Pub Date : 2024-09-18DOI: 10.1101/2024.09.17.24313817
Vladislav Yakimov, Iris Jaeger, Lukas Roell, Emanuel Boudriot, Verena Meisinger, Mattia Campana, Lenka Krcmar, Sean Halstead, Nicola Warren, Dan Siskind, Isabel Maurus, Alkomiet Hasan, Peter Falkai, Andrea Schmitt, Florian J. Raabe, Daniel Keeser, CDP Working Group, Elias Wagner, Joanna Moussiopoulou
The blood-cerebrospinal fluid barrier (BCB) builds an integral interface between the central nervous system and the periphery and appears to be impaired in a substantial proportion of individuals with schizophrenia-spectrum disorders (SSD). Even though a disruption of the BCB is associated with higher symptom severity, factors linked to BCB disruption in SSDs have been minimally investigated. To address this gap, 57 inpatients with SSD underwent cerebrospinal fluid (CSF) and blood analyses as well as comprehensive clinical assessments. In a subgroup of 28 participants structural magnetic resonance imaging (MRI) was performed. We developed a BCB dysfunction score, employing principal component analysis of CSF/serum albumin, CSF/serum IgG ratios and total protein levels in CSF, with higher values indicating stronger abnormalities. We calculated multiple regression models to explore the associations between BCB integrity and cardiometabolic, inflammatory, brain morphometric, and clinical measures respectively. BCB dysfunction score was negatively associated with high-density lipoprotein cholesterol and positively associated with total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Furthermore, we observed a trend towards a positive association between BCB dysfunction score and treatment resistance that did not survive multiple testing correction. We did not find significant associations between the BCB composite score and any other assessed cardiometabolic, inflammatory or cerebroventricular measures. These findings suggest that BCB integrity is associated with dyslipidemia in SSD, highlighting the interplay between cardiometabolic risk factors and brain health in SSD. Addressing cardiometabolic health in individuals with SSD might thus have implications beyond physical health, potentially influencing the integrity of the BCB and, consequently, clinical trajectories.
{"title":"Relationship between blood-cerebrospinal fluid barrier integrity, cardiometabolic and inflammatory factors in schizophrenia-spectrum disorders","authors":"Vladislav Yakimov, Iris Jaeger, Lukas Roell, Emanuel Boudriot, Verena Meisinger, Mattia Campana, Lenka Krcmar, Sean Halstead, Nicola Warren, Dan Siskind, Isabel Maurus, Alkomiet Hasan, Peter Falkai, Andrea Schmitt, Florian J. Raabe, Daniel Keeser, CDP Working Group, Elias Wagner, Joanna Moussiopoulou","doi":"10.1101/2024.09.17.24313817","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313817","url":null,"abstract":"The blood-cerebrospinal fluid barrier (BCB) builds an integral interface between the central nervous system and the periphery and appears to be impaired in a substantial proportion of individuals with schizophrenia-spectrum disorders (SSD). Even though a disruption of the BCB is associated with higher symptom severity, factors linked to BCB disruption in SSDs have been minimally investigated. To address this gap, 57 inpatients with SSD underwent cerebrospinal fluid (CSF) and blood analyses as well as comprehensive clinical assessments. In a subgroup of 28 participants structural magnetic resonance imaging (MRI) was performed. We developed a BCB dysfunction score, employing principal component analysis of CSF/serum albumin, CSF/serum IgG ratios and total protein levels in CSF, with higher values indicating stronger abnormalities. We calculated multiple regression models to explore the associations between BCB integrity and cardiometabolic, inflammatory, brain morphometric, and clinical measures respectively.\u0000BCB dysfunction score was negatively associated with high-density lipoprotein cholesterol and positively associated with total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Furthermore, we observed a trend towards a positive association between BCB dysfunction score and treatment resistance that did not survive multiple testing correction. We did not find significant associations between the BCB composite score and any other assessed cardiometabolic, inflammatory or cerebroventricular measures. These findings suggest that BCB integrity is associated with dyslipidemia in SSD, highlighting the interplay between cardiometabolic risk factors and brain health in SSD. Addressing cardiometabolic health in individuals with SSD might thus have implications beyond physical health, potentially influencing the integrity of the BCB and, consequently, clinical trajectories.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265316","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}
Pub Date : 2024-09-18DOI: 10.1101/2024.09.17.24313844
Patricia Kipkemoi, Jeanne E. Savage, Joseph Gona, Kenneth Rimba, Martha Kombe, Paul Mwangi, Collins Kipkoech, Eunice Chepkemoi, Alfred Ngombo, Beatrice Mkubwa, Constance Rehema, Symon M. Kariuki, Danielle Posthuma, Kirsten A. Donald, Elise Robinson, Amina Abubakar, Charles R. Newton
Background Neurodevelopmental disorders (NDDs) are a group of conditions with their onset during the early developmental period and include conditions such as autism, intellectual disability and attention deficit hyperactivity disorder (ADHD). Occurrence of NDDs is thought to be determined by both genetic and environmental factors, but data on the role of environmental risk factors for NDD in Africa is limited. This study investigates environmental influences on NDDs in children from Kenya. This case-control study compared children with NDDs and typically developing children from two studies on the Kenyan coast that did not overlap. Methods and Findings We included 172 of the study participants from the Kilifi Autism Study and 151 from the NeuroDev Study who had a diagnosis of at least one NDD and 112 and 73 with no NDD diagnosis from each study, respectively. Potential risk factors were identified using unadjusted univariable analysis and adjusted multivariable logistic regression analysis. Univariable analysis in the Kilifi Autism Study sample revealed hypoxic-ischaemic encephalopathy conferred the largest odds ratio (OR) 10.52 (95%CI 4.04 – 27.41) for NDDs, followed by medical complications during pregnancy (gestational hypertension & diabetes, eclampsia, and maternal bleeding) OR: 3.17 (95%CI 1.61 – 6.23). In the NeuroDev study sample, labour and birth complications (OR: 7.30 (2.17 – 24.61)), neonatal jaundice (OR: 5.49 (95%CI 1.61 – 18.72)) and infection during pregnancy (OR: 5.31 (1.56 – 18.11)) conferred the largest risk associated with NDDs. In the adjusted analysis, seizures before age 3 years in the Kilifi Autism study and labour and birth complications in the NeuroDev study conferred the largest increased risk. Higher parity, the child being older and delivery at home were associated with a reduced risk for NDDs. Conclusion Recognition of important risk factors such as labour and birth complications could guide preventative interventions, developmental screening of at-risk children and monitoring progress. Further studies examining the aetiology of NDDs in population-based samples, including investigating the interaction between genetic and environmental factors, are needed.
