Pub Date : 2020-01-01Epub Date: 2020-06-12DOI: 10.20900/jpbs.20200013
Courtney D Nordeck, Christopher Welsh, Robert P Schwartz, Shannon G Mitchell, Kevin E O'Grady, Laura Dunlap, Gary Zarkin, Stephen Orme, Jan Gryczynski
Substance use disorders (SUDs) are associated with significant morbidity and mortality and contribute to inefficient use of healthcare services. Hospitalized medical/surgical patients with comorbid SUD are at elevated risk of hospital readmission and poor outcomes. Thus, effective interventions are needed to help such patients during hospitalization and post-discharge. This article reports the rationale, methodological design, and progress to date on a randomized trial comparing the effectiveness of Navigation Services to Avoid Rehospitalization (NavSTAR) vs Treatmentas-Usual (TAU) for hospital medical/surgical patients with comorbid SUD (N = 400). Applying Andersen's theoretical model of health service utilization, NavSTAR employed Patient Navigation and motivational interventions to promote entry into SUD treatment, facilitate adherence to recommendations for medical follow-up and self-care, address basic needs, and prevent the recurrent use of hospital services. As part of the NavSTAR service model, Patient Navigators embedded within the SUD consultation service at a large urban hospital delivered patient-centered, proactive navigation and motivational services initiated during the hospital stay and continued for up to 3 months post-discharge. Participants randomized to TAU received usual care from the hospital and the SUD consultation service, which included referral to SUD treatment but no continued contact post-hospital discharge. Hospital service utilization will be determined via review of electronic health records and the regional Health Information Exchange. Participants were assessed at baseline and again at 3-, 6-, and 12-month follow-up on various measures of healthcare utilization, substance use, and functioning. The primary outcome of interest is time-to-rehospitalization through 12 months. In addition, a range of secondary outcomes spanning the medical and SUD service areas will be assessed. The study will include a health economic evaluation of NavSTAR. If NavSTAR proves to be effective and cost-effective in this high-risk patient group, it would have important implications for addressing the needs of hospital patients with comorbid SUD, designing hospital discharge planning services, informing cost containment initiatives, and improving public health.
{"title":"Navigation Services to Avoid Rehospitalization among Medical/Surgical Patients with Comorbid Substance Use Disorder: Rationale and Design of a Randomized Controlled Trial.","authors":"Courtney D Nordeck, Christopher Welsh, Robert P Schwartz, Shannon G Mitchell, Kevin E O'Grady, Laura Dunlap, Gary Zarkin, Stephen Orme, Jan Gryczynski","doi":"10.20900/jpbs.20200013","DOIUrl":"https://doi.org/10.20900/jpbs.20200013","url":null,"abstract":"<p><p>Substance use disorders (SUDs) are associated with significant morbidity and mortality and contribute to inefficient use of healthcare services. Hospitalized medical/surgical patients with comorbid SUD are at elevated risk of hospital readmission and poor outcomes. Thus, effective interventions are needed to help such patients during hospitalization and post-discharge. This article reports the rationale, methodological design, and progress to date on a randomized trial comparing the effectiveness of Navigation Services to Avoid Rehospitalization (NavSTAR) vs Treatmentas-Usual (TAU) for hospital medical/surgical patients with comorbid SUD (<i>N</i> = 400). Applying Andersen's theoretical model of health service utilization, NavSTAR employed Patient Navigation and motivational interventions to promote entry into SUD treatment, facilitate adherence to recommendations for medical follow-up and self-care, address basic needs, and prevent the recurrent use of hospital services. As part of the NavSTAR service model, Patient Navigators embedded within the SUD consultation service at a large urban hospital delivered patient-centered, proactive navigation and motivational services initiated during the hospital stay and continued for up to 3 months post-discharge. Participants randomized to TAU received usual care from the hospital and the SUD consultation service, which included referral to SUD treatment but no continued contact post-hospital discharge. Hospital service utilization will be determined via review of electronic health records and the regional Health Information Exchange. Participants were assessed at baseline and again at 3-, 6-, and 12-month follow-up on various measures of healthcare utilization, substance use, and functioning. The primary outcome of interest is time-to-rehospitalization through 12 months. In addition, a range of secondary outcomes spanning the medical and SUD service areas will be assessed. The study will include a health economic evaluation of NavSTAR. If NavSTAR proves to be effective and cost-effective in this high-risk patient group, it would have important implications for addressing the needs of hospital patients with comorbid SUD, designing hospital discharge planning services, informing cost containment initiatives, and improving public health.</p>","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33478440","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}
