Adults with attention deficit/hyperactivity disorder (ADHD) often present psychiatric comorbidities and, in particular, substance use disorder (SUD). ADHD-SUD comorbidity is characterized by greater severity of both disorders, earlier age of onset, higher likelihood of polydrug-abuse and suicidal behaviors, more hospitalizations, and lower treatment adherence. At the present stage, research focused on the pharmacological management of ADHD with comorbid SUD in both adolescents and adults is still lacking. Furthermore, while the short-term effects of stimulants are well studied, less is known about the chronic effects of these drugs on dopamine signaling. Current available evidence is consistent in reporting that high doses of stimulant medications in ADHD-SUD subjects have a mild to moderate efficacy on ADHD symptoms. Some data suggest that pharmacological treatment with stimulants may be beneficial for both ADHD symptoms and comorbid cocaine or amphetamine use. However, in the long run, stimulant medications may have a potential risk for misuse. For the absence of potential misuse, atomoxetine is often recommended for ADHD with comorbid cocaine or amphetamine use disorder. However, its efficacy in reducing addictive behavior is not demonstrated. In subjects with other subtypes of SUD, both atomoxetine and stimulant drugs seem to have scarce impact on addictive behavior, despite the improvement in ADHD symptomatology. In this population, ADHD treatment should be combined with SUD-specific strategies. Attention deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention, distractibility, disorganization, hyperactivity, and both behavioral and emotional impulsivity. It is the most common neurodevelopmental disorder diagnosed in childhood and persists into adolescence and adulthood in about 60–70% of cases ,2. The wIn children, the male-to-female ratio ranges from 2:1 to 10:1 and is higher in clinical samples than in the general population. With increasing age, this prevalence discrepancy between males and females diminishes . PresumaIn adults, hyperactivity usually improves, while inattention, impulsivity, and emotional dysregulation persist or even worsen, resulting in social, interpersonal, and work impairment. In addition, most adults with ADHD show numerous psychiatric comorbidities, such as alcohol/substance use, mood, anxiety, eating, and impulse control disorders, which complicate the clinical picture and therapeutic management and are associated with poor treatment outcomes .In particular, substance use disorder (SUD) comorbidity in ADHD subjects is very common, and nearly a quarter of young adults with SUD meet the diagnostic criteria for ADHD ,9. In geFrom a neurodevelopmental perspective, ADHD symptoms starts in childhood, suggesting their role as risk factors for early onset of substance use and the development of SUD. Childhood ADHD has been associated with a small to moderate increased risk of SUD in adolescence or early adulthood (with odds ratios ranging from 1.34 to 3.48 for different types of SUD) . AccordiThe dysfunctions of the brain’s inhibitory and reward systems, resulting in impulsivity and inability to delay gratification, that characterize ADHD are the main developmental risk factors for early substance use, misuse, and SUD in adolescence and early adulthood ,18. The The substances most commonly used by ADHD subjects are alcohol and/or nicotine, cannabinoids, stimulants (amphetamines and cocaine) and opiates ,23. The Currently approved pharmacological agents for youths and adults with ADHD act by increasing DA and norepinephrine (NE) transmission and include stimulant  and non-stimulant medications  . All guiIn some cases, psychiatric comorbidities  constitute a therapeutic priority. However, the coexisting symptoms of ADHD should always be considered during treatment management because they can strongly influence the clinical picture and the response to pharmacological treatment .To date, there is a paucity of research focused specifically on the pharmacological management of ADHD in comorbidity with SUD in both adolescents and adults, and the few recommendations are largely based on practice or short-term clinical trials . In adulThe current literature shows that ADHD in cocaine consumers has been identified in a range between 15.1% and 25% of the cases ,31,32. CImaging and post-mortem studies on chronic cocaine abusers showed an increase in the striatum concentration of dopamine active transporter (DAT) with respect to controls due to the chronic extracellular DA increase after multiple intoxications . SimilarLong-term treatment with stimulants at high dosages may be effective in controlling ADHD symptomatology in individuals with comorbid cocaine use disorder (CUD) ,39,40. IWhile stimulant medications have shown some efficacy in prolonging cocaine withdrawal, regardless of comorbidity with ADHD , they apIn a recent meta-analysis of randomized-controlled studies, indeed, the benefits demonstrated by prescription stimulants in patients with stimulant use disorder were mainly driven by studies on CUD . AlthougAnother problem in the treatment of adults with ADHD-CUD/ATSUD is the potential misuse of stimulants, which, however, appears to be less common with MPH than with amphetamines and seems to diminish, at least in part, with long-acting formulations . AtomoxeThe literature regarding the relationship between ADHD and SUD is mainly imprinted on cannabis or stimulant drugs ,58, leavADHD is considered a risk factor for developing AUD, with an odds ratio of 1.5 . PresumaA common pathogenic pathway between ADHD and AUD is thought to be a reduced dopaminergic activity, with AUD subjects presenting a decreased release of DA in the limbic system, and a reduced availability of dopaminergic receptors , althougOn the matter of pharmacological treatment, one study analyzed the effects of atomoxetine on ADHD symptoms and alcohol use in a sample of currently abstinent ADHD/AUD individuals. Atomoxetine was effective in reducing ADHD symptomatology, but it did not have an impact on the relapse into heavy drinking .Cannabis is the most commonly used illicit drug of abuse, the third if we consider the licit drugs . Considering the global population aged 15 to 64 years old, almost 4% used cannabis at least 1 time during 2019 , with anThe intersection and often overlapping effects of cannabis and ADHD can be challenging for the clinician. Tetrahydrocannabinol (THC) binds to cannabinoid receptors in the brain, causing feelings of well-being, euphoria, and anxiolysis, but also altering systems involved in memory, concentration, and time perception . Indeed,Neurotransmitters such as DA, serotonin, norepinephrine, gamma-aminobutyric acid (GABA), acetylcholine, histamine, and opioid peptides are also influenced by cannabis . In partIn a recent systematic review on cannabis use in ADHD, the authors did not report evidence of an impact of cannabis on cognition, measured by neuropsychological task performance, among users with ADHD compared to nonusers . On the As a general guideline, in order to treat ADHD individuals with comorbid cannabis use, it is important to reduce its consumption and possibly use melatonin in case of circadian rhythm disorders. The only clinical trial that evaluated ADHD treatment on ADHD symptoms and cannabis use found that atomoxetine, when compared to placebo, reduced ADHD symptoms, but it did not impact cannabis use, after 12 weeks of treatment .Opioids are the least common drug of abuse among ADHD subjects, and the ADHD/opioids comorbidity is thoroughly understudied. The comorbid diagnosis of ADHD among opioid use disorder (OUD) subjects seeking treatment is estimated to be around 20–25% ,92 and lADHD subjects who develop OUD are characterized by more severe addiction and comorbid psychopathology, only in part explained by the coexistence of a conduct disorder . EffectiA study compared the effects of MPH, bupropion, and placebo on a cohort of methadone-maintained subjects . The resIn conclusion, there is no clear evidence on when to start ADHD-specific treatments in subjects with OUD. Most studies seem to indicate that co-medication with ADHD treatment should be started after stabilization of opioid maintenance treatment.While a large amount of studies confirmed the beneficial effects of psychostimulants in the acute treatment of ADHD both in childhood and adulthood, fewer works address the chronic and long-term effects of these treatments on brain DA transmission, ADHD symptomatology, and functional outcomes. A systematic review of follow-up studies confirmed the greater efficacy of ADHD medication (stimulants and atomoxetine) over placebo in 5 randomized clinical trials and 11 open label extension studies of at least 24 weeks, with some naturalistic studies showing a possible role of ADHD medications in preventing depression and SUD in adulthood . RegardiWhile the acute effects of stimulants are well studied, less is known about the chronic effects of these medications on DA signaling. In fact, long-term treatment with stimulants leads to neuroadaptive changes that could explain the loss of their therapeutic efficacy observed in ADHD individuals . This efA single-photon emission computed tomography (SPECT) study analyzed DAT availability and the effect of MPH on DAT in ADHD subjects with and without cocaine dependence (CUD). At the baseline evaluation, ADHD-CUD subjects, who were abstinent for about 1.5 years, had a 25% lower DAT concentration in the striatum and a lower