a marker of astrogliosis, with positron emission tomography in participants with COVID-DC and compare with healthy control participants.</p><p><strong>Methods: </strong>In 21 COVID-DC cases and 21 healthy control participants, [¹¹C]SL25.1188 V_T was measured in the prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum. Depressive symptoms were measured with the Beck Depression Inventory-II, and cognitive symptoms were measured with neuropsychological tests.</p><p><strong>Results: </strong>[¹¹C]SL25.1188 V_T was higher in participants with COVID-DC in the prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum than in healthy control participants. Depressive symptom severity negatively correlated with [¹¹C]SL25.1188 V_T across prioritized brain regions. More recent acute COVID-19 positively correlated with [¹¹C]SL25.1188 V_T, reflecting higher values since predominance of the Omicron variant. Exploratory analyses found greater [¹¹C]SL25.1188 V_T in the hippocampus, dorsal putamen, and ventral striatum of COVID-DC participants than control participants with a major depressive episode with no history of COVID-19, and there was no relationship to cognitive testing in prioritized regions.</p><p><strong>Conclusions: </strong>Results strongly support the presence of monoamine oxidase B-labeled astrogliosis in COVID-DC throughout the regions assessed, although the association of greater astrogliosis with fewer symptoms raises the possibility of a protective role. The magnitude of astrogliosis in COVID-DC is greater since the emergence of the Omicron variant.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics Analysis of the Molecular Response to Glucocorticoids: Insights Into Shared Genetic Risk From Psychiatric to Medical Disorders.","authors":"Janine Knauer-Arloth, Anastasiia Hryhorzhevska, Elisabeth B Binder","doi":"10.1016/j.biopsych.2024.10.004","DOIUrl":"10.1016/j.biopsych.2024.10.004","url":null,"abstract":"<p><strong>Background: </strong>Alterations in the effects of glucocorticoids have been implicated in mediating some of the negative health effects associated with chronic stress, including increased risk for psychiatric disorders and cardiovascular and metabolic diseases. In this study, we investigated how genetic variants influence gene expression and DNA methylation in response to glucocorticoid receptor (GR) activation and their association with disease risk.</p><p><strong>Methods: </strong>We measured DNA methylation (n = 199) and gene expression (n = 297) in peripheral blood before and after GR activation with dexamethasone, with matched genotype data available for all samples. A comprehensive molecular quantitative trait locus (QTL) analysis was conducted, mapping GR-response methylation (me)QTLs, GR-response expression (e)QTLs, and GR-response expression quantitative trait methylation (eQTMs). A multilevel network analysis was employed to map the complex relationships between the transcriptome, epigenome, and genetic variation.</p><p><strong>Results: </strong>We identified 3772 GR-response meCpGs corresponding to 104,828 local GR-response meQTLs that did not strongly overlap with baseline meQTLs. eQTM and eQTL analyses revealed distinct genetic influences on gene expression and DNA methylation. Multilevel network analysis uncovered GR-response network trio QTLs, characterized by SNP-CpG-transcript combinations where meQTLs act as both eQTLs and eQTMs. GR-response trio variants were enriched in a genome-wide association study for psychiatric, respiratory, autoimmune, and cardiovascular diseases and conferred a higher relative heritability per SNP than GR-response meQTL and baseline QTL SNPs.</p><p><strong>Conclusions: </strong>Genetic variants modulating the molecular effects of glucocorticoids are associated with psychiatric as well as medical diseases and not uncovered in baseline QTL analyses.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic (R,S)-ketamine and (2S,6S)-hydroxynorketamine Decrease Fear Expression by Differentially Modulating Fear Neural Ensembles.","authors":"Alessia Mastrodonato, Michelle Jin, Noelle Kee, Marcos Lanio, Juliana Tapia, Liliette Quintana, Andrea Muñoz Zamora, Shi-Xian Deng, Xiaoming Xu, Donald W Landry, Christine A Denny","doi":"10.1016/j.biopsych.2024.09.024","DOIUrl":"10.1016/j.biopsych.2024.09.024","url":null,"abstract":"<p><strong>Background: </strong>We previously reported that a single injection of (R,S)-ketamine or its metabolite (2S,6S)-hydroxynorketamine (HNK) prior to stress attenuated learned fear. However, whether these drugs attenuate learned fear through divergent or convergent effects on neural activity remains to be determined.