The rapid spread of acute respiratory infections (ARIs) poses a major challenge to global public health, yet current surveillance systems relying on sentinel hospitals and laboratory testing often lack timeliness and precision. In this study, we present an integrated framework combining wastewater-based epidemiology (WBE) with machine learning to establish a fever prevalence-based early warning model for ARIs. Using wastewater data on paracetamol and ibuprofen consumption (n = 603) from Dalian, Beijing, Guangzhou, and other cities, we evaluated statistical, unsupervised, and supervised learning approaches (11 models) for anomaly detection. Based on model validation and evaluation, the interquartile range, isolation forest, neural networks, and logistic regression models demonstrated favorable performance. However, only the warning thresholds derived from the interquartile range method (3.3%) and isolation forest (3.5%) indicated that November 2021 was a non-epidemic period and November 2024 was an epidemic period, which is consistent with the influenza-like illness surveillance results from sentinel hospitals. Our findings demonstrate that WBE, when coupled with machine learning, can provide timely and precise community-level monitoring of fever prevalence, while also offering early-warning capability for fever-dominant emerging respiratory infections and previously unidentified etiological agents such as "Disease X". This approach effectively addresses the limitations of conventional surveillance, such as incomplete coverage and delayed response, and provides a scalable, evidence-based tool to strengthen public health preparedness and response.
Coughing often signals respiratory health issues. The use of dextromethorphan, available as an over-the-counter opioid antitussive in China, is largely undocumented. This study evaluates the feasibility of dextromethorphan and its metabolite dextrorphan, as wastewater-based epidemiology (WBE) biomarkers for monitoring dextromethorphan use. To determine their suitability, key criteria including urinary excretion, detectability in wastewater, unique human metabolic source, and stability were applied. Both dextromethorphan and its metabolite dextrorphan are excreted via urine (62.5 % as dextrorphan and 0.5 % as dextromethorphan) hence meet the "excreted in urine" criteria. Both biomarkers were also measured in wastewater meeting the "detectable in wastewater" criteria, and dextrorphan's concentration ratio to dextromethorphan was consistent with its excretion profile suggesting that dextrorphan also meet's the criteria of "unique source: human metabolism". In-sample stability was assessed over 72 h and both biomarkers were deemed as stable. Consequently, employing dextrorphan as a WBE biomarker enables the assessment of temporal and spatial usage trends of dextromethorphan, underscoring its practicality. Additionally, a spatio-temporal investigation across 30 Chinese cities revealed an average dextrorphan consumption of 13 mg/d/1000 inh, closely aligning with China's reported annual production estimate of 12 mg/d/1000 inh. This strong concordance supports the validity of using dextrorphan as a WBE biomarker for estimating dextromethorphan consumption. The consumption of dextromethorphan was higher in northern regions compared to southern regions. Temporally, the consumption of dextromethorphan decreased from 233 mg/d/1000 inh in 2015 to 12.3 mg/d/1000 inh in 2021, but with a notable increase in 2022 (24 mg/d/1000 inh) attributed to the COVID-19 outbreak in China in December 2022. Seasonally, the consumption of dextromethorphan in winter was higher compared to spring. This study confirms the suitability of dextrorphan as a biomarker for assessing dextromethorphan usage, and supports the application of WBE for monitoring population-level use of respiratory OTC medications.
Phosphodiesterase type V inhibitors (PDE-5is) are widely used for the treatment of erectile dysfunction, and global demand for these pharmaceuticals continues to grow. However, the circulation of unlicensed and counterfeit PDE-5is poses serious public health risks. This study employed solid-phase extraction coupled with LC-MS/MS to analyze 116 influent wastewater samples collected in Dalian, China, in order to assess the temporal and spatial trends in the community-level use of counterfeit PDE-5is. Among the three target compounds, neither tadalafil nor vardenafil was detected in any sample. Sildenafil, however, was found in 94.5% of the samples, with concentrations ranging from below the limit of quantification (LOQ) to 75.4 ng/L. Its major metabolite, desmethylsildenafil, was detected in concentrations ranging from < LOQ to 107 ng/L. Sildenafil consumption steadily increased between 2017 and 2022 (40.8 to 87.8 mg/d/1000 inh). Notably, the estimated consumption based on wastewater data far exceeded local prescription sales, which accounted for only approximately 20% of the total use, with counterfeit sildenafil use estimated to exceed 100 kg/year in Dalian. This discrepancy indicates that the majority of sildenafil is obtained through over-the-counter sales or illegal channels. For spatial analysis, wastewater treatment plants were classified according to the characteristics of the populations they served. Sildenafil consumption was substantially higher in urban areas (70.4 mg/d/1000 inh) than in rural areas (25.4 mg/d/1000 inh), indicating more widespread use of counterfeit products in urban populations. Subpopulation analysis further revealed that college students (38.5 mg/d/1000 inh) and island residents (28.6 mg/d/1000 inh) had lower levels of use compared to the general population (85.1 mg/d/1000 inh). These results highlight the potential of wastewater-based drug surveillance in tracking consumption trends of nonprescribed and counterfeit pharmaceuticals, offering robust evidence to inform regulatory efforts and improve public risk perception.
