bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling associations between neurocognition and functional course in young people with emerging mental disorders: a longitudinal cohort study
Authors: Crouse Jacob J. , Chitty Kate M. , Iorfino Frank , Carpenter Joanne S. , White Django , Nichles Alissa , Zmicerevska Natalia , Guastella Adam J. , Scott Elizabeth M. , Lee Rico S. C. , Naismith Sharon L. , Scott Jan , Hermens Daniel F. , Hickie Ian B. 
Published: February 2020

AbstractNeurocognitive impairment is commonly associated with functional disability in established depressive, bipolar and psychotic disorders. However, little is known about the longer-term functional implications of these impairments in early phase transdiagnostic cohorts. We aimed to examine associations between neurocognition and functioning at baseline and over time. We used mixed effects models to investigate associations between neurocognitive test scores and longitudinal social and occupational functioning (“Social and Occupational Functioning Assessment Scale”) at 1–7 timepoints over five-years in 767 individuals accessing youth mental health services. Analyses were adjusted for age, sex, premorbid IQ, and symptom severity. Lower baseline functioning was associated with male sex (coefficient −3.78, 95% CI −5.22 to −2.34 p < 0.001), poorer verbal memory (coefficient 0.90, 95% CI 0.42 to 1.38, p < 0.001), more severe depressive (coefficient −0.28, 95% CI −0.41 to −0.15, p < 0.001), negative (coefficient −0.49, 95% CI −0.74 to −0.25, p < 0.001), and positive symptoms (coefficient −0.25, 95% CI −0.41 to −0.09, p = 0.002) and lower premorbid IQ (coefficient 0.13, 95% CI 0.07 to 0.19, p < 0.001). The rate of change in functioning over time varied among patients depending on their sex (male; coefficient 0.73, 95% CI 0.49 to 0.98, p < 0.001) and baseline level of cognitive flexibility (coefficient 0.14, 95% CI 0.06 to 0.22, p < 0.001), such that patients with the lowest scores had the least improvement in functioning. Impaired cognitive flexibility is common and may represent a meaningful and transdiagnostic target for cognitive remediation in youth mental health settings. Future studies should pilot cognitive remediation targeting cognitive flexibility while monitoring changes in functioning.
Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child
Authors: Qi Rongfeng , Luo Yifeng , Zhang Li , Weng Yifei , Surento Wesley , Li Lingjiang , Cao Zhihong , Lu Guang Ming 
Published: February 2020

AbstractLosing one’s only child is a major traumatic life event that may lead to posttraumatic stress disorder (PTSD); however, not all parents who experience this trauma develop PTSD. Genetic variants are associated with the risk of developing PTSD. Catechol-O-methyltransferase (COMT) rs4680 and brain-derived neurotrophic factor (BDNF) rs6265 are two most well-described single-nucleotide polymorphisms that relate to stress response; however, the neural mechanism underlying their effects on adults who lost an only child remains poorly understood. Two hundred and ten Han Chinese adults who had lost their only child (55 with PTSD and 155 without PTSD) were included in this imaging genetics study. Participants were divided into subgroups according to their COMT rs4680 and BDNF rs6265 genotypes. Degree Centrality (DC)—a resting-state fMRI index reflecting the brain network communication—was compared with a three-way (PTSD diagnosis, COMT, and BDNF polymorphisms) analysis of covariance. Diagnosis state had a significant effect on DC in bilateral inferior parietal lobules and right middle frontal gyrus (MFG), where PTSD adults showed weaker DC. BDNF × diagnosis interaction effect was found in the right MFG and hippocampus, and these two regions were reversely modulated. Also, there was a significant COMT × BDNF interaction effect in left cuneus, middle temporal gyrus, right inferior occipital gyrus, and bilateral putamen, independent of PTSD diagnosis. These findings suggest that the modulatory effect of BDNF polymorphism on the MFG and hippocampus may contribute to PTSD development in bereaved adults. Interactions of COMT × BDNF polymorphisms modulate some cortices and basal ganglia, irrespective of PTSD development.
High/low cortisol reactivity and food intake in people with obesity and healthy weight
Authors: Herhaus Benedict , Ullmann Enrico , Chrousos George , Petrowski Katja 
Published: February 2020

