{"title":"The Neurocircuitry of Substance Use Disorder, Treatment, and Change: A Resource for Clinical Psychiatrists.","authors":"Caesar G Imperio, Frances R Levin, Diana Martinez","doi":"10.1176/appi.ajp.20231023","DOIUrl":"10.1176/appi.ajp.20231023","url":null,"abstract":"<p><p>Substance use disorder (SUD) is common in psychiatric patients and has a negative impact on health and well-being. However, SUD often goes untreated, and there is a need for psychiatrists, of all specialties, to address this pervasive clinical problem. In this review, the authors' goal is to provide a resource that describes treatments for SUD, using neuroscience as a framework. They discuss the effect of pharmacotherapy on craving, intoxication, and withdrawal and its ability to interrupt the cycle of substance use in SUD. The neuroscience of stress is reviewed, including medications targeting neurotransmitter systems activated by alarm and fear. Neuroplasticity and promising treatments that use this mechanism, including ketamine, psilocybin, and transcranial magnetic stimulation (TMS), are discussed. The authors conclude by listing resources and practice guidelines for physicians interested in learning more about treatments for SUD.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387310","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":"Reductions in Substance Use as Outcome Targets for Treatment Development.","authors":"Wilson M Compton, Nora D Volkow","doi":"10.1176/appi.ajp.20240841","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240841","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556947","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":"What Are the Genetic Building Blocks of Alcohol-Related Behaviors?","authors":"Joel Gelernter, Joseph D Deak","doi":"10.1176/appi.ajp.20240885","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240885","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556950","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}
Jeanne E Savage, Peter B Barr, Tanya Phung, Younga H Lee, Yingzhe Zhang, Vivia V McCutcheon, Tian Ge, Jordan W Smoller, Lea K Davis, Jacquelyn Meyers, Bernice Porjesz, Danielle Posthuma, Travis T Mallard, Sandra Sanchez-Roige
{"title":"Genetic Heterogeneity Across Dimensions of Alcohol Use Behaviors.","authors":"Jeanne E Savage, Peter B Barr, Tanya Phung, Younga H Lee, Yingzhe Zhang, Vivia V McCutcheon, Tian Ge, Jordan W Smoller, Lea K Davis, Jacquelyn Meyers, Bernice Porjesz, Danielle Posthuma, Travis T Mallard, Sandra Sanchez-Roige","doi":"10.1176/appi.ajp.20231055","DOIUrl":"10.1176/appi.ajp.20231055","url":null,"abstract":"<p><strong>Objective: </strong>Increasingly large samples in genome-wide association studies (GWASs) for alcohol use behaviors (AUBs) have led to an influx of implicated genes, yet the clinical and functional understanding of these associations remains low, in part because most GWASs do not account for the complex and varied manifestations of AUBs. This study applied a multidimensional framework to investigate the latent genetic structure underlying heterogeneous dimensions of AUBs.</p><p><strong>Methods: </strong>Multimodal assessments (self-report, interview, electronic health records) were obtained from approximately 400,000 UK Biobank participants. GWAS was conducted for 18 distinct AUBs, including consumption, drinking patterns, alcohol problems, and clinical sequelae. Latent genetic factors were identified and carried forward to GWAS using genomic structural equation modeling, followed by functional annotation, genetic correlation, and enrichment analyses to interpret the genetic associations.</p><p><strong>Results: </strong>Four latent factors were identified: Problems, Consumption, BeerPref (declining alcohol consumption with a preference for drinking beer), and AtypicalPref (drinking fortified wine and spirits). The latent factors were moderately correlated (r<sub>g</sub> values, 0.12-0.57) and had distinct patterns of associations, with BeerPref in particular implicating many novel genomic regions. Patterns of regional and cell type-specific gene expression in the brain also differed between the latent factors.</p><p><strong>Conclusions: </strong>Deep phenotyping is an important next step to improve understanding of the genetic etiology of AUBs, in addition to increasing sample size. Further effort is required to uncover the genetic heterogeneity underlying AUBs using methods that account for their complex, multidimensional nature.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387308","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}
George A Keepers, Laura J Fochtmann, Joan M Anzia, Sheldon Benjamin, Jeffrey M Lyness, Ramin Mojtabai, Mark Servis, Lois Choi-Kain, Kaz J Nelson, John M Oldham, Carla Sharp, Amanda Degenhardt, Laura J Fochtmann, John M Oldham, Seung-Hee Hong, Jennifer Medicus