{"title":"Socio-medical Factors Associated with Neurodevelopmental Disorders on the Kenyan Coast","authors":"Patricia Kipkemoi, Jeanne E. Savage, Joseph Gona, Kenneth Rimba, Martha Kombe, Paul Mwangi, Collins Kipkoech, Eunice Chepkemoi, Alfred Ngombo, Beatrice Mkubwa, Constance Rehema, Symon M. Kariuki, Danielle Posthuma, Kirsten A. Donald, Elise Robinson, Amina Abubakar, Charles R. Newton","doi":"10.1101/2024.09.17.24313844","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313844","url":null,"abstract":"Background\u0000Neurodevelopmental disorders (NDDs) are a group of conditions with their onset during the early developmental period and include conditions such as autism, intellectual disability and attention deficit hyperactivity disorder (ADHD). Occurrence of NDDs is thought to be determined by both genetic and environmental factors, but data on the role of environmental risk factors for NDD in Africa is limited. This study investigates environmental influences on NDDs in children from Kenya. This case-control study compared children with NDDs and typically developing children from two studies on the Kenyan coast that did not overlap. Methods and Findings\u0000We included 172 of the study participants from the Kilifi Autism Study and 151 from the NeuroDev Study who had a diagnosis of at least one NDD and 112 and 73 with no NDD diagnosis from each study, respectively. Potential risk factors were identified using unadjusted univariable analysis and adjusted multivariable logistic regression analysis. Univariable analysis in the Kilifi Autism Study sample revealed hypoxic-ischaemic encephalopathy conferred the largest odds ratio (OR) 10.52 (95%CI 4.04 – 27.41) for NDDs, followed by medical complications during pregnancy (gestational hypertension & diabetes, eclampsia, and maternal bleeding) OR: 3.17 (95%CI 1.61 – 6.23). In the NeuroDev study sample, labour and birth complications (OR: 7.30 (2.17 – 24.61)), neonatal jaundice (OR: 5.49 (95%CI 1.61 – 18.72)) and infection during pregnancy (OR: 5.31 (1.56 – 18.11)) conferred the largest risk associated with NDDs. In the adjusted analysis, seizures before age 3 years in the Kilifi Autism study and labour and birth complications in the NeuroDev study conferred the largest increased risk. Higher parity, the child being older and delivery at home were associated with a reduced risk for NDDs. Conclusion\u0000Recognition of important risk factors such as labour and birth complications could guide preventative interventions, developmental screening of at-risk children and monitoring progress. Further studies examining the aetiology of NDDs in population-based samples, including investigating the interaction between genetic and environmental factors, are needed.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265315","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}
Pub Date : 2024-09-17DOI: 10.1101/2024.09.15.24313713
Lu Wang, Yaira Z. Nunez, Henry Kranzler, Hang Zhou, Joel Gelernter
Opioid dependence (OD) is epidemic in the United States and it is associated with a variety of adverse health effects. Its estimated heritability is ~50%, and recent genome-wide association studies have identified more than a dozen common risk variants. However, there are no published studies of rare OD risk variants. In this study, we analyzed whole-exome sequencing data from the Yale-Penn cohort, comprising 2,100 participants of European ancestry (EUR; 1,321 OD cases) and 1,790 of African ancestry (AFR; 864 cases). A novel low-frequency variant (rs746301110) in the RUVBL2 gene was identified in EUR (p=6.59*10-10). Suggestive associations (p<1*10-5) were observed in TMCO3 in EUR, in NEIL2 and CFAP44 in AFR, and in FAM210B in the cross-ancestry meta-analysis. Gene-based collapsing tests identified SLC22A10, TMCO3, FAM90A1, DHX58, CHRND, GLDN, PLAT, H1-4, COL3A1, GPHB5 and QPCTL as top genes (p<1*10-4) with most associations attributable to rare variants and driven by the burden of predicted loss-of-function and missense variants. This study begins to fill the gap in our understanding of the genetic architecture of OD, providing insights into the contribution of rare coding variants and potential targets for future functional studies and drug development.