Psychological stress has a significant impact on individuals' quality of life and health. Traditionally, psychological stress assessment relies on self-reported tools such as the Perceived Stress Scale (PSS), which are inherently subjective. This study aims to evaluate the feasibility of using wastewater-based epidemiology (WBE) to assess cortisol and cortisone as biomarkers for psychological stress. We conducted sampling and monitoring of cortisol and cortisone concentrations at both a small-scale campus setting (five weeks) and a large-scale municipal wastewater treatment plant (12 months), calculating the mass loads of these hormones. At the campus level, while the mass load of cortisone was higher during exam weeks compared to regular class weeks, and higher in females than in males, no significant differences were observed in the mass load of cortisol. The mass load results of cortisone were consistent with the findings of the PSS-14 questionnaire. These results suggest that cortisone is a more suitable biomarker for psychological stress assessment. In the large-scale municipal wastewater samples, seasonal variations were observed, with higher levels of cortisol and cortisone in winter compared to summer, likely due to the COVID-19 outbreak in winter and the presence of external pharmaceutical sources. The results indicate that cortisone is more suitable for small-scale stress assessments, as larger-scale evaluations may be more significantly influenced by wastewater transport or sampling methodologies.
Wastewater-based epidemiology (WBE) has been widely used as a public health surveillance tool worldwide, especially since the COVID-19 pandemic. In China, the WBE approach has been adopted for monitoring illicit drug use since the early 2010s and further extended to monitoring consumption or exposure to other chemicals. Establishing a nationwide monitoring program for substance consumption has increased the population coverage from 3.5 to 382 million. However, previous similar to 200 WBE studies in China are mostly chemical-focused, with limited focus on pathogenic bacteria or viruses. Moreover, there are still challenges for the methodology as multiple factors affect the accuracy and reliability of the final back estimations. With emerging public health challenges, especially after the COVID-19 epidemic, WBE can play a more important role in China. This study summarizes achievements made in various WBE applications in China and research efforts in enhancing the accuracy and reliability of WBE results over the past decade. Future perspectives were also discussed, considering the achievements in other countries and the unique features of China. Integrating WBE estimation, both chemical and biological data, with other data would promote the development of more evidence-based strategies for public health.
New psychoactive substances are a group of synthetic or naturally occurring drugs that mimic the effects of controlled illicit drugs. With limited information around potency, effects and health risks, there is international concern around their use and thus surveillance efforts are needed for public health. This study presents a global assessment of new psychoactive substances in influent wastewater from 52 sites across 20 countries during the 2022/2023 New Year period. Using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry, 21 new psychoactive substances were detected with mitragynine, 3-methylmethcathinone, and eutylone being the most prevalent. Notably, 3,4-methylenedioxy-PV8 was identified for the first time in sites in Australia and the United States. A retrospective analysis of population normalised mass loads for 3-methylmethcathinone at European sites revealed downward trends in 2022/2023 sampling period compared to the previous years, suggesting a possible impact of regional scheduling measures. Additionally, this work demonstrates the stability of new psychoactive substances in loaded cartridges for up to four months when stored at -20 °C. These findings highlight the value of wastewater-based epidemiology for global monitoring of emerging new psychoactive substances threats and policy evaluation.
