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Characterised by the extensive use of obsidian, a blade-based tool inventory and microblade technology, the late Upper Palaeolithic lithic assemblages of the Changbaishan Mountains are associated with the increasingly cold climatic conditions of Marine Isotope Stage 2, yet most remain poorly dated. Here, the authors present new radiocarbon dates associated with evolving blade and microblade toolkits at Helong Dadong, north-east China. At 27 300–24 100 BP, the lower cultural layers contain some of the earliest microblade technology in north-east Asia and highlight the importance of the Changbaishan Mountains in understanding changing hunter-gatherer lifeways in this region during MIS 2.
Linguistic synesthesia as a productive figurative language usage has received little attention in the field of Natural Language Processing (NLP). Although linguistic synesthesia is similar to metaphor concerning involving conceptual mappings and showing great usefulness in the NLP tasks such as sentiment analysis and stance detection, the well-studied methods of metaphor detection cannot be applied to the detection of linguistic synesthesia directly. This study incorporates comprehensive linguistic features (i.e., character and radical information, word segmentation information, and part-of-speech tagging) into a neural model to detect linguistic synesthetic usages in a sentence automatically. In particular, we employ a span-based boundary detection model to extract sensory words. In addition, a joint model is proposed to detect the original and synesthetic modalities of the sensory words collectively. Based on the experiments, our model is shown to achieve state-of-the-art results on the dataset for linguistic synesthesia detection. The results prove that leveraging culturally enriched linguistic features and joint learning are effective in linguistic synesthesia detection. Furthermore, as the proposed model leverages non-language-specific linguistic features, the model would be applied to the detection of linguistic synesthesia in other languages.
Major depressive disorder (MDD) is a prevalent and disabling condition. Approximately 30-50% of patients do not respond to first-line medication or psychotherapy. Therefore, several studies have investigated the predictive potential of pretreatment severity rating or neuroimaging features to guide clinical approaches that can speed optimal treatment selection.
Objectives
To evaluate the performance of 1) severity ratings (scores of Hamilton Depression/Anxiety Scale, illness duration, and sleep quality, etc.) and demographic characteristic and 2) brain magnetic resonance imaging (MRI) features in predicting treatment outcomes for MDD. Second, to assess performance variations among varied modalities and interventions in MRI studies.
Methods
We searched studies in PubMed, Embase, Web of Science, and Science Direct databases before March 22, 2023. We extracted a confusion matrix for prediction in each study. Separate meta-analyses were performed for clinical and MRI studies. The logarithm of diagnostic odds ratio [log(DOR)], sensitivity, and specificity were conducted using Reitsma’s random effect model. The area under curve (AUC) of summary receiver operating characteristic (SROC) curve was calculated.
Subgroup analyses were conducted in MRI studies based on modalities: resting-state functional MRI (rsfMRI), task-based fMRI (tbfMRI), and structural MRI (sMRI), and interventions: antidepressant (including selective serotonin reuptake inhibitors [SSRI]) and electroconvulsive therapy (ECT). Meta-regression was conducted 1) between clinical and MRI studies and 2) among modality or intervention subgroups in MRI studies.
Results
We included ten studies used clinical features covering 6494 patients, yielded a log(DOR) of 1.42, AUC of 0.71, sensitivity of 0.61, and specificity of 0.74. In terms of MRI, 44 studies with 2623 patients were included, revealing an overall log(DOR) of 2.53. The AUC, sensitivity, and specificity were 0.89, 0.78, and 0.75.
Studies using MRI features had a higher sensitivity (0.89 vs. 0.61) in predicting treatment outcomes than clinical features (P < 0.001). RsfMRI had higher specificity (0.79 vs. 0.69) than tbfMRI subgroup (P = 0.01). No significant differences were found between sMRI and other modalities, nor between antidepressants (SSRIs and others) and ECT. Antidepressant studies primarily identified predictive imaging features in limbic and default mode networks, while ECT mainly focused on limbic network.
