{"title":"Is it possible to find reliable biomarkers to diagnose suicide risk?","authors":"Leo Sher","doi":"10.1017/neu.2023.8","DOIUrl":"https://doi.org/10.1017/neu.2023.8","url":null,"abstract":"","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"35 3","pages":"186-187"},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9942200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Norma Verdolini, Gisela Mezquida, Isabel Valli, Clemente Garcia-Rizo, Manuel Cuesta, Eduard Vieta, Miquel Bioque, Antonio Lobo, Ana González-Pinto, Laura Pina-Camacho, Iluminada Corripio, Marina Garriga, Inmaculada Baeza, Laura Martínez-Sadurní, Byron Bitanihirwe, Mary Cannon, Miquel Bernardo
Objective: Psychotic disorders exhibit a complex aetiology that combines genetic and environmental factors. Among the latter, obstetric complications (OCs) have been widely studied as risk factors, but it is not yet well understood how OCs relate to the heterogeneous presentations of psychotic disorders. We assessed the clinical phenotypes of individuals with a first episode of psychosis (FEP) in relation to the presence of OCs.
Methods: Two-hundred seventy-seven patients with an FEP were assessed for OCs using the Lewis-Murray scale, with data stratified into three subscales depending on the timing and the characteristics of the obstetric event, namely: complications of pregnancy, abnormal foetal growth and development and difficulties in delivery. We also considered other two groups: any complications during the pregnancy period and all OCs taken altogether. Patients were clinically evaluated with the Positive and Negative Syndrome Scale for schizophrenia.
Results: Total OCs and difficulties in delivery were related to more severe psychopathology, and this remained significant after co-varying for age, sex, traumatic experiences, antipsychotic dosage and cannabis use.
Conclusions: Our results highlight the relevance of OCs for the clinical presentation of psychosis. Describing the timing of the OCs is essential in understanding the heterogeneity of the clinical presentation.
{"title":"Obstetric complications and clinical presentation in first episode of psychosis.","authors":"Norma Verdolini, Gisela Mezquida, Isabel Valli, Clemente Garcia-Rizo, Manuel Cuesta, Eduard Vieta, Miquel Bioque, Antonio Lobo, Ana González-Pinto, Laura Pina-Camacho, Iluminada Corripio, Marina Garriga, Inmaculada Baeza, Laura Martínez-Sadurní, Byron Bitanihirwe, Mary Cannon, Miquel Bernardo","doi":"10.1017/neu.2023.9","DOIUrl":"https://doi.org/10.1017/neu.2023.9","url":null,"abstract":"<p><strong>Objective: </strong>Psychotic disorders exhibit a complex aetiology that combines genetic and environmental factors. Among the latter, obstetric complications (OCs) have been widely studied as risk factors, but it is not yet well understood how OCs relate to the heterogeneous presentations of psychotic disorders. We assessed the clinical phenotypes of individuals with a first episode of psychosis (FEP) in relation to the presence of OCs.</p><p><strong>Methods: </strong>Two-hundred seventy-seven patients with an FEP were assessed for OCs using the Lewis-Murray scale, with data stratified into three subscales depending on the timing and the characteristics of the obstetric event, namely: complications of pregnancy, abnormal foetal growth and development and difficulties in delivery. We also considered other two groups: any complications during the pregnancy period and all OCs taken altogether. Patients were clinically evaluated with the Positive and Negative Syndrome Scale for schizophrenia.</p><p><strong>Results: </strong>Total OCs and difficulties in delivery were related to more severe psychopathology, and this remained significant after co-varying for age, sex, traumatic experiences, antipsychotic dosage and cannabis use.</p><p><strong>Conclusions: </strong>Our results highlight the relevance of OCs for the clinical presentation of psychosis. Describing the timing of the OCs is essential in understanding the heterogeneity of the clinical presentation.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"35 3","pages":"156-164"},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9873988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The purpose of this study is to describe how to use the precision nomothetic psychiatry approach to (a) delineate the associations between schizophrenia symptom domains, including negative symptoms, psychosis, hostility, excitation, mannerism, formal thought disorders, psychomotor retardation (PHEMFP), and cognitive dysfunctions and neuroimmunotoxic and neuro-oxidative pathways and (b) create a new endophenotype class based on these features. We show that all symptom domains (negative and PHEMFP) may be used to derive a single latent trait called