Pub Date : 2020-01-01Epub Date: 2020-08-21DOI: 10.20900/jpbs.20200020
Samuel D Klein, Cheryl A Olman, Scott R Sponheim
Psychosis has been associated with neural anomalies across a number of brain regions and cortical networks. Nevertheless, the exact pathophysiology of the disorder remains unclear. Aberrant visual perceptions such as hallucinations are evident in psychosis, while the occurrence of visual distortions is elevated in individuals with genetic liability for psychosis. The overall goals of this project are to: (1) use psychophysical tasks and neuroimaging to characterize deficits in visual perception; (2) acquire a mechanistic understanding of these deficits through development and validation of a computational model; and (3) determine if said mechanisms mark genetic liability for psychosis. Visual tasks tapping both low- and high-level visual processing are being completed as individuals with psychotic disorders (IPD), first-degree biological siblings of IPDs (SibIPDs) and healthy controls (HCs) undergo 248-channel magneto-encephalography (MEG) recordings followed by 7 Tesla functional magnetic resonance imaging (MRI). By deriving cortical source signals from MEG and MRI data, we will characterize the timing, location and coordination of neural processes. We hypothesize that IPDs prone to visual hallucinations will exhibit deviant functions within early visual cortex, and that aberrant contextual influences on visual perception will involve higher-level visual cortical regions and be associated with visual hallucinations. SibIPDs who experience visual distortions-but not hallucinations-are hypothesized to exhibit deficits in higher-order visual processing reflected in abnormal inter-regional neural synchronization. We hope the results lead to the development of targeted interventions for psychotic disorders, as well as identify useful biomarkers for aberrant neural functions that give rise to psychosis.
{"title":"Perceptual Mechanisms of Visual Hallucinations and Illusions in Psychosis.","authors":"Samuel D Klein, Cheryl A Olman, Scott R Sponheim","doi":"10.20900/jpbs.20200020","DOIUrl":"10.20900/jpbs.20200020","url":null,"abstract":"<p><p>Psychosis has been associated with neural anomalies across a number of brain regions and cortical networks. Nevertheless, the exact pathophysiology of the disorder remains unclear. Aberrant visual perceptions such as hallucinations are evident in psychosis, while the occurrence of visual distortions is elevated in individuals with genetic liability for psychosis. The overall goals of this project are to: (1) use psychophysical tasks and neuroimaging to characterize deficits in visual perception; (2) acquire a mechanistic understanding of these deficits through development and validation of a computational model; and (3) determine if said mechanisms mark genetic liability for psychosis. Visual tasks tapping both low- and high-level visual processing are being completed as individuals with psychotic disorders (IPD), first-degree biological siblings of IPDs (SibIPDs) and healthy controls (HCs) undergo 248-channel magneto-encephalography (MEG) recordings followed by 7 Tesla functional magnetic resonance imaging (MRI). By deriving cortical source signals from MEG and MRI data, we will characterize the timing, location and coordination of neural processes. We hypothesize that IPDs prone to visual hallucinations will exhibit deviant functions within early visual cortex, and that aberrant contextual influences on visual perception will involve higher-level visual cortical regions and be associated with visual hallucinations. SibIPDs who experience visual distortions-but not hallucinations-are hypothesized to exhibit deficits in higher-order visual processing reflected in abnormal inter-regional neural synchronization. We hope the results lead to the development of targeted interventions for psychotic disorders, as well as identify useful biomarkers for aberrant neural functions that give rise to psychosis.</p>","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38492355","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}
Pub Date : 2020-01-01Epub Date: 2020-02-03DOI: 10.20900/jpbs.20200001
Caroline R Scherzer, Megan L Ranney, Shrenik Jain, Satya Prateek Bommaraju, John Patena, Kirsten Langdon, Evelyn Nimaja, Ernestine Jennings, Francesca L Beaudoin
Background: The majority of individuals with Opioid Use Disorder (OUD) do not receive any formal substance use treatment. Due to limited engagement and access to traditional treatment, there is increasing evidence that patients with OUDs turn to online social platforms to access peer support and obtain health-related information about addiction and recovery. Interacting with peers before and during recovery is a key component of many evidence-based addiction recovery programs, and may improve self-efficacy and treatment engagement as well as reduce relapse. Commonly-used online social platforms are limited in utility and scalability as an adjunct to addiction treatment; lack effective content moderation (e.g., misinformed advice, maliciousness or "trolling"); and lack common security and ethical safeguards inherent to clinical care.