Conclusions
Our findings suggest a robust promise for pretreatment brain MRI features in predicting treatment outcomes in MDD, offering higher accuracy than clinical studies. While tasks in tbfMRI studies differed, those studies overall had less predictive utility than rsfMRI data. For MRI studies, overlapping but distinct network level measures predicted outcomes for antidepressants and ECT.
Direct numerical simulations have been conducted to investigate turbulent Rayleigh– Bénard convection (RBC) of liquid metal in a cuboid vessel with aspect ratio $\varGamma =5$ under an imposed horizontal magnetic field. Flows with Prandtl number $Pr=0.033$, Rayleigh numbers ranging up to $Ra\leq 10^{7}$, and Chandrasekhar numbers up to $Q\leq 9 \times 10^6$ are considered. For weak magnetic fields, our findings reveal that a previously undiscovered decreasing region precedes the enhancement of heat transfer and kinetic energy. For moderate magnetic fields, we have reproduced the reversals of the large-scale flow, which are considered a reorganization process of the roll-like structures that were reported experimentally by Yanagisawa et al. (Phys. Rev. E, vol. 83, 2011, 036307). Nevertheless, the proposed approach of skewed-varicose instability has been substantiated as insufficient to elucidate fundamentally the phenomenon of flow reversal, an occurrence bearing a striking resemblance to the large-scale intermittency observed in magnetic channel flows. As we increase the magnetic field strength further, we observe that the energy dissipation of the system comes primarily from the viscous dissipation within the boundary layer. Consequently, the dependence of Reynolds number $Re$ on $Q$ approaches a scaling as $Re\,Pr/Ra^{2/3} \sim Q^{-1/3}$. At the same time, we find the law for the cutoff frequency that separates large quasi-two-dimensional scales from small three-dimensional ones in RBC flow, which scales with the interaction parameter as ${\sim }N^{1/3}$.
Accurately predicting neurosyphilis prior to a lumbar puncture (LP) is critical for the prompt management of neurosyphilis. However, a valid and reliable model for this purpose is still lacking. This study aimed to develop a nomogram for the accurate identification of neurosyphilis in patients with syphilis. The training cohort included 9,504 syphilis patients who underwent initial neurosyphilis evaluation between 2009 and 2020, while the validation cohort comprised 526 patients whose data were prospectively collected from January 2021 to September 2021. Neurosyphilis was observed in 35.8% (3,400/9,504) of the training cohort and 37.6% (198/526) of the validation cohort. The nomogram incorporated factors such as age, male gender, neurological and psychiatric symptoms, serum RPR, a mucous plaque of the larynx and nose, a history of other STD infections, and co-diabetes. The model exhibited good performance with concordance indexes of 0.84 (95% CI, 0.83–0.85) and 0.82 (95% CI, 0.78–0.86) in the training and validation cohorts, respectively, along with well-fitted calibration curves. This study developed a precise nomogram to predict neurosyphilis risk in syphilis patients, with potential implications for early detection prior to an LP.
Pyrophyllite is an important layered phyllosilicate material that is used in many fields due to its beneficial physicochemical and mechanical properties. Due to the presence of multiple defects in pyrophyllite, an in-depth investigation was conducted using density functional theory to explore the effects of Na(I), K(I), Mg(II), Ca(II) and Fe(II) doping on the atomic structure, electronic properties and mechanical characteristics of pyrophyllite. The results demonstrated that, among the studied defects, K(I) doping had the most pronounced effects on the lattice constants and bonding lengths of pyrophyllite, while the least significant effects were observed in the case of Fe(II) doping. Moreover, the partial and total densities of states and band structures of the five kinds of doped pyrophyllite also changed significantly due to the redistribution of electrons. Finally, the elastic constants of the doped pyrophyllite were lower than that of the undoped pyrophyllite. Doping with Na(I), K(I), Mg(II), Ca(II) and Fe(II) reduced the deformation resistance, stiffness and elastic wave velocity but increased the degree of anisotropy in pyrophyllite. The observed effects on the mechanical properties of pyrophyllite followed the order: Mg(II) > Fe(II) > Ca(II) >K(I) > Na(I).