overall severity of schizophrenia (OSOS). In addition, neurocognitive test results may be used to extract a general cognitive decline (G-CoDe) index, based on executive function, attention, semantic and episodic memory, and delayed recall scores. According to partial least squares analysis, the impacts of adverse outcome pathways (AOPs) on OSOS are partially mediated by increasing G-CoDe severity. The AOPs include neurotoxic cytokines and chemokines, oxidative damage to proteins and lipids, IgA responses to neurotoxic tryptophan catabolites, breakdown of the vascular and paracellular pathways with translocation of Gram-negative bacteria, and insufficient protection through lowered antioxidant levels and impairments in the innate immune system. Unsupervised machine learning identified a new schizophrenia endophenotype class, named major neurocognitive psychosis (MNP), which is characterised by increased negative symptoms and PHEMFP, G-CoDe and the above-mentioned AOPs. Based on these pathways and phenome features, MNP is a distinct endophenotype class which is qualitatively different from simple psychosis (SP). It is impossible to draw any valid conclusions from research on schizophrenia that ignores the MNP and SP distinctions.
{"title":"Major neurocognitive psychosis: a novel schizophrenia endophenotype class that is based on machine learning and resembles Kraepelin's and Bleuler's conceptions.","authors":"Michael Maes","doi":"10.1017/neu.2022.32","DOIUrl":"https://doi.org/10.1017/neu.2022.32","url":null,"abstract":"<p><p>The purpose of this study is to describe how to use the precision nomothetic psychiatry approach to (a) delineate the associations between schizophrenia symptom domains, including negative symptoms, psychosis, hostility, excitation, mannerism, formal thought disorders, psychomotor retardation (PHEMFP), and cognitive dysfunctions and neuroimmunotoxic and neuro-oxidative pathways and (b) create a new endophenotype class based on these features. We show that all symptom domains (negative and PHEMFP) may be used to derive a single latent trait called overall severity of schizophrenia (OSOS). In addition, neurocognitive test results may be used to extract a general cognitive decline (G-CoDe) index, based on executive function, attention, semantic and episodic memory, and delayed recall scores. According to partial least squares analysis, the impacts of adverse outcome pathways (AOPs) on OSOS are partially mediated by increasing G-CoDe severity. The AOPs include neurotoxic cytokines and chemokines, oxidative damage to proteins and lipids, IgA responses to neurotoxic tryptophan catabolites, breakdown of the vascular and paracellular pathways with translocation of Gram-negative bacteria, and insufficient protection through lowered antioxidant levels and impairments in the innate immune system. Unsupervised machine learning identified a new schizophrenia endophenotype class, named major neurocognitive psychosis (MNP), which is characterised by increased negative symptoms and PHEMFP, G-CoDe and the above-mentioned AOPs. Based on these pathways and phenome features, MNP is a distinct endophenotype class which is qualitatively different from simple psychosis (SP). It is impossible to draw any valid conclusions from research on schizophrenia that ignores the MNP and SP distinctions.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"35 3","pages":"123-137"},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9517875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: This study aimed to evaluate the retinal nerve fibre layer changes among different group of patients with schizophrenia and compare it with healthy controls by using swept-source optical coherence tomography.
Methodology: Patients with first-episode schizophrenia (n = 21) in remission (n = 35) or with treatment-resistant schizophrenia (TRS) (n = 35) and 36 healthy controls were evaluated for retinal thickness.
Results: Patients with psychotic illnesses had significantly lower sub-foveal choroidal thickness (effect size 0.84-0.86), when compared to the healthy controls. When patients with first-episode schizophrenia were compared with patients with TRS, TRS patients had significant lower sub-foveal choroidal thickness (left eye) when the various confounders (such as age, gender, duration of treatment, smoking, current medications, body mass index, waist circumference, blood pressure, fasting glucose, HbA1c, presence or absence of metabolic syndrome) were taken into account. When the patients with TRS were compared with healthy controls, initially significant differences were observed for the macular volume (left and right) and the ganglion cell thickness (right eye) but these differences disappeared after controlling for the various covariates.