Methods: This present study will develop a novel, artificial-intelligence (AI) enabled, mobile treatment delivery method that fulfills the need for a robust, secure, technology-based peer support platform to support patients with OUD. Forty adults receiving outpatient buprenorphine treatment for OUD will be asked to pilot a smartphone-based mobile peer support application, the "Marigold App", for a duration of six weeks. The program will use (1) a prospective cohort study to obtain text message content and feasibility metrics, and (2) qualitative interviews to evaluate usability and acceptability of the mobile platform.
Anticipated findings and future directions: The Marigold mobile platform will allow patients to access a tailored chat support group 24/7 as a complement to different forms of clinical OUD treatment. Marigold can keep groups safe and constructive by augmenting chats with AI tools capable of understanding the emotional sentiment in messages, automatically "flagging" critical or clinically relevant content. This project will demonstrate the robustness of these AI tools by adapting them to catch OUD-specific "flags" in peer messages while also examining the adoptability of the platform itself within OUD patients.
{"title":"Mobile Peer-Support for Opioid Use Disorders: Refinement of an Innovative Machine Learning Tool.","authors":"Caroline R Scherzer, Megan L Ranney, Shrenik Jain, Satya Prateek Bommaraju, John Patena, Kirsten Langdon, Evelyn Nimaja, Ernestine Jennings, Francesca L Beaudoin","doi":"10.20900/jpbs.20200001","DOIUrl":"https://doi.org/10.20900/jpbs.20200001","url":null,"abstract":"<p><strong>Background: </strong>The majority of individuals with Opioid Use Disorder (OUD) do not receive any formal substance use treatment. Due to limited engagement and access to traditional treatment, there is increasing evidence that patients with OUDs turn to online social platforms to access peer support and obtain health-related information about addiction and recovery. Interacting with peers before and during recovery is a key component of many evidence-based addiction recovery programs, and may improve self-efficacy and treatment engagement as well as reduce relapse. Commonly-used online social platforms are limited in utility and scalability as an adjunct to addiction treatment; lack effective content moderation (e.g., misinformed advice, maliciousness or \"trolling\"); and lack common security and ethical safeguards inherent to clinical care.</p><p><strong>Methods: </strong>This present study will develop a novel, artificial-intelligence (AI) enabled, mobile treatment delivery method that fulfills the need for a robust, secure, technology-based peer support platform to support patients with OUD. Forty adults receiving outpatient buprenorphine treatment for OUD will be asked to pilot a smartphone-based mobile peer support application, the \"Marigold App\", for a duration of six weeks. The program will use (1) a prospective cohort study to obtain text message content and feasibility metrics, and (2) qualitative interviews to evaluate usability and acceptability of the mobile platform.</p><p><strong>Anticipated findings and future directions: </strong>The Marigold mobile platform will allow patients to access a tailored chat support group 24/7 as a complement to different forms of clinical OUD treatment. Marigold can keep groups safe and constructive by augmenting chats with AI tools capable of understanding the emotional sentiment in messages, automatically \"flagging\" critical or clinically relevant content. This project will demonstrate the robustness of these AI tools by adapting them to catch OUD-specific \"flags\" in peer messages while also examining the adoptability of the platform itself within OUD patients.</p>","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37718371","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}
The results of large genome-wide association studies of schizophrenia (SZ) can be used to calculate an individual’s polygenic risk for SZ (e.g., [1]). This polygenic risk score (PRS) is a weighted sum of SZ risk alleles, and thus holds promise to be used in clinical care someday, e.g., in prevention, diagnosis and treatment of mental disorders (e.g., [2]). It can be used to uncover other phenotypes, such as behavioral traits or disorders, that are influenced by SZ-PRS, and this issue of the Journal of Psychiatry and Brain Science aims to summarize some of the knowledge that has emerged to this regard. Three reviews and two original research articles are contained in this Virtual Special Issue. Schaupp, Schulze and Budde [3] provide an excellent summary of studies researching the associations of SZ-PRS and cognition. Their finding of inconsistent results, both in patients and the general population, albeit characteristic for a developing field, points to a need for larger sample sizes when studying the genetics of cognition, and highlights further methodological problems. Adorjan and Papiol [4] review the relationship of cannabis consumption, SZ, and the SZ-PRS, and discuss accumulating evidence that a high polygenic risk for SZ may be predisposing individuals to cannabis abuse. Thus, consumption of cannabis may not only be understood as an environmental risk factor for SZ, but also as a type of gene-environment correlation/interaction. The