Major depressive disorder (MDD) is characterized by both clinical symptoms and cognitive deficits. Prior studies have typically examined either symptoms or cognition correlated with brain measures, thus causing a notable paucity of stable brain markers that capture the full characteristics of MDD. Brain controllability derived from newly proposed brain model integrating both metabolism (energy cost) and dynamics from a control perspective has been considered as a sensitive biomarker for characterizing brain function. Thus, identifying such a biomarker of controllability related to both symptoms and cognition may provide a promising state monitor of MDD.
Objectives
To assess the associations between two multi-dimensional clinical (symptoms and cognition) and brain controllability data of MDD in an integrative model.
Methods
Sparse canonical correlation analysis (sCCA) was used to investigate the association between brain controllability at a network level and both clinical symptoms and cognition in 99 first-episode medication-naïve patients with MDD. The potential mediation effect of cognition on relationship between controllability and symptoms was also tested.
Results
Average controllability was significantly correlated with both symptoms and cognition (rmean=0.54, PBonferroni=0.03). Average controllability of dorsal attention network (DAN) (r=0.46) and visual network (r=0.29) had the highest correlation with both symptoms and cognition. Among clinical variables, depressed mood (r=-0.23) , suicide(r=-0.25), work and activities(r=-0.27), gastrointestinal symptoms (r=-0.25) were significantly negatively associated with average controllability, while cognitive flexibility (r=0.29) was most strongly positively correlated with average controllability. Additionally, cognitive flexibility fully mediated the association between average controllability of DAN and depressed mood (indirect effect=-0.11, 95% CI [-0.18, -0.04], P=0.001) in MDD.
Conclusions
Brain average controllability was correlated with both clinical symptoms and cognition in first-episode medication-naïve patients with MDD. The results suggest that average controllability of DAN and visual network reached high associations with clinical variates in MDD, thus these brain features may serve as stable biomarkers to control the brain functional states transitions to be relevant to cognitions deficits and clinical symptoms of MDD. Additionally, altered average controllability of DAN in patients could induce impairment of cognitive flexibility, and thus cause severe depressed mood, indicating that controllability of DAN may be a potential intervention target for alleviating depressed mood through improving cognitive flexibility in MDD.
Recently, Scholten and Read (2014) found new violations of dominance in intertemporal choice. Although adding a small receipt before a delayed payment or adding a small delayed receipt after an immediate receipt makes the prospect objectively better, it decreases the preference for that prospect (better is worse). Conversely, although adding a small payment before a delayed receipt or adding a small delayed payment after an immediate payment makes the prospect objectively worse, it increases the preference for that prospect (worse is better). Scholten and Read explained these violations in terms of a preference for improvement. However, to produce violations such as these, we find that the temporal sequences need not be constructed as Scholten and Read suggested. In this study, adding a small receipt before a dated receipt (thus constructed as improving) or adding a receipt after a dated payment (thus constructed as improving) decreases preferences for those prospects. Conversely, adding a small payment after a dated receipt (thus constructed as deteriorating) or adding a small payment before a delayed payment (thus constructed as deteriorating) increases preferences for those prospects.