AbstractIncreased food intake, termed “comfort eating”, is a pathologic coping mechanism in chronic stress. Cortisol reactivity under stress is a potent predictor of stress-induced eating behavior affecting the body mass index (BMI). However, cortisol reactivity and food intake under stress in people with obesity has not been evaluated. The aim of this study was to investigate the effect of high/low cortisol reactivity on food intake in people with obesity and healthy weight test controls, following standardized stress induction and a resting condition. Thirty-six men and women with obesity (BMI: 33.00 ± 3.23 kg/m²), as well as 36 age- and gender-matched healthy weight controls (BMI: 21.98 ± 1.81 kg/m²) were categorized into high cortisol reactors (HCR) and low cortisol reactors (LCR) in the Trier Social Stress Test (TSST). Following the TSST and a resting condition, the food intake of all participants was recorded in a standardized laboratory meal. Obese HCR demonstrated a significantly higher food intake than LCR (t (34) = −2.046, p ≤ 0.05). However, there were no significant differences between HCR and LCR in the healthy weight controls (p = 0.26). In addition, HCR of the people with obesity showed lower values in the emotion coping strategy of cognitive reappraisal than obese LCR (t (32) = 2.087, p ≤ 0.05). In conclusion, the magnitude of the cortisol reactivity to stress predicts stress-induced food intake in people with obesity, but not in the healthy weight controls. Limited use of cognitive reappraisal in emotion regulation in the obese HCR may be a marker of vulnerability to stress-induced eating.
Stress genomics revisited: gene co-expression analysis identifies molecular signatures associated with childhood adversity
Authors: Dieckmann Linda , Cole Steve , Kumsta Robert 
Published: February 2020

AbstractChildhood adversity is related to an increased risk for psychopathology in adulthood. Altered regulation of stress response systems, as well as the changes in stress-immune interplay have been suggested as potential mechanisms underlying these long-term effects. We have previously shown altered transcriptional responses to acute psychosocial stress in adults reporting the experience of childhood adversity. Here, we extend these analyses using a network approach. We performed a co-expression network analysis of genome-wide mRNA data derived from isolated monocytes, sampled 3 h after stress exposure from healthy adults, who experienced childhood adversity and a matched control group without adverse childhood experiences. Thirteen co-expression modules were identified, of which four modules were enriched for genes related to immune system function. Gene set enrichment analysis showed differential module activity between the early adversity and control group. In line with previous findings reporting a pro-inflammatory bias following childhood adversity, one module included genes associated with pro-inflammatory function (hub genes: IL6, TM4SF1, ADAMTS4, CYR61, CCDC3), more strongly expressed in the early adversity group. Another module downregulated in the early adversity group was related to platelet activation and wound healing (hub genes: GP9, CMTM5, TUBB1, GNG11, PF4), and resembled a co-expression module previously found over-expressed in post-traumatic stress disorder resilient soldiers. These discovery analysis results provide a system wide and more holistic understanding of gene expression programs associated with childhood adversity. Furthermore, identified hub genes can be used in directed hypothesis testing in future studies.
A polygenic predictor of treatment-resistant depression using whole exome sequencing and genome-wide genotyping
Authors: Fabbri Chiara , Kasper Siegfried , Kautzky Alexander , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Forloni Gianluigi , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Uher Rudolf , Lewis Cathryn M. , Serretti Alessandro 
Published: February 2020

AbstractTreatment-resistant depression (TRD) occurs in ~30% of patients with major depressive disorder (MDD) but the genetics of TRD was previously poorly investigated. Whole exome sequencing and genome-wide genotyping were available in 1209 MDD patients after quality control. Antidepressant response was compared to non-response to one treatment and non-response to two or more treatments (TRD). Differences in the risk of carrying damaging variants were tested. A score expressing the burden of variants in genes and pathways was calculated weighting each variant for its functional (Eigen) score and frequency. Gene-based and pathway-based scores were used to develop predictive models of TRD and non-response using gradient boosting in 70% of the sample (training) which were tested in the remaining 30% (testing), evaluating also the addition of clinical predictors. Independent replication was tested in STAR*D and GENDEP using exome array-based data. TRD and non-responders did not show higher risk to carry damaging variants compared to responders. Genes/pathways associated with TRD included those modulating cell survival and proliferation, neurodegeneration, and immune response. Genetic models showed significant prediction of TRD vs. response and they were improved by the addition of clinical predictors, but they were not significantly better than clinical predictors alone. Replication results were driven by clinical factors, except for a model developed in subjects treated with serotonergic antidepressants, which showed a clear improvement in prediction at the extremes of the genetic score distribution in STAR*D. These results suggested relevant biological mechanisms implicated in TRD and a new methodological approach to the prediction of TRD.
Threat-induced anxiety during goal pursuit disrupts amygdala–prefrontal cortex connectivity in posttraumatic stress disorder
Authors: Sun Delin , Gold Andrea L. , Swanson Chelsea A. , Haswell Courtney C. , Brown Vanessa M. , Stjepanovic Daniel ,   VA Mid-Atlantic MIRECC Workgroup, Beckham Jean C. , Brancu Mira , Calhoun Patrick S. , Dedert Eric , Elbogen Eric B. , Green Kimberly T. , Kimbrel Nathan , Kirby Angela , McCarthy Gregory , Moore Scott D. , Runnals Jennifer J. , Swinkels Cindy , Tupler Larry A. , Van Voorhees Elizabeth E. , Weiner Richard D. , LaBar Kevin S. , Morey Rajendra A. 
Published: February 2020