{"title":"The American Psychiatric Association Practice Guideline for the Treatment of Patients With Borderline Personality Disorder.","authors":"George A Keepers, Laura J Fochtmann, Joan M Anzia, Sheldon Benjamin, Jeffrey M Lyness, Ramin Mojtabai, Mark Servis, Lois Choi-Kain, Kaz J Nelson, John M Oldham, Carla Sharp, Amanda Degenhardt, Laura J Fochtmann, John M Oldham, Seung-Hee Hong, Jennifer Medicus","doi":"10.1176/appi.ajp.24181010","DOIUrl":"https://doi.org/10.1176/appi.ajp.24181010","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556949","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}
Devon K Grey, Juliann B Purcell, Kristen N Buford, Mark A Schuster, Marc N Elliott, Susan Tortolero Emery, Sylvie Mrug, David C Knight
{"title":"Discrimination Exposure, Neural Reactivity to Stress, and Psychological Distress.","authors":"Devon K Grey, Juliann B Purcell, Kristen N Buford, Mark A Schuster, Marc N Elliott, Susan Tortolero Emery, Sylvie Mrug, David C Knight","doi":"10.1176/appi.ajp.20220884","DOIUrl":"https://doi.org/10.1176/appi.ajp.20220884","url":null,"abstract":"<p><strong>Objective: </strong>Discrimination exposure has a detrimental impact on mental health, increasing the risk of depression, anxiety, and posttraumatic stress. The impact discrimination exposure has on mental health is likely mediated by neural processes associated with emotion expression and regulation. However, the specific neural processes that mediate the relationship between discrimination exposure and mental health remain to be determined. The present study investigated the relationship adolescent discrimination exposure has with stress-elicited brain activity and mental health symptoms in young adulthood.</p><p><strong>Methods: </strong>A total of 301 participants completed the Montreal Imaging Stress Task while functional MRI data were collected. Discrimination exposure was measured four times from ages 11 to 19, and stress-elicited brain activity and psychological distress (depression, anxiety, posttraumatic stress) were assessed in young adulthood (age 20).</p><p><strong>Results: </strong>Stress-elicited dorsolateral and dorsomedial prefrontal cortex (PFC), inferior parietal lobule (IPL), and hippocampal activity varied with discrimination exposure. Activity within these brain regions varied with the cumulative amount and trajectory of discrimination exposure across adolescence (initial exposure, change in exposure, and acceleration of exposure). Depression, anxiety, and posttraumatic stress symptoms varied with discrimination exposure. Stress-elicited activity within the dorsolateral PFC and the IPL statistically mediated the relationship between discrimination exposure and psychological distress.</p><p><strong>Conclusions: </strong>The findings suggest that adolescent discrimination exposure may alter the neural response to future stressors (i.e., within regions associated with emotion expression and regulation), which may in turn modify susceptibility and resilience to psychological distress. Thus, differences in stress-elicited neural reactivity may represent an important neurobiological mechanism underlying discrimination-related mental health disparities.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543057","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}
Shawn Kamboj, Erin L Carlson, Bradley P Ander, Kari L Hanson, Karl D Murray, Julie L Fudge, Melissa D Bauman, Cynthia M Schumann, Andrew S Fox
{"title":"Translational Insights From Cell Type Variation Across Amygdala Subnuclei in Rhesus Monkeys and Humans.","authors":"Shawn Kamboj, Erin L Carlson, Bradley P Ander, Kari L Hanson, Karl D Murray, Julie L Fudge, Melissa D Bauman, Cynthia M Schumann, Andrew S Fox","doi":"10.1176/appi.ajp.20230602","DOIUrl":"https://doi.org/10.1176/appi.ajp.20230602","url":null,"abstract":"<p><strong>Objective: </strong>Theories of amygdala function are central to our understanding of psychiatric and neurodevelopmental disorders. However, limited knowledge of the molecular and cellular composition of the amygdala impedes translational research aimed at developing new treatments and interventions. The aim of this study was to characterize and compare the composition of amygdala cells to help bridge the gap between preclinical models and human psychiatric and neurodevelopmental disorders.</p><p><strong>Methods: </strong>Tissue was dissected from multiple amygdala subnuclei in both humans (N=3, male) and rhesus macaques (N=3, male). Single-nucleus RNA sequencing was performed to characterize the transcriptomes of individual nuclei.