last review article of Bengesser and Reininghaus [5] highlights the interesting finding that the SZ-PRS may be used to delineate bipolar disorder patients that respond to lithium from those who do not [6], and can be understood to emphasize the need for biologically-based diagnosis of mental disorders. The original research article of Yasmeen, Papiol, Falkai, Schulze, & Bickeböller [7] researches effects of SZ-PRS in correlated target phenotypes, using both in-silico and empirical data of the PsyCourse study [8]. Results of empirical analyses show that the addition of SZ-PRS to statistical models explaining psychosocial functioning (the Global Assessment of Functioning score) improves model fit, which is further increased when current symptom status is additionally taken into account. Finally, the neuroimaging study of Eberle et al. [9] demonstrates that polygenic scores for SZ can be used to gain a more fundamental understanding of gene-environment interactions. In this study, the authors researched connectivity of the nucleus accumbens, a major component of the brain’s reward circuitry. In healthy individuals, polygenic risk for SZ was associated with a shift towards SZ-like Open Access
{"title":"Phenotypic Effects of Polygenic Risk for Schizophrenia: What Have We Learned So Far?","authors":"U. Heilbronner","doi":"10.20900/jpbs.20190019","DOIUrl":"https://doi.org/10.20900/jpbs.20190019","url":null,"abstract":"The results of large genome-wide association studies of schizophrenia (SZ) can be used to calculate an individual’s polygenic risk for SZ (e.g., [1]). This polygenic risk score (PRS) is a weighted sum of SZ risk alleles, and thus holds promise to be used in clinical care someday, e.g., in prevention, diagnosis and treatment of mental disorders (e.g., [2]). It can be used to uncover other phenotypes, such as behavioral traits or disorders, that are influenced by SZ-PRS, and this issue of the Journal of Psychiatry and Brain Science aims to summarize some of the knowledge that has emerged to this regard. Three reviews and two original research articles are contained in this Virtual Special Issue. Schaupp, Schulze and Budde [3] provide an excellent summary of studies researching the associations of SZ-PRS and cognition. Their finding of inconsistent results, both in patients and the general population, albeit characteristic for a developing field, points to a need for larger sample sizes when studying the genetics of cognition, and highlights further methodological problems. Adorjan and Papiol [4] review the relationship of cannabis consumption, SZ, and the SZ-PRS, and discuss accumulating evidence that a high polygenic risk for SZ may be predisposing individuals to cannabis abuse. Thus, consumption of cannabis may not only be understood as an environmental risk factor for SZ, but also as a type of gene-environment correlation/interaction. The last review article of Bengesser and Reininghaus [5] highlights the interesting finding that the SZ-PRS may be used to delineate bipolar disorder patients that respond to lithium from those who do not [6], and can be understood to emphasize the need for biologically-based diagnosis of mental disorders. The original research article of Yasmeen, Papiol, Falkai, Schulze, & Bickeböller [7] researches effects of SZ-PRS in correlated target phenotypes, using both in-silico and empirical data of the PsyCourse study [8]. Results of empirical analyses show that the addition of SZ-PRS to statistical models explaining psychosocial functioning (the Global Assessment of Functioning score) improves model fit, which is further increased when current symptom status is additionally taken into account. Finally, the neuroimaging study of Eberle et al. [9] demonstrates that polygenic scores for SZ can be used to gain a more fundamental understanding of gene-environment interactions. In this study, the authors researched connectivity of the nucleus accumbens, a major component of the brain’s reward circuitry. In healthy individuals, polygenic risk for SZ was associated with a shift towards SZ-like Open Access","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45174911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A psychotic disorder is a multifactorial phenomenon in which not only environmental influences but also genetic factors play an important role. Evidence indicates that psychotic disorders are characterized by a complex mode of inheritance with high polygenicity, in which a large number of common genetic variants with small effects are relevant. One way to measure this polygenic risk is the calculation of polygenic risk scores (PRS). These reflect the complex multifactorial interaction of coding and regulatory DNA variants in the development of mental illness. It is known that the use of cannabis in patients with schizophrenia (SCZ) is much higher than in the general population. Although an exact clinical prognosis based on PRS is not possible at the present, the results found by PRS investigations so far are quite promising. Initial results suggest that people with SCZ and an increased polygenic risk of schizophrenia are more likely to use cannabis. According to these results, the connection between mental illnesses and cannabis use could therefore not simply be seen as an environmental risk, but rather explained as a gene-environment correlation.