DAT occupancy after 2 weeks of MPH treatment compared to ADHD subjects without SUD. In this study, MPH response was less pronounced in the ADHD with CUD population than in those without. However, the difference between the two groups was not statistically significant. These findings are in line with other controlled studies showing small effects of MPH treatment in ADHD individuals with CUD .Overall, scientific data on the long-term effects and, consequently, the recommended duration and doses of prescribed stimulant treatment in adults with ADHD are still unconclusive, with few high-quality studies. From a clinical point of view, the use of long-lasting stimulant treatments for ADHD symptoms, even at high doses in ADHD-SUD individuals, seems to have a limited long-term efficacy and still a potential risk of misuse and addiction.Although, in the clinical setting, SUD is one of the most common comorbidities in adult ADHD subjects, data on the impact of SUD on treatment response of ADHD symptoms with stimulant medications or atomoxetine are still scarce. In particular, none of these drugs have been tested in long-term clinical trials, not allowing their long-term effectiveness to be clarified. Furthermore, many ADHD subjects that psychiatrists deal with in routinary clinical practice, who often have several psychiatric comorbidities and reduced adherence to treatment, are usually excluded from clinical trials. In light of these important gaps, the International Collaboration on ADHD and Substance Abuse (ICASA) foundation designed and conducted the International Naturalistic Cohort Study of ADHD and SUD (INCAS) . This prAccording to some authors , interveIndeed, the reported improvement of ADHD symptoms in subjects with comorbid SUD should not discourage ADHD treatment see . The oveBox 1-Attention deficit/hyperactivity disorder (ADHD) may represent a risk factor for early-onset substance use disorder (SUD).-Treating ADHD symptoms during childhood or adolescence with stimulant medications may reduce the risk of developing SUDs in adulthood.-Comorbidity between ADHD, especially the combined type, and SUD is very common and results in increased severity of both disorders.-The substances most commonly used by ADHD individuals are stimulants , cannabinoids, alcohol, and opiates.-In subjects with comorbid cocaine or amphetamine use disorder, high-dose stimulant medications are needed to improve ADHD symptomatology.-In individuals with predominantly inactive ADHD, stimulant medications may also have a positive impact on cocaine withdrawal. Less consistent data have emerged regarding the impact of these medications on amphetamine use disorder.-In individuals with alcohol, cannabis, or opiate use disorder, pharmacological therapy for ADHD appears to have little impact on addictive behaviors, despite improvement in ADHD symptomatology.-Despite the paucity of studies on pharmacological management of ADHD-SUD comorbidity, substance abuse should not discourage ADHD treatment.-In individuals with ADHD-SUD comorbidity, especially those with a history of amphetamine/cocaine abuse, attention should be paid to the risk of stimulant misuse.-Methylphenidate has a lower risk of abuse than amphetamines, especially in extended-release formulations.-Atomoxetine is often recommended for individuals with ADHD in comorbidity with cocaine use disorder, but its effectiveness in reducing addictive behavior has yet to be proven.-Given its low abuse potential, bupropion may have a role in treating ADHD individuals with comorbid cocaine abuse and depression.-Although the beneficial effects of psychostimulants in the acute treatment of ADHD are widely confirmed, stimulants may lose their therapeutic efficacy in the long term, especially in comorbid SUD subjects.Obviously, attention should be paid to the risk of abuse of stimulant medications in ADHD-SUD individuals, especially if they use cocaine or amphetamines. Close monitoring for signs of abuse, such as not attending appointments or requesting higher doses or more prescriptions of the drug, is essential after initiating treatment. In this population, extended-release MPH formulations are recommended. For those with active SUD and/or high risk of abuse, non-stimulants, such as atomoxetine and bupropion, should be considered .Alongside pharmacological treatment, psychotherapeutic interventions play a role in the management of ADHD-SUD subjects. Indeed, psychoeducation of patients and family members to enhance knowledge about the condition, natural history, and prognosis are critical to improve recognition and treatment of the ADHD-SUD comorbidity . In addiFinally, the wide range of other psychiatric conditions often associated with ADHD in adults suggest to adopt an individualized therapeutic plan and not only an ADHD targeted treatment.In the future, larger randomized clinical trials and naturalistic studies with longer follow-ups in adult subjects with ADHD and comorbid SUD are needed to better define the long-term efficacy and safety of ADHD medications.


Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits.n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD, we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results.We used genome-wide association study (GWAS) summary statistics for ADHD  = 0.966, 95% credible interval (CrI) = ] and increased lifetime number of sexual partners . We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight  and time spent watching television , and evidence for a bidirectional effect for age of first sexual intercourse , odds of decreased age completed full-time education  and years of schooling .Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories. Key MessagesOur results are consistent with a causal effect of attention deficit/hyperactivity disorder (ADHD) genetic liability decreasing average total household income and increasing lifetime number of sexual partners.We detect a positive effect of the liability of anthropometric traits (arm predicted mass and weight) and of time spent watching television on ADHD.We show evidence for a bidirectional negative effect between liability of ADHD and of education outcomes (years of schooling and age completed full-time education), age of first sexual intercourse and past tobacco smoking for non-heavy smokers.,,,Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a prevalence of around 5.3% in childhood and 2.8% in adulthood.,ADHD is characterized by a persistent pattern of inattentive, hyperactive and impulsive behaviour; however, its clinical presentation is heterogeneous, with a wide spectrum of severity and symptoms that often overlap with other conditions.Most studies undertaken to date have reported association between ADHD and comorbid traits, but inferring causality can be more challenging due to the potential effect of confounding factors or reverse causality. Different strategies have been developed to overcome these inference problems, and the causality for ADHD and a number of traits have been tested using: (i) longitudinal analyses, some of them undertaken in twins; (ii) Mendelian randomization (MR), which uses genetic variants as proxies for an exposure  to test for a causal effect on an outcome,,,Overall, the evidence from causal inference analyses undertaken for ADHD is hard to interpret, in some cases due to the limited number of strategies applied,n = 31 772) which fulfilled the following inclusion criteria: (i) sample size [N effective = 4 × N cases × N controls/(N cases + N controls) for binary traits] >5000; (ii) results available in more than 450 000 genetic variants; (iii) European ancestry; (iv) non sex-specific; and (v) more than three independent genome-wide significant signals (P <5.00e-08). This reduced the number of traits to 1259 (IJE online). At this point we removed traits related to diet (n = 52), to metabolites’ levels (n = 132), to procedural metrics or biological samples (n = 76) and to clinical traits (n = 600), except those related to neurological, psychiatric and mental health; and selected traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, psychiatric and mental health or personality and psychosocial factors. We then removed duplicated and unordered categorical traits . The MR-Base summary statistics used for these 124 traits were obtained from different sources: European Bioinformatics Institute (EBI) database,http://www.nealelab.is/uk-biobank],We selected GWAS summary statistics available in the MR-Base databasen = 150, . Finally2 <0.001 or distance >10 000 kb) with P <5.00e-08 in the exposure, and variants meeting the threshold for both the exposure and the outcome were removed. For exposure variants not found in the outcome, GWAS proxies were used instead . ADHD liability genetic instruments are provided in IJE online). False-discovery rate (FDR) across all tests considered was used to correct for multiple testing.We ran two-sample MR in both directions to assess the potential causal relationship between ADHD and every selected trait, using the multiplicative random effects inverse variance weighted (IVW) method as the main analysis.P <0.05, we undertook sensitivity analyses to assess the robustness of the findings under weaker assumptions, given that the genetic variants used as instruments must meet three assumptions for IVW results to be valid: (i) robust association with the exposure; (ii) no horizontal pleiotropy, or association with the outcome through a pathway independent of the exposure; and (iii) independence of confounders that