阿片类药物依赖（OD）在美国流行，并与多种不良健康影响相关。据估计，其遗传率约为 50%，最近的全基因组关联研究已经发现了十几种常见的风险变异。然而，目前还没有关于罕见 OD 风险变异的公开研究。在这项研究中，我们分析了来自耶鲁-宾夕法尼亚大学队列的全外显子组测序数据，其中包括 2100 名欧洲血统（EUR；1321 个 OD 病例）和 1790 名非洲血统（AFR；864 个病例）的参与者。在欧洲人中发现了 RUVBL2 基因中的一个新型低频变异体（rs746301110）（p=6.59*10-10）。在欧洲人中的TMCO3、非洲人中的NEIL2和CFAP44以及跨种系荟萃分析中的FAM210B中都观察到了提示性关联（p<1*10-5）。基于基因的折叠测试发现，SLC22A10、TMCO3、FAM90A1、DHX58、CHRND、GLDN、PLAT、H1-4、COL3A1、GPHB5和QPCTL是最重要的基因（p<1*10-4），其中大多数关联归因于罕见变异，并由预测的功能缺失和错义变异所驱动。这项研究开始填补我们对 OD 遗传结构认识上的空白，为罕见编码变异的贡献以及未来功能研究和药物开发的潜在靶点提供了见解。
{"title":"Whole-exome sequencing study of opioid dependence offers novel insights into the contributions of exome variants","authors":"Lu Wang, Yaira Z. Nunez, Henry Kranzler, Hang Zhou, Joel Gelernter","doi":"10.1101/2024.09.15.24313713","DOIUrl":"https://doi.org/10.1101/2024.09.15.24313713","url":null,"abstract":"Opioid dependence (OD) is epidemic in the United States and it is associated with a variety of adverse health effects. Its estimated heritability is ~50%, and recent genome-wide association studies have identified more than a dozen common risk variants. However, there are no published studies of rare OD risk variants. In this study, we analyzed whole-exome sequencing data from the Yale-Penn cohort, comprising 2,100 participants of European ancestry (EUR; 1,321 OD cases) and 1,790 of African ancestry (AFR; 864 cases). A novel low-frequency variant (rs746301110) in the RUVBL2 gene was identified in EUR (p=6.59*10-10). Suggestive associations (p<1*10-5) were observed in TMCO3 in EUR, in NEIL2 and CFAP44 in AFR, and in FAM210B in the cross-ancestry meta-analysis. Gene-based collapsing tests identified SLC22A10, TMCO3, FAM90A1, DHX58, CHRND, GLDN, PLAT, H1-4, COL3A1, GPHB5 and QPCTL as top genes (p<1*10-4) with most associations attributable to rare variants and driven by the burden of predicted loss-of-function and missense variants. This study begins to fill the gap in our understanding of the genetic architecture of OD, providing insights into the contribution of rare coding variants and potential targets for future functional studies and drug development.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"119 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265317","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}
Pub Date : 2024-09-16DOI: 10.1101/2024.09.15.24313329
Dashiell D Sacks, Yiyi Wang, Asja Abron, Kaitlin M Mulligan, Caroline M Kelsey, Wanze Xie, Charles A Nelson, Michelle Bosquet Enlow
Background: Anxiety and depression are highly prevalent in youth and can cause significant distress and functional impairment. The presence of maternal anxiety and depression are well-established risk factors for child internalizing psychopathology, yet the responsible mechanisms linking the two remain unclear. Methods: We examined the potential mediating and moderating roles of EEG frontal alpha asymmetry (FAA) in the intergenerational transmission of internalizing symptoms in a longitudinal sample of N = 323 mother-child dyads. Self-report maternal internalizing symptoms were evaluated at child age 3 years and 5 years, child EEG at 5 years, and parent-report child internalizing symptoms at age 7 years. Mediation was evaluated via bootstrapped (N = 5000) confidence intervals. Results: We found significant associations among maternal internalizing (anxiety, depressive) symptoms at child ages 3 and 5 years, child FAA at age 5 years, and child internalizing symptoms at age 7 years. There was a significant mediation effect, whereby greater maternal anxiety and depressive symptoms at age 3 years were significantly associated with greater relative right FAA in children at age 5 years, which, in turn, was significantly associated with greater child internalizing symptoms at age 7 years (ps<.001). There was no moderating effect of FAA on the association between maternal internalizing symptoms at age 5 years and child internalizing symptoms at age 7 years. Conclusions: Greater right frontal asymmetry may be a neurophysiological mechanism that mediates the intergenerational transmission of internalizing symptoms.