Conclusions: Compared to healthy controls, patients with schizophrenia, psychotic illnesses have thinning of the retina, especially in the sub-foveal choroidal thickness.
{"title":"A comparative study of retinal layer changes among patients with schizophrenia and healthy controls.","authors":"Abhilaksh Kango, Sandeep Grover, Vishali Gupta, Swapnajeet Sahoo, Ritu Nehra","doi":"10.1017/neu.2022.35","DOIUrl":"https://doi.org/10.1017/neu.2022.35","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to evaluate the retinal nerve fibre layer changes among different group of patients with schizophrenia and compare it with healthy controls by using swept-source optical coherence tomography.</p><p><strong>Methodology: </strong>Patients with first-episode schizophrenia (<i>n</i> = 21) in remission (<i>n</i> = 35) or with treatment-resistant schizophrenia (TRS) (<i>n</i> = 35) and 36 healthy controls were evaluated for retinal thickness.</p><p><strong>Results: </strong>Patients with psychotic illnesses had significantly lower sub-foveal choroidal thickness (effect size 0.84-0.86), when compared to the healthy controls. When patients with first-episode schizophrenia were compared with patients with TRS, TRS patients had significant lower sub-foveal choroidal thickness (left eye) when the various confounders (such as age, gender, duration of treatment, smoking, current medications, body mass index, waist circumference, blood pressure, fasting glucose, HbA1c, presence or absence of metabolic syndrome) were taken into account. When the patients with TRS were compared with healthy controls, initially significant differences were observed for the macular volume (left and right) and the ganglion cell thickness (right eye) but these differences disappeared after controlling for the various covariates.</p><p><strong>Conclusions: </strong>Compared to healthy controls, patients with schizophrenia, psychotic illnesses have thinning of the retina, especially in the sub-foveal choroidal thickness.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"35 3","pages":"165-176"},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9512055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Błażej Misiak, Patryk Piotrowski, Agnieszka Cyran, Krzysztof Kowalski, Jerzy Samochowiec, Marcin Jabłoński, Piotr Plichta, Łukasz Łaczmański, Paulina Żebrowska, Dorota Kujawa, Igor Łoniewski, Mariusz Kaczmarczyk
Objective: The pathogenesis of schizophrenia is multidimensional and intensively studied. The gut-brain axis disturbances might play a significant role in the development of schizophrenia.
Methods: We compared the gut microbiota of 53 individuals with schizophrenia and 58 healthy controls, using the 16S rRNA sequencing method. Individuals with schizophrenia were assessed using the following scales: the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Social and Occupational Functioning Assessment Scale and the Repeatable Battery for the Assessment of Neuropsychological Status.
Results: No significant between-group differences in α-diversity measures were observed. Increased abundance of Lactobacillales (order level), Bacilli (class level) and Actinobacteriota (phylum level) were found in individuals with schizophrenia regardless of potential confounding factors, and using two independent analytical approaches (the distance-based redundancy analysis and the generalised linear model analysis). Additionally, significant correlations between various bacterial taxa (the Bacteroidia class, the Actinobacteriota phylum, the Bacteroidota phylum, the Coriobacteriales order and the Coriobacteria class) and clinical manifestation (the severity of negative symptoms, performance of language abilities, social and occupational functioning) were observed.
Conclusions: The present study indicates that gut microbiota alterations are present in European patients with schizophrenia. The abundance of certain bacterial taxa might be associated with the severity of negative symptoms, cognitive performance and general functioning. Nonetheless, additional studies are needed before the translation of our results into clinical practice.