influence the exposure and the outcome.For IVW results with FDR corrected ,,,2GX< 0.9 we implemented the method of simulation extrapolation (SIMEX) to obtain an adjusted estimate of the causal effect.et al.,,We used weighted median and weighed mode methods, which only require a subset of variants to be valid instruments and are robust to outliers.P <0.05; (ii) the same direction of effect as the IVW beta estimate and P <0.05 was found for the weighted median and mode, MR PRESSO, IVW after Steiger filtering and when there was also evidence of pleiotropy (MR-Egger intercept P <0.05), MR-Egger or SIMEX if We considered that there was evidence of a causal relationship if: (i) IVW FDR 2 <0.01; distance >250 kb) associated to the exposure with P <1.00e-03 were included, and the cause v1.2.0 R package was used for these analyses.P <1.21e-03).For those traits that met the MR sensitivity criteria, we also ran causal analysis using summary effect estimates (CAUSE).P <0.05 for one anthropometric trait when ADHD was the exposure, 17 when ADHD was considered as the outcome and seven in both directions (IJE online). After sensitivity analyses there was evidence of a positive effect of the genetic liability of eight traits  on ADHD . Also, evidence meeting the multiple comparison correction was found with CAUSE for a causal effect of arm predicted mass and weight on ADHD , with also suggestive evidence (ΔELPD P <0.05) of a positive effect for the remaining traits   . Of them2 = 63.896%), and although removing one outlier in the MR-PRESSO analysis reduced the heterogeneity and the causal effect estimate, measured as odds of maternal smoking per unit increase in log odds ratio [log(OR)] of ADHD, it remained significant  , ΔELPD P = 1.08e-010, respectively]  was detected for alcohol intake frequency, age of first sexual intercourse and lifetime number of sexual partners when ADHD was the exposure and for Townsend deprivation index in the other direction  was shown in the CAUSE analysis for a causal effect of the genetic liability of ADHD on the remaining smoking-related traits and on all alcohol-related traits, except for alcohol intake versus 10 years previously, which showed an effect in the opposite direction, and for Townsend deprivation index, which showed an effect in both directions ], higher odds of a increased lifetime number of sexual partners  and a negative effect in both directions for age first had sexual intercourse  , Table 2P = 0.025, In the IVW analysis, there was no evidence of a causal effect when ADHD was considered as outcome, but evidence for an effect of ADHD as exposure was found in all longevity-related traits, decreasing maternal, paternal and combined age of death or attained age and decreasing the odds of both parents being in the top 10% of survival . HoweverP = 2.34e-04] (We found evidence of an increase in the odds of major depression per unit increase in the log(OR) of ADHD in the IVW analysis  , Table 2.34e-04] .ΔELPD P = 2.13e-03, P = 7.34e-03, In the IVW analysis, we found evidence of an effect for ADHD as exposure on one trait, with ADHD as outcome for nine traits and in both directions for three traits . The effOverall, the direction of the causal effect size estimates was consistent between IVW MR and CAUSE for all analyses undertaken and, in general, CAUSE effect size estimates were smaller than those estimated by IVW MR  and 2.In the present study we assessed for the first time the causal relationships between ADHD and a broad range of ADHD-related traits, applying complementary approaches. Through this comprehensive strategy we found consistent evidence across methods for a causal effect of the genetic liability of anthropometric measures and time spent watching television on ADHD, for the genetic liability of ADHD on average household income and major depressive disorder, and a bidirectional relationship with educational achievement, smoking and sexual behaviour.,,Our findings give support to the relationship between ADHD and risk-taking behaviours and to existing evidence indicating that ADHD is an entry point into a harmful life trajectory, where ADHD individuals are more likely to engage in behaviours that put them at risk for negative outcomes, including smoking, problematic substance use or unsafe sexual behaviour.Our results also support a positive effect of time spent watching television on ADHD, which goes in line with a reported association between ADHD and television usage and with evidence from longitudinal studies reporting an effect of increased screen time worsening a child’s development and increasing risk for autism spectrum disorder.,,,In addition, our findings strengthen previous evidence linking ADHD with academic, employment and financial problems.,,Along these lines, we also found evidence for liability of lower age at first sexual intercourse and of lower rate of past tobacco smoking in non-heavy smokers increasing the odds of ADHD. Evidence from the literature has linked related traits such as young parental age or maternal smoking with increased risk of ADHD in children,,We also show evidence consistent with a positive effect of anthropometric measures on ADHD, a finding which is likely related to the effect of BMI liability on ADHD, reported in a previous MR study.Our findings also confirm the effect of ADHD liability on major depression and the lack thereof when using a broader definition,The results of the present study should be interpreted in the light of several limitations, as follows.Given that we aimed to give an overview of potential causal relationships between ADHD and a considerable number of related traits, using publicly available summary statistics datasets, it was not feasible to tailor the analytical strategy separately for each trait or to carefully curate each phenotype. This may have prevented us from identifying additional evidence for causal relationships, as may be the case for birthweight mentioned above,Aiming to avoid false-positive results, we designed a strict analysis pipeline. We undertook a comprehensive set of sensitivity analyses, including the weighted mode, recently reported to maintain the correct type I error rate in a diverse set of scenarios but also to be too conservative, particularly for large sample sizes.Despite undertaking this range of different analyses, each one under a different set of assumptions, and selecting only results that were consistent across methods, we still identified some temporally implausible relationships. These associations could be explained statistically because the instruments were used as measures of the liability for a trait, not necessarily its observed manifestation,Some of the scenarios where MR sensitivity analyses have been carried out may not have been optimal for their performance: for instance, the limited number of genetic instruments available for ADHD (particularly relevant for MR Egger) or the difference in sample size between the exposure and the outcome in some comparisons (relevant for Steiger filtering). It may be that under more suitable circumstances, MR sensitivity analyses would be more efficient in detecting false-positive results.In addition, genetic variants could be associated with more than one trait, which would make it difficult to ascertain which one is the true causal exposure. This is particularly relevant when analysing correlated traits, as it is the case in this study. Further sensitivity analyses, which were out of the scope of this study, excluding variants associated with other traits or undertaking mediation analysis would contribute to deepen our understanding and provide more robust evidence for the causal relationships identified. For instance, multivariable MR analyses have been used to detect an effect of educational attainment mediating the relationship between BMI and ADHD.We must be cautious when comparing effect sizes between analyses with ADHD as exposure and outcome, since they are often presented in different scales, and there are a number of assumptions that need to hold for reliable interpretation of causal effects for binary exposures.,There are some methodological issues that should also be considered. Given the large resources of GWAS summary statistics currently available and the flourishment of MR-related methods being developed, there is a huge potential for MR analyses to shed light into the causal relationships between many complex traits. We should, however, also bear in mind their limitations when designing studies and interpreting results. In order to avoid the effect of horizontal pleiotropy, which is relevant given that emerging results from GWAS point to a large number of genetic variants being associated with multiple traits,Our results are consistent with a causal effect of the genetic liability of ADHD on average household income and major depressive disorder, of the genetic liability of anthropometric measures and time spent watching television on ADHD, and of a bidirectional relationship with educational achievement, smoking and sexual behaviour. Additional analyses with complementary study designs to avoid the effect of potential biases will be required to follow up these findings. However, our results may still contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD, and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories.Ethics approval was not required for this study, since no new data were generated and only summary statistics were analysed.dyac128_Supplementary_DataClick here for additional data file.