{"title":"EEG frontal alpha asymmetry mediates the association between maternal and child internalizing symptoms in childhood","authors":"Dashiell D Sacks, Yiyi Wang, Asja Abron, Kaitlin M Mulligan, Caroline M Kelsey, Wanze Xie, Charles A Nelson, Michelle Bosquet Enlow","doi":"10.1101/2024.09.15.24313329","DOIUrl":"https://doi.org/10.1101/2024.09.15.24313329","url":null,"abstract":"Background: Anxiety and depression are highly prevalent in youth and can cause significant distress and functional impairment. The presence of maternal anxiety and depression are well-established risk factors for child internalizing psychopathology, yet the responsible mechanisms linking the two remain unclear. Methods: We examined the potential mediating and moderating roles of EEG frontal alpha asymmetry (FAA) in the intergenerational transmission of internalizing symptoms in a longitudinal sample of N = 323 mother-child dyads. Self-report maternal internalizing symptoms were evaluated at child age 3 years and 5 years, child EEG at 5 years, and parent-report child internalizing symptoms at age 7 years. Mediation was evaluated via bootstrapped (N = 5000) confidence intervals.\u0000Results: We found significant associations among maternal internalizing (anxiety, depressive) symptoms at child ages 3 and 5 years, child FAA at age 5 years, and child internalizing symptoms at age 7 years. There was a significant mediation effect, whereby greater maternal anxiety and depressive symptoms at age 3 years were significantly associated with greater relative right FAA in children at age 5 years, which, in turn, was significantly associated with greater child internalizing symptoms at age 7 years (ps<.001). There was no moderating effect of FAA on the association between maternal internalizing symptoms at age 5 years and child internalizing symptoms at age 7 years.\u0000Conclusions: Greater right frontal asymmetry may be a neurophysiological mechanism that mediates the intergenerational transmission of internalizing symptoms.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269412","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}
Pub Date : 2024-09-16DOI: 10.1101/2024.09.14.24313641
Nikki Horne Stricker, Ryan D Frank, Elizabeth A Boots, Winnie Z Fan, Teresa J Christianson, Walter K Kremers, John L Stricker, Mary M Machulda, Julie A Fields, John A Lucas, Jason Hassenstab, Paula A Aduen, Gregory S Day, Neill R Graff-Radford, Clifford R Jack, Jonathan Graff-Radford, Ronald C Petersen
Objective: Few normative data for unsupervised, remotely-administered computerized cognitive measures are available. We examined variables to include in normative models for Mayo Test Drive (a multi-device remote cognitive assessment platform) measures, developed normative data, and validated the norms. Method: 1240 Cognitively Unimpaired (CU) adults ages 32-100-years (96% white) from the Mayo Clinic Study of Aging and Mayo Alzheimer Disease Research Center with Clinical Dementia Rating of 0 were included. We converted raw scores to normalized scaled scores and derived regression-based normative data adjusting for age, age2, sex and education (base model); alternative norms are also provided (age+age2+sex; age+age2). We assessed additional terms using an a priori cut-off of 1% variance improvement above the base model. We examined low test performance rates (<-1 standard deviation) in independent validation samples (n=167 CU, n=64 mild cognitive impairment (MCI), n=14 dementia). Rates were significantly different when 95% confidence intervals (CI) did not include the expected 14.7% base rate. Results: No model terms met the a priori cut-off beyond the base model, including device type, response input source (e.g., mouse, etc.) or session interference. Norms showed expected low performance rates in CU and greater rates of low performance in MCI and dementia in independent validation samples. Conclusion: Typical normative models appear appropriate for remote self-administered MTD measures and are sensitive to cognitive impairment. Device type and response input source did not explain enough variance for inclusion in normative models but are important for individual-level interpretation. Future work will increase inclusion of individuals from under-represented groups.
{"title":"Mayo Normative Studies: regression-based normative data for remote self-administration of the Stricker Learning Span, Symbols Test and Mayo Test Drive Screening Battery Composite and validation in individuals with Mild Cognitive Impairment and dementia","authors":"Nikki Horne Stricker, Ryan D Frank, Elizabeth A Boots, Winnie Z Fan, Teresa J Christianson, Walter K Kremers, John L Stricker, Mary M Machulda, Julie A Fields, John A Lucas, Jason Hassenstab, Paula A Aduen, Gregory S Day, Neill R Graff-Radford, Clifford R Jack, Jonathan Graff-Radford, Ronald C Petersen","doi":"10.1101/2024.09.14.24313641","DOIUrl":"https://doi.org/10.1101/2024.09.14.24313641","url":null,"abstract":"Objective: Few normative data for unsupervised, remotely-administered computerized cognitive measures are available. We examined variables to include in normative models for Mayo Test Drive (a multi-device remote cognitive assessment platform) measures, developed normative data, and validated the norms. Method: 1240 Cognitively Unimpaired (CU) adults ages 32-100-years (96% white) from the Mayo Clinic Study of Aging and Mayo Alzheimer Disease Research Center with Clinical Dementia Rating of 0 were included. We converted raw scores to normalized scaled scores and derived regression-based normative data adjusting for age, age2, sex and education (base model); alternative norms are also provided (age+age2+sex; age+age2). We assessed additional terms using an a priori cut-off of 1% variance improvement above the base model. We examined low test performance rates (<-1 standard deviation) in independent validation samples (n=167 CU, n=64 mild cognitive impairment (MCI), n=14 dementia). Rates were significantly different when 95% confidence intervals (CI) did not include the expected 14.7% base rate. Results: No model terms met the a priori cut-off beyond the base model, including device type, response input source (e.g., mouse, etc.) or session interference. Norms showed expected low performance rates in CU and greater rates of low performance in MCI and dementia in independent validation samples.\u0000Conclusion: Typical normative models appear appropriate for remote self-administered MTD measures and are sensitive to cognitive impairment. Device type and response input source did not explain enough variance for inclusion in normative models but are important for individual-level interpretation. Future work will increase inclusion of individuals from under-represented groups.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269411","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}
Pub Date : 2024-09-14DOI: 10.1101/2024.09.13.24313611
Danylyna Shpakivska-Bilan, Gianluca Susi, David Zhou, Jesus Cabrera Alvarez, Blanca P Carvajal, Ernesto Pereda, Maria Eugenia Lopez, Ricardo Bruna, Fernando Maestu, Stephanie R Jones
A typical pattern observed in M/EEG recordings of Mild Cognitive Impairment (MCI) patients progressing to Alzheimer's disease is a continuous slowing of brain oscillatory activity. Definitions of oscillatory slowing are imprecise, as they average across time and frequency bands, masking the finer structure in the signal and potential reliable biomarkers of the disease. Recent studies show that high averaged band power can result from transient increases in power, termed 'events' or 'bursts'. To better understand MEG oscillatory slowing in AD progression, we analyzed features of high-power oscillatory events and their relationship to cognitive decline. MEG resting-state oscillations were registered in age-matched patients with MCI who later convert (CONV, N=41) or do not convert (NOCONV, N=44) to AD, in a period of 2.5 years. To distinguish future CONV from NOCONV, we characterised the rate, duration, frequency span and power of transient high-power events in the alpha and beta band in anterior cingulate (ACC) and precuneus (PC). Results revealed event-like patterns in resting-state power in both the alpha and beta-bands, however only beta-band features were predictive of conversion to AD, particularly in PC. Specifically, compared to NOCONV, CONV had a lower number of beta events, along with lower power events and a trend toward shorter duration events in PC (p < 0.05). Beta event durations were also significantly shorter in ACC (p < 0.01). Further, this reduced expression of beta events in CONV predicted lower values of mean relative beta power, increased probability of AD conversion, and poorer cognitive performance. Our work paves the way for reinterpreting M/EEG slowing and examining beta event features as a new biomarker along the AD continuum, and a potential link to theories of inhibitory cognitive control in neurodegeneration. These results may bring us closer to understanding the neural mechanisms of the disease that help guide new therapies.