{"title":"Gut microbiota alterations in stable outpatients with schizophrenia: findings from a case-control study.","authors":"Błażej Misiak, Patryk Piotrowski, Agnieszka Cyran, Krzysztof Kowalski, Jerzy Samochowiec, Marcin Jabłoński, Piotr Plichta, Łukasz Łaczmański, Paulina Żebrowska, Dorota Kujawa, Igor Łoniewski, Mariusz Kaczmarczyk","doi":"10.1017/neu.2022.38","DOIUrl":"https://doi.org/10.1017/neu.2022.38","url":null,"abstract":"<p><strong>Objective: </strong>The pathogenesis of schizophrenia is multidimensional and intensively studied. The gut-brain axis disturbances might play a significant role in the development of schizophrenia.</p><p><strong>Methods: </strong>We compared the gut microbiota of 53 individuals with schizophrenia and 58 healthy controls, using the 16S rRNA sequencing method. Individuals with schizophrenia were assessed using the following scales: the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Social and Occupational Functioning Assessment Scale and the Repeatable Battery for the Assessment of Neuropsychological Status.</p><p><strong>Results: </strong>No significant between-group differences in α-diversity measures were observed. Increased abundance of Lactobacillales (order level), Bacilli (class level) and Actinobacteriota (phylum level) were found in individuals with schizophrenia regardless of potential confounding factors, and using two independent analytical approaches (the distance-based redundancy analysis and the generalised linear model analysis). Additionally, significant correlations between various bacterial taxa (the Bacteroidia class, the Actinobacteriota phylum, the Bacteroidota phylum, the Coriobacteriales order and the Coriobacteria class) and clinical manifestation (the severity of negative symptoms, performance of language abilities, social and occupational functioning) were observed.</p><p><strong>Conclusions: </strong>The present study indicates that gut microbiota alterations are present in European patients with schizophrenia. The abundance of certain bacterial taxa might be associated with the severity of negative symptoms, cognitive performance and general functioning. Nonetheless, additional studies are needed before the translation of our results into clinical practice.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"35 3","pages":"147-155"},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9890212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jan Exner, Gunnar Deuring, Erich Seifritz, Annette Beatrix Brühl
Background: To evoke a therapeutically effective seizure, electrical stimulation in electroconvulsive therapy (ECT) has to overcome the combined resistivity of scalp, skull and other tissues. Static impedances are measured prior to stimulation using high-frequency electrical alternating pulses, dynamic impedances during passage of the stimulation current. Static impedance can partially be influenced by skin preparation techniques. Earlier studies showed a correlation between dynamic and static impedance in bitemporal and right unilateral ECT.
Objective: This study aims at assessing the correlation of dynamic and static impedance with patient characteristics and seizure quality criteria in bifrontal ECT.
Methods: We performed a cross-sectional single-centre retrospective analysis of ECT treatments at the Psychiatric University Hospital Zurich between May 2012 and March 2020 and used linear mixed-effects regression models in 78 patients with a total of 1757 ECT sessions.
Results: Dynamic and static impedance were strongly correlated. Dynamic impedance was significantly correlated with age and higher in women. Energy set and factors positively (caffeine) and negatively (propofol) affecting seizure at the neuronal level were not associated with dynamic impedance. For secondary outcomes, dynamic impedance was significantly related to Maximum Sustained Power and Average Seizure Energy Index. Other seizure quality criteria showed no significant correlation with dynamic impedance.
Conclusion: Aiming for low static impedance might reduce dynamic impedance, which is correlated with positive seizure quality parameters. Therefore, good skin preparation to achieve low static impedance is recommended.
