Most research on cognitive performance among individuals with Attention Deficit/Hyperactivity Disorder (ADHD) focuses on younger persons and on cognitive variability within speeded response-time tasks. Dispersion, i.e., variability across a range of cognitive domains, is emerging as a promising indicator of age-related and pathological cognitive impairment. However, there has yet to be an evaluation of differences in dispersion among older adults with and without ADHD. We address this gap by assessing associations of age and ADHD status with dispersion. We hypothesize older adults will exhibit greater dispersion than comparatively younger adults and explore whether individuals with ADHD exhibit greater dispersion than individuals without ADHD. In a sample of 231 adults from the Longitudinal Aging Study Amsterdam , 23 individuals met DSM-IV criteria for ADHD and 208 were classified as neurotypically functioning. Participants completed 13 tasks spanning domains of attention, fluency, memory, processing speed, and reasoning. Dispersion across the tasks was calculated as an intraindividual standard deviation. We regressed dispersion on age and ADHD status and adjusted for sex. Older age was significantly associated with greater dispersion . However, dispersion profiles did not vary as a function of ADHD status . Preliminary results suggest that dispersion across cognitive tasks may not be a sensitive marker of ADHD in older adults, although statistical power to detect differences was relatively low in the current study. As expected, age was a significant predictor of increased dispersion, consistent with accounts of age-related changes in neurological integrity.


ADHD is a neurodevelopmental disorder that frequently persists throughout adulthood. Binaural Beats (BB) are auditory perceptions occurring when two soundwaves of slightly different frequency are carried separately to the ears; they might modulate brain activity and performance.To evaluate BB efficacy on studing performance, mind-wandering, and core symptoms of a sample of adult ADHD outpatientsIn this randomized-controlled trial we recruited a sample of University students in pharmacological treatment for adult ADHD. A track with 15 Hz BB (415 Hz to right and 400 Hz to the left ear) was delivered to the intervention group; whereas, a placebo track consisting of two identical frequencies (400 Hz) was administered to control group. The RCT consisted of a baseline assessment (T0) and two fortnightly follow-ups (T1-T2). Each time, the patient filled the ADHD-RS-5  and the MEWS  and executed an online version of SART (Sustained Attention to Response Task). The effect of self-administered acoustic stimulation during individual studying sessions was estimated by a subjective studying performance (SSP) evaluation questionnaire.A significant improvement of SSP from baseline assessment (T1) to the last observation (T3) was detected in BB group only . A significant between-group contrast for SSP was also found at T3. No other significant changes were detected for ADHD-RS, MEWS and SART at p<.05 level.BB seem to improve subjective studying performance and ADHD symptoms severity. These preliminary findings must be confirmed in larger sample.No significant relationships.


Previous research conducted with samples of children suggest that individuals with attention-deficit/hyperactivity disorder (ADHD) have altered fatty acid concentrations and may have increased systemic inflammation. Whether these differences are also apparent in other populations of individuals with heightened ADHD symptoms  is unknown. The goal of the current study was to examine whether there are ADHD-associated differences in polyunsaturated fatty acid concentrations or pro-inflammatory cytokine concentrations during pregnancy, a developmental period when fatty acid concentrations and systemic inflammation have implications for the health of both the pregnant person and the developing child. We hypothesized that plasma levels of the ratio of omega-6s to omega-3s (n-6:n-3) and plasma inflammatory cytokine levels would be higher in individuals with heightened ADHD symptoms, consistent with previous findings in children with ADHD.N = 68) came from a prospective study of pregnant community volunteers who were oversampled for ADHD symptoms. During the 3rd trimester, plasma concentrations of fatty acids and the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed. Dietary intake was examined in the 3rd trimester using three 24-h recalls conducted by trained dietitians and by examining plasma levels of conjugated linoleic acid (n-6) and α-linolenic acid (n-3), essential fatty acids that must come from dietary intake.Data (p < 0.01) and higher TNF-α concentrations  relative to controls. There were no group differences in dietary variables, as assessed by self-report and via plasma concentrations of essential fatty acids. IL-6 was not reliably associated with ADHD status in this sample.The group with heightened ADHD symptoms had higher n-6:n-3s (β = 0.30, Pregnant individuals with ADHD, on average, had higher plasma n-6:n-3s and higher TNF-α concentrations relative to controls. A difference was not detected in their dietary intake of fatty acids or other relevant nutrients. Though these null findings are inconclusive, they are consistent with the hypothesis that ADHD-associated differences in plasma fatty acid concentrations are the result of ADHD-associated differences in fatty acid metabolism, rather than simply differences in dietary intake. Interest in the nutritional correlates of attention-deficit/hyperactivity disorder (ADHD) has grown over the last two decades, with