从轻度认知功能障碍（MCI）患者的 M/EEG 记录中观察到的一种典型模式是大脑振荡活动持续减慢。振荡减慢的定义并不精确，因为它们是时间和频带的平均值，掩盖了信号中的精细结构和疾病的潜在可靠生物标志物。最近的研究表明，高平均频带功率可能来自功率的瞬时增加，称为 "事件 "或 "爆发"。为了更好地了解 AD 进展过程中的 MEG 振荡减慢，我们分析了高功率振荡事件的特征及其与认知能力下降之间的关系。我们对年龄匹配的 MCI 患者的 MEG 静息态振荡进行了登记，这些患者在 2.5 年的时间内转为（CONV，41 人）或未转为（NOCONV，44 人）AD。为了区分未来的CONV和NOCONV，我们对前扣带回（ACC）和楔前区（PC）α和β波段瞬时高功率事件的速率、持续时间、频率跨度和功率进行了表征。结果显示，阿尔法和贝塔波段的静息态功率都有类似事件的模式，但只有贝塔波段的特征可预测向注意力缺失症的转化，尤其是在PC中。具体来说，与 NOCONV 相比，PC 中 CONV 的 beta 事件数量较少，同时事件功率较低，事件持续时间呈缩短趋势（p < 0.05）。ACC 中的β事件持续时间也明显较短（p < 0.01）。此外，CONV 中贝塔事件表达的减少预示着平均相对贝塔功率值的降低、AD 转换概率的增加以及认知能力的下降。我们的研究为重新解释 M/EEG 减慢和检查 beta 事件特征铺平了道路，将其作为 AD 连续体的一种新的生物标志物，并与神经变性中的抑制性认知控制理论建立了潜在联系。这些结果可能会使我们更接近于了解该疾病的神经机制，从而有助于指导新的疗法。
{"title":"High power transient 15-29Hz beta event features as early biomarkers of Alzheimer's Disease conversion: a MEG study","authors":"Danylyna Shpakivska-Bilan, Gianluca Susi, David Zhou, Jesus Cabrera Alvarez, Blanca P Carvajal, Ernesto Pereda, Maria Eugenia Lopez, Ricardo Bruna, Fernando Maestu, Stephanie R Jones","doi":"10.1101/2024.09.13.24313611","DOIUrl":"https://doi.org/10.1101/2024.09.13.24313611","url":null,"abstract":"A typical pattern observed in M/EEG recordings of Mild Cognitive Impairment (MCI) patients progressing to Alzheimer's disease is a continuous slowing of brain oscillatory activity. Definitions of oscillatory slowing are imprecise, as they average across time and frequency bands, masking the finer structure in the signal and potential reliable biomarkers of the disease. Recent studies show that high averaged band power can result from transient increases in power, termed 'events' or 'bursts'. To better understand MEG oscillatory slowing in AD progression, we analyzed features of high-power oscillatory events and their relationship to cognitive decline.\u0000MEG resting-state oscillations were registered in age-matched patients with MCI who later convert (CONV, N=41) or do not convert (NOCONV, N=44) to AD, in a period of 2.5 years. To distinguish future CONV from NOCONV, we characterised the rate, duration, frequency span and power of transient high-power events in the alpha and beta band in anterior cingulate (ACC) and precuneus (PC). Results revealed event-like patterns in resting-state power in both the alpha and beta-bands, however only beta-band features were predictive of conversion to AD, particularly in PC. Specifically, compared to NOCONV, CONV had a lower number of beta events, along with lower power events and a trend toward shorter duration events in PC (p < 0.05). Beta event durations were also significantly shorter in ACC (p < 0.01). Further, this reduced expression of beta events in CONV predicted lower values of mean relative beta power, increased probability of AD conversion, and poorer cognitive performance. Our work paves the way for reinterpreting M/EEG slowing and examining beta event features as a new biomarker along the AD continuum, and a potential link to theories of inhibitory cognitive control in neurodegeneration. These results may bring us closer to understanding the neural mechanisms of the disease that help guide new therapies.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265275","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}
Pregnancy is a psycho-neuro-endocrinological transition phase in which a plethora of hormone levels rise substantially, modulating socioemotional functions, brain structures, and networks and thus presenting a window of vulnerability for mental health. A transdiagnostic factor for psychopathology is emotion regulation, which is influenced by sex hormones, such as estradiol (E2), across the menstrual cycle on the behavioral and neural level. Whether this is also the case in the antepartum period remains unknown. For the first time, behavioral and neural emotion regulation were investigated in healthy primiparous pregnant females with extremely high E2 levels during the second trimester (N = 15) using a functional magnetic resonance imaging (fMRI) paradigm. Results were compared with naturally-cycling females with high E2 levels (after E2-administration, N = 16) and low E2 levels (early follicular phase, N = 16). Although pregnant females reported the lowest trait use of cognitive reappraisal, all females successfully regulated their emotions by applying cognitive reappraisal in the scanner. On the neural level, all females had increased activity in the left middle frontal gyrus during downregulation of negative emotions. Pregnant females showed no significant differences in functional connectivity (psychophysiological interaction, resting-state) related to emotion regulation compared to the nonpregnant group. However, group differences emerged for amygdala activation. In pregnant females, increased amygdala activity predicted reduced regulation success and was positively associated with depression scores. This first fMRI study during pregnancy indicates that depression scores are reflected in heightened amygdala activity already observable in the antepartum period. Thus, through its association with reduced regulation success, increased amygdala activity suggests a neural risk marker for peripartum mental health. Future research needs to investigate emotion regulation in pregnant and postpartum women to further understand pregnancy-related changes and associations of mood, emotional and neural functions. Eventually, this will allow enhanced identification, prevention, and treatment of peri- and postpartum mental ill-health.