{"title":"Genetic Risk of Psychosis in Relation to Cannabis Use: Findings from Polygenic Risk Score Approaches","authors":"K. Adorjan, S. Papiol","doi":"10.20900/jpbs.20190018","DOIUrl":"https://doi.org/10.20900/jpbs.20190018","url":null,"abstract":"A psychotic disorder is a multifactorial phenomenon in which not only environmental influences but also genetic factors play an important role. Evidence indicates that psychotic disorders are characterized by a complex mode of inheritance with high polygenicity, in which a large number of common genetic variants with small effects are relevant. One way to measure this polygenic risk is the calculation of polygenic risk scores (PRS). These reflect the complex multifactorial interaction of coding and regulatory DNA variants in the development of mental illness. It is known that the use of cannabis in patients with schizophrenia (SCZ) is much higher than in the general population. Although an exact clinical prognosis based on PRS is not possible at the present, the results found by PRS investigations so far are quite promising. Initial results suggest that people with SCZ and an increased polygenic risk of schizophrenia are more likely to use cannabis. According to these results, the connection between mental illnesses and cannabis use could therefore not simply be seen as an environmental risk, but rather explained as a gene-environment correlation.","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47064092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Psychiatric Genetics is a relatively new field that was defined by groups of researchers interested in the familial aggregation of psychiatric disorders, and spurred on by the escalating new field of molecular genetics beginning in the 1980s. This manuscript contributes to a special issue honoring the career of Elliot S. Gershon, a true pioneer and critical thinker, who contributed substantially to the development of this field and also its stimulating meetings that brought colleagues together to discuss the latest research findings. It details the role Dr. Gershon played in establishing the precursor of the International Society of Psychiatric Genetics (ISPG) and how he remains in a leadership role on its Board of Directors and was honored with one of the ISPG Lifetime Achievement Awards.
精神病学遗传学是一个相对较新的领域，它是由对精神疾病家族聚集感兴趣的研究小组定义的，并受到20世纪80年代开始的分子遗传学新领域的推动。这份手稿为纪念艾略特·s·格尔森(Elliot S. Gershon)的职业生涯做出了贡献，他是一位真正的先驱和批判性思想家，他对这一领域的发展做出了重大贡献，也为同事们聚集在一起讨论最新研究成果而召开了鼓舞人心的会议。它详细介绍了Gershon博士在建立国际精神病学遗传学学会(ISPG)的前身中所扮演的角色，以及他如何在其董事会中担任领导角色，并荣获ISPG终身成就奖之一。
{"title":"An Historical Perspective on Psychiatric Genetics, the International Society of Psychiatric Genetics and the Role of Elliot Gershon","authors":"L. DeLisi","doi":"10.20900/jpbs.20190015","DOIUrl":"https://doi.org/10.20900/jpbs.20190015","url":null,"abstract":"Psychiatric Genetics is a relatively new field that was defined by groups of researchers interested in the familial aggregation of psychiatric disorders, and spurred on by the escalating new field of molecular genetics beginning in the 1980s. This manuscript contributes to a special issue honoring the career of Elliot S. Gershon, a true pioneer and critical thinker, who contributed substantially to the development of this field and also its stimulating meetings that brought colleagues together to discuss the latest research findings. It details the role Dr. Gershon played in establishing the precursor of the International Society of Psychiatric Genetics (ISPG) and how he remains in a leadership role on its Board of Directors and was honored with one of the ISPG Lifetime Achievement Awards.","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67610439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Eberle, Y. Peterse, Filip Jukic, B. Müller-Myhsok, D. Czamara, Jade Martins, Vanessa Schmoll, M. Czisch, E. Binder, P. Sämann
Epidemiological and genetic studies suggest that schizophrenia (SCZ) is associated with both polygenic and environmental risk factors. Little is known if these factors project on common functional circuits relevant to the pathophysiology of SCZ. Here we focussed on resting state functional MRI (rsfMRI) as a biological measure to investigate if genetic and environmental factors for SCZ risk affect the same circuits in healthy controls as well as patients. For this, we compared the effects of a polygenic risk score for SCZ (PGRS), childhood adversity (CA) and their interaction on functional connectivity density (FCD) mapping and nucleus accumbens (NAcc) seed connectivity between 23 patients with SCZ or schizoaffective disorder and 253 healthy subjects. Patients demonstrated strong FCD increases compared with healthy controls mainly in subcortical nuclei including the NAcc, replicating previous reports. In healthy subjects, FCD of the NAcc was positively correlated with both the PGRS and the PGRS-CA-interaction. Both for high PGRS and PGRS-CA-interaction, fine-mapping revealed higher connectivity between the NAcc and visual association cortices. In conclusion, polygenic risk for SCZ shifted global and regionally specific connectivity of the NAcc in healthy subjects into the direction of the connectivity pattern observed in SCZ, and this shift was intensified by higher levels of CA.
