Deficits in executive functioning, especially in inhibitory control, are present in children born very premature and/or with very low birth weight (VP/VLBW) and in children with attention-deficit/hyperactivity disorder (ADHD). To evaluate whether ADHD imposes additional inhibitory control (IC) deficits in preschoolers born VP/VLBW. 79 VP/VLBW (4 to 7 years) children were assessed for ADHD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children – Present and Lifetime Version (K-SADS-PL). IC was measured with Conners’ Kiddie Continuous Performance Test (K-CPT 2) and the Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF-P).Results: No significant differences were found between ADHD (n = 24) and non-ADHD children (n = 55) for any of the measures (p = 0.062 to p = 0.903). Both groups had deficits in most K-CPT 2 scores compared to normative samples, indicating poor IC and inconsistent reaction times. ADHD does not aggravate IC deficits in VP/VLBW children. Either neuropsychological tasks and parent reports of executive functions (EFs) may not be sensitive enough to differentiate VP/VLBW preschoolers with and without ADHD, or these children’s EFs are already so impaired that there is not much room for additional impairments imposed by ADHD. Prematurity can also be classified according to birth weight: extremely low birth weight (ELBW): < 1,000 grams and very low birth weight (VLBW): 1,000 to < 1,500 grams.2 Our study will focus on very preterm and/or very low birth weight (VP/VLBW) children.Preterm birth is defined as birth occurring before 37 full weeks of gestation. Around the world, its prevalence ranges from 5% to 18%.3 these groups are still at high risk of death and disability.2 For instance, several structures of the central nervous system may be compromised in VP/VLBW children.4 Abnormalities of brain structure may, in turn, translate to neuropsychological deficits in executive functions.3Although the survival rates for VP and VLBW babies have increased over recent years due to advances in perinatal and neonatal care,5 This disorder is characterized by inattention and/or hyperactivity/impulsivity interfering with functioning.6 The validity of ADHD diagnosis in preschool children has been established.7 Overall, neuropsychological studies of preschoolers with ADHD show similar results to studies of school-aged children,8 including deficits in response inhibition, delay aversion, working memory, and sustained attention.10 Inhibitory control is an executive control function that enables an ongoing response to be stopped. It enables inhibition and alteration of inappropriate strategies, such as detecting and correcting an error in an academic task.11 Preschool children with ADHD tend to perform significantly worse in inhibitory control tasks and inventories, when compared to those without the disorder.14Prematurity is frequently associated with neurodevelopmental disorders, such as ADHD.15 few studies have investigated whether ADHD is associated with additional impairment of inhibitory control performances in premature children. To our knowledge, only one study has compared preterm children with and without ADHD using a neuropsychological task. Both neurophysiological and neuropsychological tasks were used, and inhibitory impairments and reaction time variability were only found in preterm and term children with ADHD.16 It is crucial to note, however, that this study had a limited sample of 21 preterm participants.Although ADHD is a prevalent disorder in children born prematurely and/or at very low birth weight,Based on the literature reviewed above, we aimed to assess whether ADHD imposes additional inhibitory control deficits on VP/VLBW preschool children. Since ADHD and prematurity are both associated with inhibitory control deficits, we hypothesized that premature infants with ADHD would present greater impairment in this function when compared to those without the disorder.This is a case control study in which preschool children born very prematurely (less than 32 weeks) and/or with very low birth weight (under 1500g) diagnosed with ADHD were compared to those without the disorder. The sample included children between 4 and 7 years of age at the time of assessment who had previously been hospitalized at the neonatology unit of our university hospital in Porto Alegre , in the state of Rio Grande do Sul, Brazil). The survivors among those born from January 1st, 2010 to July 31st, 2012 were eligible for the study (n = 129). Children diagnosed with either a genetic syndrome, cerebral palsy, or congenital infections (HIV or syphilis) were excluded from the sample ,Participants provided verbal agreement to participation in the study and parents provided written informed consent. This study was approved by the ethics committee at the HCPA (protocol number 15-0384).18 of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)19 composed of four subtests: block design, comprehension, picture completion, and arithmetic. Inhibitory control was measured using a computerized task (K-CPT 2), performed by the children, and a behavioral inventory (BRIEF-P), responded by parents or legal guardians. These instruments are described below:Trained psychologists assessed children in a single session. IQ was estimated using a short version20 is a computerized task designed to assess inhibitory control, sustained attention and visual-motor speed. The participant is asked to respond (by pressing the space bar) to all targets presented on a computer screen, but refrain from responding to non-targets.Conners’ Kiddie Continuous Performance Test (K-CPT 2)21 : an inhibitory self-control index (ISCI), a flexibility index (FI), and an emergent metacognition index (EMI). A translated Brazilian Portuguese version was adapted and provided by the publisher, Psychological Assessment Resources (PAR Inc.).The Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF-P) evaluates daily behaviors associated with specific domains of executive functioning, based on parents’ reports. Three indexes based on theoretical and empirical factor analysis findings are providedt test for continuous variables. Variables with p ≤ 0.10 were included in the model (IQ and ODD). Since neuropsychological test scores are influenced by developmental aspects, age was also included in the models because scores were analyzed uncorrected for age. K-CPT 2 and BRIEF-P scores were analyzed using two independent analyses of covariance (ANCOVAs), comparing ADHD against non-ADHD groups. The analyses were performed using version 18.0 of the Statistical Package for the Social Sciences for Windows  and p < 0.05 was considered significant. Effect size was calculated using partial eta squared and its magnitude defined according to the following interpretation: eta squared < 0.06 = small; 0.06-0.14 = medium, > 0.14 = large effect size.22 The frequency of cases with worse performance (> 1 standard deviation from normative data) was also calculated, and between-group (ADHD vs. non-ADHD) differences were investigated using chi-square tests. Normative scores for both tests were obtained respectively from a Brazilian sample23 and the American sample used for the original BRIEF-P manual.21Descriptive analyses were conducted to characterize the sample. Potential confounders investigated were age, IQ, gender, gestational age, socioeconomic status, and comorbidities , using the chi-square test for categorical variables and the 24Data from 79 participants were analyzed for BRIEF-P scores. Nine participants refused to finish the K-CPT 2, or their assessments were considered invalid, resulting in a total sample of 70 children with K-CPT 2 data. Demographic and clinical data can be found in Findings emerging from ANCOVAs did not reveal significant differences between ADHD and non-ADHD groups, either for any of the BRIEF-P scores or for K-CPT 2 variables (p = 0.062 to p = 0.903). All effect sizes were small   . CorrelThe frequency of cases with worse performance (> 1 standard deviation [SD] from the normative mean) on both instruments was also analyzed. Regarding BRIEF-P scores, 12 children (15.2%) satisfied this condition for the ISCI. For the FI and the EMI, 6 (7.6%) and 17 (21.5%) children respectively were included in the groups with the worst performance. No association was found between ADHD and worse performance in BRIEF-P indexes see  .Regarding worse K-CPT 2 performance (defined as > 1 SD from the normative mean), 69 children (98.6%) fulfilled this condition for the hit reaction time standard deviation (HRT SD) index, 60 (85.7%) for variability, 42 (60%) for hit reaction time block change (HRT block change), and 55 (78.6%) for hit reaction time interstimulus-interval (HRT ISI). The numbers of children classified with worse performance according to the results for the indexes were as follows: omissions 38 (54.3%), commissions 31 (44.3%), perseverations 15 (21.4%), and HRT 20 (28.6%). We also did not find an association between ADHD and worse performance in the K-CPT 2 scores see  .25 Investigations with adults born prematurely at VLBW support these findings and show that preterm birth has long-term consequences,26 including neurocognitive deficits.27Consistent findings of behavioral and/or cognitive profiles in preterm born children have provided evidence of a “preterm phenotype”. Psychiatric disorders, especially ADHD, anxiety, and autism spectrum disorder, are the most prevalent among subjects born preterm. This preterm behavioral phenotype is usually found in association with cognitive impairment.14 and in children born very prematurely.28 However, to our knowledge, only one study has compared inhibitory control in VP/VLBW children with and without ADHD. Contrary to our original hypothesis, our results revealed no significant differences in inhibitory control between VP/VLBW children with and without ADHD.Specifically with relation to inhibitory control, current evidence shows that a deficit is present both in ADHD,29 The type of measurement selected  can also influence the results, either by their intercorrelations or by their associations with ADHD.30 This is why we used both a performance measure (K-CPT 2) and a parent-rated behavior scale (BRIEF-P). We found consistent results across instruments, indicating no differences between ADHD and non-ADHD groups. Also, as described in the literature, correlations between the two types of measures were low.In general, weak correlations are found between tests of executive function performance and behavior scales in the literature.31 This could have influenced our results since a global developmental delay characterizes our sample.Given this finding, we also analyzed whether the groups’ results were 1 SD or more from the normative mean, indicating a deficit in comparison to the normative samples for K-CPT2 and BRIEF-P. We chose a lenient threshold, of one standard deviation or 15.9% from the normal distribution mean, to identify cases that showed even a mild difficulty. The BRIEF-P results indicated that the ADHD group had a slightly higher frequency than that predicted by a normal distribution in the inhibitory self-control and emergent metacognition scales. This was only observed for emergent metacognition in the non-ADHD group. Nevertheless, the differences were not significant, and at least 70.83% of the children had performance considered to be in the normal range in both groups. Although previous studies show that EF deficits are present in ADHD and VP/VLBW patients, rating scales focus on a global and less specific observation of executive functioning in the everyday context. They also depend on parent ratings, which might be biased by different development expectations.32Overall, K-CPT 2 scores indicated a higher number of participants in the clinical-suggestive range, with no significant differences between groups. Omissions, commissions, HRT, and HRT block change results indicated that 26 to 67% of the children had performance more than one standard deviation from the normative mean, independent of group status. These measures are related to