{"title":"Neural emotion regulation during pregnancy - a fMRI study investigating a transdiagnostic mental health factor in healthy first-time pregnant women","authors":"Franziska Weinmar, Lydia Kogler, Elisa Rehbein, Carmen Morawetz, Inger Sundstroem-Poromaa, Alkistis Skalkidou, Birgit Derntl","doi":"10.1101/2024.09.13.24313410","DOIUrl":"https://doi.org/10.1101/2024.09.13.24313410","url":null,"abstract":"Pregnancy is a psycho-neuro-endocrinological transition phase in which a plethora of hormone levels rise substantially, modulating socioemotional functions, brain structures, and networks and thus presenting a window of vulnerability for mental health. A transdiagnostic factor for psychopathology is emotion regulation, which is influenced by sex hormones, such as estradiol (E2), across the menstrual cycle on the behavioral and neural level. Whether this is also the case in the antepartum period remains unknown. For the first time, behavioral and neural emotion regulation were investigated in healthy primiparous pregnant females with extremely high E2 levels during the second trimester (N = 15) using a functional magnetic resonance imaging (fMRI) paradigm. Results were compared with naturally-cycling females with high E2 levels (after E2-administration, N = 16) and low E2 levels (early follicular phase, N = 16). Although pregnant females reported the lowest trait use of cognitive reappraisal, all females successfully regulated their emotions by applying cognitive reappraisal in the scanner. On the neural level, all females had increased activity in the left middle frontal gyrus during downregulation of negative emotions. Pregnant females showed no significant differences in functional connectivity (psychophysiological interaction, resting-state) related to emotion regulation compared to the nonpregnant group. However, group differences emerged for amygdala activation. In pregnant females, increased amygdala activity predicted reduced regulation success and was positively associated with depression scores. This first fMRI study during pregnancy indicates that depression scores are reflected in heightened amygdala activity already observable in the antepartum period. Thus, through its association with reduced regulation success, increased amygdala activity suggests a neural risk marker for peripartum mental health. Future research needs to investigate emotion regulation in pregnant and postpartum women to further understand pregnancy-related changes and associations of mood, emotional and neural functions. Eventually, this will allow enhanced identification, prevention, and treatment of peri- and postpartum mental ill-health.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265433","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}
Pub Date : 2024-09-14DOI: 10.1101/2024.09.12.24313575
Roy H Perlis, Ata Uslu, Sergio A. Barroilhet, Paul A. Vohringer, Mauricio Santillana, Matthew A. Baum, James N. Druckman, Katherine Ognyanova, David Lazer
Background: While the NIMH Research Domain Criteria framework stresses understanding how neuropsychiatric phenotypes vary across populations, little is known outside of small clinical cohorts about conspiratorial thoughts as an aspect of cognition. Methods: We conducted a 50-state non-probability internet survey conducted in 6 waves between October 6, 2022 and January 29, 2024, with respondents age 18 and older. Respondents completed the American Conspiratorial Thinking Scale (ACTS) and the 9-item Patient Health Questionnaire (PHQ-9). Survey-weighted regression models were used to examine sociodemographic and clinical associations with ACTS score, and associations with vaccination status. Results: Across the 6 survey waves, there were 123,781 unique individuals. After reweighting, a total of 78.6% of respondents somewhat or strongly agreed with at least one conspiratorial idea; 19.0% agreed with all four of them. More conspiratorial thoughts were reported among those age 25 - 54, males, individuals who finished high school but did not start or complete college, those with household income between $25,000 and $50,000 per year, and those who reside in rural areas, as well as those with greater levels of depressive symptoms. Endorsing more conspiratorial thoughts was associated with a significantly lower likelihood of being vaccinated against COVID-19. Discussion: A substantial proportion of US adults endorsed at least some conspiratorial thinking, which varied widely across population subgroups. The extent of correlation with non-vaccination suggests the importance of considering such thinking in designing public health strategies.