AbstractTo investigate how unpredictable threat during goal pursuit impacts fronto-limbic activity and functional connectivity in posttraumatic stress disorder (PTSD), we compared military veterans with PTSD (n = 25) vs. trauma-exposed control (n = 25). Participants underwent functional magnetic resonance imaging (fMRI) while engaged in a computerized chase-and-capture game task that involved optimizing monetary rewards obtained from capturing virtual prey while simultaneously avoiding capture by virtual predators. The game was played under two alternating contexts—one involving exposure to unpredictable task-irrelevant threat from randomly occurring electrical shocks, and a nonthreat control condition. Activation in and functional connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) was tested across threat and nonthreat task contexts with generalized psychophysiological interaction (gPPI) analyses. PTSD patients reported higher anxiety than controls across contexts. Better task performance represented by successfully avoiding capture by predators under threat compared with nonthreat contexts was associated with stronger left amygdala–vmPFC functional connectivity in controls and greater vmPFC activation in PTSD patients. PTSD symptom severity was negatively correlated with vmPFC activation in trauma-exposed controls and with right amygdala–vmPFC functional connectivity across all participants in the threat relative to nonthreat contexts. The findings showed that veterans with PTSD have disrupted amygdala–vmPFC functional connectivity and greater localized vmPFC processing under threat modulation of goal-directed behavior, specifically related to successfully avoiding loss of monetary rewards. In contrast, trauma survivors without PTSD relied on stronger threat-modulated left amygdala–vmPFC functional connectivity during goal-directed behavior, which may represent a resilience-related functional adaptation.
Shared and distinct resting functional connectivity in children and adults with attention-deficit/hyperactivity disorder
Authors: Guo Xiaojie , Yao Dongren , Cao Qingjiu , Liu Lu , Zhao Qihua , Li Hui , Huang Fang , Wang Yanfei , Qian Qiujin , Wang Yufeng , Calhoun Vince D. , Johnstone Stuart J. , Sui Jing , Sun Li 
Published: February 2020

AbstractAttention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, with a shift of symptoms including less hyperactivity/impulsivity and more co-morbidity of affective disorders in ADHDadult. Many studies have questioned the stability in diagnosing of ADHD from childhood to adulthood, and the shared and distinct aberrant functional connectivities (FCs) between ADHDchild and ADHDadult remain unidentified. We aim to explore shared and distinct FC patterns in ADHDchild and ADHDadult, and further investigated the cross-cohort predictability using the identified FCs. After investigating the ADHD-discriminative FCs from healthy controls (HCs) in both child (34 ADHDchild, 28 HCs) and adult (112 ADHDadult,77 HCs) cohorts, we identified both shared and distinct aberrant FC patterns between cohorts and their association with clinical symptoms. Moreover, the cross-cohort predictability using the identified FCs were tested. The ADHD-HC classification accuracies were 84.4% and 81.0% for children and male adults, respectively. The ADHD-discriminative FCs shared in children and adults lie in the intra-network within default mode network (DMN) and the inter-network between DMN and ventral attention network, positively correlated with total scores of ADHD symptoms. Particularly, inter-network FC between somatomotor network and dorsal attention network was uniquely impaired in ADHDchild, positively correlated with hyperactivity index; whereas the aberrant inter-network FC between DMN and limbic network exhibited more adult-specific ADHD dysfunction. And their cross-cohort predictions were 70.4% and 75.6% between each other. This work provided imaging evidence for symptomatic changes and pathophysiological continuity in ADHD from childhood to adulthood, suggesting that FCs may serve as potential biomarkers for ADHD diagnosis.
Dietary creatine intake and depression risk among U.S. adults
Authors: Bakian Amanda V. , Huber Rebekah S. , Scholl Lindsay , Renshaw Perry F. , Kondo Douglas 
Published: February 2020