inattention, impulsivity, speed of processing, and vigilance, respectively. With regard specifically to commissions, which is a measure related to impulsivity and inhibitory control, 38% of the ADHD group and 46% of the non-ADHD group fell within the clinical range, as suggested by the literature.33 Few studies have investigated this issue in premature children. Adolescents born prematurely show an impairment in reaction time variability when compared to controls. Regardless, this impairment is milder than the impairment observed in term-born ADHD adolescents.15 However, this result was not observed in the same sample when a different cognitive test was analyzed.34 Although this construct still remains understudied in prematurity, it is well established that a higher than usual RTV is present in ADHD and is also a marker of general psychopathology.35 The pathophysiology of RTV is usually associated with abnormal frontal lobe volume and/or activation.33 Cortical maturation of the frontal lobe is delayed in ADHD children,36 and a meta-analysis showed an overall reduction in brain volume, including white and gray matter in VP/VLBW school-aged children.37 Specifically in preschool children, a delay in normal cortical and surface development is associated with prematurity.38Regarding reaction time variability (RTV), 76.2% to 100% of the sample had impaired performance and once again no differences were found between groups. This variability is associated with most childhood psychiatric disorders, traumatic brain injury, dementia, and aging populations.39 Moreover, results of a meta-analysis also showed that ADHD is associated with lower overall cognitive ability when compared to healthy controls.40Another critical aspect to discuss is that our sample was characterized by a below-average mean IQ, irrespective of group. However, this is not an unexpected finding since low birth weight is also associated with below-average IQ. The high degree of nervous system immaturity and the greater susceptibility to neonatal complications may lead to cognitive impairment. The cerebral networks of children with low birth weight are less connected brain networks, with lower brain volumes and lower cortical surface area, which might result in impaired cognitive functions.41 Although many variables are included in the broader concept of executive functions, they are separable to a certain degree and differently correlated to each other as well as to the many areas of the brain.42 Among all other executive functions, inhibition has been found to have a low correlation to IQ.43 The same is valid for RTV: although higher inconsistency is related to lower IQ, the variance explained by IQ is usually small.44 A recent meta-analysis showed evidence for a low to moderate correlation with matrix intelligence tests - which are less affected by cultural aspects.45 Considering the above, the participants’ low IQ may only partially explain the deficits in inhibitory control and RTVs found in our sample.The nature of the relationship between intelligence and executive functions is still controversial.Our findings should be understood in the context of some limitations. Although the low average IQ observed in our sample is a common finding in VP/VLBW children and it may not fully explain our results, we cannot discard it as a limitation. Further studies investigating the performance of average-IQ preterm/low-birth preschoolers might improve our understanding of the impact of ADHD on executive functions in this population. Additionally, our moderate sample size in both groups might have decreased the power for detection of between-group differences. However, it is essential to note that all between-group ES were small for both BRIEF-P and K-CPT 2 scores.Furthermore, the absence of a full-term control sample imposes limitations on our analyses, making us rely on normative data for comparisons. Still, regarding K-CPT 2 and BRIEF-P, validity studies for the Brazilian population were not available. Finally, another aspect we did not adequately control was use of medications. Although none of the participants were using ADHD medication, we do not have information accurately recorded in our dataset about other clinical medications that might interfere with inhibitory control.This study provides evidence of performance deficits on inhibitory control tests in preschool children born VP and/or with VLBW. Presence of ADHD did not impose any additional burden on the children’s test performance. Parents’ reports seem to be less sensitive for capturing executive deficits in this population. Impairment in RTV, a more basic cognitive process, was found in most participants, independent of group status. Our findings suggest either that assessment of EFs using neuropsychological tasks and parent reports may not be sufficiently sensitive to differentiate between ADHD and non-ADHD in VP/VLBW preschool children, or that these children already have a level of impairment in executive functions that does not leave much room for additional impairment. More large-scale studies investigating the nature and long-term effects of inhibitory control deficits in these vulnerable populations are needed.


Fra1 (ad-fra1) or silenced for Fra1 (si-fra1) and then treated with atRA. BMSCs treated with atRA and treated with ad-fra1 showed decreased mRNA and protein levels of key adipogenic genes  and adipogenesis-associated genes ; atRA had a stronger inhibitory effect on adipogenesis compared with that in the ad-fra1 group. Adipogenic gene expression in Fra1-silenced BMSCs was significantly upregulated. Compared with that in the atRA group, the si-fra1 + atRA also upregulated adipogenic gene expression. However, compared with si-fra1, si-fra1 + atRA significantly inhibited adipogenic differentiation. Chromatin immunoprecipitation showed that RARG directly regulates Fra1 and FRA1 directly regulates Pparg2 and Cebpa. The results supported the conclusion that atRA inhibits BMSC adipogenesis partially through the RARG-FRA1-PPARG2 or the CEBPA axis or both. Thus, vitamin A might be used to treat obesity and its related diseases.Obesity, caused by an increased number and volume of adipocytes, is a global epidemic that seriously threatens human health. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into adipocytes. All-trans retinoic acid  inhibits the adipogenic differentiation of BMSCs through its receptor RARG. The expression level of FRA1  in atRA-treated BMSCs increased, suggesting that atRA-mediated inhibition of BMSCs adipogenesis involves FRA1. BMSCs were transfected with adenovirus overexpressing  Obesity is a major risk in many diseases, including type 2 diabetes, cardiovascular dysfunction, musculoskeletal disorders, Alzheimer's disease, and cancers  [Currently, obesity is considered a major health hazard and a global epidemic. The World Health Organization reported that in 2016, there were over 19 billion adults who were overweight, and 6.5 billion adults were obese ( breast) , even im breast) . Mesench breast) . The dif breast) , 9. ExplIn vitro and in vivo studies have demonstrated atRA as a key regulator in adipose tissue metabolism and obesity [Pparg2 promoter to directly regulate its expression [Vitamin A is an important fat-soluble micronutrient with well-established roles in embryonic development, reproduction, neuronal cell growth, immune function, and vision –13. All- obesity –17. Our  obesity . Howeverpression . How atRin vivo demonstrated that Fra1 overexpression  caused severe lipodystrophy in Fra1 transgenic mice. In addition, previous research in our laboratory showed that the mRNA and protein expression levels of Fra1 in BMSCs increased significantly after atRA intervention [in vitro to explore the regulatory mechanism of FRA1 in atRA-induced inhibition of the adipocyte differentiation signaling pathway.Activator protein-1 (AP1) is an important transcription factor family that regulates cell proliferation and differentiation, which consist of the FOS family  and JUN family  . In recervention . These oFra1 overexpression (ad-fra1) and an adenovirus short hairpin RNA (shRNA) plasmid to silence Fra1 (si-fra1) were designed and produced by Obio Technology Corp. . The Fra1 gene sequence was synthesized and inserted into vector pAdeno-MCMV-3Flag-PA2-EGFP, to obtain adenovirus vector pAdeno-MCMV-Fra1-3Flag-PA2-EGFP ad-fra1. The si-fra1 shRNA sequences were inserted into vector pDKD-CMV-eGFP-U6, taking advantage of the AgeI and EcoRI enzymes to construct the shuttle plasmid and skeleton plasmid of the target gene in HEK293 cells. Three si-fra1 target sequences were used: Y7339 ATCCACTGCAATTCCTGGC, Y7340 TTCTTGTCTTCTTCTGGGA, and Y7341 TGCTACTCTTTCGATGGGC.The plasmids used in this study were designed to function in rat species. An adenovirus plasmid for n = 16, obtained from Chongqing Medical University Animal Care Centre, Chongqing, China) as described previously [2. Third-generation BMSCs were used for all experiments [2 incubators .BMSCs were obtained from the bone marrow of 2-week-old male Sprague-Dawley (SD) rats (eviously . In detaeriments . BMSCs w5 cells well−1). After overnight culture, the culture medium was exchanged and BMSCs were transduced with si-fra1 adenovirus (Y7340) at various MOI  at 37°C in a humidified 5% CO2, 95% air incubator for 12 h. The supernatant was then removed, fresh medium was added, and the cells were incubated for 72 h. The amount of fluorescence in the BMSCs was observed under a microscope  under green fluorescence excitation. BMSCs were seeded into a 6-well plate (2 × 106 cells well−1), the adenovirus (MOI 120) was into each well, grouped as follows: ad-fra1, si-fra1  vector, and blank. The Fra1 overexpression and knockdown efficiency were determined using quantitative real-time reverse transcription PCR (qRT-PCR).BMSCs were seeded into a 24-well plate (6 × 106 cells well−1); 6–8 h later, the medium was replaced at 2 ml per well. Adenoviral transient infection was carried out when the fusion degree of BMSCs reached more than 95%. The groups were set as follows: ad-fra1, si-fra1 (Y7340), vector + atRA, si-fra1 + atRA, and vector. Adenoviruses were added to the BMSCs and cultured at 37°C with 5% CO2 for 12 h. Thereafter, the BMSCs were washed with phosphate-buffered saline (PBS)  and fed with adipogenic differentiation medium A . In addition, atRA , dissolved in pure ethanol, was added to vector + atRA and si-fra1 + atRA groups to achieve a concentration of 5 µmol·L−1. Seventy-two hours later, we replaced medium A with fresh medium B and cultured the cells for 24 h. Fresh atRA was added to both medium A and B for the vector + atRA and si-fra1 + atRA groups. Medium A contained 87.5% BMSCs adipogenic differentiation basal medium A, 10% FBS, 1% penicillin-streptomycin, 1% glutamine, 0.2% insulin, 0.1% 3-isobutyl-1-methylxanthine (IBMX), 0.1% rosiglitazone, and 0.1% dexamethasone. Medium B (Cyagen) comprised 87.8% BMSCs adipogenic differentiation basal medium B, 10% FBS, 1% penicillin-streptomycin, 1% glutamine, and 0.2% insulin. In general, the adipogenic process comprised culturing BMSCs in medium A (2 ml per well) for 72 h. Old medium A was replaced with medium B (2 ml per well) for another 24 h. After that, the old medium B was replaced with fresh medium A at the same volume. This cycle was repeated three to five times until lipid droplets formed.BMSCs were seeded into a 6-well plate (2 × 10nd day of adipogenic induction and then washed with 1 × PBS twice. Oil red O dye solution (Cyagen) was formulated with 60% oil red O storage solution and 40% distilled water and filtered by neutral filter paper. Then, the BMSCs were stained with oil red O solution in a biosafety cabinet  for 60 min. After the oil red O dye solution was absorbed, the cells were washed three times with 1 ×  PBS. Next, adipogenic staining was observed under a microscope (n = 3 per group). Finally, the oil red O stained images were analyzed using ImageJ software , following the methods described by Xia et al. [BMSCs were fixed with 4% neutral formaldehyde for 30 min in room temperature on the 22a et al. .n = 7 per group). The primer sequences used in this experiment are shown in Gapdh served as a control gene. All primers were synthesized by Huada Gene Company . Fold-changes were compared after standardization with Gapdh and calculated using the 2−ΔΔCt method [Total RNA was extracted from cells using an RNA-Quick Purification kit  according to manufacturer's instructions. The RNA concentration was measured using spectrophotometer . Then reverse transcription of RNA into cDNA was performed following the PrimeScript Buffer kit instructions. QRT-PCR analysis was performed using a thermocycler  and SYBR-Green Realtime-PCR Kit  according to the manufacturer's instructions . An ECL Prime kit  and an ECL Imaging system  were used to analyze the levels of immunoreactive proteins. ImageJ software was used to analysis the intensity of the protein bands.Western blotting was performed as previously described . Some adn = 6 per group). Primers for the rat Fra1, Pparg2, and Cebpa genes were as follows: Fra1 primer sense TCAGGAGTTCAAGGCCAGTC, antisense 5′-CTCTGGAAGGAGGTGTGAGG-3′; Pparg2 primer sense 5′-CACTGGGAAGTTGGAGAAGGAA-3′, antisense 5′-TCTGGGGATTTGTGATGTTGAA-3′; Cebpa primer sense 5′-ATAAAGACGCACAATCTCAGCACTCT-3′, anti-sense 5′-GTCACCCACTTCCAGCCAACC-3′. The qRT-PCR samples were subjected to 1% agarose gel electrophoresis to confirm and detect the amplified fragments under a UV light  [–ΔΔCT, where ΔΔCT = .ChIP was performed using a Millipore company a ChIP kit  following its manufacturer's protocol and according to the details from Lai's report . In briedge, UK) . Fold ent test (two sets of data) or one-way analysis of variance (ANOVA) (>2 sets of data) as data. Adjusted p values were calculated using Tukey's HSD post hoc analyses. The significance level was set at p < 0.05.All data were represented by the mean ± SEM. GraphPad Prism 5.0 software  was used for this analysis. The data from the oil red O staining, qRT-PCR, western blotting, and ChIP-qPCR were analyzed using an unpaired Student's BMSCs were transduced with adenoviral si-fra1 (Y7339), which also expressed the enhanced green fluorescent protein (EGFP). The intracellular fluorescence intensity was used to evaluate transfection efficiency of adenovirus. Si-fra1 was infected at a MOI 100, 110, 120, 130, 150, 160, 180, and 200, and the intracellular fluorescence intensities were detected after 72 h of adenovirus transfection. The transfection efficiency, as determined by percentage of BMSCs containing green fluorescence, were 8.2%, 18.2%, 51.4%, 58.8%, 59.3%, 56.1%, 52.7%, and 66.1% at MOI of 100, 110, 120, 130, 150, 160, 180, and 200, respectively. There was a significant difference between the result for a MOI 120 and that for 110. However, above a MOI 120, the difference was not significant. Therefore, we chose adenovirus at a MOI of 120 for subsequent experiments.Fra1 mRNA expression. As expected, compared with the blank and vector, adenovirus ad-fra1 upregulated Fra1 mRNA expression (p < 0.001), and adenovirus si-fra1 could markedly reduce the expression of the Fra1 mRNA (p < 0.001). Y7340 had the most significant silencing effect and thus was chosen for future experiments. Fra1 expression was not significantly different between the blank and vector. Figures are shown in Supplementary Fra1 gene overexpression and silencing were successful. In addition, the adenoviral vector itself would not affect the expression level of Fra1. In the latter experiment, we used the vector as the control group and the Fra1 expression levels were maintained over 3 weeks.Expression of untransduced (blank), vector, ad-fra1, and si-fra1  mRNA was detected using qRT-PCR to confirm the level of α/β/γ) via noncovalent bonds. RARγ plays an important role in the retinoic acid signaling pathway [μmol/L atRA and then induced for adipogenesis according to the previously mentioned method. After 8 days of treatment, qRT-PCR was used to analyze the expression of Rarg in the mRNA level. Using the vector group as the control group, Rarg mRNA expression was significantly increased in the vector + atRA group (p < 0.001) (p < 0.001)  . Western Figures . These dμmol/L atRA in BMSCs. After 22 days of adipogenic differentiation treatment, oil red O staining was performed to reveal the accumulation of fat-characterized adipocytes. The number of lipid droplets in the BMSCs treated with atRA was significantly fewer than those in the vector group (p < 0.001). Similarly, inhibition of differentiation to mature adipocytes and accumulation of lipid droplets were observed in the BMSCs overexpressing Fra1 (p < 0.001), as indicated by a decreased number of Oil-Red-O-positive cells. ImageJ was used to analyze the pictures of Oil-Red-O staining, which was significantly inhibited compared with that in the vector only group , Fabp (fatty acid binding protein), Lpl (lipoprotein lipase), and Plin (Perilipin) are adipogenesis-associated genes. Proteins and mRNA were extracted from BMSCs after 8 days of adipogenesis induction. QRT-PCR demonstrated markedly increased Fra1 expression in the ad-fra1 group compared with that in the vector group (p < 0.001). Using the vector group as the control group, Fra1 mRNA expression was increased in the vector + atRA group (p < 0.05). Conversely, both in the ad-fra1 and vector + atRA groups, the mRNA expression levels of Pparg2, Cebpa and the adipogenesis associated genes  decreased strongly . The mRNA expression levels of Cebpa and Pparg2 in the si-fra1 group were significantly upregulated compared with those in the vector group   . Westernctively) . The mRN   . Westernctively) . The mRNctively) . The incctively) . Thus, tFra1, we conducted a ChIP-qPCR experiment using anti-RARG antibodies. The ChIP-qPCR analysis clearly showed that the RARG protein was present on the Fra1 promoter in BMSCs, with statistically significant enrichment after atRA treatment (p < 0.001) (Fra1 is in the following sequence: TCCATCTCAATTGACCTTCCTCCAC. This site is 823 bp 5′ to the transcription initiation site (Fra1 expression by binding to its promoter region.Previous research in our laboratory identified that atRA inhibits BMSC adipogenic differentiation by activating RARG . The dat< 0.001) . Agarose< 0.001) . The Genion site . TherefoFra1 downregulated Pparg2 and Cebpa expression. Conversely, Fra1 silencing upregulated Pparg2 and Cebpa expression. To clarify the relationship between FRA1 and Pparg2 and Cebpa, we conducted ChIP-qPCR tests using anti-FRA1 antibodies. The results showed that FRA1 protein was present at the Pparg2 promoter in BMSCs and was significantly enriched after atRA treatment (p < 0.05)  . Agarose < 0.05) . The Proion site . The ChIreatment . Agarosea sample . The Genion site . Overall95 < BMI) was significantly lower than that in the normal weight group [in vitro was confirmed in 3T3-L1 cells [Vitamin A was the first identified fat-soluble vitamin. Its physiological functions include maintaining visual function , promotiht group . A similht group . Studiesht group , 40. In L1 cells . These sin vitro. Our previous work found that atRA has a significant potential to inhibit the BMSCs' differentiation into adipocytes [Pparg2 directly [Pparg2 and Cebpa and adipocyte associated genes decreased significantly.BMSCs can be directed to differentiate into mature adipocytes ipocytes . During ipocytes . Howeverdirectly . The resFra1 mRNA was highly expressed in the atRA intervention group [Fra1 showed few lipid droplets after oil red O staining and showed a significant decrease in adipogenic gene expression. The results were validated at the mRNA and protein levels. By contrast, BMSCs silenced for Fra1 showed increased amounts of lipid droplets after oil red O staining. Furthermore, key adipogenic genes and adipogenesis-related genes showed higher expression in the si-fra1 group. This confirmed that FRA1 has an inhibitory effect on the induced adipogenic differentiation of BMSCs.FRA1 is a member of the AP-1 family. A previous study found that on group . Luther on group . TherefoFra1. The mRNA and protein levels of Fra1 in the ad-fra1 group were almost 40 times and 10 times higher, respectively, than those in the atRA intervention group. However, treatment with atRA caused stronger inhibition of adipogenesis. This was specifically reflected in the expression of key adipogenic genes (Pparg2 and Cebpa) and adipocyte-associated genes. The PPARG2 and CEBPA protein levels also confirmed this result. In addition, after oil red O staining, a small amount of lipid droplets could be seen in the ad-fra1 group, but there were almost no lipid droplets in the atRA group. We hypothesized that silencing Fra1 could promote BMSCs' adipogenic differentiation. Results from qRT-PCR, western blotting, and oil red O staining supported this hypothesis. We also found that although there were no statistical differences in the mRNA expression of Fra1 between si-fra1 group and the si-fra1 + atRA group. Because of the role of atRA, the adipogenic ability in BMSCs was further inhibited in the si-fra1 + atRA group.Although both atRA and FRA1 play a negative role in BMSCs' adipogenic differentiation, they have different efficiencies. Both ad-fra1 and atRA could increase the expression of α/β/γ), and retinoid X receptors (RXRα/β/γ), which combine as a heterodimer to regulate target genes by binding to specific binding elements [Fra1 gene. ChIP-qPCR analysis identified an 823 bp 5′ to the transcription initiation site of the Fra1 promoter that contained a unique RAR binding site, which suggested that this proximal RAR binding site would be sufficient to drive the repression of Fra1 transcription by RARG. In addition, we analyzed the regulatory relationship between FRA1 and Pparg2 in a ChIP-qPCR experiment. The results showed that the DNA precipitated by the anti-FRA1 antibodies could amplify the promoter region sequence of Pparg2. These results indicated that FRA1 could directly regulate Pparg2 expression by binding to its promoter region. Hasenfuss et al.'s findings also supported this result [Pparg2 gene transcriptional activity [Cebpa gene fragments and found that FRA1 was present at the Cebpa promoter in BMSCs. Similarly, Luther et al. detected FRA1 could directly inhibit Cebpa transcription [AtRA induces bioactivity by activating its nuclear receptors, RARs  effector protein SMAD family member 3 (SMAD3). SMAD3 interacts with CCAAT enhancer binding protein beta (CEBPB) to interfere with the binding of CEBP DNA to other transcription factors, thereby interfering with the adipogenic signaling pathway [in vitro by upregulating the gene expression of transcription factors preadipocyte factor 1 (PREF1), SRY-box 9 (SOX9), and Kruppel-Like Factor 2 (KLF2) by activating RARG receptors. Retinoic acid receptor response elements (RAREs) are present in the promoter regions of these transcription factor genes [Compared with the effect of FRA1 alone, atRA has a stronger inhibitory effect on adipogenesis. This suggested that atRA could inhibit adipogenesis via other pathways. Studies have shown that retinoic acid can stimulate the expression of transforming growth factor  pathway . Ayala-S pathway . In addior genes –49. Furtor genes . Thus, aTaken together, our results show that atRA inhibits adipogenic differentiation of BMSCs by upregulating FRA1 signaling. We investigated FRA1 and atRA in the adipogenic differentiation of rat BMSCs. Both of them play a negative role in BMSC adipogenic differentiation. The molecular mechanism involves atRA exerting its effect via its nuclear receptor RARG and downregulating the expression of PPARG2 and CEBPA in the adipogenic differentiation of BMSCs by upregulating FRA1. In brief, the RARG-FRA1-PPARG2 or CEBPA axes, or both, are effective in the process of atRA inhibition of adipogenic differentiation of BMSCs. However, there might be other signaling pathways involved in atRA-mediated inhibition of BMSC adipogenesis, which should be explored in the future study. This deeper understanding of the molecular mechanism by which atRA inhibits BMSC adipogenesis supports the use of vitamin A to treat obesity and related diseases.