substantial attention paid to the role of polyunsaturated fatty acids (PUFAs). Most of this research has focused on whether omega(n)-3 fatty acid levels, either consumed in the diet or measured in circulation, differ between individuals with and without ADHD. Results generally suggest that ADHD is associated with lower plasma n-3 fatty acid concentrations –3 howeveResearch looking at the n-6:n-3 in individuals with and without ADHD is more limited than studies of n-3s alone (there have been fewer than 10 studies to date), but these studies also support a picture of altered fatty acid status in ADHD , 14. As First, while the previous studies on this topic are informative, they have been conducted almost exclusively with samples of children or adolescents and have utilized data from samples that are predominantly male. While this focus on male youth is consistent with the known demographics of ADHD [which is more common in males  and is tArguably, if there were to be a group of individuals with ADHD that these results would be least likely to extend to, it would be pregnant individuals. Previous research shows that there are sex differences in fatty acid synthesis that are the result of sex hormone-induced alterations in the expression of desaturase and elongase enzymes , 22; theSecond, there exists ambiguity as to whether ADHD-associated differences in the n-6:n-3 in plasma reflect differences in fatty acid metabolism or if they are due to ADHD-associated differences in dietary intake (either in the form of diet or n-3 supplementation). One hypothesis is that these disparities are the result of metabolic differences ; this hyvia recalled dietary intake or by concentrations of essential fatty acids), this would be consistent with the hypothesis that there are ADHD-associated differences in the metabolism rather than the consumption of fatty acids.To examine dietary-intake differences in individuals with and without ADHD, the gold standard is 24-h recall data conducted by trained dietitians. A second source of information about dietary intake comes from examining blood levels of essential fatty acids . Most relevant here are the essential fatty acids linoleic acid (n-6) and α-linolenic acid (n-3) . If n-6:The third remaining question revolves around the relations among fatty acid concentrations, systemic inflammation, and ADHD. Increased systemic inflammation has been implicated in the etiology and pathophysiology of ADHD –37, yet To address these outstanding questions, the goal of the current study was to test:Does the ratio of n-6s to n-3s in plasma differ in pregnant individuals with and without heightened symptoms of ADHD?Are there differences in dietary intake of fatty acids  between individuals with and without heightened symptoms of ADHD?Do pregnant individuals with heightened symptoms of ADHD have higher plasma cytokine concentrations (IL-6 and TNF-α) than controls? Is the ratio of n-6s to n-3s in plasma related to greater cytokine concentrations?We hypothesized that, on average, individuals with heightened symptoms of ADHD would have higher plasma n-6:n3s and higher plasma concentrations of IL-6 and TNF-α. We also hypothesized that a higher n-6:n-3 would be positively correlated with inflammation. Consistent with the hypothesis that there are fatty acid conversion or metabolic differences in ADHD, we hypothesized that there would be no ADHD-associated differences in dietary intake or in essential fatty acid concentrations.a priori, given presumed effects of fatty acid supplementation on plasma fatty acid concentrations, and given the large literature linking adiposity and pro-inflammatory cytokine concentrations  were recruited through an urban hospital-based outpatient prenatal clinic in the second trimester of pregnancy and were followed into the postpartum period. After enrolling in the study with the first target child, six participants conceived a second child and completed all of the same assessments for their second pregnancy, resulting in data on six sibling pairs and yielding a final analytic sample of N = 68). This nesting of children within families was handled statistically .Data came from a prospective longitudinal study described previously , 51. Thevia surveys. Participants also reported on their dietary intake within 2 weeks of their laboratory visit. Participant medical records were reviewed for information about their health. Oregon Health & Science University's (OHSU) Institutional Review Board approved all procedures, and written informed consent was obtained from all participants.To serve the goals of the overarching project, an effort was made to oversample for individuals who endorsed a current or childhood history of ADHD or high levels of current ADHD symptoms (see full description of ADHD status definition below). Exclusion criteria included high-risk or medically complicated pregnancy, extreme life circumstances , being <18 years old, and active substance use . Data used in the current analyses came from laboratory visits when participants were 37 weeks pregnant. At this visit, participants provided a blood sample and reported on demographic information Pregnant person age (years) and highest completed education  were self-reported.n = 36) met this criterion. In this manuscript, we will refer to these individuals as the heightened ADHD symptoms (vs. control) group, given their history of or current levels of significant ADHD symptomatology, though we recognize that this shorthand does not adequately capture all of the nuance of our measurement.Pregnant person ADHD status was defined as a current or childhood history of ADHD or current elevated