The same trend was observed when using the sex-specific cutoff points . Higher consumption of added sugar from beverages may increase the risk of ADHD symptoms in Thai medical students. This finding supports the implementation of health policies that promote healthy consumption behaviors among medical students.Attention deficit hyperactivity disorder (ADHD) significantly affects the well-being of medical students in various aspects. Sugar-sweetened beverages (SSBs) pose a potential risk of ADHD. Our study aimed to determine the prevalence of ADHD symptoms and the association between consumption of added sugar in common beverages and ADHD symptoms in Thai medical students. An online cross-sectional survey was conducted among medical students at Chiang Mai University from May 2022 to April 2023. The consumption of added sugar from common beverages in Thailand was assessed using the Thai Adolescence Sugar Sweetened Beverage Intake (THASSI) questionnaire. An Adult ADHD Self-Report Scale (ASRS) score ≥ 3 identified the presence of ADHD symptoms. Multivariable logistic regression was used for the analysis. Of 441 participants, 29.9% had ADHD symptoms. Daily consumption of added sugar from beverages higher than 25 g/day showed an increased risk of ADHD symptoms (adjusted odds ratio (OR) 1.80, 95%CI 1.15 to 2.84,  Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition characterized by symptoms including inappropriate levels of inattentiveness, hyperactivity, and impulsivity ,2. ADHD Some evidence suggests a possible association between the consumption of sugar-sweetened beverages (SSBs) or caffeine and ADHD symptoms . SeveralPrevious research has often focused on examining the consumption of SSBs and ADHD in children. Most of these studies have not identified the dose–response characteristics of added sugar in relation to ADHD symptoms or suggested practical limits for healthy consumption. It is important to note that ADHD can also manifest in adults ,5. NotabWe conducted an online cross-sectional survey among medical students at Chiang Mai University from May 2022 to April 2023. The survey was developed using the Research Electronic Data Capture (REDCap) platform [The target population consisted of undergraduate medical students in their 1st year to 6th year in the academic year 2022. We excluded participants who reported current active underlying medical conditions, those who had been previously diagnosed with mood disorders such as ADHD, major depressive disorder (MDD), anxiety disorder, and bipolar disorders, and participants who did not complete the Thai version of the Adult ADHD Self-Report Scale (ASRS) screener questionnaire .The online survey consisted of three parts. In the first part, participants were asked to provide information on general demographic characteristics, including age, sex, current academic year, weight, height, body mass index, underlying conditions, and current medication. Additionally, they were asked to provide ADHD-relevant characteristics such as family history of ADHD , family The primary determinant was the total daily amount of added sugar consumed from common beverages, measured in grams (g). To estimate this value, participants were asked to complete the THASSI questionnaire, which required them to provide retrospective information about the beverages they consumed during the previous week. The THASSI questionnaire specifically focuses on 10 common types of beverages, namely sweetened drinks/water, sweetened carbonated soft drinks, energy drinks, coffee, sweetened green tea, sweetened yogurt drinks, sweetened vegetable and fruit juice, sweetened herbal drinks, sweetened soy milk, and sweetened milk .Participants were asked to select the type of packaging  and size of the beverage they consumed from the provided lists in the THASSI questionnaire. This questionnaire comprehensively covers common beverage products available in the Thai market. They were then required to specify the amount consumed per occasion and the average frequency of consumption per week for each item. The THASSI questionnaire provides the volume of each beverage in milliliters (mL) and the added sugar content per mL for each item. Consequently, the total amount of added sugar from each item can be calculated by multiplying the added sugar content per mL by the total volume consumed within a week. To determine the daily consumption, the weekly consumption amount was divided by 7. Finally, we calculated the total daily consumption of added sugar from all types of beverages by summing up the daily amounts consumed of each type of beverage together.Since there was no established standard consumption threshold specifically for added sugar from beverages, we divided the total daily consumption for each participant into three equally proportioned tertiles. This categorization enabled us to observe any potential dose–response relationship. Furthermore, we categorized the total daily consumption based on the added sugar limit recommended by the American Heart Association (AHA) . The oveDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) [The diagnosis of ADHD is typically conducted by a physician using the (DSM-IV) . But for(DSM-IV) , a self-The primary endpoint was the presence of ADHD symptoms as determined using the Thai ASRS version 1.1, which serves as a reliable screening tool for adult ADHD . The quep-values less than 0.05 were considered statistically significant, whereas p-values between 0.05 and 0.10 were considered borderline significant.All statistical analyses were performed using Stata version 18 . Categorical variables were described using frequency and percentage. Numerical variables with normal distribution were described using mean and standard deviation (SD), whereas variables with skewed distribution were described using median and interquartile range (IQR). A non-parametric test for linear trends was used to identify significant trends across total added-sugar consumption tertiles. Fisher’s exact probability test was used to compare the proportions between two independent groups. The Mann–Whitney U test was used to test the differences in non-normally distributed numerical variables between two independent groups. Multivariable logistic regression was employed to investigate the association between the main determinants of interest  and the presence of ADHD symptoms. The model was adjusted for potential confounding variables, including age, sex, BMI, history of ADHD in the family, family income, monthly allowance, maternal and paternal education, sleeping duration, and screen time. Adjusted odds ratios (aORs) and their corresponding 95% confidence intervals (CIs) were reported for each determinant. Additionally, as the total daily consumption represented a combination of ten different beverages, separate analyses were conducted for each one. The consumption amount for each beverage type was categorized into tertiles or median as appropriate. The multivariable logistic models for each beverage type were adjusted with the same confounding variables as the primary model, along with the consumption amounts of the other beverages.We also conducted an additional analysis to explore the association between other potential factors, including all demographic and ADHD-relevant clinical characteristics, and the presence of ADHD symptoms. Multivariable logistic regression analysis was also employed. Added sugar consumption exceeding the AHA-recommended limits was included in the model as a confounder to be adjusted.Of a total number of 1472 medical students invited during the 2022 academic year, 534 (36.3%) responded to the survey. We excluded 19 students who had a history of active underlying medical conditions or had been previously diagnosed with mood disorders including ADHD and 74 students who did not complete the ASRS screener questionnaire. Finally, 441 students were included in the analysis, accounting for 30.0% of all students.The average age of the students was 20.6, with a male-to-female ratio of 1:1. Almost 60% of the responders were from students in pre-clinical years. p = 0.048) . The most prevalent ADHD symptoms identified were trouble wrapping up final details (48.8%), followed by trouble remembering appointments (37.0%) and trouble getting things in order (34.0%). No significant trends of ASRS v1.1 risk score and proportion of students with ADHD symptoms were identified across daily added sugar consumption tertiles . However= 0.048) .p = 0.061). On the other hand, when the daily consumption was classified based on sex-specific cutoff points , the association with ADHD symptoms was significant (p = 0.046). From the univariable analysis, students categorized in higher tertiles according to their daily consumption of added sugar from beverages showed a tendency to have ADHD symptoms without statistical significance. Students who reported a consumption of added sugar from beverages higher than 25 g/day regardless of their sex showed a borderline statistically significant association with ADHD symptoms (p = 0.011). We also identified a significant association between a higher daily consumption of added sugar from beverages and ADHD symptoms when the sex-specific cutoff points were used . Higher tertiles of consumption showed only borderline statistically significant associations with ADHD symptoms   .p = 0.043), green tea , and soy milk .p = 0.033) and having more than 7 h of daily screen time  significantly increased the risk of ADHD symptoms in our data  may significantly increase the risk of ADHD symptoms. We also identified three types of beverages, sweetened drinks/water, green tea, and soy milk, that have the potential to increase ADHD symptoms. However, these findings still require further confirmation.The prevalence of ADHD symptoms in our study was found to be 29.9%, closely resembling the reported prevalence of ADHD among medical students in the US in 2019, which was 30.4% . The preIt was observed that the consumption of added sugar from common beverages exceeding sex-specific recommendations  was associated with an increased risk of ADHD symptoms. This finding aligns with a previous study that reported an association between high consumption of SSBs and ADHD symptoms ,18. InteOne potential mechanism through which sugary drinks may impact ADHD symptoms is by disrupting the gut–brain axis pathway. The gut–brain axis serves as a bidirectional communication system between the gastrointestinal tract and the central nervous system. High consumption of sugary drinks has been observed to alter the composition of the gut microbiota due to an unfavorable nutritional environment . This alOur study found three types of beverages that may increase the risk of ADHD symptoms. The first involves sweetened drinks/water, which, as the name suggests, is quite straightforward. The predominant component of these beverages is sugar, which may elevate the risk of ADHD symptoms through various described mechanisms, such as disrupting the gut–brain axis pathway. The second type is green tea; our data imply that drinking it may be associated with a higher risk of ADHD symptoms. Our findings differ from those of previous studies that have shown the potential benefits of caffeine and L-theanine, which is found in green tea, in reducing ADHD symptoms . The difBesides the amount of added sugar in beverages, two additional factors have been identified as being associated with the presence of ADHD symptoms among Thai medical students: being overweight and having daily screen time exceeding 7 h. The association between overweight/obesity and ADHD has been a subject of conflict for the last two decades ,47. It iThis study had several strengths and implications. Firstly, we examined the association between the quantity of added sugar consumption from common beverages in Thai market and ADHD symptoms, specifically among medical students. To the best of our knowledge, this study may be one of the first to examine this important issue in this population and has found that there might be a dose–response relationship between the amount of added sugar in consumed beverages and the presence of ADHD symptoms. Most importantly, using AHA-recommended cutoff values to determine inappropriate amounts of added sugar could provide clearer guidance to promote healthier beverage consumption among medical students. Secondly, data collection for the determinants and outcome was performed using standardized tools validated in the Thai population. However, there are also limitations to consider. Firstly, the proportion of sugar in Thai beverages does not have a standardized measurement, which may have resulted in some inaccuracies when assessing sugar consumption through the questionnaire. Secondly, the study design was cross-sectional, and as a result, causality between the associated factors and ADHD symptoms could not be determined. The design also limits our ability to examine the effect of added-sugar consumption on ADHD symptoms in a longitudinal aspect. Thirdly, due to this study’s design, there might be some recall bias. A prospective study could enhance the accuracy of the data. Fourthly, this study was conducted within the context of the Faculty of Medicine, Chiang Mai University, and the findings may not be generalizable to other communities or contexts. Therefore, future studies should aim to include larger sample sizes and diverse cultural and contextual settings to further investigate this relationship. Finally, since our research domain was focused entirely on medical students, the association between the amount of added sugar from common beverages consumed and the presence of ADHD symptoms identified in this study might not be generalizable to other strata of society. It is important that the existence of this association be examined and confirmed both in the general population and among subgroups within it. While evidence of an association in the general population can inform public health policy, it does not necessarily imply that all underlying subgroups are affected in the same way. Analyzing data from specific subgroups can spotlight particular segments of the population that may be at higher risk than average.Increased consumption of added sugar from common beverages may elevate the likelihood of ADHD symptoms among Thai medical students. Our findings highlight the critical need to promote healthier consumption habits among this population specifically. Adopting such measures could potentially mitigate ADHD symptoms among medical students, thereby enhancing their overall well-being and quality of life.


Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood and adult behavioral disorder. Internet searches for ADHD information are rising, particularly for diagnosis and treatment. Despite effective ADHD treatments, research suggests that there are delays in seeking help for ADHD. Identifying ways to shorten delays is important for minimizing morbidity associated with ADHD. One way to shorten these delays is to improve internet health information resources. Research shows that parents of children with ADHD feel that much of the information available is technical and not tailored for their child’s needs and verbal instructions given by health care providers were too pharmacologically focused with limited information about how to manage and support ADHD symptoms in daily living. A majority of parents search the internet for general and pharmacological information for ADHD and prefer web-based resources for learning about ADHD, but web-based resources may be inaccurate and of low quality. Ensuring accurate information through the internet is an important step in assisting parents and adults in making informed decisions about the diagnosis and treatment of ADHD.Although a great deal of information regarding ADHD is available on the internet, some information is not based on scientific evidence or is difficult for stakeholders to understand. Determining gaps in access to accurate ADHD information and stakeholder interest in the type of information desired is important in improving patient engagement with the health care system, but minimal research addresses these needs. This study aims to determine the information needs and formatting needs of web-based content for adults with ADHD and parents of children with ADHD in order to improve user experience and engagement.This was a 3-phase study consisting of in-depth phone interviews about experiences with ADHD and barriers searching for ADHD-related information, focus groups where participants were instructed to consider the pathways by which they made decisions using web-based resources, and observing participants interacting with a newly developed website tailored for adults with potential ADHD and caregivers of children who had or might have ADHD. Phase 1 individual interviews and phase 2 focus groups identified the needs of the ADHD stakeholders related to website content and format. Interview and focus group findings were used to develop a website. Phase 3 used think-aloud interviews to evaluate website usability to inform the tailoring of the website based on user feedback.Interviews and focus group findings revealed preferences for ADHD website information and content, website layout, and information sources. Themes included a preference for destigmatizing information about ADHD, information specific to patient demographics, and evidence-based information tailored to lay audiences.ADHD stakeholders are specifically seeking positive information about ADHD presented in a user-friendly format. Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder characterized by developmentally distinct levels of impulsivity, hyperactivity, and inattention. ADHD is the most prevalent behavioral disorder affecting children, with estimates ranging from 5% to 11%, and is one of the most common psychiatric disorders affecting adults 4.4%) . Based o.4% . BasAlthough significant benefits are seen with the treatment of ADHD, research suggests that the delay in seeking help for ADHD is on average 3.96 years in children and 13 years in adults . FindingParents are the primary group of caregivers seeking information about ADHD diagnosis and treatment. Research shows that parents of children with ADHD feel that much of the information available is technical and not tailored to their child’s needs. In addition, they felt as if the verbal instructions given by health care providers were too medicine-focused with limited information about how to manage and support ADHD symptoms in daily living . Over 80Although the impact of ADHD on children, adults, and society is well described in the literature, there continues to be a significant delay in seeking help for ADHD. Stigma, misinformation, and lack of information contribute to this delay. With the internet becoming a rapidly growing source of health care knowledge, it is essential to determine ways of utilizing its power to educate large populations. Communicating accurate information through the internet is an important step in assisting patients and adults in making informed decisions about the diagnosis and treatment of ADHD. This study aims to address gaps in knowledge access through interviews and focus groups with the stakeholders seeking this information, including adults with ADHD.The objective of this study was to improve the quality and usability of a website based on the information and user needs of adults and parents of children with ADHD in order to ensure individuals in need of ADHD information have accurate, easy-to-access information in the hopes of improving knowledge acquisition, user experience, and self-efficacy in relation to ADHD. We achieved this goal by identifying the information needs and preferences of stakeholders (family members and children or adults with ADHD) around ADHD, gathering stakeholder feedback to develop a website meeting these needs and preferences, and assessing the ways in which users interact with and access information on the website.Participants were recruited through a search of existing networks of ADHD parents , advocates, educators, and primary care providers, including public steering committees and the Institute’s recruitment volunteer registry.A qualitative framework was used to explore the informational needs of adults with ADHD and parents of children with ADHD for the purpose of designing a website dedicated to providing educational resources to the general public. This was a 3-phased study. The study team consisted of experts in qualitative inquiry, health services researchers, a sociologist, a behavioral pediatrician, and a licensed psychologist with expertise in ADHD. The research team interviewed individual participants to gather data regarding ADHD information needs, moderated focus groups to gather data regarding decision-making strategies and website format preferences, and guided participants in a think-aloud interview utilizing the newly developed website.Phase 1 consisted of in-depth phone interviews where participants were asked to discuss their experiences with ADHD, barriers they encountered searching for ADHD-related information , and information preferences .Phase 2 consisted of focus groups where participants were instructed to consider the pathways by which they made decisions (in the presence or absence of the needed information) as well as the important aspects of information, points of access, and decision-making points. During this phase, participants were also guided through an activity to sketch preferred layouts for websites that they visited when seeking information related to ADHD. Participants were asked to share their sketches to highlight the attributes of the layouts that made navigating the website and accessing information easier. Using the findings from phase 1 and phase 2, a website was developed by content experts at a university, neurodevelopmental center.In phase 3, we observed participants interact with the newly developed website to understand the ways in which our target audience used the website. Interviews consisted of participants navigating through the newly developed website while thinking aloud. Participants’ internet searches were recorded using screen capture software .The investigators transcribed the interviews and used thematic analysis to identify common, data-driven themes and to describe patterns found in the data. Phase 2 participant sketches of preferred website layouts  were comThis study was reviewed and approved by the University of California, Davis Internal Review Board (project #:816998). All participants signed an informed consent outlining what their participation involved, the purpose of the study, and their rights and role as a participant. During the session, the study team reviewed the informed consent document to ensure participants understood the informed consent process. Recordings from the interviews and think-out-loud exercises were deleted, transcribed, and deidentified. Recordings were stored in a secure file folder that only the study team had access to. Parents of children with ADHD and adults with ADHD participating in the focus groups received a US $25 Amazon gift card, educators received a US $50 Amazon gift card, and clinicians received a US $100 Amazon gift card.In total, 15 in-depth interviews were conducted in phase 1 illuminating participants’ needs for stakeholder-specific and evidence-based information.All persons interviewed indicated that there is a dearth of information regarding ADHD and that a centralized source that could provide quality information  is needed. All stakeholders expressed that information should be tailored to individual interests and needs. For example, a website includes tabs linked to information for specific populations.Regardless of stakeholder type, interview participants stated that information should be presented and framed by different stakeholders’ perspectives. For example, information regarding the signs and symptoms of ADHD should be presented by age and stage of development. A mother of 2 children with ADHD stated that parents often “want to know what are the symptoms, how to get diagnosed, and a checklist.” Stakeholders also expressed a need for strategies to guide discussions about ADHD with nonclinicians. Specifically, several parents expressed the need for education on communicating with teachers, family, and friends about their child’s ADHD. Clinicians requested information about how to talk to parents about ADHD, including an ADHD handout explaining basic information about ADHD.Evidence-based research includes both contemporary journal papers and summaries of studies that are straightforward and easily understood by lay audiences. Participants expressed a specific need for information about medication and its management, such as dosing in various contexts , and side effects were also requested. Parents expressed a need for links to assessment tools and a list of resources including websites, therapists, community services, and readings. Almost all participants stated that if the website were linked to a locally known institute for neurodevelopmental disorders at a university or other “trustworthy” sources that it would be seen as reputable.Two focus groups conducted (N=13 participants) in phase 2 identified participants’ information preferences and seeking strategies. Participants are seeking out information that is destigmatized and tools to identify ADHD-related behaviors and relevant support resources.Adults with ADHD frequently expressed wanting to read or watch videos of individuals who have overcome the challenges associated with ADHD, while highlighting the many unique talents and skills of those with ADHD. A female partner of an adult male who was diagnosed with ADHD said, “there are a lot of great things that come from having ADHD and I want him to see that.”Adult participants were more likely than the parental group to express concern regarding the stigma associated with ADHD and expressed negative characteristics are typically associated