In this study, series of non-ionic surfactants from Span and Tween are evaluated for their ability to affect the viscosity profile of cyclopentane hydrate slurry. The surfactants; Span 20, Span 40, Span 80, Tween 20, Tween 40 and Tween 80 were selected and tested to provide different hydrophilic–hydrophobic balance values and allow evaluation their solubility impact on hydrate formation and growth time. The study was performed by using a HAAKE ViscotesterTM 500 at 2 °C and a surfactant concentration ranging from 0.1 wt%–1 wt%. The solubility characteristic of the non-ionic surfactants changed the hydrate slurry in different ways with surfactants type and varying concentration. The rheological measurement suggested that oil-soluble Span surfactants was generally inhibitive to hydrate formation by extending the hydrate induction time. However, an opposite effect was observed for the Tween surfactants. On the other hand, both Span and Tween demonstrated promoting effect to accelerate hydrate growth time of cyclopentane hydrate formation. The average hydrate crystallization growth time of the blank sample was reduced by 86% and 68% by Tween and Span surfactants at 1 wt%, respectively. The findings in this study are useful to understand the rheological behavior of surfactants in hydrate slurry. Clathrate hydrates—also known as gas hydrates—are solid compounds that form when a suitable size substance (gas/liquid) is encapsulated in a 3-dimensional network water cage held together through hydrogen bonding ,2,3. TheClathrate hydrates pose major operational threats to oil and gas flow assurance . The incIt has been reported that cationic surfactants are effective anti-agglomerant low dosage hydrate inhibitor (AA-LDHI) ,25. ThesOn the other hand, anionic surfactants promote hydrate formation by participating partly in the gas hydrate clathrate formation causing reduction in adhesion forces among hydrate molecules allowing for a larger particle surface area for hydrate growth . It has Recent morphology study has reported some non-ionic surfactants such as Span 80 and Tween 65 as potential additives to prevent hydrate formation. However, limited work has been done to understand the effects of non-ionic surfactant concentrations on hydrate formation and growth. In addition, their rheological behaviors have not been well studied in literature . DependiMany gas hydrate studies involve using liquid cyclopentane as hydrate former to test the performance of new compounds ,31,32,33The size and structure of cyclopentane lends itself to efficient space filling of structure II (sII) cavities, as shown by Spans and Tweens are non-ionic surfactants that are used as emulsifying agents in the preparation of stable emulsion systems for many applications . They arOn the other hand, Tweens are produced from ethoxylation of Spans to increase HLB range and enhance hydrophilic solubility to yield stable oil-in-water emulsion system . Tweens Delgodo-Linares et al.  evaluateIn addition, Liua et al.  studied The effects of hydrophilic–lipophilic balance (HLB) number for series of non-ionic sorbitan monoester on equilibrium condition of cyclopentane hydrate in water-in-oil emulsion was reported by Baek et al . The perKaranjkar et al.  revealed2/min to 0.068 mm2/min (of pure water), nearly an order of magnitude slower than that found for pure water at 0.590 mm2/min. High molecular weight (1845 g/mol) and HLB (10.5) contributed to a large energy of desorption at an interface and are believed to be the sources of Tween 65 hydrate inhibiting properties. They further suggested that hydrate morphology is affected by the type and concentration of surfactants. However, the rheological analysis of surfactants type and concentrations are not well understood and studied in literature. Most hydrate slurry rheology studies are limited to Span 80. There are few studies in open literature that employ rheological approach to study hydrate slurry behavior in the presence of surfactants. In particular, tween-based surfactants. In addition, understanding the effect of surfactants concentration on hydrate slurry is necessary to provided effect guidelines in their practical applications. Therefore, in this article, the rheological slurry of cyclopentane hydrate is evaluation in the presence of three series of Span and Tween surfactants at different concentrations.Recently, Dann and Rosenfeld  studied The list of chemicals used in this work is tabulated in The tested sample mixture comprised of 50% volume of cyclopentane and 50% water at 25 °C. Representing a mixture of 9.0 mL cyclopentane mixed with 9.0 mL of deionized water in a 50-mL glass sample bottle and gently tilted upside-down 50 times. Slow-and-gentle mixing was applied only to well the mixture well but was not intended to produce a tight emulsion with the surfactant present. The sample with Span and Tween were prepared by first prepared the desired Span–Tween concentration (0.1 wt%–1.0 wt%). After which the cyclopentane and deionized water were used to dilute the Span and Tween surfactants, respectively before the mixtures were put together in the glass sample bottle.−1. This was done to allow cyclopentane hydrate to form. Due to the long probabilistic nature of cyclopentane hydrate formation, the sample mixtures were seeded at the interface at the experimental temperature about 60 min at the start of the experiment [The rheological properties of semi-solid hydrate slurry were studied using HAAKE ViscotesterTM 550. The viscometer is designed with a rotational speed preset and measure the flow resistance of a slurry fluid. The torque maintaining the set speed is proportional to the fluid viscosity, so all final information on the viscosity, shear stress and the shear rate were obtained from the torque required, the set speed and the geometry factors for the applied sensor. The study was performed with a cylindrical concentric geometry. The temperature of the viscometer is controlled by an attached external water bath system. In each experimental run, the desired prepared sample mixture of water and cyclopentane (with or with Span/Tween) is loaded into the viscometer sample holder at a preset temperature of 15 °C. The temperature of the water bath is then lowered to the desired experimental temperature 2 °C at a rate of 0.21 °C/min, with the controlled shear rate of 50 speriment . The timperiment . Furtheri) is estimated from h and Tseed are the time taken for hydrate to start forming and when seed where added to the mixture, respectively. The hydrate crystallization/growth time (Gt) is calculated form G is the time taken for complete hydrate formation.The hydrate induction time and crystallization/growth time were estimated to evaluate the effect of Span and Tween on cyclopentane hydrate. The induction time describes the time taken for a noticeable crystal to form. It allows the analysis of how fast or slow it would take for hydrate to form. On the other hand, the cyclopentane hydrate crystallization time is the time taken for a complete hydrate to form and the maximum viscosity achieved. The hydrate induction time  are potentially delaying the initialization of hydrate formation by extending the induction time for hydrate to crystalline. The best hydrate induction time inhibition impact of Span surfactants occurred in Span 20 at lower concentration (0.1 wt%). While Span 40 best prolonged the hydrate crystallization time at 0.1 wt%. However, both Span and Tween promoted cyclopentane hydrate crystallization time at all concentrations due to their surfactant behavior. Hence, confirming their potential anti-agglomeration impact via quickly achieving critical hydrate size that eliminates agglomeration and provide easy hydrate slurry that can be transported. The water-soluble Tween surfactants  demonstrate higher hydrate promoting impact than Span surfactants. The findings in this study will help provide insight into the rheological effect of surfactants on the hydrate slurry. The changes in fluid viscosity following hydrate slurry formation is useful information when performing fluid dynamic calculation in pipeline fluid transmission and process design for gas storage and potential application to CO


Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are more common in children with cerebral palsy (CP) than in the general population, but may still be underdiagnosed. This study aimed to estimate screen-positive ASD and ADHD in a population-based group of 264 school-aged children with CP born 1999–2006 from the CP register of western Sweden. Validated parent-completed questionnaires were used at a median age of 12 years 11 months (range 8–17 years). Three different scales were used to detect signs of ASD and ADHD, respectively. Response rate was 88% (232/264). In 19 children, all in the most disabled group, the screening procedure was not feasible due to too few questionnaire items completed, leaving 213 for analyses. One third (74/213) of the children screened positive for ASD and half of the children (106/213) for ADHD, which was about twice as often as ASD/ADHD diagnoses had been clinically identified. Children with intellectual disability, epilepsy and/or impaired speech ability more often screened positive for ASD as well as ADHD. Severe motor impairment was more frequently associated with screen-positive ASD, but not ADHD. Neither sex nor CP type was associated with screen-positive ASD/ADHD. In conclusion, school-aged children with CP very often screened positive for ASD and/or ADHD. The prevalence of ASD and ADHD is most likely underestimated in children with CP. These screening findings require further investigations. Cerebral palsy (CP) is the most common cause of motor disability in childhood, affecting about 2 per 1000 live births  problemsThere is growing evidence that neuropsychiatric disorders, primarily autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), are more prevalent in children with CP than in the general population –16. A reA previous study by our group, where medical records of children in a population-based group with CP were scrutinised regarding identified neuropsychiatric