symptoms of ADHD, defined as >80th percentile on the Barkley Adult ADHD Rating scale (BAARS-IV) Quick Screen . Fifty-t2 EDTA tubes , centrifuged, and plasma was separated, aliquoted, and frozen at −80°C until assay. Plasma fatty acids were analyzed by direct transesterification using a Trace GC coupled to a DSQ mass spectrometer (ThermoElectron) as described previously (Plasma fatty acids were assessed using blood samples collected in the 3rd trimester (34–37 weeks gestation). Blood was drawn by venipuncture into Keviously . N-6 fat2).Participants' medical records were reviewed for pre-pregnancy body mass index ; blood was drawn, processed, and stored in the same manner. Blood draws were scheduled around participant prenatal care appointments. While this helped to minimize participant burden, it precluded our ability to completely standardized the exact time of day that the blood draw occurred. While most study visits were collected in the early to mid-morning, not all were.Plasma concentrations of IL-6 were measured by enzyme-linked immunosorbent assays , R&D Systems, Inc., Minneapolis, MN) according to the manufacturer's instructions and as described previously . All staPlasma concentrations of TNF-α  were assayed using Luminex polystyrene bead-based multiplex immunoassays  according to the manufacturer's instructions and as described previously . This paDiet during pregnancy was measured by three, non-consecutive 24-h diet recalls that were conducted over the phone by trained dietitians in the 3rd trimester of pregnancy. Trained staff, overseen by a dietitian certified in the procedure, used the multi-pass method  and NutrWhether the participant reported taking a fish oil or fatty acid supplement during the previous 30 days  was also recorded. Individuals who endorsed taking a fatty acid supplement typically reported taking a supplement that contained n-3 fatty acids , though the specific ingredients varied between participants. Forty-one percent of participants reported taking a fish oil or fatty acid supplement in the previous 30 days.plus 8.5  using the robust maximum likelihood estimator. This estimator can accommodate non-normally distributed data. Missing data were handled using full information maximum likelihood  for all study variables are presented in Our hypotheses were tested using a series of linear regressions. To examine whether there were ADHD group differences in the n-6:n3 (Hypothesis 1), we ran two regression models. In the first model, the plasma n-6:n-3 was regressed on ADHD status and on a variable that captured whether the participant was taking a fatty acid supplement or not. In the second model, the plasma AA:EPA was regressed on ADHD status and fatty acid supplement status. Two regressions were used to test Hypothesis 2 (whether there are ADHD-associated differences in cytokine levels), one where TNF-α was regressed on ADHD status and on fatty acid supplementation status and pre-pregnancy BMI, and a second where IL-6 was regressed on the same variables. In four additional models, we examined the association between the n-6:n-3 and cytokine levels, where (a) TNF-α was regressed on the n-6:n-3, (b) TNF-α was regressed on the AA:EPA, (c) IL-6 was regressed on the n-6:n-3, and (d) IL-6 was regressed on the AA:EPA. Given the dearth of research relating these metrics in pregnant individuals (particularly in the context of ADHD), these models were run once without covariates and a second time, controlling for fatty acid supplementation and pre-pregnancy BMI to provide the full context for these results. To address Hypothesis 3 (whether there are ADHD-associated dietary differences), each 24-h dietary intake variable was regressed on the ADHD status variable and on fatty acid supplementation status. Additionally, concentrations of the essential fatty acids conjugated linoleic acid and α-linolenic acid were regressed on ADHD status , again controlling for fatty acid supplementation status.Participants were on average 30.49 years old  at enrollment. Ninety-one percent of the sample was non-Hispanic White . The median completed education was a Bachelor's degree, with a range from some college but no degree to receiving a doctorate. See t-tests and chi squared tests to compare the ADHD and control groups on these variables indicated that the ADHD group differed from controls for the following plasma concentrations: the heightened ADHD symptoms group had higher n-6:n-3s (p = 0.04), higher AA:EPAs (p = 0.007), lower EPA concentrations (p = 0.03) and higher TNF-α concentrations (p < 0.001). ADHD-associated increases in plasma AA (p = 0.06) and plasma total n-6s (p = 0.07) were marginally significant. None of the 24-h recall dietary data differed between heightened ADHD symptoms and control groups (ps > 0.33). The heightened ADHD symptoms and control groups also did not differ in the percentage of individuals who reported taking a fish oil or fatty acid supplement in the previous 30 days .p = 0.008) and the AA:EPA . These estimates are adjusted for whether the participant was taking a fish oil or fatty acid supplement, which was not significantly related to the n-6:n-3 (p = 0.72) but was negatively associated with the AA:EPA  in these models.The results of the regressions used to test Hypothesis 1 are presented in p = 0.017) and that plasma AA concentrations were higher  among individuals with ADHD, relative to controls. There were no significant differences in concentrations of total n-3s or total n-6s, or in any of the other individual fatty acid (ps ranged from 0.16 to 0.98) when supplementation was considered.In supplemental analyses, we also examined whether the