Metabolically healthy obesity (MHO) might be an alternative valuable target in obesity treatment. We aimed to assess whether alternative Mediterranean (aMED) diet and Dietary Approaches to Stop Hypertension (DASH) diet were favourably associated with obesity and MHO phenotype in a Chinese multi-ethnic population. We conducted this cross-sectional analysis using the baseline data of the China Multi-Ethnic Cohort study that enrolled 99 556 participants from seven diverse ethnic groups. Participants with self-reported cardiometabolic diseases were excluded to eliminate possible reverse causality. Marginal structural logistic models were used to estimate the associations, with confounders determined by directed acyclic graph (DAG). Among 65 699 included participants, 11·2 % were with obesity. MHO phenotype was present in 5·7 % of total population and 52·7 % of population with obesity. Compared with the lowest quintile, the highest quintile of DASH diet score had 23 % decreased odds of obesity (OR = 0·77, 95 % CI 0·71, 0·83, Ptrend < 0·001) and 27 % increased odds of MHO (OR = 1·27, 95 % CI 1·10, 1·48, Ptrend = 0·001) in population with obesity. However, aMED diet showed no obvious favourable associations. Further adjusting for BMI did not change the associations between diet scores and MHO. Results were robust to various sensitivity analyses. In conclusion, DASH diet rather than aMED diet is associated with reduced risk of obesity and presents BMI-independent metabolic benefits in this large population-based study. Recommendation for adhering to DASH diet may benefit the prevention of obesity and related metabolic disorders in Chinese population.
As the corona virus disease 2019 (COVID-19) pandemic continues around the world, understanding the transmission characteristics of COVID-19 is vital for prevention and control. We conducted the first study aiming to estimate and compare the relative risk of secondary attack rates (SARs) of COVID-19 in different contact environments. Until 26 July 2021, epidemiological studies and cluster epidemic reports of COVID-19 were retrieved from SCI, Embase, PubMed, CNKI, Wanfang and CBM in English and Chinese, respectively. Relative risks (RRs) were estimated in pairwise comparisons of SARs between different contact environments using the frequentist NMA framework, and the ranking of risks in these environments was calculated using the surface under the cumulative ranking curve (SUCRA). Subgroup analysis was performed by regions. Thirty-two studies with 68 260 participants were identified. Compared with meal or gathering, transportation (RR 10.55, 95% confidence interval (CI) 1.43–77.85), medical care (RR 11.68, 95% CI 1.58–86.61) and work or study places (RR 10.15, 95% CI 1.40–73.38) had lower risk ratios for SARs. Overall, the SUCRA rankings from the highest to the lowest were household (95.3%), meal or gathering (81.4%), public places (58.9%), daily conversation (50.1%), transportation (30.8%), medical care (18.2%) and work or study places (15.3%). Household SARs were significantly higher than other environments in the subgroup of mainland China and sensitive analysis without small sample studies (<100). In light of the risks, stratified personal protection and public health measures need to be in place accordingly, so as close contacts categorising and management.
The effects of early thiamine use on clinical outcomes in critically ill patients with acute kidney injury (AKI) are unclear. The purpose of this study was to investigate the associations between early thiamine administration and clinical outcomes in critically ill patients with AKI. The data of critically ill patients with AKI within 48 h after ICU admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. PSM was used to match patients early receiving thiamine treatment to those not early receiving thiamine treatment. The association between early thiamine use and in-hospital mortality due to AKI was determined using a logistic regression model. A total of 15 066 AKI patients were eligible for study inclusion. After propensity score matching (PSM), 734 pairs of patients who did and did not receive thiamine treatment in the early stage were established. Early thiamine use was associated with lower in-hospital mortality (OR 0·65; 95 % CI 0·49, 0·87; P < 0·001) and 90-d mortality (OR 0·58; 95 % CI 0·45, 0·74; P < 0·001), and it was also associated with the recovery of renal function (OR 1·26; 95 % CI 1·17, 1·36; P < 0·001). In the subgroup analysis, early thiamine administration was associated with lower in-hospital mortality in patients with stages 1 to 2 AKI. Early thiamine use was associated with improved short-term survival in critically ill patients with AKI. It was possible beneficial role in patients with stages 1 to 2 AKI according to the Kidney Disease: Improving Global Outcomes criteria.