disorders, supported these findings. ASD was diagnosed in 18% and ADHD in 21% . We alsoASD screening studies in CP are scarce, often small and not population-based , 11. A NThe first aim of this study was to estimate the prevalence of ASD and ADHD screen positivity in a well-defined population-based group of children with CP from the CP register of western Sweden, and compare with already identified diagnoses of ASD and ADHD. The second aim was to describe if and how screening positive for ASD and ADHD was associated with sex, gestational age, CP type, gross motor function, intellectual level, epilepsy and speech ability.The study population, derived from the CP register of western Sweden, comprised eight birth-year cohorts of children and adolescents with CP born between 1999 and 2006 [CP types were classified according to the Surveillance of Cerebral Palsy in Europe (SCPE); into unilateral spastic CP (USCP), bilateral spastic CP (BSCP), dyskinetic CP and ataxic CP . Gross mGestational-age groups were considered: extremely preterm , very preterm (28–31 weeks), moderately preterm (32–36 weeks) and term (37 completed weeks or more).Intellectual level was defined as normal if IQ was ≥ 85, and borderline intellectual functioning if IQ was 70–84. Intellectual disability -5)  was defiVisual impairment was defined as an acuity of not more than 0.3 in the best eye with correction, and severe visual impairment was defined as an acuity of not more than 0.1 in the best eye with correction or the presence of functional blindness. Hearing impairment included sensorineural impairment or deafness, unilateral or bilateral. Epilepsy was defined as epilepsy under treatment according to the medical records. Speech was classified with the Viking Speech Scale (VSS) ; level INeuropsychiatric disorders in this study included ASD and ADHD. These diagnoses were derived from the medical records and had been coded according to ICD-10. Three autism spectrum diagnoses were found: autistic disorder, atypical autism and Asperger syndrome. ASD is used here for all three categories.n = 169) or after one or two reminders (n = 63). Twenty-four questionnaires were not returned despite reminders , the father (n = 31), both parents (n = 69), or the foster mother (n = 1). The median age at screening was 12 years 11 months (range 8 years 4 months—17 years 10 months).The 232 received questionnaires were completed by either the mother  . We defiThe DBC is a suite of instruments for the assessment of behavioural and emotional problems in developmental and intellectual disabilities . The DBCThe ABC was developed to measure levels of autistic behaviour in individuals with severe disabilities . The 57 In summary three scales were used to define ASD screen positivity  and three scales were used to define screen positivity for ADHD  Table . Since tNot all items had been completed in all questionnaires. Overall, data were missing in nearly 9% of all items. The instruments used differed in this respect; in SNAP 11% of the items were not completed, in ASSQ 11%, in SDQ 9%, in DBC 8% and in ABC 7%. For most children the questionnaire was applicable. In four out of five questionnaires a maximum of ten items out of all 282 were uncompleted. If less than three quarters of all items were completed in all three scales for ASD and ADHD, respectively, and no scale reached cut-off level, the questionnaire was considered not possible to evaluate.The study was approved by The Regional Ethical Review Board in Gothenburg, ref 398–12.χ2 test for independence was used, and for the comparison in a group with an ordinal scale, the Cochran–Armitage χ2 test for trends was used. A p value of < 0.05 was regarded as statistically significant.The aims of this study were descriptive, and statistics were used to compare groups. For the association between categorical variables, the χ2 test for independence was used. In Table The population-based basis is described in Table The screening response rate was 88% (232 questionnaires out of 264). The responders represented the whole group of children with CP regarding sex, gestational age, CP type, GMFCS level, intellectual level, visual and hearing impairment, epilepsy and speech ability. Overall there were no major differences between the responders and the non-responders. Significant differences were seen in three subgroups: gestational age 28–31 weeks, dyskinetic CP and borderline intellectual functioning  for either ASD or ADHD or both. Seventy-four (35%) screened positive for ASD and 106 (50%) for ADHD. There was an overlap of screening positive for both ASD and ADHD in 61 children (29%) . An ADHD diagnosis had been registered in 49 of the 213 children.The screening results of ASD and ADHD and registered diagnoses of ASD and ADHD are shown in Table Of the 42 children with an ASD diagnosis, 33 screened positive for ASD (sensitivity 79%). Of the remaining nine children, five screened positive for ADHD only. Of the 49 children with an ADHD diagnosis, 42 screened positive for ADHD (sensitivity 86%). The children with ASD or ADHD diagnoses who screened negative did not differ from the children who screened positive regarding sex, gestational age, CP type, GMFCS level or other associated impairments.χ2 = 8.91; p = 0.003), but screening for ASD showed no significant differences between gestational age groups  and 29 of the 98 girls (30%) screened positive, and for ADHD, 62 of the 115 boys (54%) and 44 of the 98 girls (45%) , while no association was seen between ADHD screening positivity and GMFCS levels  and ADHD   Fig. . This asχ2 = 12.36; p < 0.001) as well as ADHD   as well as ADHD , although no associations between diagnosed ASD and/or ADHD and speech ability were seen (Table Children with epilepsy screened positive more often than children without epilepsy, for ASD (In this population-based screening study, we found that a very large proportion of children with CP screened positive for ASD or ADHD or both. One third of the children screened positive for ASD and half of the children for ADHD. The rates were higher than expected; about double of already identified diagnoses in the same group of children.This screening study was designed to have high sensitivity, but with stricter cut-off levels the proportion screening positive would still have been high. For example, if an ASSQ cut-off of 17 rather than 15 had been used, the ASD screen positivity rate would still be 32%, instead of 35%. Nevertheless, the questionnaire did not identify all children diagnosed with ASD and/or ADHD. For ADHD, three of the nine children with a registered diagnosis who screened negative were on treatment with stimulants, which may have led to a considerable decrease in ADHD symptoms.The DBC-HI has been evaluated in a pilot study resulting in suggestions for two different cut-off levels used for different purposes , and we One important finding was that the instruments used were not appropriate for the most severely disabled children, i.e. children at GMFCS level V and profound ID. In 19 children the questionnaires were impossible to evaluate, due to too few completed items. Children with very severe impairments may not have enough abilities or expressions for the questionnaires to be feasible. In the remaining questionnaires regarding the children at GMFCS level V, fewer screened positive than in the less disabled children. In the study by Bjørgaas et al. , the samASD as well as ADHD screen positivity increased the more severe other impairments; ID, impaired speech ability and epilepsy. ASD screen positivity also increased with more severe motor impairment, while this association was not seen for ADHD. The comparison with already identified diagnoses of ASD and ADHD revealed a clear difference since diagnoses most often decreased with increasing other impairments. The gap between screening positivity and identified diagnoses was bigger the more severe other impairments, which may reflect diagnostic difficulties in children with several impairments.There was no significant male preponderance for either ASD or ADHD in this study, in contrast to the screening findings of the Bergen Child Study , 29.Participants in this study all belonged to a well-defined population-based group of children with CP, from the CP register of western Sweden , 2. The A limitation of the study is that information on the children came only from one source, the parents. This source of information is probably sufficient for most children with CP, but it may be hard for some parents to accept their children’s impairments, seeking other explanations for their problems. Conversely, some parents may look for impairments that more “objective” assessment would not pick up on. Additional teacher ratings would have been valuable. Another limitation is that the DBC, apart from the other screening instruments, has not been validated in Swedish, although that has been done in nearby countries.Another important point is that all children who screened positive would likely not meet full diagnostic criteria for ASD and/or ADHD after comprehensive clinical assessment. Further investigations are needed in these children, but even in children where diagnostic criteria are not met, the symptoms could still be impairing and important to consider when planning support.Our findings support the hypothesis that the prevalence of neuropsychiatric impairments in children with CP is underestimated. Children with one neurodevelopmental disability are at greater risk of also having other neurodevelopmental disabilities  and shouThis population-based study of children with CP indicates a higher prevalence of ASD and ADHD than previously described; one third of the children with CP may have ASD and half may have ADHD. These findings require further follow-up investigations pertaining to identifying the most suitable instruments for neuropsychiatric evaluation in children with CP, particularly for the more severely disabled children. It would also be valuable to assess the screen positive children without diagnoses more in depth to come closer to the true prevalence of ASD and ADHD in children with CP.