{"title":"Dynamic impedance is correlated with static impedance and seizure quality parameters in bifrontal electroconvulsive therapy.","authors":"Jan Exner, Gunnar Deuring, Erich Seifritz, Annette Beatrix Brühl","doi":"10.1017/neu.2023.10","DOIUrl":"https://doi.org/10.1017/neu.2023.10","url":null,"abstract":"<p><strong>Background: </strong>To evoke a therapeutically effective seizure, electrical stimulation in electroconvulsive therapy (ECT) has to overcome the combined resistivity of scalp, skull and other tissues. Static impedances are measured prior to stimulation using high-frequency electrical alternating pulses, dynamic impedances during passage of the stimulation current. Static impedance can partially be influenced by skin preparation techniques. Earlier studies showed a correlation between dynamic and static impedance in bitemporal and right unilateral ECT.</p><p><strong>Objective: </strong>This study aims at assessing the correlation of dynamic and static impedance with patient characteristics and seizure quality criteria in bifrontal ECT.</p><p><strong>Methods: </strong>We performed a cross-sectional single-centre retrospective analysis of ECT treatments at the Psychiatric University Hospital Zurich between May 2012 and March 2020 and used linear mixed-effects regression models in 78 patients with a total of 1757 ECT sessions.</p><p><strong>Results: </strong>Dynamic and static impedance were strongly correlated. Dynamic impedance was significantly correlated with age and higher in women. Energy set and factors positively (caffeine) and negatively (propofol) affecting seizure at the neuronal level were not associated with dynamic impedance. For secondary outcomes, dynamic impedance was significantly related to Maximum Sustained Power and Average Seizure Energy Index. Other seizure quality criteria showed no significant correlation with dynamic impedance.</p><p><strong>Conclusion: </strong>Aiming for low static impedance might reduce dynamic impedance, which is correlated with positive seizure quality parameters. Therefore, good skin preparation to achieve low static impedance is recommended.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"35 3","pages":"177-185"},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Armando L Morera-Fumero, Estefania Diaz-Mesa, Lourdes Fernandez-Lopez, Pedro Abreu-Gonzalez, Manuel S Henry-Benitez
Objective: The s100b inflammatory protein is involved in schizophrenia pathophysiology. We aim at studying the evolution of the s100b serum levels in acutely relapsed paranoid schizophrenia patients at three different time points (admission, discharge and 3 months after hospital discharge 3MAHD).
Methods: Twenty-three paranoid schizophrenia inpatients meeting DSM-IV criteria participated in the research. Twenty-three healthy subjects matched by age, gender and season acted as the control group. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Serum s100b levels were determined at 12:00 and 24:00 h with an enzyme-linked immunoassay kit.
Results: Patients had significant higher serum s100b levels at admission and discharge (12:00 h) than the group of healthy subjects. At admission and discharge, s100b serum levels at 24 h had decreased compared to the 24:00 h s100b levels of the healthy subjects. At 3MAHD patients and healthy subjects had similar levels of serum s100b protein. Positive and negative PANSS scores decreased significantly between admission and discharge. Positive and negative PANSS scores decreased between discharge and 3MAHD, but these changes had no statistical significance.
Conclusions: Our study confirms that the acute inflammatory response produced in acutely relapsed patients is reversed after 3 month of hospital discharge. The variations of serum s100b concentrations when the patients suffer from an acute relapse may be a useful predictor of disease evolution.