with ADHD. An adult participant explained the stigma associated with ADHD, “having ADHD is like running in mud, you are putting forth a lot of effort but making little progress and it’s important to know that you are not broken but that you just learn differently.”Parents with children who have or are suspected of having ADHD expressed a desire for 3-minute videos on how to recognize and address specific behavior associated with ADHD and ways of addressing such behaviors, information about co-occurring disorders, and short videos focusing on a variety of learning techniques.Both groups of participants reported wanting information about ADHD support groups and community resources that are age-appropriate and concise information that is easy to understand and presented in a clear, colorful format. Additionally, both groups expressed the need for having access to evidence-based practices, techniques, and tools provided by a trusted source.The research team conducted 6 think-aloud interviews to assess the newly created website’s user-friendliness and usefulness with individuals who self-reported a diagnosis of ADHD or identified as being a parent of a child with ADHD. The research team identified factors that improve the website’s intuitive design, the ways in which participants attribute of trustworthiness of the website and information, and website layouts that improve website impressions.When prompted to search for information about ADHD, most participants searched the top portion of the website (menus representing the Institute and its university) that were not part of the website designed for this study. Many expressed frustrations that they could not find what they were looking for because they were intuitively drawn to the main tabs at the top of the page. For example, when searching for scientific information on ADHD, some went to the research tab and found current clinical trials rather than peer-reviewed ADHD resources.A few participants went straight to the search box to look for information or resources on ADHD while others said they overlooked the search box as it did not stand out on the page. Often those who found and used the search box eventually found the information that they were looking for.When scrolling down the page looking for information on how to cope with ADHD, for example, some said if they were home alone, they would have left the page and used a search engine to locate the information they were seeking. This occurred for two primary reasons (1) participants were searching for the exact words “coping with ADHD” and could not immediately find this information or (2) they did not take the time required to read an entire document to find the information. Some participants reported they were searching for more bulleted lists. However, there are bulleted lists on the website, so these frustrations may be more of a design issue rather than a content problem.Participants also commented on specific design and layout elements that they perceive as helpful to website navigation such as font type, size, color, and background. One adult participant reported that “soft and inviting” fonts such as Comic Sans are desirable in addition to darker color fonts against light backgrounds.Many participants expressed confidence in the information provided on the website because of its association with the local university and more specifically an institute well-known for its work in neurodevelopmental disorders in the region. There were a couple of participants who were not as concerned with the quality of the information provided on the website, stating that “if you google symptoms of ADHD you will find the same information.” This implies that there is little or no variation in content, especially concerning “basic information.”In general, participants were drawn to easy-to-understand bullet lists, colorful graphics, and videos. Participants experienced challenges with using the search function and recommendations for improvement included the need for a better search feature and clear drop-down menus.Throughout all 3 phases of the study, there were overarching themes of participants’ desire for ADHD content that is current evidence-based information, used a strength-based approach to addressing ADHD, and included other resources and tools as well as website design that includes interactive infographics and videos, and is user-friendly for navigation see . In addiContent specificCurrent evidence-based information:Peer-reviewed papersLinks to additional resources or websitesStrength-based approach:Address attention-deficit/hyperactivity disorder (ADHD)–related stigmaCareer options for those with ADHDPositive attributes Resources:Local physicians, counselors, and support groupsLinks to ADHD blogs, books, webinars, and podcastsList of helpful smartphone appsDiagnostic assessmentsDesign specificInteractive infographics:Chat featureBulletin boardsVideos:Success storiesNeurodiversityUser-friendly navigation:Tabs or menusAmple white spaceBullet pointsTool kit formatThe objective of this study was to determine the information and formatting preferences of ADHD stakeholders to build a user-informed website. Participants indicated both strengths and areas of improvement regarding ADHD websites.This study addressed the question of how individuals might assess whether the information is trustworthy and credible. Participants in this study knew to look for information from credible sources, such as peer-reviewed literature or connections with credible institutions, and requested evidence-based information from peer-reviewed journals that were easily understood by a lay audience. Individuals seeking information about ADHD have a preference for a higher level of credibility of information and know how to identify highly credible information.The presentation format of ADHD-related content is as important as the information itself must be user-friendly. Participants emphasized the potential impact website design has on whether the information presented is accurately understood. The majority of participants reported that regardless of the quality of available content, a website must contain certain features such as drop-down menus that are located at the top of the page, a search menu, interactive design, and information presented through infographics and videos. A commonly expressed concern about many existing ADHD websites is that stakeholder preferences are not always factored into the design. For example, a balance between what one could consider attention-grabbing and distracting must be considered when presenting information in the form of images. The colors, font type, and size mattered to the majority of participants.Although many of the information needs and format preferences expressed by ADHD stakeholders are similar to those associated with other health conditions, there were themes that appeared to be unique in this population. One of the most striking findings was that the majority of adult participants with ADHD expressed that they were seeking destigmatized and positive information about ADHD, specifically success stories and information on strengths associated with ADHD. This finding reinforces the importance of focusing not only on appropriate evaluation and evidence-based treatment of ADHD but also on how differences can be used in a beneficial way. Interestingly, social stigma was not a theme specifically raised by the parents of children with ADHD in this study. That being said, a study from 2010 showed that 44% of parents were concerned about societal views of the ADHD label and 40% felt isolated and rejected . Mental A second theme focused on obtaining evidence-based and up-to-date treatment information in a format that is easy to understand. Participants specifically requested peer-reviewed literature and evidence-based treatments but struggled to find that information in an easily understood format. Unfortunately, people are overwhelmed with new “treatments” for ADHD, but it is considerably challenging to separate those supported by appropriate evidence versus those that are not. This has been shown to be one of the barriers to evidence-based treatment of ADHD .This study was limited geographically, and the results may not be generalizable to other regions because of the availability of resources specific to this region. The sample size for each phase was small. All participants had an educational level beyond high school and thus, may not represent individuals with less education. Participants involved were also sophisticated enough to seek out support groups for ADHD  and a university center for neurodevelopmental disorders; therefore, individuals with less knowledge of how to access these resources may not be well-represented in this sample. Furthermore, this study is a snapshot of the information-seeking experiences of individuals during a specific time period and since then there may have been other resources made available to these individuals. Last, this study was limited to English-language health information resources only.This study explores the process of creating a user-informed ADHD website. ADHD stakeholders (adults with ADHD and parents of children with ADHD) provided suggestions pertaining to both desired content and the design of a website dedicated to providing a wide spectrum of ADHD content in a user-friendly format. Participants identified ways to best address the unmet informational needs of ADHD stakeholders including providing evidence-based content that can easily be understood by nonacademic audiences, success stories from those who have ADHD, awareness of neurodiversity, nonstigmatized perspectives, and access to medical and educational resources. Participants also provided feedback regarding how to best design a website devoted to ADHD information sharing including limited text, bullet points, an interactive format, a search feature, and clearly identifiable menu options. Creating a dedicated ADHD website informed and tested by a variety of stakeholders can advance public knowledge while increasing the self-efficacy needed to improve the overall quality of life of those impacted by ADHD.Evaluation of the accuracy of information on the internet provides important insight into the type of information encountered but does not provide insight into how health information is used by the lay public. Previous studies assessing the influence of internet health information have not inquired as to how information influenced decisions and stopped short of assessing the quality of the information used ,24. GiveThis study introduced the concept that many ADHD information seekers have a high level of sophistication, specifically looking for evidence-based practices and peer-reviewed literature about ADHD. Future educational websites and materials should focus on providing higher-level information in formats that are accessible to all information seekers. This study highlighted the importance of providing destigmatized information about ADHD. Utilizing asset-based messaging can help provide positive information about ADHD and techniques to use the unique traits of those with ADHD. Although future research in this area is critical to further understand the information needs of those affected by ADHD, many improvements currently can be made that will allow ADHD stakeholders to have better access to the information and decrease the stigma that continues to be associated with ADHD.