Dual-process theory is a widely utilized modelling tool in the behavioral sciences. It conceptualizes decision-making as an interaction between two types of cognitive processes, some of them fast and intuitive, others slow and reflective. We make a novel contribution to this literature by exploring differences between adults with clinically diagnosed ADHD and healthy controls for a wide range of behaviors. Given the clinical picture and nature of ADHD symptoms, we had a strong a priori reason to expect differences in intuitive vs reflective processing; and thus an unusually strong case for testing the predictions of dual-process theory. We found mixed results, with overall weaker effects than expected, except for risk taking, where individuals with ADHD showed increased domain sensitivity for gains vs losses. Some of our predictions were supported by the data but other patterns are more difficult to reconcile with theory. On balance, our results provide only limited empirical support for using dual-process theory to understand basic social and economic decision-making. These deficits are due to difficulties within three symptom clusters: (a) inattention causing careless mistakes, low frustration tolerance and problems in focusing on paperwork, reading, organizing and thinking through complex tasks; (b) hyperactivity resulting in difficulties sitting still and relaxing, tendency to work long hours or more than one job and (c) impulsivity expressed in acting and talking impulsively, overspending, frequently changing jobs and relationships, engaging in kick-seeking and/or antisocial behaviors4. Overall, these symptom clusters represent a reduced ability to act with forethought, and control impulsive action. A prior literature has shown that ADHD is associated with deficits in neurocognitive domains linked to executive functions such as response inhibition and working memory10. The very nature of these symptoms and deficits therefore renders individuals with ADHD ideal for testing the predictions of dual-process theory related to impulse control and emotional arousal.Attention deficit hyperactivity disorder (ADHD) in adults presents clinically with functional deficits in various aspects of life such as education, work performance, relationships, parenting, social and economic status17. Intuitive processes are typically characterized as being fast, automatic, effortless, and emotional. Reflective processes, conversely, are slower and more controlled, effortful, and deliberative. The dual-process typology has shaped empirical and theoretical work in many areas of psychology and neuroscience18 and it constitutes a theoretical foundation for highly influential ideas in behavioral economics, such as the planner-doer model of Thaler and Shefrin19 and subsequent theoretical work on hyperbolic discounting and impulse-control problems21. It can also rationalize core results in the heuristics and biases research program, including prospect theory22. However, from an empirical point of view, substantial uncertainty remains regarding the relevance of using dual-process theory to understand decision-making, because the literature to date has been unable to establish empirical regularities that are robustly linked to behavioral disparities in intuitive vs reflective decision-making.Dual-process theory conceptualizes decision-making as resulting from the interaction between intuitive and reflective cognitive processes25. We therefore expect adults with ADHD to rely more heavily on intuitive cognitive processing when making decisions.The goal of our paper is to examine how and to what extent intuitive decision-making influences basic social and economic decision-making that is central to understanding a wide variety of everyday behavior: (i) altruistic behavior, (ii) moral judgment, (iii) risky choices, and (iv) intertemporal choices. To this end, we develop predictions using dual-process theory in each of these four domains and subsequently test them in an experiment, by comparing the choices made by medication-naïve adults with ADHD to a healthy control group. According to a dual-process framework for understanding decision-making, poor executive control should lead individuals to rely more heavily on intuition when making decisions26. For reviews, see Fromell, et al.27, Rand, et al.28, Capraro26 on altruistic behavior and moral judgment; and Deck and Jahedi29 and Drichoutis and Nayga30 for risky or intertemporal decision-making under cognitive load. One recent and unusually large experimental study found that time pressure seemed to increase the reflection effect of prospect theory for decisions involving risks31, but other studies have found different results32. Moreover, Lindner and Rose33 found that time pressure increased rather than decreased patience in intertemporal choice, which goes against the canonical prediction of dual-process theory that intuition should favor immediate rewards.The previous experimental literature has used different types of state manipulations, for example time pressure and cognitive load or other depletion tasks, to invoke decision states thought to temporarily heighten individuals’ reliance on intuitive cognitive processing when making their decisions. Common to the four domains of decision-making under consideration in this study is that prior work has found inconsistent effects, in most cases converging toward small or insignificant findings when assessed meta-analytically or in literature reviews. An exception is the domain of moral judgment where the literature points toward a more robust link between intuition and deontological judgments34 and display an unusually high rate of discounting37, with difficulties in several aspects of financial decision-making38, the majority of findings are still based on studies with children or adolescents, and few studies consistently sampled from a medication-naïve subject pool, see e.g. the updated meta-analyses by Dekkers, et al.39 and Marx, et al.40. Studying medication naïve subjects is critical for a valid test of hypotheses about decision making in ADHD, because treatment with stimulant medications is highly effective to improve cognitive function in ADHD. In addition, there is no work we are aware of that used an experimental approach to investigate altruistic behavior or moral judgment in persons with ADHD.One possible explanation for the disparate findings in the previous literature is that manipulations are too weak to induce behavioral effects that are robust across studies and contexts. We circumvent this issue by exploiting variation in quantitative traits linked to ADHD, where there is a strong a priori reason to expect a differential between intuitive and reflective processing, and thus a stronger case for testing predictions of dual-process theory. This is the first study of its kind to systematically explore differences between adults with clinically diagnosed ADHD and healthy individuals for a wide range of social and economic decision tasks. Our study therefore makes a novel contribution to the growing experimental literature examining the behavioral correlates of intuitive decision-making. We also contribute directly to the medical literature that seeks to characterize decision-making in persons with ADHD. Although some studies in this field have shown that adults with ADHD have problems with reward-based decision-making17. Type 1 processing is thought to be autonomous and fast. It runs without effort and makes minimal demands on working memory resources. In contrast, Type 2 processing is slow and controlled, loads heavily on working memory and supports hypothetical thinking and mental simulation13. Table Dual-process theory distinguishes between two types of cognitive processing involved in reasoning and decision-making, one fast and intuitive, the other slow and reflective41. Impulsivity and inattention, which are core symptoms of ADHD, are two important factors heightening decision-makers’ reliance on the default responses generated by intuitive Type 1 processing42. We therefore developed hypotheses for decision-making in individuals with ADHD assuming increased reliance on the intuitive features of cognitive processing.In dual-process theory, choice and judgment is a product of interaction between the two types of processing. A common view is that Type 1 processing generates default responses that may or may not be overruled by subsequent Type 2 processing44. The central argument is that people internalize behavioral strategies that are typically advantageous in everyday life, and then use them as intuitive default responses in novel settings, for example in a lab experiment. These default responses can then be overruled by subsequent Type 2 processing, if people take the time and effort to engage in the more cognitively demanding task of calculating the optimal strategy for this particular setting. In a social dilemma, there is a tension between individually optimal behavior (selfishness) and socially optimal behavior (full cooperation) in the short term, e.g. for one-shot interactions; but in the real world, where most interactions are repeated, it is often advantageous for everyone to cooperate. Based on this we would expect individuals with heightened reliance on Type 1 processing to be more likely to cooperate, even in situations where it does not maximize individual payoffs.The recent literature on intuitive versus reflective altruism builds on prior work that examined whether intuition promotes cooperation in social dilemmas. Rand et al. developed a theory of social heuristics, where default responses generated by intuitive Type 1 processing favor typically successful behaviors28. This means that intuitive default responses based on a social heuristic should be more similar to the optimal strategy that people will arrive at through subsequent Type 2 processing, and we therefore expect intuitive and reflective altruism to be largely similar26. This is also in line with recent meta-analyses of studies using state manipulations, e.g. time pressure or cognitive load, to induce more intuitive decision-making28.In contrast to cooperation, altruism is typically not advantageous in everyday life, because it involves only unilateral giving without strategic concernsAltruistic behavior is similar for individuals with and without ADHD.26). The general finding in this literature is that intuitive Type 1 processing seems to be associated with deontological judgments, i.e., it is morally unacceptable to harm people for the greater good. This finding is in line with the theory of emotional engagement in moral judgment developed by Greene, et al.45, where automatic emotional Type 1 processing drives deontological judgments, and more effortful and controlled Type 2 processing drives consequential decision-making and utilitarian judgments46. The central idea is that our intuitive reaction to a sacrificial dilemma will characteristically center on the moral prerogative that ‘it is morally wrong to hurt an innocent person, no matter the consequences,’ and thus if we are not willing or given time to further reason about the full consequences for everyone involved, this would be our judgment. However, some people will overrule this response once they have conducted a utilitarian calculation of the pros and cons of their actions, which typically requires more controlled and effortful cognitive processing. We therefore expect that individuals with heightened reliance on Type 1 processing are more likely to make deontological judgments in sacrificial dilemmas.A large body of literature has examined the influence of intuitive versus reflective decision-states on moral judgment in sacrificial hypothetical dilemmas, where individuals must decide whether to harm one individual to save a greater number of individuals  but less often in the loss domain (consistent with risk seeking).48. From the perspective of dual-process theory, the relative attractiveness of these two rewards will depend on the degree to which different types of cognitive processing are engaged in the evaluation procedure. Whereas the immediate reward is salient and thus easy to evaluate via intuitive Type 1 processing, the delayed reward is more abstract and thus requires greater involvement of Type 2 processing, because some degree of mental simulation of future possibilities is needed to fully assess how useful the reward would be at some distant date13.Intertemporal choice involves making decisions between different rewards that are distributed across time. In this context, the choices people make will typically depend on their patience, which is conceptualized as their tolerance of waiting for a given reward that is delivered at a future date. A common task used in the experimental literature involves choosing between a smaller reward delivered immediately and a larger reward delivered with delay13. In a seminal paper, McClure, et al.49 found increased activation in the evolutionary old limbic and paralimbic brain systems when immediate rewards were chosen but also that activation declined rapidly as both the sooner and later rewards were delayed. In contrast, evolutionary newer prefrontal areas that are typically associated with deliberation and higher cognition showed increased activation when delayed rewards were chosen. Other studies have found similar patterns of activation during intertemporal