{"title":"Endophenotype Potential of Nucleus Accumbens Functional Connectivity: Effects of Polygenic Risk for Schizophrenia Interacting with Childhood Adversity","authors":"C. Eberle, Y. Peterse, Filip Jukic, B. Müller-Myhsok, D. Czamara, Jade Martins, Vanessa Schmoll, M. Czisch, E. Binder, P. Sämann","doi":"10.20900/JPBS.20190011","DOIUrl":"https://doi.org/10.20900/JPBS.20190011","url":null,"abstract":"Epidemiological and genetic studies suggest that schizophrenia (SCZ) is associated with both polygenic and environmental risk factors. Little is known if these factors project on common functional circuits relevant to the pathophysiology of SCZ. Here we focussed on resting state functional MRI (rsfMRI) as a biological measure to investigate if genetic and environmental factors for SCZ risk affect the same circuits in healthy controls as well as patients. For this, we compared the effects of a polygenic risk score for SCZ (PGRS), childhood adversity (CA) and their interaction on functional connectivity density (FCD) mapping and nucleus accumbens (NAcc) seed connectivity between 23 patients with SCZ or schizoaffective disorder and 253 healthy subjects. Patients demonstrated strong FCD increases compared with healthy controls mainly in subcortical nuclei including the NAcc, replicating previous reports. In healthy subjects, FCD of the NAcc was positively correlated with both the PGRS and the PGRS-CA-interaction. Both for high PGRS and PGRS-CA-interaction, fine-mapping revealed higher connectivity between the NAcc and visual association cortices. In conclusion, polygenic risk for SCZ shifted global and regionally specific connectivity of the NAcc in healthy subjects into the direction of the connectivity pattern observed in SCZ, and this shift was intensified by higher levels of CA.","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43079032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Ou, Kuokuo Li, Hui Guo, K. Xia, Zhengmao Hu, Jingping Zhao, Fengyu Zhang
Background: ULK4 genetic variants have been implicated for adult-onset psychiatric disorders, and common variants are associated with hematologic and cardiologic disorders at genome-wide significance. This study aimed to examine the pleiotropic effect of ULK4 on the risk of autism, cis-association with mRNA and impact on antipsychotic treatment response in humans. Methods: The clinical genetic data comprised one cohort of autism case-parent triad sample in the Han Chinese and three cohorts of family-based samples in the European ancestry, from Autism Genetic Research Exchange, the Autism Genome Project and the Simons Foundation for Autism Research Initiative; mRNA expression in postmortem human prefrontal cortex across the lifespan and different brain regions of postmortem human brain and other tissues from two independent datasets were used for examining the cis-association with ULK4 variants. Antipsychotic treatment response data were from the Clinical Antipsychotic Trials in Intervention Effectiveness in patients with chronic schizophrenia. Transmission disequilibrium test was used to examine the genetic association with autism. General linear regression analysis was performed for cis-association with mRNA expression. The Cox proportion hazard model was used to analyze the primary outcome, the time to discontinued use of antipsychotics. Results: Multiple functional SNPs including rs2272007 in strong linkage disequilibrium at ULK4 were associated with autism in the Han Chinese sample (minimum p < 0.00071) which survived the Bonferroni correction for multiple testing. SNP rs2272007 and other SNPs were significantly associated with ULK4 expression in postmortem human prefrontal cortex in subjects across the lifespan and multiple brain areas in two independent datasets. In addition, two SNPs rs7651623 (Hazard Ratio, HR = 16.33; p = 5.00 × 10−4) and rs2030431 (HR = 17.25; p = 3.00 × 10−4) in strong LD were associated with the risk of discontinuing use of antipsychotic medications in the patients with schizophrenia. SNP rs2272007, perfect LD with rs7651623, was associated with treatment response in olanzapine only (HR = 4.22; p = 0.0034). Conclusion: We provide evidence at multiple layers for ULK4 common genetic variants associated with the risk of autism. This may have clinical implication for translational research and precision psychiatry