The surfactants were prepared via one-pot reductiveamination, allowing the introduction of different alkyl chain lengthsand methyl modifications. Optimal reaction conditions were establishedto achieve high yields and easy purification. The synthesized surfactantsincluding the tertiary amines exhibited desirable properties, includingsolubility, foamability, and reduction of surface tension. Notably,the anionic surfactants derived from d-GalA demonstratedbetter solubility and foam performance compared to those derived from l-Ara. In addition, these surfactants exhibited surface tensionand critical micelle concentration (CMC) comparable to those of thecommercial surfactant sodium lauryl ether sulfate (SLES). Furthermore,the biodegradable surfactant GalA1.8 displayed excellentemulsifying properties and low skin irritation potential. On the l-Ara surfactant with a short chain, Ara1.6 haspotential as a hydrotrope. These findings suggest that biobased surfactantsderived from SBP monosaccharides have promising applications in variousindustries, including pharmaceuticals, cosmetics, detergents, andchemicals.Herein, we reporta method for the synthesis of biobased surfactantsderived from sugar beet pulp (SBP) monosaccharides,  l-Ara and d-GalA using a simple and environmentally benignprocess. The surfactant properties of the prepared derivatives offerversatile potential applications in cosmetics and detergents.Herein, we report the synthesis of biobasedsurfactantsderived from the sugar beet pulp-derived monosaccharides  Hence, this source of biomassdoes not interfere with food production and does not require additionalarable land.5 Agricultural side streamsare available at a large scale in the form of residues produced duringcultivation, harvesting, and processing of crops. Depending on thefeedstock, biomass is available in the form of leftover straw, roots,leaves, cobs, pulps, peels, and seeds.6The utilization ofbiomass has become a subject of great interestas a sustainable alternative for products derived from nonrenewableresources.7 Yearly, sugar beets are being processed into 36.4 millionmetric tons of sucrose worldwide. During this process, an equal amountof SBP is obtained, which is a cheap and abundant source of biomass.7 Moreover, SBP is particularly attractive because its utilizationdoes not affect food production to an appreciable extent. Currently,SBP is being sold as animal feed, has a low commercial value, andis rich in polysaccharides such as pectin and cellulose and hemicellulose.These polysaccharides can be enzymatically processed to provide variousmonosaccharides such as d-galacturonic acid and l-arabinose (l-Ara).10 Effortsdirected at the large-scale recovery of pure d-GalA and l-Ara may enable their production at large scale in a sustainablemanner.11 This makes them an interestingstarting material for the production of high-value commercial products.13Sugar beet pulp (SBP) is an interesting source of agriculturalwaste, which is obtained during the production of sucrose 1.7 Yearl14 Surfactants or surface active agents have the ability to reducethe surface tension and are therefore essential ingredients in thepharmaceutical, cosmetic, detergent, and chemical industries.15 Microbial biosurfactants such as rhamnolipids and sophorolipidscan be produced in various microorganisms and from different feedstocks.16 Carbohydrate-based surfactants can also be preparedvia chemical synthesis from monosaccharides isolated from biomass.The commercial production of carbohydrate-based surfactants startedin the 1980s and is mostly based on sucrose and glucose derivatives.21 Much less is known about surfactants derived from l-Araand d-GalA, monosaccharides that can be obtained from SBPin bulk quantities without direct competition with food production.23The hydrophilic nature of monosaccharides enablestheir applicationas the polar headgroup for the synthesis of biobased surfactants.d-GalA and l-Ara via one-pot reductive amination. Different chain lengths ofalkylamines were introduced using this method, leading to a varietyof secondary amine products. Using a second hydrogenation with formaldehyde,novel surfactants containing a tertiary amine were also prepared.In particular, we found that the tertiary amine surfactants are moresoluble in water and display favorable surfactant properties suchas foamability, stable foams, and emulsions, lowered surface tensionof solutions, and a variable critical micelle concentration.25 Hence, this class of molecules may represent a promising set ofbiobased surfactants derived from sugar beet pulp.Herein, we report a simple,green method to prepare biobased surfactantsderived from the SBP monosaccharides 27 This reactioncan be used to selectively modify monosaccharides by making use ofthe aldehyde present in the open form with secondary or tertiary amines.29 Several sugar monomers converting into their corresponding aminesvia reductive amination reactions have been reported.30 For example, a reaction with d-glucose, methylamine,and a reducing agent affords N-methylglucamine, aprecursor in the synthesis of Glucopure.32 In contrast to glucose-based surfactants,much less is known about the reductive amination reactions with theSBP monosaccharides l-Ara and d-GalA.19 Hence, we set out to investigate the synthesisand properties of biobased surfactants based on l-Ara and d-GalA formed by the reductive amination with various alkylamines.Reductive amination of carbonyl-containingcompounds is an effectivemethod to form C–N bonds.d-GalA via reductive aminationusing primary or secondary amines . We will refer to the compounds accordingto their monosaccharide abbreviations, l-arabinose (Ara)and d-galacturonic acid , followed by a number denotingthe optional presence of a methyl group (1) and the length of thealkyl chain (6–12). Reaction conditions were optimized to developan efficient and environmentally benign process  was obtainedusing precipitation as a purification method. Under the same conditions,a secondary amine was used to afford the corresponding tertiary amine GalA1.8. However, this product was obtained in a much loweryield (19%), which was likely the result of its higher solubilityand hence poor recovery using the precipitation protocol  of GalA1.8 . Moreover, two other modifications were introduced:a variety of alkyl chain lengths and R1 may or may notbe methylated. Due to the commercially available N-methylalkyl chains (R1 = Me) with 6, 8, and 12 carbonchains, these were used to react with the two sugars to obtain sixdifferent surfactants. Using the reactions conditions of Ara1.6Ara1.8, and Ara1.12 were synthesized in 85–95%yield with GalA1.6, GalA1.8, and GalA1.12 synthesized in 86–90%. The N-methyldecylchain was not commercially available; hence, the corresponding surfactantswere made via a one-pot two-step synthesis starting from the respectivecommercially available primary amine  and GalA1.10 (73%).To investigate the properties of the methyl modification on the surfactants(R1 = Me), previously described reference surfactants weresynthesized including an N-alkyl chain (R1 = H).22 Primary alkyl amines with 6,8, 10, and 12 carbon chain length were used to react with l-Ara and d-GalA. Because poor solubility purification wasdifficult, some of them were synthesized via the previously describedmethod (1 =H) were obtained in lower or similar yields than with methyl modification(R1 = Me).With the optimal reactionconditions established, we set out toexplore the synthesis of a panel of biobased surfactants using aterials 2. These Page S9 for experimental details). Various physicochemical properties suchas solubility, foamability, surface tension, and critical micelleconcentration (CMC) were determined  was determined to compare them with their methylated counterparts(R1 = Me). All methylated compounds (R1 = Me)showed an increased solubility compared to their corresponding nonmethylatedcounterparts (R1 = H). An interesting example is the solubilityof Ara1.6, which is 30% and much higher than that ofnon-N-methylated Ara6 (0.75%). We presumethat this effect is caused by the disruption of surfactant stackingby the addition of the methyl group, which in turn increases the solubilityof the surfactant.To establish the optimal applicationof