{"title":"Serum s100b protein levels as a neuroinflammatory biomarker of acutely relapsed paranoid schizophrenia patients.","authors":"Armando L Morera-Fumero, Estefania Diaz-Mesa, Lourdes Fernandez-Lopez, Pedro Abreu-Gonzalez, Manuel S Henry-Benitez","doi":"10.1017/neu.2022.37","DOIUrl":"https://doi.org/10.1017/neu.2022.37","url":null,"abstract":"<p><strong>Objective: </strong>The s100b inflammatory protein is involved in schizophrenia pathophysiology. We aim at studying the evolution of the s100b serum levels in acutely relapsed paranoid schizophrenia patients at three different time points (admission, discharge and 3 months after hospital discharge 3MAHD).</p><p><strong>Methods: </strong>Twenty-three paranoid schizophrenia inpatients meeting DSM-IV criteria participated in the research. Twenty-three healthy subjects matched by age, gender and season acted as the control group. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Serum s100b levels were determined at 12:00 and 24:00 h with an enzyme-linked immunoassay kit.</p><p><strong>Results: </strong>Patients had significant higher serum s100b levels at admission and discharge (12:00 h) than the group of healthy subjects. At admission and discharge, s100b serum levels at 24 h had decreased compared to the 24:00 h s100b levels of the healthy subjects. At 3MAHD patients and healthy subjects had similar levels of serum s100b protein. Positive and negative PANSS scores decreased significantly between admission and discharge. Positive and negative PANSS scores decreased between discharge and 3MAHD, but these changes had no statistical significance.</p><p><strong>Conclusions: </strong>Our study confirms that the acute inflammatory response produced in acutely relapsed patients is reversed after 3 month of hospital discharge. The variations of serum s100b concentrations when the patients suffer from an acute relapse may be a useful predictor of disease evolution.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"35 3","pages":"138-146"},"PeriodicalIF":3.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9890210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-14DOI: 10.1101/2023.05.13.23289938
M. Campbell, S. Dalvie, A. Shadrin, D. van der Meer, K. O’Connell, O. Frei, O. Andreassen, Dan J Stein, J. Rokicki
Background: The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remains largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions, and the genetic overlap with psychiatric disorders. Methods: We applied multivariate GWAS to genetic and T1-weighted MRI data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid posterior, central, mid anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine SNP-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits. Results: We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 x 10-8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid anterior, 29 in the central, 7 in the mid posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 x 10-6). LDSC estimated the heritability of CC to (h2SNP=0.38, SE=0.03), and subregions ranging from 0.22 (SE=0.02) to 0.37 (SE=0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg=-0.09, SE=0.03; p=5.9 x 10-3) and drinks consumed per week (rg=-0.09, SE=0.02; p=4.8 x 10-4), and volume of the mid anterior subregion with BD (rg=-0.12, SE=0.02; p=2.5 x 10-4), major depressive disorder (rg=-0.12, SE=0.04; p=3.6 x 10-3), drinks consumed per week (rg=-0.13, SE=0.04; p=1.8 x 10-3) and cannabis use (rg=-0.09, SE=0.03; p=8.4 x 10-3). Conclusions: Our results demonstrate that the CC has a polygenic architecture implicating multiple genes, and show that CC subregion volumes are heritable. We found distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialization. Significant genetic correlation between volumes of the CC and bipolar disorder, drinks per week, major depressive disorder and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.
背景:胼胝体(CC)是一种具有高遗传性的大脑结构,在精神疾病中具有潜在作用。然而,CC的遗传结构以及与精神疾病的遗传联系在很大程度上仍不清楚。我们研究了CC体积及其亚区的遗传结构,以及与精神疾病的遗传重叠。方法:我们将多变量GWAS应用于英国生物库40894名个体的遗传和T1加权MRI数据,旨在促进基因发现,并评估FreeSurfer 7.1获得的CC五个亚区(后部、中后部、中部、中前部和前部)体积的多效性效应。多变量GWAS结合所有子区域运行,相关变量共同变化。使用MAGMA进行基因集富集分析。连锁不平衡评分回归(LDSC)用于确定基于SNP的CC总体积及其亚区体积的遗传力,以及它们与相关精神特征的遗传相关性。结果:我们确定了70个独立的基因座,这些基因座在CC的五个亚区具有分布效应(p<5×10-8)。此外,我们在前部亚区确定了33个重要位点,23个在前部中部,29个在中部,7个在后部,56个在后部亚区。基因集分析显示,156个重要基因对CC亚区的体积有贡献(p<2.6 x 10-6)。LDSC估计CC的遗传力为(h2SNP=0.38,SE=0.03),亚区的遗传力范围为0.22(SE=0.02)至0.37(SE=0.03)。我们发现总CC容量与双相情感障碍(BD,rg=0.09,SE=0.03;p=5.9 x 10-3)和每周饮酒量(rg-0.09,SE=0.02;p=4.8 x 10-4)之间存在显著的遗传相关性,重度抑郁障碍(rg=0.12,SE=0.04;p=3.6 x 10-3)、每周饮酒量(rg=0.13,SE=0.4;p=1.8 x 10-3。结论:我们的结果表明CC具有涉及多个基因的多基因结构,并表明CC亚区体积是可遗传的。我们发现不同的遗传因素参与了前部和后部亚区的发育,这与它们不同的功能专门化一致。CC量和双相情感障碍、每周饮酒量、重度抑郁障碍和大麻消费亚区域量与精神特征之间存在显著的遗传相关性,值得注意,值得进一步研究。