AbstractCreatine monohydrate is actively being researched for its antidepressant effects, yet little is known about the link between dietary creatine and depression risk. This study examines the association between dietary creatine and depression in U.S. adults, using data from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). Patient health questionnaire, dietary creatine intake and covariates were obtained on 22,692 NHANES participants ≥20 years of age. Depression prevalence was calculated within quartiles of dietary creatine intake. Adjusted logistic regression models were formulated to determine the relationship between dietary creatine intake and depression risk. Additional covariates included income to poverty ratio, race/ethnicity, sex, age, education level, body mass index, healthcare access, smoking status, physical activity, and antidepressant/anxiolytic medication use. Models were further stratified by sex, age group, and antidepressant/anxiolytic medication use. Depression prevalence was 10.23/100 persons (95% CI: 8.64–11.83) among NHANES participants in the lowest quartile of dietary creatine intake compared with 5.98/100 persons (95% CI: 4.97–6.98) among participants in the highest quartile (p < 0.001). An inverse association was measured between dietary creatine and depression (adjusted odds ratio (AOR) = 0.68, 95% CI: 0.52–0.88). Dietary creatine’s negative association with depression was strongest in females (AOR = 0.62, 95% CI: 0.40–0.98), participants aged 20–39 years (AOR = 0.52, 95% CI: 0.34–0.79) and participants not taking antidepressant/anxiolytic medication (AOR = 0.58, 95% CI: 0.43–0.77). Study results indicate a significant negative relationship between dietary creatine and depression in a nationally representative adult cohort. Further research is warranted to investigate the role creatine plays in depression, particularly among women and across the lifespan.
Behavior and interaction imaging at 9 months of age predict autism/intellectual disability in high-risk infants with West syndrome
Authors: Ouss Lisa , Palestra Giuseppe , Saint-Georges Catherine , Leitgel Gille Marluce , Afshar Mohamed , Pellerin Hugues , Bailly Kevin , Chetouani Mohamed , Robel Laurence , Golse Bernard , Nabbout Rima , Desguerre Isabelle , Guergova-Kuras Mariana , Cohen David 
Published: February 2020

AbstractAutomated behavior analysis are promising tools to overcome current assessment limitations in psychiatry. At 9 months of age, we recorded 32 infants with West syndrome (WS) and 19 typically developing (TD) controls during a standardized mother–infant interaction. We computed infant hand movements (HM), speech turn taking of both partners (vocalization, pause, silences, overlap) and motherese. Then, we assessed whether multimodal social signals and interactional synchrony at 9 months could predict outcomes (autism spectrum disorder (ASD) and intellectual disability (ID)) of infants with WS at 4 years. At follow-up, 10 infants developed ASD/ID (WS+). The best machine learning reached 76.47% accuracy classifying WS vs. TD and 81.25% accuracy classifying WS+ vs. WS−. The 10 best features to distinguish WS+ and WS− included a combination of infant vocalizations and HM features combined with synchrony vocalization features. These data indicate that behavioral and interaction imaging was able to predict ASD/ID in high-risk children with WS.
Neuregulin 3 rs10748842 polymorphism contributes to the effect of body mass index on cognitive impairment in patients with schizophrenia
Authors: Zhou Yongjie , Li Yuhuan , Meng Yujie , Wang Jiesi , Wu Fengchun , Ning Yuping , Li Yi , Cassidy Ryan M. , Li Zezhi , Zhang Xiang Yang 
Published: February 2020