{"title":"ULK4 Genetic Variants Have Pleiotropic Effect on Risk of Autism, Associated with Brain mRNA Expression and Antipsychotic Treatment Response","authors":"J. Ou, Kuokuo Li, Hui Guo, K. Xia, Zhengmao Hu, Jingping Zhao, Fengyu Zhang","doi":"10.20900/JPBS.20190010","DOIUrl":"https://doi.org/10.20900/JPBS.20190010","url":null,"abstract":"Background: ULK4 genetic variants have been implicated for adult-onset psychiatric disorders, and common variants are associated with hematologic and cardiologic disorders at genome-wide significance. This study aimed to examine the pleiotropic effect of ULK4 on the risk of autism, cis-association with mRNA and impact on antipsychotic treatment response in humans. Methods: The clinical genetic data comprised one cohort of autism case-parent triad sample in the Han Chinese and three cohorts of family-based samples in the European ancestry, from Autism Genetic Research Exchange, the Autism Genome Project and the Simons Foundation for Autism Research Initiative; mRNA expression in postmortem human prefrontal cortex across the lifespan and different brain regions of postmortem human brain and other tissues from two independent datasets were used for examining the cis-association with ULK4 variants. Antipsychotic treatment response data were from the Clinical Antipsychotic Trials in Intervention Effectiveness in patients with chronic schizophrenia. Transmission disequilibrium test was used to examine the genetic association with autism. General linear regression analysis was performed for cis-association with mRNA expression. The Cox proportion hazard model was used to analyze the primary outcome, the time to discontinued use of antipsychotics. Results: Multiple functional SNPs including rs2272007 in strong linkage disequilibrium at ULK4 were associated with autism in the Han Chinese sample (minimum p < 0.00071) which survived the Bonferroni correction for multiple testing. SNP rs2272007 and other SNPs were significantly associated with ULK4 expression in postmortem human prefrontal cortex in subjects across the lifespan and multiple brain areas in two independent datasets. In addition, two SNPs rs7651623 (Hazard Ratio, HR = 16.33; p = 5.00 × 10−4) and rs2030431 (HR = 17.25; p = 3.00 × 10−4) in strong LD were associated with the risk of discontinuing use of antipsychotic medications in the patients with schizophrenia. SNP rs2272007, perfect LD with rs7651623, was associated with treatment response in olanzapine only (HR = 4.22; p = 0.0034). Conclusion: We provide evidence at multiple layers for ULK4 common genetic variants associated with the risk of autism. This may have clinical implication for translational research and precision psychiatry","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46454523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. González-Rodríguez, M. Estève, A. Álvarez, A. Guàrdia, J. Monreal, D. Palao, J. Labad
While gender differences in the psychopathology and clinical course of schizophrenia have been extensively reported, the potential for analogous differences in delusional disorder has been understudied. Our aim in this paper is to focus on the recent literature on delusional disorder and to explore gender aspects. This is a non-systematic, narrative and critical review. The review is divided into the following main sections: gender differences in epidemiology, symptomatology, phenotypic factor analyses, psychiatric comorbidity, response and adherence to medications, and clinical trajectories. Culture-bound delusional syndromes are also addressed, and potential causes for gender differences and their treatment are critically discussed. Although DMS-5 reports no gender differences in the frequency of delusional disorder or in delusional content, several studies have found erotomania to be more frequent in women. There seem also to be gender differences in affective and substance abuse comorbidity, which may prove clinically important. The loss of the neuroprotection conferred by estrogens during the reproductive period in women may trigger depressive symptoms after menopause. The interaction of age and gender has been insufficiently studied as is also the case for selective cultural pressures on men and women and their impact on the content of delusions. Studies designed to focus on gender differences in response to treatment are currently needed in delusional disorder