{"title":"Distributed Genetic Effects of the Corpus Callosum Subregions Suggest Links to Neuropsychiatric Disorders and Related Traits","authors":"M. Campbell, S. Dalvie, A. Shadrin, D. van der Meer, K. O’Connell, O. Frei, O. Andreassen, Dan J Stein, J. Rokicki","doi":"10.1101/2023.05.13.23289938","DOIUrl":"https://doi.org/10.1101/2023.05.13.23289938","url":null,"abstract":"Background: The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remains largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions, and the genetic overlap with psychiatric disorders. Methods: We applied multivariate GWAS to genetic and T1-weighted MRI data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid posterior, central, mid anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine SNP-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits. Results: We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 x 10-8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid anterior, 29 in the central, 7 in the mid posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 x 10-6). LDSC estimated the heritability of CC to (h2SNP=0.38, SE=0.03), and subregions ranging from 0.22 (SE=0.02) to 0.37 (SE=0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg=-0.09, SE=0.03; p=5.9 x 10-3) and drinks consumed per week (rg=-0.09, SE=0.02; p=4.8 x 10-4), and volume of the mid anterior subregion with BD (rg=-0.12, SE=0.02; p=2.5 x 10-4), major depressive disorder (rg=-0.12, SE=0.04; p=3.6 x 10-3), drinks consumed per week (rg=-0.13, SE=0.04; p=1.8 x 10-3) and cannabis use (rg=-0.09, SE=0.03; p=8.4 x 10-3). Conclusions: Our results demonstrate that the CC has a polygenic architecture implicating multiple genes, and show that CC subregion volumes are heritable. We found distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialization. Significant genetic correlation between volumes of the CC and bipolar disorder, drinks per week, major depressive disorder and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"1 1","pages":"1-21"},"PeriodicalIF":3.8,"publicationDate":"2023-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41735974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-25DOI: 10.1101/2023.04.19.23288847
Michael Maes, M. Rachayon, K. Jirakran, A. Sughondhabirom, A. Almulla, P. Sodsai
Early flow cytometry studies revealed T cell activation in major depressive disorder (MDD) (Maes et al., 1990-1993). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2. Using flow cytometry, we determined the percentage of CD20+CB2+, CD3+CB2+, CD4+CB2+, CD8+CB2 and FoxP3+CB1+ cells in 19 healthy controls and 29 MDD patients in 5 conditions: baseline, stimulation with anti-CD3/CD28 with or without 0.1 mug/mL, 1.0 mug/mL or 10.0 mug/mL CBD. We found that CB2+ was significantly higher in CD20+ than CD3+ and CD4+, and CD8+ cells. Stimulation with anti-CD3/CD8 beads increases the number of CB2-bearing CD3+, CD4+, and CD8+ cells, as well as CB1-bearing FoxP3+ cells. There was an inverse association between the number of reduced CD4+CB2+ and IRS profiles, including M1 macrophage, T helper-(Th)-1 and Th-17 phenotypes. MDD is characterized by lowered basal FoxP3+CB1+% and higher CD20+CB2+%. 33.2% of the variance in the depression phenome (including severity of depression, anxiety, and current suicidal behaviors) is explained by CD20+CB2+% (positively) and CD3+CB2+% (inversely). All 5 immune cell populations were significantly increased by 10 mug/mL CBD administration. In conclusion, reductions in FoxP3+CB1+% and CD3+/CD4+CB2+% contribute to deficits in immune homeostasis in MDD, while increased CD20+CB2+% may contribute to the pathophysiology of MDD by activating T-independent humoral immunity.