The South Qinling block, a segment of the Yangtze craton involved in the Qinling–Dabie orogen, is critical for understanding the tectonic evolution of eastern China. However, the tectonic setting of the South Qinling block and the northern margin of the Yangtze block during middle Neoproterozoic time has long been the subject of debate, with two distinctly different models (continental rift or volcanic arc) proposed. Here, a comprehensive study of zircon U–Pb geochronology and geochemistry has been carried out on the Chengwan granitic pluton from the Suizao terrane in the South Qinling block. The granites are monzogranite and syenogranite in lithology, and are mainly composed of potash feldspar, quartz, plagioclase and biotite. This suite has long been regarded as a Palaeozoic magmatic pluton, but zircon U–Pb ages of 809 ± 9 Ma and 816 ± 4 Ma are obtained in this study. The granites are metaluminous to strongly peraluminous with high alkali contents, and exhibit highly fractionated features, including high SiO2, low Zr/Hf ratios, rare earth element tetrad effects and enrichment of K and Rb. They show Hf–Nd isotopic decoupling, which may be genetically related to their petrogenetic process. Based on the geochemical features and the positive εHf(t) values of the zircons, it is indicated that the granites may have been derived from partial melting of juvenile tonalitic rocks by biotite breakdown under fluid-absent conditions. The Chengwan granite geochemically belongs to the A2-subtype granites, suggesting that it might have formed in a post-orogenic tectonic setting. The highly fractionated A-type granite in this study may represent extensional collapse shortly after the collisional events in the South Qinling block, and thus indicate a tectonic regime switch, from compression to extension, as early as middle Neoproterozoic time. Integrating our new data with documented magmatic, metamorphic and sedimentary events during middle Neoproterozoic time in the region may support a continental rift model, and argues against arc models.
The current epidemic of type 2 diabetes mellitus (T2DM) significantly affects human health worldwide. Activation of brown adipocytes and browning of white adipocytes are considered as a promising molecular target for T2DM treatment. Mulberry leaf, a traditional Chinese medicine, has been demonstrated to have multi-biological activities, including anti-diabetic and anti-inflammatory effects. Our experimental results showed that mulberry leaf significantly alleviated the disorder of glucose and lipid metabolism in T2DM rats. In addition, mulberry leaf induced browning of inguinal white adipose tissue (IWAT) by enhancing the expressions of brown-mark genes as well as beige-specific genes, including uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), PRD1-BF-1-RIZ1 homologous domain containing protein 16 (PRDM16), cell death inducing DFFA-like effector A (Cidea), CD137 and transmembrane protein 26 (TMEM26). Mulberry leaf also activated brown adipose tissue (BAT) by increasing the expressions of brown-mark genes including UCP1, PGC-1α, PPARα, PRDM16 and Cidea. Moreover, mulberry leaf enhanced the expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) genes that are responsible for mitochondrial biogenesis in IWAT and BAT. Importantly, mulberry leaf also increased the expression of UCP1 and carnitine palmitoyl transferase 1 (CPT-1) proteins in both IWAT and BAT via a mechanism involving AMP-activated protein kinase (AMPK) and PGC-1α pathway. In conclusion, our findings identify the role of mulberry leaf in inducing adipose browning, indicating that mulberry leaf may be used as a candidate browning agent for the treatment of T2DM.
To explore the association between dietary Na intake and non-alcoholic fatty liver disease (NAFLD) in a nationally representative sample of the US population.
Design:
In this cross-sectional study, the associations between Na intake and NAFLD, defined by the hepatic steatosis index (HSI) and the fatty liver index (FLI), were assessed through multivariable logistic regression models.
Setting:
Communities in the USA from 2007 to 2014.
Participants:
Men and women aged 20 years and older.