choice53. Studies also indicate altered VS  activation in reward anticipation and delivery in adults with ADHD54. We therefore expect increased preference for immediate rewards  in individuals with heightened reliance on Type 1 processing.A dual-process view of intertemporal choice is supported by neuroimaging studies that map differential activation in distinct neural systems to evaluation of monetary rewards delivered at different points in timeIndividuals with ADHD will choose the smaller-sooner reward more often in intertemporal choices.One hundred and eighty-four participants took up the study, n = 50 in the ADHD group and n = 134 in the control group. Both groups were similar in terms of background characteristics, including sex, age, and education  = 2.22, p = 0.14, n = 160. Within the ADHD group, the correlations between Qb test score and performance on the tests were weak and insignificant .We found no significant differences between the ADHD group and the control group on the Cognitive reflection test (CRT) or the Jellybean task. The tendency was for the ADHD group to perform worse on CRT but better on the Jellybean task. On CRT, the average number of correct responses (out of three questions) was 0.76 (SD = 0.92) in the ADHD group and 0.94 (SD = 1.11) in the control group, estimated mean difference = – 0.16, SE = 0.16, t(156) = –0.99, p = 0.11, 95% CI, – 0.03, 0.25. The data is thus consistent with population effects where individuals with ADHD are at most three percentage points (lower bound on the 95% CI) more selfish than individuals without ADHD, which is a negligible difference in this context; but we cannot rule out small to moderate effects in the opposite direction. Within the ADHD group, there was no correlation between manifestation of core ADHD symptoms, measured by a standardized score on the Qb test, and altruistic behavior . Taken together, we find moderate support for the hypothesis that altruistic behavior is similar for individuals with and without ADHD.We found no statistically significant difference between the ADHD group and the control group on the binary dictator game Fig. A. The avp = 0.54, 95% CI, – 0.14, 0.07. The data are thus consistent with population effects where the difference between individuals with and without ADHD is smaller than 14 percentage points, which is a reasonably small effect in this context. Within the ADHD group, there was a small but insignificant positive correlation between Qb test score and individuals’ propensity to make utilitarian moral judgments . Taken together, we find evidence against a difference in moral judgment between participants with and without ADHD, and there is thus no support for our hypothesis that individuals with ADHD are less likely to make utilitarian judgments in sacrificial dilemmas.There was no overall difference in moral judgment between the ADHD group and the control group Fig. A. The avp = 0.05, 95% CI, – 0.001, 0.27). We found a tendency for the reverse pattern in the loss domain, but the difference between the groups decreased when the magnitude of the certain loss became sufficiently large . Looking at the 95% CIs, we see that the data is clearly not consistent with population effects where individuals with ADHD are (i) less risk taking in the gain domain but (ii) more risk taking in the loss domain, as we had hypothesized. We reach a similar conclusion when we analyze the combined data for each individual within the ADHD group. The effects tend to go in the same direction as in the case–control comparison, but they are small and not significant. There is a weakly positive correlation between Qb test score and the propensity to take risks in the gain domain , but there is no clear pattern in the loss domain .Participants with ADHD were more risk taking in the gain domain compared to the control group Fig. A. For exrge Fig. B. The avp = 0.01, 95% CI, 0.06, 0.40). Similarly, within the ADHD group, there was a positive correlation between Qb test score and individuals’ propensity to take more risks in the gain domain vis-à-vis the loss domain, Spearman’s ρ = 0.31, p = 0.03, n = 50. These final results suggest increased domain sensitivity for risk taking in persons with ADHD.There was, however, a comparatively strong effect within subjects, suggesting that individuals with ADHD make greater adjustments to their risk taking in the gain vs the loss domain. To summarize this effect we calculated for each individual the difference between the proportion of risky choices in the gain domain and the proportion of risky choices in the loss domain. We find that on average, for individuals with ADHD the mean (SD) difference in risk taking between gain and loss domains was 0.27 (0.44), and for participants in the control group the corresponding figure was 0.04 (0.55). Thus, there was a larger gain–loss difference within individuals in the ADHD group compared to the control group  = 2.70, p = 0.05, 95% CI, 0.002, 0.26). We can see in Fig. Participants with ADHD were more impatient than controls Fig. . The aveρ = 0.23, p = 0.10, n = 50. The point correlation appears to be stronger for trials with a short horizon  compared to trials with a slightly longer horizon , but we cannot separate these two effects statistically. Taken together, we find support for our hypothesis that individuals with ADHD would show increased impatience in intertemporal choices, but the estimated effects are weaker (noisier) than expected.A similar pattern of decision-making emerges when we restrict the analysis to participants in the ADHD group. There is an overall positive but insignificant correlation between Qb test scores and the proportion of impatient choices, Spearman’s 27.In this study, we used quantitative traits in adults with ADHD to test predictions of dual-process theory across several domains of social and economic decision-making. The clinical picture of adult ADHD is dominated by hyperactivity, inattention and impulse-control problems together with deficits in executive functions such as inhibition and working memory. We therefore reasoned that individuals with ADHD would rely more heavily on the intuitive features of cognitive processing when making decisions compared to a healthy control group. Overall, we find mixed results. We do confirm important aspects of our hypotheses, most notably linked to intertemporal choices and altruistic behavior. The null result for altruism was expected from a dual-process point of view and it is clearly in line with previous results in the literature that used experimental manipulations to induce intuitive versus reflective decision states45 and the overall tendency in the empirical literature, reviewed in Capraro26. However, we observed no difference in moral judgment between individuals with ADHD and healthy controls in our data. Whereas this finding goes against some previous results in the literature, it is consistent with findings in Białek and De Neys55 and Tinghög, et al.56, who failed to confirm effects of cognitive load or time pressure on moral judgments. Our finding is also in line with the recent strand of literature on ‘utilitarian intuitions.’ Here, Bago and De Neys57 used a two-response paradigm and observed that most utilitarian responses materialized immediately and seemed not to require calculated deliberation, which goes against the corrective view of dual-process theory where utilitarian judgments are typically seen as products of controlled and effortful Type 2 processing.In contrast, for moral judgment and decisions involving risks we found moderate to strong evidence against our hypotheses. For moral judgment, we had expected a higher proportion of deontological judgments in individuals with ADHD, based on the theory of emotion/intuition-based moral judgment31, who used an identical task with similar stake sizes, but instead of comparing across groups with different traits, they used time pressure to invoke intuitive decision-making. They found that time pressure led to less risk taking in the gain domain but more risk taking in the loss domain, which is consistent with the hypothesis that the reflection effect of prospect theory becomes more pronounced under intuitive decision-making. We had expected a similar effect for individuals with ADHD vis-à-vis healthy controls, but our results strongly reject such a pattern; if anything, we found the opposite tendency, where individuals with ADHD seemed to take more risks in the gain domain but fewer risks in the loss domain. A bias for risky choices in the gain domain is potentially consistent with shared dopaminergic mechanisms underlying reward valuation and impulsivity58, and with earlier studies indicating altered reward processing in ADHD with decreased striatal activation in reward anticipation60 and higher activation in the orbitofrontal cortex with gain outcomes60, suggesting that individuals with ADHD may attribute higher value to gains. These conflicting results together with the disparate findings in the previous literature using different types of manipulations, such as time pressure, cognitive load or other depletion tasks, suggest that more work is needed to better understand the interplay of cognitive processes underlying the characteristic choice patterns of prospect theory, which in itself appears to be a highly robust and replicable empirical phenomenon61.Our results for decisions involving risks are difficult to reconcile with the findings in Kirchler, et al.62. Indeed, this is where we found the strongest link between ADHD and decision-making; individuals with ADHD made greater adjustments to their risk taking when moving from the gain domain to the loss domain, and a similar effect was found within the ADHD group when assessed based on aggregate scores on the Quantified behavioral test. Altogether, this finding suggests increased domain sensitivity for risk taking in persons with ADHD, which is a new result in the literature. Note, however, that it was based on data-contingent analyses and should not be interpreted as conclusive until replicated in future studies.No previous study used the dictator game or trolley dilemmas to characterize decision-making in adults with clinically diagnosed ADHD vis-à-vis healthy controls; we found substantial similarity in decision-making between individuals with and without ADHD on both these tasks. In contrast, risk taking in persons with ADHD has been widely studied, but this literature has largely focused on adaptive decision-making rather than decisions from description (such as standard prospect theory gambles). For example, only a handful of the studies covered by recent meta-analyses on risk taking concerned decisions from description with adult subjects, and none made a clear comparison between gain and loss domains66. Dual-process theories increasingly recognize that biases and fallacies in decision-making should not be attributed exclusively to intuitive processing67. Thus, one argument against CRT is that it conflates normative choice with intuitive thinking propensities65. Another argument against CRT comes from the observation that many people fail to solve the task even when the  correct answer is blocked out by design, suggesting that CRT errors can be the result of many different processes and is not exclusive to a failure to engage in reflective thinking63. Our results are less surprising when these newer developments in the field are taken into account. They are also consistent with the finding that trait impulsivity (which is a core symptom of ADHD) is only modestly linked to performance on CRT68.We had expected a stronger effect on the Cognitive Reflection Test (CRT), which has traditionally been used to demonstrate, and capture, differences in cognitive processing. However, an emerging literature questions whether this task is sensitive enough to reliably capture interpersonal differences in intuitive versus reflective processing-propensities69, which underscores the need for studies regarding decision-making in ADHD across the life-span. Participants in the control group were recruited as matched controls to around half of the participants in the ADHD group. As noted, this resulted in a balanced sample, but since not all participants with ADHD had a uniquely matched control we used a standard between-group analysis-strategy. Another strength is that we cover four different domains of decision-making and our results are therefore interesting to several distinct literatures on intuition versus reflection. The dictator game and risk tasks were incentivized but the intertemporal choice task was hypothetical. This is a limitation that might have affected our results, but it should be seen in the light of previous methodological work concluding that there is in fact little evidence of systematic differences between incentivized and hypothetical experiments on intertemporal choices, in contrast to e.g. experiments on risk taking or altruism, where incentives seem to play a larger role72.Our study has several strengths, including a unique sample consisting of medication naïve clinically diagnosed adults with ADHD balanced against healthy controls on age, sex and education. Adults with ADHD diagnosed in adulthood may differ from children and adolescents with ADHDGiven our relatively small sample size, the results on each task should be interpreted with some caution. A priori we had 80% power