{"title":"Conspiratorial thinking in a 50-state survey of American adults","authors":"Roy H Perlis, Ata Uslu, Sergio A. Barroilhet, Paul A. Vohringer, Mauricio Santillana, Matthew A. Baum, James N. Druckman, Katherine Ognyanova, David Lazer","doi":"10.1101/2024.09.12.24313575","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313575","url":null,"abstract":"Background: While the NIMH Research Domain Criteria framework stresses understanding how neuropsychiatric phenotypes vary across populations, little is known outside of small clinical cohorts about conspiratorial thoughts as an aspect of cognition. Methods: We conducted a 50-state non-probability internet survey conducted in 6 waves between October 6, 2022 and January 29, 2024, with respondents age 18 and older. Respondents completed the American Conspiratorial Thinking Scale (ACTS) and the 9-item Patient Health Questionnaire (PHQ-9). Survey-weighted regression models were used to examine sociodemographic and clinical associations with ACTS score, and associations with vaccination status.\u0000Results: Across the 6 survey waves, there were 123,781 unique individuals. After reweighting, a total of 78.6% of respondents somewhat or strongly agreed with at least one conspiratorial idea; 19.0% agreed with all four of them. More conspiratorial thoughts were reported among those age 25 - 54, males, individuals who finished high school but did not start or complete college, those with household income between $25,000 and $50,000 per year, and those who reside in rural areas, as well as those with greater levels of depressive symptoms. Endorsing more conspiratorial thoughts was associated with a significantly lower likelihood of being vaccinated against COVID-19.\u0000Discussion: A substantial proportion of US adults endorsed at least some conspiratorial thinking, which varied widely across population subgroups. The extent of correlation with non-vaccination suggests the importance of considering such thinking in designing public health strategies.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265274","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}
Pub Date : 2024-09-14DOI: 10.1101/2024.09.13.24313599
Mengqi Niu, Jing Li, Victoria Sarafian, Michael Maes
Background: Fibromyalgia (FM) is a chronic disorder characterized by widespread pain and immune dysregulation. Emerging evidence suggests that gut microbiota and inflammatory proteins may contribute to the development of FM. Objective: The aim of this study was to investigate the causal relationships between gut microbiota, inflammatory proteins (cytokines/chemokines), and FM using bidirectional Mendelian randomization (MR) and meta-analysis approaches. Methods: MR analyses were conducted using genetic data from European populations, employing methods such as MR-IVW, MR-Egger, and MR-weighted median. Reverse MR was also performed, with FM treated as the exposure. A meta-analysis was conducted to consolidate the findings. Results: Ruminococcus gauvreauii was identified as a risk factor for FM, while Enterorhabdus, Parabacteroides, Butyricicoccus, and Prevotella 9 were found to be protective. Five inflammatory proteins C-X-C motif chemokine 5 (CXCL5), S100-A12, Leukemia inhibitory factor receptor (LIFR), Monocyte chemoattractant protein 2 (MCP-2/CCL8), and Tumor necrosis factor (TNF-α) exhibited protective associations, while Natural killer cell receptor 2B4 (NKCR-2B4/CD244) and Interleukin-12 subunit beta (IL-12β) were associated with an increased risk of FM. Conclusion: This study highlights the role of gut microbiota and inflammatory proteins (cytokines/chemokines) in the pathogenesis of FM. Through Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the findings suggest their involvement in immune regulation, inflammatory responses, and viral pathways. These findings provide new insights into potential therapeutic targets for modulating gut health and immune responses, opening new avenues for future research and clinical interventions.
背景：纤维肌痛（FM）是一种以广泛性疼痛和免疫调节失调为特征的慢性疾病。新出现的证据表明，肠道微生物群和炎性蛋白可能会导致 FM 的发生：本研究旨在利用双向孟德尔随机化（MR）和荟萃分析方法研究肠道微生物群、炎症蛋白（细胞因子/趋化因子）和 FM 之间的因果关系：采用 MR-IVW、MR-Egger 和 MR 加权中位数等方法，利用欧洲人群的遗传数据进行 MR 分析。此外，还进行了反向 MR 分析，将 FM 视为暴露。为了巩固研究结果，还进行了荟萃分析：结果：高乌头反刍球菌（Ruminococcus gauvreauii）被确定为 FM 的危险因素，而肠杆菌（Enterorhabdus）、副乳杆菌（Parabacteroides）、丁酸球菌（Butyricicoccus）和前驱菌 9（Prevotella 9）则具有保护作用。五种炎症蛋白C-X-C motif趋化因子5（CXCL5）、S100-A12、白血病抑制因子受体（LIFR）、单核细胞趋化蛋白2（MCP-2/CCL8）和肿瘤坏死因子（TNF-α）具有保护作用，而自然杀伤细胞受体2B4（NKCR-2B4/CD244）和白细胞介素-12亚基β（IL-12β）则与FM风险增加有关：本研究强调了肠道微生物群和炎症蛋白（细胞因子/趋化因子）在 FM 发病机制中的作用。通过基因本体（GO）功能富集和京都基因和基因组百科全书（KEGG）通路分析，研究结果表明它们参与了免疫调节、炎症反应和病毒通路。这些发现为调节肠道健康和免疫反应的潜在治疗靶点提供了新的见解，为未来的研究和临床干预开辟了新的途径。
{"title":"A multi-omics bidirectional mendelian randomization study and meta-analysis on the causal relationship between gut microbiota, inflammatory proteins, and fibromyalgia.","authors":"Mengqi Niu, Jing Li, Victoria Sarafian, Michael Maes","doi":"10.1101/2024.09.13.24313599","DOIUrl":"https://doi.org/10.1101/2024.09.13.24313599","url":null,"abstract":"Background: Fibromyalgia (FM) is a chronic disorder characterized by widespread pain and immune dysregulation. Emerging evidence suggests that gut microbiota and inflammatory proteins may contribute to the development of FM.\u0000Objective: The aim of this study was to investigate the causal relationships between gut microbiota, inflammatory proteins (cytokines/chemokines), and FM using bidirectional Mendelian randomization (MR) and meta-analysis approaches.\u0000Methods: MR analyses were conducted using genetic data from European populations, employing methods such as MR-IVW, MR-Egger, and MR-weighted median. Reverse MR was also performed, with FM treated as the exposure. A meta-analysis was conducted to consolidate the findings.