{"title":"What We Know and Still Need to Know about Gender Aspects of Delusional Disorder: A Narrative Review of Recent Work","authors":"A. González-Rodríguez, M. Estève, A. Álvarez, A. Guàrdia, J. Monreal, D. Palao, J. Labad","doi":"10.20900/JPBS.20190009","DOIUrl":"https://doi.org/10.20900/JPBS.20190009","url":null,"abstract":"While gender differences in the psychopathology and clinical course of schizophrenia have been extensively reported, the potential for analogous differences in delusional disorder has been understudied. Our aim in this paper is to focus on the recent literature on delusional disorder and to explore gender aspects. This is a non-systematic, narrative and critical review. The review is divided into the following main sections: gender differences in epidemiology, symptomatology, phenotypic factor analyses, psychiatric comorbidity, response and adherence to medications, and clinical trajectories. Culture-bound delusional syndromes are also addressed, and potential causes for gender differences and their treatment are critically discussed. Although DMS-5 reports no gender differences in the frequency of delusional disorder or in delusional content, several studies have found erotomania to be more frequent in women. There seem also to be gender differences in affective and substance abuse comorbidity, which may prove clinically important. The loss of the neuroprotection conferred by estrogens during the reproductive period in women may trigger depressive symptoms after menopause. The interaction of age and gender has been insufficiently studied as is also the case for selective cultural pressures on men and women and their impact on the content of delusions. Studies designed to focus on gender differences in response to treatment are currently needed in delusional disorder","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43152411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Jaeschke, D. Blackmore, Natalie J. Groves, M. Al-Amin, S. Alexander, T. Burne
It is well established that vitamin D is essential in calcium homeostasis and bone metabolism. Recent evidence has exposed further roles of vitamin D in adult brain function, specifically indicating that low vitamin D levels during adulthood may be related to cognitive impairment. We have recently shown that adult vitamin D (AVD) deficiency disrupts hippocampal-dependent learning and structural brain connectivity in BALB/c mice. The BALB/c mouse strain is more vulnerable to social stress compared with other resilient mouse strains, such as C57BL/6J mice. Therefore, the primary aim of this research was to examine C57BL/6J mice exposed to varying levels of vitamin D (0, 1500 and 15,000 IU/vitamin D3/kg referred to as deficient, control and elevated, respectively) for 10 weeks. The mice were assessed for hippocampal-dependent learning using the active place avoidance (APA) task. Mice were tested for behaviours that could alter performance on the APA task, and hippocampal tissue was analysed for catecholamine and protein expression. Vitamin D status did not affect spatial learning and memory, general behavioural domains, or catecholamine or protein expression in C57BL/6J mice. Overall, these results indicate that, in contrast to BALB/c mice, vitamin D status does not impact on hippocampal-dependent behaviour in young and healthy, adult male C57BL/6J mice
{"title":"Vitamin D Levels Are Not Associated with Hippocampal-Dependent Learning in Young Adult Male C57BL/6J Mice: A Negative Report","authors":"K. Jaeschke, D. Blackmore, Natalie J. Groves, M. Al-Amin, S. Alexander, T. Burne","doi":"10.20900/jpbs.20190008","DOIUrl":"https://doi.org/10.20900/jpbs.20190008","url":null,"abstract":"It is well established that vitamin D is essential in calcium homeostasis and bone metabolism. Recent evidence has exposed further roles of vitamin D in adult brain function, specifically indicating that low vitamin D levels during adulthood may be related to cognitive impairment. We have recently shown that adult vitamin D (AVD) deficiency disrupts hippocampal-dependent learning and structural brain connectivity in BALB/c mice. The BALB/c mouse strain is more vulnerable to social stress compared with other resilient mouse strains, such as C57BL/6J mice. Therefore, the primary aim of this research was to examine C57BL/6J mice exposed to varying levels of vitamin D (0, 1500 and 15,000 IU/vitamin D3/kg referred to as deficient, control and elevated, respectively) for 10 weeks. The mice were assessed for hippocampal-dependent learning using the active place avoidance (APA) task. Mice were tested for behaviours that could alter performance on the APA task, and hippocampal tissue was analysed for catecholamine and protein expression. Vitamin D status did not affect spatial learning and memory, general behavioural domains, or catecholamine or protein expression in C57BL/6J mice. Overall, these results indicate that, in contrast to BALB/c mice, vitamin D status does not impact on hippocampal-dependent behaviour in young and healthy, adult male C57BL/6J mice","PeriodicalId":73912,"journal":{"name":"Journal of psychiatry and brain science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43744111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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