AbstractThere is evidence that obesity or higher body mass index is correlated with cognitive impairment in schizophrenia. Recent studies have demonstrated that genetic risk factors, such as the NRG3, are correlated with both elevated BMI and reduced cognitive function. In present study, we aimed to determine whether possession of the NRG3 rs10748842 influences the correlation between elevated BMI and reduced cognitive ability in schizophrenia. To our knowledge, this has never been examined before. A total of 625 inpatients with schizophrenia and 400 controls were recruited. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. We used multiple analysis of covariance (MANCOVA), analyses of covariance (ANCOVA), Pearson correlations, partial correlations, and multivariate regression analysis to test the influence of NRG3 rs10748842 on the aforementioned variables. All RBANS five sub-scores and total score were lower in patients than those in controls (all p < 0.001). Patients carrying NRG3 rs10748842 TC + CC heterozygous genotype had lower attention score compared to TT homozygous genotype (adjusted F = 4.77, p = 0.029). BMI was positively associated with language score in patients (β = 0.387, t = 2.59, p = 0.01). Interestingly, we further found positive association between BMI and language score in TT carriers (partial correlations: r = 0.13, adjusted p = 0.004; multivariate regression: β = 0.42, t = 2.66, p = 0.008), but not in CT + CC carrier (p > 0.05). Our study demonstrated that NRG3 rs10748842 was associated with cognitive impairments, especially attention performance in schizophrenia. Moreover, NRG3 rs10748842 altered the effect of BMI on cognitive impairments as measured by the RBANS language score in chronic patients with schizophrenia.
The role of H1 antihistamines in contralateral breast cancer: a Danish nationwide cohort study
Authors: Bens Annet , Dehlendorff Christian , Friis Søren , Cronin-Fenton Deirdre , Jensen Maj-Britt , Ejlertsen Bent , Lash Timothy L. , Kroman Niels , Mellemkjær Lene 
Published: February 2020

Abstract
Background
Preclinical studies have shown both pro- and antineoplastic effects of antihistamines. Here, we evaluated the effect of H1 antihistamines on contralateral breast cancer (CBC) risk, and whether cationic amphiphilic (CAD) antihistamines could increase the sensitivity to chemotherapy.

Methods
From the Danish Breast Cancer Group clinical database, we identified all women aged ≥20 years with a first-time diagnosis of breast cancer during 1996–2012. Information on drug use, CBC and potential confounding factors was retrieved from nationwide registries. Using Cox proportional hazard regression models, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with H1-antihistamine use.

Results
We identified 52,723 patients with breast cancer with a total of 310,583 person-years of follow-up. Among them, 1444 patients developed a new primary tumour in the contralateral breast. Post-diagnosis use of H1 antihistamines (≥2 prescriptions) was not strongly associated with CBC risk (HR 1.08, 95% CI: 0.90–1.31) compared with non-use (<2 prescriptions). Use of CAD antihistamines among patients receiving chemotherapy was not associated with a decrease in CBC risk.

Conclusions
Taken together, our findings do not suggest any association of H1-antihistamine use with CBC development.
TG01/GM-CSF and adjuvant gemcitabine in patients with resected RAS-mutant adenocarcinoma of the pancreas (CT TG01-01): a single-arm, phase 1/2 trial
Authors: Palmer Daniel H. , Valle Juan W. , Ma Yuk Ting , Faluyi Olusola , Neoptolemos John P. , Jensen Gjertsen Trine , Iversen Berit , Amund Eriksen Jon , Møller Anne-Sophie , Aksnes Anne-Kirsti , Miller Robert , Dueland Svein 
Published: February 2020

Abstract
Background
TG01 is the first cancer immunotherapy targeting KRAS oncogenic mutations. This study assessed the safety and efficacy of TG01/GM-CSF in patients with resected pancreatic adenocarcinoma.

Methods
Patients with stage I or II pancreatic adenocarcinoma who had undergone surgical resection (R0 or R1) received adjuvant gemcitabine with TG01/GM-CSF using two schedules of vaccination. Immune response was defined as a positive delayed-type hypersensitivity (DTH) response and/or positive T-cell proliferation assay.

Results
Thirty-two patients were enrolled between February 2013 and May 2016. Nineteen were treated with the high antigen burden, with four serious adverse reactions considered possibly related to TG01 treatment, including three allergic reactions. On this basis, a further 13 patients received a modified vaccination schedule with reduced antigen burden, with no serious adverse events related to TG01. Ninety-five percent patients in the main cohort and 92% in the modified cohort had a positive immune response. Median overall survival (OS) was 33.1 months, and median disease-free survival (DFS) was 13.9 months for the main cohort. For the modified cohort, the median OS was 34.3 months and median DFS was 19.5 months.

Conclusions
TG01/GM-CSF with gemcitabine was well tolerated, with high levels of immune activation. OS and DFS compare favourably with published data for adjuvant gemcitabine.

Clinical trial registration
This clinical trial was registered at ClinicalTrials.gov (NCT02261714).