</p><p><strong>Methods: </strong>129S6/SvEv male mice were injected with saline, (R,S)-ketamine, or (2S,6S)-HNK 1 week before a 3-shock contextual fear conditioning paradigm. Five days later, mice were re-exposed to the aversive context and euthanized 1 hour later to quantify active cells. Brains were processed for c-fos immunoreactivity, and neural networks were built with a novel, wide-scale imaging pipeline.</p><p><strong>Results: </strong>We found that (R,S)-ketamine and (2S,6S)-HNK attenuated learned fear. Fear-related neural activity was altered in dorsal CA3 following (2S,6S)-HNK; ventral CA3 and CA1, infralimbic and prelimbic regions, insular cortex, retrosplenial cortex, piriform cortex, nucleus reuniens, and periaqueductal gray following both (R,S)-ketamine and (2S,6S)-HNK; and in the paraventricular nucleus of the thalamus (PVT) following (R,S)-ketamine. Dorsal CA3 and ventral hippocampus activation correlated with freezing in the (R,S)-ketamine group, and retrosplenial cortex activation correlated with freezing in both (R,S)-ketamine and (2S,6S)-HNK groups. (R,S)-ketamine increased connectivity between cortical and subcortical regions while (2S,6S)-HNK increased connectivity within these regions.</p><p><strong>Conclusions: </strong>This work identifies novel nodes in fear networks that involve the nucleus reuniens, piriform cortex, insular cortex, periaqueductal gray, and retrosplenial cortex that can be targeted with neuromodulatory strategies or pharmaceutical compounds to treat fear-induced disorders. This approach could be used to optimize target engagement and dosing strategies of existing medications.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Association Study Meta-Analysis of 9619 Cases With Tic Disorders.","authors":"Nora I Strom, Matthew W Halvorsen, Jakob Grove, Bergrún Ásbjörnsdóttir, Pétur Luðvígsson, Ólafur Thorarensen, Elles de Schipper, Julia Bäckmann, Per Andrén, Chao Tian, Thomas Damm Als, Judith Becker Nissen, Sandra M Meier, Jonas Bybjerg-Grauholm, David M Hougaard, Thomas Werge, Anders D Børglum, David A Hinds, Christian Rück, David Mataix-Cols, Hreinn Stefánsson, Kari Stefansson, James J Crowley, Manuel Mattheisen","doi":"10.1016/j.biopsych.2024.07.025","DOIUrl":"10.1016/j.biopsych.2024.07.025","url":null,"abstract":"<p><strong>Background: </strong>Despite the significant personal and societal burden of tic disorders (TDs), treatment outcomes remain modest, necessitating a deeper understanding of their etiology. Family history is the biggest known risk factor, and identifying risk genes could accelerate progress in the field.</p><p><strong>Methods: </strong>Expanding upon previous sample size limitations, we added 4800 new TD cases and 971,560 controls and conducted a genome-wide association study (GWAS) meta-analysis with 9619 cases and 981,048 controls of European ancestry. We attempted to replicate the results in an independent deCODE genetics GWAS (885 TD cases and 310,367 controls). To characterize GWAS findings, we conducted several post-GWAS gene-based and enrichment analyses.</p><p><strong>Results: </strong>A genome-wide significant hit (rs79244681, p = 2.27 × 10^-8) within MCHR2-AS1 was identified, although it was not replicated. Post-GWAS analyses revealed a 13.8% single nucleotide polymorphism heritability and 3 significant genes: BCL11B, NDFIP2, and RBM26. Common variant risk for TD was enriched within genes preferentially expressed in the cortico-striato-thalamo-cortical circuit (including the putamen, caudate, nucleus accumbens, and Brodmann area 9) and 5 brain cell types (excitatory and inhibitory telencephalon neurons, inhibitory diencephalon and mesencephalon neurons, and hindbrain and medium spiny neurons). TD polygenic risk was enriched within loss-of-function intolerant genes (p = .0017) and high-confidence neurodevelopmental disorder genes (p = .0108). Of 112 genetic correlations, 43 were statistically significant, showing high positive correlations with most psychiatric disorders. Of the 2 single nucleotide polymorphisms previously associated with TDs, one (rs2453763) replicated in an independent subsample of our GWAS (p = .00018).