</p><p><strong>Results: </strong>The results reveal substantial heterogeneity between regions, even when restricted to inhibitory or excitatory neurons. Consistent with previous work, the data highlight the complexities of individual marker genes for uniquely targeting specific cell types. Cross-species analyses suggest that the rhesus monkey model is well-suited to understanding the human amygdala, but also identify limitations. For example, a cell cluster in the ventral lateral nucleus of the amygdala (vLa) is enriched in humans relative to rhesus macaques. Additionally, the data describe specific cell clusters with relative enrichment of disorder-related genes. These analyses point to the human-enriched vLa cell cluster as relevant to autism spectrum disorder, potentially highlighting a vulnerability to neurodevelopmental disorders that has emerged in recent primate evolution. Further, a cluster of cells expressing markers for intercalated cells is enriched for genes reported in human genome-wide association studies of neuroticism, anxiety disorders, and depressive disorders.</p><p><strong>Conclusions: </strong>Together, these findings shed light on the composition of the amygdala and identify specific cell types that can be prioritized in basic science research to better understand human psychopathology and guide the development of potential treatments.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543058","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}
Gita A Pathak, Frank R Wendt, Adam X Maihofer, Kerry J Ressler, Murray B Stein, Karestan C Koenen, Caroline M Nievergelt, Renato Polimanti
{"title":"Identifying Genetically Inferred Effects Linking Posttraumatic Stress Disorder to Women's Health, Lipid Disorders, and Malaria Medications.","authors":"Gita A Pathak, Frank R Wendt, Adam X Maihofer, Kerry J Ressler, Murray B Stein, Karestan C Koenen, Caroline M Nievergelt, Renato Polimanti","doi":"10.1176/appi.ajp.20230832","DOIUrl":"https://doi.org/10.1176/appi.ajp.20230832","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387309","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}
Dominique Arion, John F Enwright, Guillermo Gonzalez-Burgos, David A Lewis
{"title":"Cell Type-Specific Profiles and Developmental Trajectories of Transcriptomes in Primate Prefrontal Layer 3 Pyramidal Neurons: Implications for Schizophrenia.","authors":"Dominique Arion, John F Enwright, Guillermo Gonzalez-Burgos, David A Lewis","doi":"10.1176/appi.ajp.20230541","DOIUrl":"10.1176/appi.ajp.20230541","url":null,"abstract":"<p><strong>Objective: </strong>In schizophrenia, impaired working memory is associated with transcriptome alterations in layer 3 pyramidal neurons (L3PNs) in the dorsolateral prefrontal cortex (DLPFC). Distinct subtypes of L3PNs that send axonal projections to the DLPFC in the opposite hemisphere (callosal projection [CP] neurons) or the parietal cortex in the same hemisphere (ipsilateral projection [IP] neurons) play critical roles in working memory. However, how the transcriptomes of these L3PN subtypes might shift during late postnatal development when working memory impairments emerge in individuals later diagnosed with schizophrenia is not known. The aim of this study was to characterize and compare the transcriptome profiles of CP and IP L3PNs across developmental transitions from prepuberty to adulthood in macaque monkeys.</p><p><strong>Methods: </strong>The authors used retrograde labeling to identify CP and IP L3PNs in the DLPFC of prepubertal, postpubertal, and adult macaque monkeys, and used laser microdissection to capture these neurons for RNA sequencing.</p><p><strong>Results: </strong>At all three ages, CP and IP L3PNs had distinct transcriptomes, with the number of genes differentially expressed between neuronal subtypes increasing with age. For IP L3PNs, age-related shifts in gene expression were most prominent between prepubertal and postpubertal animals, whereas for CP L3PNs such shifts were most prominent between postpubertal and adult animals.</p><p><strong>Conclusions: </strong>These findings demonstrate the presence of cell type-specific profiles and developmental trajectories of the transcriptomes of PPC-projecting IP and DLPFC-projecting CP L3PNs in monkey DLPFC. The evidence that IP L3PNs reach a mature transcriptome earlier than CP L3PNs suggests that these two subtypes differentially contribute to the maturation of working memory performance across late postnatal development and that they may be differentially vulnerable to the disease process of schizophrenia at specific stages of postnatal development.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to Cappon and Pascual-Leone.","authors":"","doi":"10.1176/appi.ajp.20240643correction","DOIUrl":"https://doi.org/10.1176/appi.ajp.20240643correction","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":null,"pages":null},"PeriodicalIF":15.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339417","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}