Results:
A total of 11 022 participants were included in the HSI-defined NAFLD analysis, and a subsample of 5320 participants was included in the FLI-defined NAFLD analysis. Compared with the lowest quartile of Na intake, the highest quartile had a multivariate-adjusted OR and 95 % CI of 1·46 (1·29, 1·65) for NAFLD as defined by HSI, and 1·41 (1·18, 1·69) for NAFLD as defined by FLI. This association was, to some degree, attenuated but remained significant after adjusting for several related metabolic parameters, including BMI, hypertension, hypercholesterolaemia, and diabetes.
Conclusions:
Findings from the current study indicate that dietary Na intake is positively associated with NAFLD in US adults.
This research communication describes associations between variation in the fatty acid binding protein 4 gene (FABP4) and milk fat composition in New Zealand Holstein-Friesian × Jersey cross dairy cows. After correcting for the effect of the amino acid substitution p.K232A in diacylglycerol O-acyltransferase 1 (DGAT1), which is associated with variation in many milk fatty acid (FA) component levels, the effect of FABP4 c.328A/G on milk FA levels was typically small. For the five genotypes analysed, the AB cows produced more medium-chain fatty acids than CC cows (P < 0.05), and more C14:0 FA than AA and AC cows (P < 0.05). The AA and AC cows produced less C22:0 FA (P < 0.01) than the BC cows, and the AC cows produced more C24:0 FA (P < 0.05) than was produced by the BC cows. Cows of genotype CC produce more long-chain fatty acids than cows of genotype BC (P < 0.05).
Malnutrition and acute kidney injury (AKI) are common complications in hospitalised patients, and both increase mortality; however, the relationship between them is unknown. This is a retrospective propensity score matching study enrolling 46 549 inpatients, aimed to investigate the association between Nutritional Risk Screening 2002 (NRS-2002) and AKI and to assess the ability of NRS-2002 and AKI in predicting prognosis. In total, 37 190 (80 %) and 9359 (20 %) patients had NRS-2002 scores <3 and ≥3, respectively. Patients with NRS-2002 scores ≥3 had longer lengths of stay (12·6 (sd 7·8) v. 10·4 (sd 6·2) d, P < 0·05), higher mortality rates (9·6 v. 2·5 %, P < 0·05) and higher incidence of AKI (28 v. 16 %, P < 0·05) than patients with normal nutritional status. The NRS-2002 showed a strong association with AKI, that is, the risk of AKI changed in parallel with the score of the NRS-2002. In short- and long-term survival, patients with a lower NRS-2002 score or who did not have AKI achieved a significantly lower risk of mortality than those with a high NRS-2002 score or AKI. Univariate Cox regression analyses indicated that both the NRS-2002 and AKI were strongly related to long-term survival (AUC 0·79 and 0·71) and that the combination of the two showed better accuracy (AUC 0·80) than the individual variables. In conclusion, malnutrition can increase the risk of AKI and both AKI and malnutrition can worsen the prognosis that the undernourished patients who develop AKI yield far worse prognosis than patients with normal nutritional status.
Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
Receiver Autonomous Integrity Monitoring (RAIM) provides an integrity service for Global Navigation Satellite Systems (GNSS). The conventional RAIM algorithm is based on the assumption of a single fault and typically uses the forward-backward method, which is based on the w-test or correlation analysis methods, to exclude the faults. It is suitable for single fault detection and exclusion, while it can lead to inefficiency, can be misleading and can even fail in the exclusion of multiple faults. To solve this problem, an improved method based on consensus voting of the w-test and correlation analysis methods is presented. To verify the performance of the improved method, tests using Global Positioning System (GPS)/BeiDou System (BDS) data have been carried out in comparison with the conventional methods in terms of false and correct faults exclusion rate and computational complexity in the case of a different number of faults. Results show that the improved method has almost the same correct exclusion rate compared to the conventional RAIM in the case of a single fault. It is worth noting that the improved method has a higher correct exclusion probability and computational efficiency as well as a lower possibility of false exclusion in the case of multiple faults.
Depression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders.
Methods
Here we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD2018 and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on AD, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes.
Results
Importantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzed p values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase.
Conclusion
Taken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and AD.