This study assessed the ability of diffusive gradients in thin-films organics (o-DGT) to monitor illicit drug use at the community level. The o-DGT devices were deployed at designated sampling sites along the pipelines of two wastewater treatment plants (WWTPs) located on an island and in a coastal city. The concentrations of target compounds, including methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA), benzoylecgonine (BE, a metabolite of cocaine), and ketamine (KET), were determined using high-performance liquid chromatography-tandem mass spectrometry. Cotinine (COT), a biomarker of nicotine and tobacco intake, was also monitored to estimate the population size in each sampling region. The o-DGT was validated as a reliable tool for measuring COT and drugs levels in wastewater. The results revealed high detection rates (100 %) and concentrations (3.65 similar to 1135 ng/L) of METH in both WWTPs sampling sites, suggesting its prevalence in the studied areas. Additionally, the study found a 100 % detection rate of MDMA in the studied island samples, indicating a higher prevalence of MDMA abuse. The concentrations of BE and KET were relatively low, ranging from below detection limit (
Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
Magnetic molecularly imprinted polymers (MMIPs) were synthesized by bulk polymerization using N-methylphenethylamine as a dummy template for selective extraction of four amphetamine-type stimulants (ATSs) in sewage and urine. The MMIPs were characterized by scanning electron microscopy, vibrating sample magnetometer, Fourier transform infrared spectroscopy and thermogravimetric analysis, revealing a porous structure (35-60 µm) with a saturation magnetization of 1.8 emu/g, enabling rapid magnetic separation within 1 min. Adsorption kinetics followed a pseudo-second-order model, achieving over 80% adsorption within 10 min and an imprinting factor of 2.4-3.3, demonstrating high selectivity for ATSs over structural analogs. Optimized magnetic solid-phase extraction (MSPE) conditions yielded recoveries over 81% with relative standard deviation (RSD) below 5.5%. Coupled with high performance liquid chromatography-tandem mass spectrometry, the proposed MMIPs-MSPE method exhibited a linear range of 1-100 ng/mL, low detection limits (5.2-19 ng/L), and quantification limits (17.0-65.0 ng/L). The pre-concentration factor of ATSs was 19.3-19.9. Successful application to real sewage and urine samples confirmed robust matrix interference resistance and reliability (recoveries: 82.1%-116%, RSD < 6.4%). This study provides a sensitive, reusable, and environmentally friendly approach for monitoring ATSs in environmental and forensic matrices.
Important biogeochemical processes occur in sediments at fine scales. Sampling techniques capable of yielding information with high resolution are therefore needed to investigate chemical distributions and fluxes and to elucidate key processes affecting chemical fates. In this study, a high-resolution diffusive gradients in thin-films (DGT) technique was systematically developed and tested in a controlled sediment system to measure organic contaminants, antibiotics, for the first time. The DGT probe was used to resolve compound distributions at the mm scale. It also reflected the fluxes from the sediment pore-water and remobilization from the solid phase, providing more dynamic information. Through the fine scale detection, a reduction of re-supply was observed over time, which was concentration and location dependent. Compared to the Rhizon sampling method, antibiotic concentrations obtained by DGT probes were less than the pore-water concentrations, as DGT measures the labile fraction of the compounds. The DGT probe was also tested on an intact sediment core sampled from a lake in China and used to measure the distribution of labile antibiotics with depth in the core at the mm scale. ENVIRONMENTAL IMPLICATION: The abuse of antibiotics and widespread of their residues influences the ecosystem, induces the generation of super-bacteria, and finally poses threat to human health. Sediments adsorbs pollutants from the aquatic environment, while may also release them back to the environment. We systematically developed DGT probe approach for measuring antibiotics in sediment in situ in high resolving power, it provides information at fine scale to help us investigate biogeochemical processes take place in sediment and sediment-water interface.
Magnetic surface imprinted polymer microspheres (Fe3O4@MIPs) were successfully synthesized via Pickering emulsion polymerization, utilizing N-Methylphenethylamine as a surrogate template for amphetamine-type drugs. Fe3O4@MIPs not only possessed excellent dispersibility and enough magnetic properties in aqueous solutions, but also displayed good selectivity towards six amphetamines, with an imprinting factor ranging from 1.8 to 2.6. The adsorption kinetics closely aligned with the pseudo-second-order model, and the adsorption efficiency exceeds 80% for each amphetamine at equilibrium. Fe3O4@MIPs were then employed as the efficient adsorbents for the extraction of amphetamine drugs. Extraction parameters, including sample pH, the mass of adsorbent, and the type and volume of eluting solvent, were carefully optimized. In combination with the high performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-MS/MS), a selective magnetic solid-phase extraction (MISPE) method utilizing Fe3O4@MIPs was developed for the detection of six amphetamines in water samples. The limits of detection and limits of quantitation were determined to be 5.2∼23 ng L−1 and 17∼77 ng L−1, respectively. Recoveries for the six target drugs from lake water and sewage samples fell within the range of 87.2∼110%. Additionally, the MISPE-HPLC-MS/MS method exhibited excellent repeatability, with a precision below 8.5% at two spiking levels. The prepared Fe3O4@MIPs possessed the advantages of high selectivity, straightforward preparation, facile separation and good reusability, and was highly suitable for the efficient extraction of amphetamine-type substances in complex environmental water.