the prepared surfactants,their properties were established (see termined 3.24 Sinc1 = Me) were determined. Foamwas created in a measuring cylinder with an Ultraturrax, and the foamvolume (in mL) was monitored over 30 min . Furthermore,a compound can be classified as a surfactant if it decreases the air–waterinterfacial force and lowers the surface tension of the system. Thesurface tension and corresponding critical micelle concentration (CMC)of the synthesized surfactants were measured using a tensiometer . The l-Ara-based compounds Ara1.8, Ara1.10, and Ara1.12 hada lower surface tension  than thatof SLES (33.8 mN/m). In addition, the CMC of these surfactantswas comparable to that of SLES, indicating that withlow concentrations between 0.01 and 0.25%, micelles are formed. Thesefindings demonstrate that these molecules display suitable propertiesto be used as surface-active agents. Likewise, the anionic surfactantsderived from d-GalA, GalA1.8, GalA1.10, and GalA1.12 reduced the surface tension to 32.1, 32.9, and 33.9mN/m at a CMC of 1.15, 0.06, and 0.1%, respectively, similar to thecommercial surfactant. Interestingly, anionic surfactants GalA1.12 and SLES, both with a 12-carbon chain, had very similarfoamability and surface tension performance. This would suggest thata potential application as a wetting agent could be interesting forthese compounds. Finally, we compared the performance of the SBP-derivedsurfactants to Glucopure, a commercially available biobased surfactantbased on glucose. Performance was very similar in terms of the solubility,foamability, surface tension, and CMC.Thefoamability and surface tension of the more soluble and interestingmethylated surfactants  for experimentaldetails). To this end, detergency and emulsion properties of the newsurface-active agents were determined using the TurbiscanLab protocols(Table S1 and Page S11). Emulsions consistingof 6% oil, 1% surfactant, and 93% H2O were prepared. Thecommercially available surfactant alkylpolyglucoside with a six-carbonchain (APG-6) is a well-known oil-in-water emulsifierand was used as a reference. The emulsion with APG-6 hada TSI score of 11.1. The sample of GalA1.8 showed morestability with a TSI of 1.6 . The Turbiscan was used to measure the transmittance andbackscattering of pulsed near-infrared light (880 nm) to monitor thestability of emulsions, which are then expressed as the TSI, witha low TSI score referring to a stable emulsion . Zein is a protein found in corn and isan accepted mimic of skin proteins. The more zein is solubilized bythe surfactant, the harsher the potential to irritate and dry thehuman skin. Notably, it is an indication of its harshness to the skinand allows a comparison of our surfactants to some commercially availablesurfactants, even though in vivo testing is always the most idealfor measuring mildness. SDS and SLES arecommercial surfactants and known to be harsh on the skin.34 Hence, SDS is set as a default of 100 to comparewith the potentials of other surfactants, which are all executed inDuplo (Table S2 and Page S12). Moreover,the surfactants were measured at different pH values, a pH of 4–5,7, and at its original pH as is. SLES showed a skin irritationpotential value of 49 at a pH of 7, thus half as irritating as SDS.In contrast, our biobased surfactants all have very low values between0 and 3 (Table S2). For example, GalA1.8 had a zein score of 1 at pH 7  or the differencein solubility of the two surfactants.To investigate if the prepared surfactant may becompatiblewitha personal care application, the skin irritation potential was investigatedusing zein solubilization tests . Biodegradation is important in order to prevent pollutionof the environment. The commercially available surfactant SLES has a primary degradation of 94% in 30 days,35 depending on the initial concentration, using the Organizationfor Economic Cooperation and Development (OECD) 301 procedure.36 This procedure was used to test GalA1.8 resulting in a faster biodegradability and was followed by CO2 production . Furthermore, the condition to evaluatethe toxicity of GalA1.8 on the inoculum revealed thatCO2 production from acetate was not inhibited by GalA1.8, suggesting that the compound was not significantlytoxic to the inoculum.The biodegradation ofthe novel surfactant Ara1.6 and GalA1.6 are not suitable for application as a surfactant becausethey do not foam and form stable oil-in-water emulsions. We reasonedthat due to their high solubility, they may act as a hydrotrope, compoundsthat enhance the solubility and reduce the viscosity of other organicsubstances in water.38 One well-known example is sodiumxylene sulfonate (SXS), a commercially available hydrotrope.39 To evaluate the hydrotropic behavior of Ara1.6 and GalA1.6 against SXS as a benchmark, we conducted experimentsusing a hydrophobic dye Disperse Red 13 (DR-13) dissolved in water.DR-13 is insoluble in water, and hence, the solution has a low absorptionat 525 nm (see Page S15 for details). Uponthe increased solubilization of DR-13 in water by the addition ofa hydrotrope, the solution absorption will also increase, which wasdetected using a ultraviolet–visible (UV–vis) spectrophotometerat a wavelength of 525 nm.39 The obtainedabsorbance (Abs) values for DR-13, in relation to the molar concentrationof Ara1.6, GalA1.6, SXS, and the cosolventacetone, are plotted in Figure S4 (PageS15). SXS exhibited an Abs of 1866 L mol–1 cm–1 at a concentration of 0.9 M (40 wt %), indicatingthat the dye could be dissolved with a low concentration of SXS. Acetone,as a cosolvent, showed the same solubilization potential (Abs at 1829),however, only at high concentrations. Our surfactant Ara1.6 demonstrated significant solubilization capabilities at a very lowconcentration of 0.25 M with an Abs at 1854. This result suggeststhat Ara1.6 can be effectively employed as a hydrotropein various applications such as improving the solubility of less solublesurfactants in cosmetic formulations. To exclude pH effects on thesolubilization of the DR-13 dye upon addition of the Ara1.6 compound, the experiment was also carried out in a buffer, whichled to a very similar performance to SXS. Finally, we utilized Ara1.6 to boost the solubility of Ara 1.10 . Addition of Ara1.6 effectively enhanced the solubility of a 1% solution of Ara1.10.The results mentioned above have revealedthe potential applicationsof the synthesized surfactants, particularly those with alkyl chainsof eight carbons or more, as effective cleaning, emulsifying, andfoaming agents. The shorter chain derivatives l-Ara and d-GalAwas developed. By employing one-pot reductive amination, a varietyof surfactants with different alkyl chain lengths and methyl modificationswas synthesized. We optimized the reaction conditions to achieve highyields and easy purification, eliminating the need for excess reagentsand using (bio)ethanol as the solvent. Furthermore, we conducted acomprehensive evaluation of various surfactant properties, includingsolubility, foamability, surface tension, emulsion stability, skinirritation, and biodegradability. Remarkably, the newly synthesizedmethylated biobased compounds from the Ara1.X and GalA1.X series exhibited increased solubility compared totheir nonmethylated counterparts (R1 = H). Additionally,surfactants containing octyl, decyl, and dodecyl alkyl chains, like GalA1.8, displayed foamability and surface tension comparableto those of SLES, a commonly used commercial surfactant. On the otherhand, the study demonstrated the effectiveness of the short six-alkylchain-containing surfactant Ara1.6 as a hydrotrope. Thesefindings demonstrate the promising potential of SBP-derived molecules,which not only exhibit nonirritating properties but also demonstratecomparable or improved performance compared to existing commerciallyavailable molecules. By employing a sustainable hydrogenation processto generate the key N-methylalkyl (R1 =Me) compounds, we have successfully synthesized biobased surfactantswith interesting properties for various ecofriendly applications.Further scale up and application testing are needed to identify theultimate application of the developed molecules.A simple method to prepare biobased surfactantsderived from sugarbeet pulp (SBP) monosaccharides