to detect a medium-sized difference between the ADHD group and the control group. For the null results on altruism and morality, this implies that our results speak strongly against the existence of medium to large differences between individuals with ADHD and population controls, but it is still possible that smaller effects exist. Still, given the close link between the neurocognitive deficits commonly observed in individuals with ADHD and the core features of dual-process theory, we had a strong case for expecting relatively large behavioral differences between the groups; in particular given that all subjects in the ADHD group were medication-naïve clinically diagnosed patients. Arguably, this alleviates some of the concerns that our study was inadequately powered to detect meaningful effect sizes given the objective of our paper.Dual-process theory is a useful and widely utilized tool for organizing our thinking about the cognitive foundations of decision-making. In its most general form, this theory (or collection of theories) characterizes decision-making as the upshot of guided interaction between different types of cognitive processes, some of them fast and intuitive, others slow and reflective. Our main idea with this paper was to broadly characterize intuitive versus reflective decision-making for a wide variety of tasks, by exploiting variation in quantitative traits linked to ADHD. Given the clinical picture and the nature of ADHD symptoms, we have a strong reason to expect heightened reliance on intuitive cognitive processing in individuals with ADHD, and we can thus infer how this influences decision-making by observing differences and similarities between individuals with and without ADHD. The fact that we found so few strong differences between these two groups supports a general conclusion that intuition versus reflection should not be seen as stable decision-making traits. Our findings are overall consistent with the trends in many of the separate literatures that used state manipulations to invoke relatively more intuitive or reflective decision-making, where effects on average seem to be small, judging by recent summaries of the literatures. Taken together, the results from our study together with these recent developments suggest that the empirical case for using a general dual-processing distinction to understand basic patterns in social and economic decision-making is weaker than previously thought.The study was designed as a between-subject observational design comparing medication naïve adult subjects with ADHD with a healthy control group. All subjects answered anonymously on a computer. The experiment was divided into blocks associated with dependent variables. Block order was fixed but the order of the questions within each block was randomized. Before the experiment begun, subjects were informed that one of their decisions would be randomly assigned for real payment. All participants gave written informed consent. All methods were carried out in accordance with relevant guidelines and regulations. The study was approved by the Regional Ethics Review Board in Linköping, Sweden (Dnr 2014/43-31).74. Clinical assessment prior to and independent of the study included interview by specialist or senior resident in psychiatry with training in diagnosing ADHD, and assessment by experienced psychologist or psychiatrist of current and childhood DSM-IV-TR 75 symptoms and functional impairment, using DIVA (Diagnostic Interview for Adult ADHD)76 and structured MINI 5 interview 77. Childhood onset according to DSM-IV criteria was established based on self-report and when possible (76% of cases) also by informant report . Diagnostic procedure also included blood sample for alcohol markers, including blood phosphatidylethanol (PEth)78, and drug urine screening. All patients fulfilled criteria for diagnosis and were offered ADHD medication after diagnosis and agreed to start medication after completing the study. A Qb-test  was used as an objective measure for current symptoms of hyperactivity, impulsivity and inattention. The Qb-test combines attention measures derived from omission errors in a computer based version of the continuous performance test (CPT), impulsivity measures based on CPT commission errors, and a high resolution motion tracking system based on an infrared camera following a tracer attached to a headband the subject is wearing during assessment. Qb-test results are expressed as a score standardized around zero compared to a sex and age balanced normative Swedish population sample79. In our analyses we used each participant’s test score averaged over the three components, hyperactivity, inattention, and impulsivity, respectively (mean Qb test score).Adult medication naïve patients recently diagnosed with ADHD were recruited from the outpatient department of the Psychiatric Clinic at the Linköping University Hospital. Patients were referred by their treating psychiatrists or psychologist to the research group. ADHD was screened with the Adult ADHD Self-Report Scale (ASRS), validated for screening of adult ADHD and officially translated to Swedish in 2007, with diagnosis probable at 17 points or more on either subtype scales  and highly probable at 24 and aboveInclusion criteria were ADHD DSM-IV diagnosis, age 18 or older, ability to read and understand Swedish language, and signed informed consent. Exclusion criteria were concomitant autism, severe ongoing psychiatric disorder, including bipolar disorder, schizophrenia, severe obsessive–compulsive disorder (OCD); and ongoing substance-use disorder (SUD), defined as SUD within the last six months and/or positive urine drug screening or blood PEth above cut-off. Further, individuals with conditions impairing ability to understand written instruction and/or give written informed consent to the study, such as severe dyslexia, intellectual disability, as well as individuals with previous or ongoing ADHD medication (stimulants or atomoxetine), or psychoactive medication deemed to influence decision-making, such as sedatives, were excluded. Concomitant mild or moderate depression, social phobia, or generalized anxiety-disorder diagnosis with stable medication did not warrant exclusion.p < 0.05) a mean difference of d = 0.47 between the ADHD group and the control group, using a two-sided t-test, and a medium to large correlation (ρ = 0.39) between manifestation of core ADHD symptoms and the relevant dependent variables from our behavioral tasks.A total of 59 patients, mean age 31.1 years, 44% male, were referred to the research group. Two did not meet inclusion criteria, two declined participation, two were excluded due to ongoing medication, one for ongoing substance use, and two patients did not show up for the study visit. Thus we included 50 recently diagnosed, medication naïve adults with ADHD, mean age 31.3 years, 44% male, using consecutive sampling; and 134 population controls, mean age 33.6 years, 43% male. All but three had combined ADHD subtype. The remaining three had mainly inattentive subtype, but their Qb-tests indicated significant hyperactivity/ impulsivity that did not differ from the remaining sample. Thirteen of the ADHD participants were diagnosed with comorbid anxiety disorder, four with depressive disorder , two with personality disorder and two with unspecified eating disorder. Controls were recruited in collaboration with Origo Group and drawn from a sample of the general adult population previously included in their subject pool. These participants were recruited as matched controls, on age, sex, and education, to around half of the participants in the ADHD group. Our final sample yielded 80% power to detect  can be found in the Supplementary materials. All participants received a show-up fee of SEK 150 (approx. 15 USD) for participation in the experiment. Participants were informed that this fee could increase or decrease depending on their decisions. At the end of the experiment, one decision was randomly selected to add or subtract from the initial sum.prop. altruistic choices) for altruistic behavior was calculated as the proportion of choices where the participant donated their show-up fee to charity. The dictator game is a workhorse for studying fairness preferences in experiments since it involves no strategic concerns related to behavior81.Altruistic behavior was measured using a binary dictator game, where individuals chose between keeping their show-up-fee for themselves and giving it to charity. Participants were presented with four separate decisions (different charities), in randomized order. Our main dependent variable  for moral judgment was calculated as the proportion of utilitarian choices the participant made.Moral judgments were measured using sacrificial moral dilemmas where subjects had to decide whether to harm a single individual in order to maximize overall good71. Subjects made risky choices in both the gain domain and in the loss domain. In the gain domain, subjects made four choices between a 50/50-gamble (lottery) with the chance of gaining SEK 100 (appr. $10) and a certain gain that varied between SEK 35 and 50. The decisions in the loss domain were additive inverses of the decisions in the gain domain, meaning that subjects made four choices between a lottery with a 50/50-chance of losing SEK 100 and a certain loss that varied between SEK 35 and 50. The order of trials was randomized within each domain, and the gain domain was always elicited before the loss domain. Our main dependent variable (prop. risky choices) for each domain was calculated as the proportion of trials where the participant chose the lottery over the safe amount.For decisions involving risks, we used a set of incentivized binary choices between a lottery and a safe amount of money. The lottery was identical but the safe amount varied systematically across trials49. In all trials, the smaller-sooner amount was fixed at SEK 100 and the larger-later amount was fixed at SEK 110. The trials differed systematically on two dimensions, (i) whether the horizon was 1, 4, or 5 days, and (ii) whether the smaller-sooner amount was delivered with a front-end delay of 0, 1, 10, or 20 days. The horizon is the delay (in days) between the sooner date of delivery and the later date of delivery, and front-end delay is the delay between today and the sooner date of delivery. For example, a trial with a 1-day horizon and a 10-day front-end delay is a choice between SEK 100 delivered in 10 days and SEK 110 delivered in 11 days. All rewards were hypothetical in this task. There were eight trials in total and they appeared in random order for each individual. Whether an individual chooses the smaller-sooner reward or the larger-later reward in a given trial depends on his or her patience, and we calculated our main dependent variable (prop. impatient choices) as the proportion of trials where the participant chose the smaller-sooner reward.Intertemporal choice was measured using a prototypical task where subjects made repeated choices between smaller rewards delivered sooner and larger rewards delivered later85 and the Jellybean Task86. The Cognitive Reflection Test involves three questions where there is an intuitive but wrong answer. For example, one of the questions was asked as follows: “A bat and a ball cost $1.10. The bat costs $1.00 more than the ball. How much does the ball cost?” Here, an intuitive answer that springs to mind quickly is that the ball costs 10 cents, but the correct answer is 5 cents. We calculate our dependent variable for this test as the number of correct answers (0–3) submitted by the participant. The Jellybean Task involves a hypothetical decision between two bowls containing 100 and 10 jellybeans respectively. Subjects are asked to imagine that they can draw one jellybean from one of the bowls, hidden behind a screen. If they draw a colored jellybean, they win five Euro. The two bowls are depicted with a label below the large bowl saying “9% colored jellybeans” and a label below the small bowl saying “10% colored jellybeans”. Here, the intuitive choice is to draw from the large bowl, as it contains a higher absolute number of colored jellybeans, but it is clearly better to draw from the small bowl because it contains a larger number of jellybeans in relative terms. Our dependent variable for the Jellybean Task is an indicator variable for choosing the smaller bowl.In addition to the four behavioral tasks explained above, we measured cognitive reflection using the Cognitive Reflection TestFor each behavioral task in the experiment, we estimated the difference in the relevant dependent variable between the ADHD group and the control group using a linear regression with robust standard errors and controlling for age and sex. We also calculated Spearman’s rank correlation coefficient for the relevant dependent variable and participants’ average score from the Qb-test, used as a proxy measure for ADHD severity. For decisions involving risks, these analyses were conducted separately for the gain domain and the loss domain. For intertemporal choices, our main focus was on the aggregated dependent variable but we also conducted tests separately for long and short horizon. Main results from the regressions are reported in the text and more detailed information can be found in Supplementary material Table Supplementary Information.