</p><p><strong>Conclusions: </strong>This GWAS was still underpowered to identify high-confidence, replicable loci, but the results suggest imminent discovery of common genetic variants for TDs.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytic CREB in Nucleus Accumbens Promotes Susceptibility to Chronic Stress.","authors":"Leanne M Holt, Trevonn M Gyles, Eric M Parise, Angelica M Minier-Toribio, Matthew Rivera, Tamara Markovic, Szu-Ying Yeh, Eric J Nestler","doi":"10.1016/j.biopsych.2024.09.021","DOIUrl":"10.1016/j.biopsych.2024.09.021","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence implicates astrocytes in stress and depression in both rodent models and human major depressive disorder. Despite this, little is known about the transcriptional responses to stress of astrocytes within the nucleus accumbens (NAc), a key brain reward region, and their influence on behavioral outcomes.</p><p><strong>Methods: </strong>We used whole-cell sorting, RNA sequencing, and bioinformatic analyses to investigate the NAc astrocyte transcriptome in male mice in response to chronic social defeat stress (CSDS). Immunohistochemistry was used to determine stress-induced changes in astrocytic CREB (cAMP response element binding protein) within the NAc. Finally, astrocytic regulation of depression-like behavior was investigated using viral-mediated manipulation of CREB in combination with CSDS.</p><p><strong>Results: </strong>We found a robust transcriptional response in NAc astrocytes to CSDS in stressed mice, with changes seen in both stress-susceptible and stress-resilient animals. Bioinformatic analysis revealed CREB, a transcription factor widely studied in neurons, as one of the top-predicted upstream regulators of the NAc astrocyte transcriptome, with opposite activation states implicated in resilient versus susceptible mice. This bioinformatic deduction was confirmed at the protein level with immunohistochemistry. Moreover, NAc astrocyte morphological complexity correlated with CREB activation and was reduced selectively in astrocytes of resilient mice. Viral overexpression of CREB selectively in NAc astrocytes promoted susceptibility to chronic stress.</p><p><strong>Conclusions: </strong>Together, our data demonstrate that the astrocyte transcriptome responds robustly to CSDS and that transcriptional regulation in astrocytes contributes to depressive-like behaviors. A better understanding of transcriptional regulation in astrocytes may reveal unknown molecular mechanisms underlying neuropsychiatric disorders.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress Molecular Signaling in Interaction With Cognition.","authors":"Justina F Lugenbühl, Eva M G Viho, Elisabeth B Binder, Nikolaos P Daskalakis","doi":"10.1016/j.biopsych.2024.09.023","DOIUrl":"10.1016/j.biopsych.2024.09.023","url":null,"abstract":"<p><p>Exposure to stressful life events is associated with a high risk of developing psychiatric disorders with a wide variety of symptoms. Cognitive symptoms in stress-related psychiatric disorders can be particularly challenging to understand, both for those experiencing them and for health care providers. To gain insights, it is important to capture stress-induced structural, epigenomic, transcriptomic, and proteomic changes in relevant brain regions such as the amygdala, hippocampus, locus coeruleus, and prefrontal cortex that result in long-lasting alterations in brain function. In this review, we will emphasize a subset of stress molecular mechanisms that alter neuroplasticity, neurogenesis, and balance between excitatory and inhibitory neurons. Then, we discuss how to identify genetic risk factors that may accelerate stress-driven or stress-induced cognitive impairment. Despite the development of new technologies such as single-cell resolution sequencing, our understanding of the molecular effects of stress in the brain remains to be deepened. A better understanding of the diversity of stress effects in different brain regions and cell types is a prerequisite to open new avenues for mechanism-informed prevention and treatment of stress-related cognitive symptoms.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Lesion-Related Human Aggression to a Common Brain Network.","authors":"Shaoling Peng, Frederic L W V J Schaper, Shira Cohen-Zimerman, Gillian N Miller, Jing Jiang, Rob P W Rouhl, Yasin Temel, Shan H Siddiqi, Jordan Grafman, Michael D Fox, Alexander L Cohen","doi":"10.1016/j.biopsych.2024.09.022","DOIUrl":"10.1016/j.biopsych.2024.09.022","url":null,"abstract":"<p><strong>Background: </strong>Aggression exacts a significant toll on human societies and is highly prevalent among neuropsychiatric patients. The neural mechanisms of aggression are unclear and treatment options are limited.