{"title":"Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviors: effects of in vitro cannabidiol administration.","authors":"Michael Maes, M. Rachayon, K. Jirakran, A. Sughondhabirom, A. Almulla, P. Sodsai","doi":"10.1101/2023.04.19.23288847","DOIUrl":"https://doi.org/10.1101/2023.04.19.23288847","url":null,"abstract":"Early flow cytometry studies revealed T cell activation in major depressive disorder (MDD) (Maes et al., 1990-1993). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2. Using flow cytometry, we determined the percentage of CD20+CB2+, CD3+CB2+, CD4+CB2+, CD8+CB2 and FoxP3+CB1+ cells in 19 healthy controls and 29 MDD patients in 5 conditions: baseline, stimulation with anti-CD3/CD28 with or without 0.1 mug/mL, 1.0 mug/mL or 10.0 mug/mL CBD. We found that CB2+ was significantly higher in CD20+ than CD3+ and CD4+, and CD8+ cells. Stimulation with anti-CD3/CD8 beads increases the number of CB2-bearing CD3+, CD4+, and CD8+ cells, as well as CB1-bearing FoxP3+ cells. There was an inverse association between the number of reduced CD4+CB2+ and IRS profiles, including M1 macrophage, T helper-(Th)-1 and Th-17 phenotypes. MDD is characterized by lowered basal FoxP3+CB1+% and higher CD20+CB2+%. 33.2% of the variance in the depression phenome (including severity of depression, anxiety, and current suicidal behaviors) is explained by CD20+CB2+% (positively) and CD3+CB2+% (inversely). All 5 immune cell populations were significantly increased by 10 mug/mL CBD administration. In conclusion, reductions in FoxP3+CB1+% and CD3+/CD4+CB2+% contribute to deficits in immune homeostasis in MDD, while increased CD20+CB2+% may contribute to the pathophysiology of MDD by activating T-independent humoral immunity.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"1 1","pages":"1-40"},"PeriodicalIF":3.8,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49444265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Alzheimer's disease (AD) has prolonged asymptomatic or mild symptomatic periods. Given that there is an increase in treatment options and that early intervention could modify the disease course, it is desirable to devise biological indices that may differentiate AD and nonAD at mild cognitive impairment (MCI) stage.
Methods: Based on two well-acknowledged observations of background slowing (attenuation in alpha power and enhancement in theta and delta powers) and early involvement of posterior cingulate cortex (PCC, a neural hub of default-mode network), this study devised novel neural markers, namely, spectral ratios of alpha1 to delta and alpha1 to theta in the PCC.
Results: We analysed 46 MCI patients, with 22 ADMCI and 24 nonADMCI who were matched in age, education, and global cognitive capability. Concordant with the prediction, the regional spectral ratios were lower in the ADMCI group, suggesting its clinical application potential.
Conclusion: Previous research has verified that neural markers derived from clinical electroencephalography may be informative in differentiating AD from other neurological conditions. We believe that the spectral ratios in the neural hubs that show early pathological changes can enrich the instrumental assessment of brain dysfunctions at the MCI (or pre-clinical) stage.
{"title":"Regional spectral ratios as potential neural markers to identify mild cognitive impairment related to Alzheimer's disease.","authors":"Tien-Wen Lee, Gerald Tramontano","doi":"10.1017/neu.2022.18","DOIUrl":"https://doi.org/10.1017/neu.2022.18","url":null,"abstract":"<p><strong>Objective: </strong>Alzheimer's disease (AD) has prolonged asymptomatic or mild symptomatic periods. Given that there is an increase in treatment options and that early intervention could modify the disease course, it is desirable to devise biological indices that may differentiate AD and nonAD at mild cognitive impairment (MCI) stage.</p><p><strong>Methods: </strong>Based on two well-acknowledged observations of background slowing (attenuation in alpha power and enhancement in theta and delta powers) and early involvement of posterior cingulate cortex (PCC, a neural hub of default-mode network), this study devised novel neural markers, namely, spectral ratios of alpha1 to delta and alpha1 to theta in the PCC.</p><p><strong>Results: </strong>We analysed 46 MCI patients, with 22 ADMCI and 24 nonADMCI who were matched in age, education, and global cognitive capability. Concordant with the prediction, the regional spectral ratios were lower in the ADMCI group, suggesting its clinical application potential.</p><p><strong>Conclusion: </strong>Previous research has verified that neural markers derived from clinical electroencephalography may be informative in differentiating AD from other neurological conditions. We believe that the spectral ratios in the neural hubs that show early pathological changes can enrich the instrumental assessment of brain dysfunctions at the MCI (or pre-clinical) stage.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"35 2","pages":"118-122"},"PeriodicalIF":3.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9103745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}