New antibiotic contaminants have been detected in both surface waters and natural ice across cold regions. However, few studies have revealed distinctions between their ice and aqueous photochemistry. In this study, the photodegradation and effects of the main dissolved substances on the photolytic kinetics were investigated for sulfonamides (SAs) and fluoroquinolones (FQs) in ice/water under simulated sunlight. The results showed that the photolysis of sulfamethizole (SMT), sulfachloropyridazine (SCP), enrofloxacin (ENR) and difloxacin (DIF) in ice/water followed the pseudo-first-order kinetics with their quantum yields ranging from 4.93 × 10−3 to 11.15 × 10−2. The individual antibiotics experienced disparate photodegradation rates in ice and in water. This divergence was attributed to the concentration-enhancing effect and the solvent cage effect that occurred in the freezing process. Moreover, the main constituents (Cl−, HASS, NO3− and Fe(III)) exhibited varying degrees of promotion or inhibition on the photodegradation of SAs and FQs in the two phases (p < 0.05), and these effects were dependent on the individual antibiotics and the matrix. Extrapolation of the laboratory data to the field conditions provided a reasonable estimate of environmental photolytic half-lives (t1/2,E) during midsummer and midwinter in cold regions. The estimated t1/2,E values ranged from 0.02 h for ENR to 14 h for SCP, which depended on the reaction phases, latitudes and seasons. These results revealed the similarities and differences between the ice and aqueous photochemistry of antibiotics, which is important for the accurate assessment of the fate and risk of these new pollutants in cold environments.
Since the onset of COVID-19, respiratory diseases have emerged as a focal concern within the field of public health. This study aims to reveal the prevalence of acute respiratory infectious diseases by screening antipyretic, antiviral, and antibiotic biomarkers through wastewater analysis. Samples were collected over a seven-day period each year in 2022, 2023, and 2024 from a northern city in China, assessing the concentrations of two antipyretics (paracetamol and ibuprofen), one antiviral drug (oseltamivir), eleven antibiotics, and three pathogens (influenza A, influenza B, and Mycoplasma pneumoniae). The usage of most antipyretics and antibiotics was higher in 2023 and 2024, primarily due to the outbreak of COVID-19 in 2023 and the prevalence of influenza A, influenza B, and Mycoplasma pneumoniae in 2024. The prevalence assessed using antipyretics (2.68 %) and pathogens (2.70 %) demonstrated a high degree of consistency, whereas the prevalence estimated using antibiotics and antiviral drugs was only 0.53 % and 0.36 %, respectively. Antibiotics are generally used to treat a broad spectrum of bacterial infections rather than targeting a specific pathogen, so their presence in wastewater may not directly reflect the prevalence of a particular disease. In contrast, antipyretics and specific pathogens exhibit a stronger correlation, suggesting that they may serve as more reliable biomarkers than antiviral and antibiotic drugs. The research findings offer alternative biomarkers, such as antipyretics, aside from pathogens, for the assessment of acute respiratory infectious diseases.
It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.
A causal relationship has been reported between the average population salt (sodium chloride) intake and the increased risk of stroke and cardiovascular and cerebrovascular diseases in some epidemiological and clinical studies.The World Health Organization has recommended that a sodium intake of <2 g/day is preventive against cardiovascular disease,although the current intake is in excess in most countries.Among the variousmethods for evaluating dietary salt intake,
Wastewater surveillance is an effective and objective approach to monitor contaminant releases and drug usage in the catchment, the estimation requires accurate measurement. In this study, a novel diffusive gradients in thin-film (DGT) technique based on molecularly imprinted polymers (MIPs) for selective measurement of a class of widely prescribed cardiovascular drugs (β-blockers) in wastewater was developed. The synthesized MIPs showed strong affinity and selectivity for the target compounds. The MIP-DGT had large effective capacities, its performance was independent of a wide range of environmental conditions, including pH (4.58 - 8.89), ionic strength (0.01 - 0.5 M) and dissolved organic matter (< 20 mg L-1). Biofouling had little effect on the uptake of target compounds within 7 days. MIP-DGT devices were applied in a Chinese urban WWTP alongside an auto-sampler. Metoprolol concentrations detected were much higher than other β-blockers. Concentrations obtained using MIP-DGT were comparable to the 24 h composite samples using an autosampler. The estimated daily consumption calculated based on the data obtained with MIP-DGT implied that metoprolol and propranolol were the most popular β-blockers in the studied area. Overall, the results in this study demonstrate that the MIP-DGT is a cost-effective, reliable and efficient tool for in situ wastewater monitoring.