</p><p><strong>Methods: </strong>Using a recently validated lesion network mapping technique, we derived an aggression-associated network by analyzing data from 182 patients who had experienced penetrating head injuries during their service in the Vietnam War. To test whether damage to this lesion-derived network would increase the risk of aggression-related neuropsychiatric symptoms, we used the Harvard Lesion Repository (N = 852). To explore potential therapeutic relevance of this network, we used an independent deep brain stimulation dataset of 25 patients with epilepsy, in which irritability and aggression are known potential side effects.</p><p><strong>Results: </strong>We found that lesions associated with aggression occurred in many different brain locations but were characterized by a specific brain network defined by functional connectivity to a hub region in the right prefrontal cortex. This network involves positive connectivity to the ventromedial prefrontal cortex, dorsolateral prefrontal cortex, frontal pole, posterior cingulate cortex, anterior cingulate cortex, temporal-parietal junction, and lateral temporal lobe and negative connectivity to the amygdala, hippocampus, insula, and visual cortex. Among all 24 neuropsychiatric symptoms included in the Harvard Lesion Repository, criminality demonstrated the most alignment with our aggression-associated network. Deep brain stimulation site connectivity to this same network was associated with increased irritability.</p><p><strong>Conclusions: </strong>We conclude that brain lesions associated with aggression map to a specific human brain circuit, and the functionally connected regions in this circuit provide testable targets for therapeutic neuromodulation.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Communication in Ras Pathway Disorders: A Comprehensive Review From Genetics to Behavior in Neurofibromatosis Type 1 and Noonan Syndrome.","authors":"Monica Siqueiros-Sanchez, Yaffa Serur, Chloe A McGhee, Taylor F Smith, Tamar Green","doi":"10.1016/j.biopsych.2024.09.019","DOIUrl":"10.1016/j.biopsych.2024.09.019","url":null,"abstract":"<p><p>Neurofibromatosis type 1 (NF1) and Noonan syndrome (NS) are neurogenetic syndromes caused by pathogenetic variants encoding components of the Ras-ERK-MAPK (Ras/extracellular signal-regulated kinase/mitogen-activated protein kinase) signaling pathway (Ras pathway). NF1 and NS are associated with differences in social communication and related neuropsychiatric risks. During the last decade, there has been growing interest in Ras-linked syndromes as models to understand social communication deficits and autism spectrum disorder. We systematically review the literature between 2010 and 2023 focusing on the social communication construct of the Research Domain Criteria framework. We provide an integrative summary of the research on facial and nonfacial social communication processes in NF1 and NS across molecular, cellular, neural circuitry, and behavioral domains. At the molecular and cellular levels, dysregulation in the Ras pathway is intricately tied to variations in social communication through changes in GABAergic (gamma-aminobutyric acidergic), glutamatergic, and serotonergic transmission, as well as inhibitory/excitatory imbalance. Neural circuitry typically associated with learning, attention, and memory in NF1 and NS (e.g., corticostriatal connectivity) is also implicated in social communication. We highlight less-researched potential mechanisms for social communication, such as white matter connectivity and the default mode network. Finally, key gaps in NF1 and NS literature are identified, and a roadmap for future research is provided. By leveraging genetic syndrome research, we can understand the mechanisms associated with behaviors and psychiatric disorders.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscribers Page","authors":"","doi":"10.1016/S0006-3223(24)01564-6","DOIUrl":"10.1016/S0006-3223(24)01564-6","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"96 9","pages":"Page A2"},"PeriodicalIF":9.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142357570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}