\u0000Results: Ruminococcus gauvreauii was identified as a risk factor for FM, while Enterorhabdus, Parabacteroides, Butyricicoccus, and Prevotella 9 were found to be protective. Five inflammatory proteins C-X-C motif chemokine 5 (CXCL5), S100-A12, Leukemia inhibitory factor receptor (LIFR), Monocyte chemoattractant protein 2 (MCP-2/CCL8), and Tumor necrosis factor (TNF-α) exhibited protective associations, while Natural killer cell receptor 2B4 (NKCR-2B4/CD244) and Interleukin-12 subunit beta (IL-12β) were associated with an increased risk of FM.\u0000Conclusion: This study highlights the role of gut microbiota and inflammatory proteins (cytokines/chemokines) in the pathogenesis of FM. Through Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the findings suggest their involvement in immune regulation, inflammatory responses, and viral pathways. These findings provide new insights into potential therapeutic targets for modulating gut health and immune responses, opening new avenues for future research and clinical interventions.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265273","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}
Pub Date : 2024-09-13DOI: 10.1101/2024.09.12.24313544
Kristin Rodney-Wolf, Julian Schmitz
In the context of multiple global crises, including the COVID-19 pandemic, climate change, and global conflicts, children and adolescents worldwide are experiencing heightened psychological stress. As the foundation for lifelong mental health is established during childhood and adolescence, early prevention and treatment of mental health problems, such as through psychotherapy, are crucial. In Germany, current outpatient psychotherapeutic care capacities appear inadequate, while systematic evaluations of the care situation are lacking. This study investigates the state of statutory health insurance-funded outpatient psychotherapeutic care for children and adolescents in Germany and evaluates various methodological approaches for its assessment. We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Publications from January 2018 to December 2023 were sourced from PubPsych, PubMed, APA PsycInfo, Google Scholar, and ProQuest. Included studies reported quantitative primary data on the mental health of community samples of children and adolescents in Germany or their outpatient psychotherapeutic care. We included 41 publications comprising epidemiological studies, administrative data, and psychotherapist and patient reports. A lack of systematic and standardized research approaches resulted in significant variance in data. Nonetheless, qualitative analysis revealed that approximately one four children and adolescents in Germany is affected by mental health problems, while one in six to seven children and adolescents requires psychotherapeutic treatment. Yet, only up to one in fifty receives guideline-based psychotherapy. Most requests for initial psychotherapeutic consultations are unmet, with waiting times for guideline-based psychotherapy exceeding six months for at least half of the patients. Overall, our findings suggest that outpatient psychotherapeutic care for children and adolescents in Germany is still insufficient. They advocate for a systematic, multimodal, and longitudinal assessment of statutory health insurance-funded outpatient psychotherapeutic care, along with an expansion of treatment capacities to enhance access for children and adolescents in Germany.
{"title":"Scoping Review: Outpatient Psychotherapeutic Care for Children and Adolescents in Germany - Status Quo and Challenges in Assessment","authors":"Kristin Rodney-Wolf, Julian Schmitz","doi":"10.1101/2024.09.12.24313544","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313544","url":null,"abstract":"In the context of multiple global crises, including the COVID-19 pandemic, climate change, and global conflicts, children and adolescents worldwide are experiencing heightened psychological stress. As the foundation for lifelong mental health is established during childhood and adolescence, early prevention and treatment of mental health problems, such as through psychotherapy, are crucial. In Germany, current outpatient psychotherapeutic care capacities appear inadequate, while systematic evaluations of the care situation are lacking. This study investigates the state of statutory health insurance-funded outpatient psychotherapeutic care for children and adolescents in Germany and evaluates various methodological approaches for its assessment. We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Publications from January 2018 to December 2023 were sourced from PubPsych, PubMed, APA PsycInfo, Google Scholar, and ProQuest. Included studies reported quantitative primary data on the mental health of community samples of children and adolescents in Germany or their outpatient psychotherapeutic care. We included 41 publications comprising epidemiological studies, administrative data, and psychotherapist and patient reports. A lack of systematic and standardized research approaches resulted in significant variance in data. Nonetheless, qualitative analysis revealed that approximately one four children and adolescents in Germany is affected by mental health problems, while one in six to seven children and adolescents requires psychotherapeutic treatment. Yet, only up to one in fifty receives guideline-based psychotherapy. Most requests for initial psychotherapeutic consultations are unmet, with waiting times for guideline-based psychotherapy exceeding six months for at least half of the patients. Overall, our findings suggest that outpatient psychotherapeutic care for children and adolescents in Germany is still insufficient. They advocate for a systematic, multimodal, and longitudinal assessment of statutory health insurance-funded outpatient psychotherapeutic care, along with an expansion of treatment capacities to enhance access for children and adolescents in Germany.","PeriodicalId":501388,"journal":{"name":"medRxiv - Psychiatry and Clinical Psychology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265427","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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