The complexity around the dynamic markets for new psychoactive substances (NPS) forces researchers to develop and apply innovative analytical strategies to detect and identify them in influent urban wastewater. In this work a comprehensive suspect screening workflow following liquid chromatography - high resolution mass spectrometry analysis was established utilising the open -source InSpectra data processing platform and the HighResNPS library. In total, 278 urban influent wastewater samples from 47 sites in 16 countries were collected to investigate the presence of NPS and other drugs of abuse. A total of 50 compounds were detected in samples from at least one site. Most compounds found were prescription drugs such as gabapentin (detection frequency 79%), codeine (40%) and pregabalin (15%). However, cocaine was the most found illicit drug (83%), in all countries where samples were collected apart from the Republic of Korea and China. Eight NPS were also identified with this protocol: 3-methylmethcathinone 11%), eutylone (6%), etizolam (2%), 3-chloromethcathinone (4%), mitragynine (6%), phenibut (2%), 25I-NBOH (2%) and trimethoxyamphetamine (2%). The latter three have not previously been reported in municipal wastewater samples. The workflow employed allowed the prioritisation of features to be further investigated, reducing processing time and gaining in confidence in their identification.
Previous studies have predominantly focused on morphine for clinical use, codeine, and heroin as potential contributors, neglecting the possible contribution from poppy straws in Chinese traditional medicines. To determine the sources of morphine, this study collected influent samples from 150 wastewater treatment plants in 49 cities across the South and North of China for monitoring five substances, including morphine, codeine, 6-acetylmorphine, methadone, and tramadol. Positive matrix factorization (PMF) found that poppy straws (59.1%) and morphine for clinical use (28.5%) were identified as major contributors, while codeine (9.20%) and heroin (3.20%) contributed less. To validate the PMF results, a comparison was made with the International Narcotics Control Board (INCB) survey. The mass load of morphine derived from different sources, as determined by the INCB data survey, fell within the 95% confidence interval calculated by PMF, indicating consistency between the two surveys. Based on the PMF sources, morphine use from poppy straws and clinical purposes was calculated to be 11.8 mg/d/1000 inh and 9.55 mg/d/1000 inh, respectively. Consumption of codeine and heroin was estimated at 9.45 mg/d/1000 inh and 0.64 mg/d/1000 inh, respectively. The quantitative analysis of morphine sources in wastewater provides an accurate assessment of the four sources of morphine in Chinese wastewater.
Metformin, the unique first choice medicine for type 2 diabetes (T2D) in the US and Europe, was not widely adopted in China until recently. We measured metformin in wastewater samples, collected in major cities in China every 2 years from 2014 to 2020, to understand spatial and temporal trends of metformin use in T2D treatment in China. The estimated metformin use (mg/day/person) increased significantly from 1.6 +/- 1.8 in 2014 to 4.2 +/- 3.6 in 2016, then to 7.0 +/- 8.8 in 2018, and 9.2 +/- 9.0 in 2020. Metformin use increased nationally and in all seven geographical regions. Our findings reflect the broader uptake of metformin for treatment of T2D in China in accordance with expert recommendations. There was higher metformin use in the North than in the South of China, reflecting similar spatial trends in obesity rate in China. Wastewater analysis is likely to be a cost-effective way to monitor T2D treatment across China in the future.
With rapid economic development, an increasing number of people suffer from mental health diseases, which are gradually receiving the attention of society. However, basic data from surveys of mental disorders are limited. Composite influent samples were collected from 26 wastewater treatment plants in 23 major cities in China. The concentrations of the psychoactive drugs diphenhydramine, fluoxetine, doxepin, imipramine, sulpiride, zolpidem, carbamazepine, and flunitrazepam in the wastewater were determined. The detection frequency of diphenhydramine, sulpiride, and carbamazepine was close to 100 %, whereas that of the compounds was lower than 35 %. Carbamazepine had the highest mean consumption (31.1 mg/d/1000 people), followed by diphenhydramine (10.4 mg/d/1000 people) and sulpiride (11.3 mg/d/1000 people). Wastewater-based epidemiology (WBE) estimates of the average use of the three drugs were lower than those from the drug statistics data. Consumption of diphenhydramine in northern China was higher than that in southern China. A correlation analysis of psychotropic and illicit drugs revealed a correlation between sulpiride and heroin use, which may be related to the adverse effects of sulpiride treatment after heroin withdrawal. Psychotropic drug use is associated with both economic and social factors. We found associations between the use of the three drugs and age, occupation, and obesity, which are risk factors for mental disorders. The results showed that the monitoring of psychotropic drug using WBE has a certain reference value for public health care and for improving the understanding of mental disorders.