ADHD-associated differences in the n-3 and n-6 fatty acids listed in p < 0.001) were higher in individuals with heightened ADHD symptoms, even after controlling for both fatty acid supplementation status  and pre-pregnancy BMI . Contrary to expectation, IL-6 concentrations were not significantly different between the heightened ADHD symptoms and control groups  in this model, though pre-pregnancy BMI was associated with higher IL-6 concentrations , as expected.As can be seen in p = 0.004) and with greater TNF-α concentrations . However, these associations did not survive after controlling for BMI and fatty acid supplement use . The n-6:n-3 was not significantly associated with IL-6 or TNF-α concentrations in either model.As presented in ps ranged from 0.20 to 0.94. They also did not differ in essential fatty acid concentrations in plasma .The heightened ADHD symptoms and control groups did not differ from one another on any of the 24-h recall dietary intake measures , polyunsaturated fatty acids, n-3 fatty acids, saturated fatty acids, and the ratio of polyunsaturated fatty acids to saturated fatty acids), Utilizing data from a unique sample of pregnant individuals, the current study examined whether there are ADHD-associated differences in polyunsaturated fatty acid or pro-inflammatory cytokine concentrations during pregnancy, a developmental period when maternal fatty acid status and inflammation have implications for the health of both the pregnant person and the developing child , 56–59. The current study found that pregnant individuals with ADHD differed from controls in the n-6:n-3 using two metrics that have been used in previous research, the sum of total n-6s divided by the sum of total n-3s and the ratio of arachidonic acid to eicosapentaenoic acid concentrations (AA:EPA). Unsurprisingly, results were similar across these metrics. The observed ADHD group differences in the n-6:n-3 persisted even after controlling for whether the participant was taking a fish oil or fatty acid supplement or not. Despite n-3 supplementation being well-studied as a potential complementary treatment for ADHD , 60, fewThe ADHD and control groups did not differ reliably in their self-reported 24-h dietary recalls of PUFA intake  or on other relevant nutrients, including total calories, total fat, MUFAs, SFAs and the PUFA:SFA ratio. There also were no reliable differences in plasma concentrations of conjugated linoleic acid and α-linolenic acid, fatty acids that can only come from dietary intake. Though not conclusive, our observation that there are differences in the plasma n-6:n-3 in the absence of differences in dietary intake is consistent with the purported ADHD-associated differences in the metabolism of fatty acids or in the conversion of essential fatty acids to longer-chain fatty acids . For exaThis study also examined whether pro-inflammatory cytokine concentrations differed between pregnant individuals with and without ADHD. We found that pregnant individuals with heightened ADHD symptoms, on average, had higher plasma concentrations of TNF-α, relative to controls. Previous research has shown that heightened gestational inflammation is associated with other types of psychiatric symptoms during pregnancy  , 51, butConsistent with the assertion that a greater n-6:n-3 is indicative of a more pro-inflammatory state, we found a positive association between the AA:EPA ratio and plasma concentrations of both IL-6 and TNF-α in models that did not include covariates. However, these effects did not survive controlling for pre-pregnancy BMI. Interestingly, in their study of pregnant individuals with prenatal depression, Chang et al.  similarlvia the n-6:n-3 in the brain may provide a connection between ADHD, PUFAs, and inflammation.The precise mechanistic connection between ADHD, PUFAs and inflammation is not fully elucidated, but see  for a coThis study had a number of strengths. This is the first study to examine fatty acid or cytokine differences in pregnant individuals with and without heightened ADHD symptoms. Though differences in n-6:n-3 and pro-inflammatory cytokine concentrations have been observed in children with ADHD , 39, no This study also had limitations, including our small sample size. Though samples of this size are common in this literature, we may have lacked sufficient power to detect some effects, for example a difference in plasma IL-6 based on ADHD status. Thus, the null findings in this study should be viewed as inconclusive. In this first study investigating these associations in pregnant individuals, we focused on plasma concentrations of fatty acids, which reflect current fatty acid levels. Future studies on this topic should also examine fatty acid levels in red blood cell membranes, which reflect more chronic  levels of fatty acids. Examination of other plasma lipid levels  during pregnancy and may also yield important insights. While the unique nature of our sample  is a strength of this study, it may limit generalizability of our findings. Future research should examine these associations utilizing data from participants residing in other countries as well as in non-pregnant populations. We examined two pro-inflammatory cytokines in our analyses (selected because they were shown to be related to ADHD in previous research) that were assessed at one timepoint in pregnancy. Future research should examine a wider range of relevant immune factors, assessed at multiple times in pregnancy. While our study included measurement of ADHD symptomatology assessed using a well-validated and widely used scale with established norms, we did not assess ADHD diagnosis, which also may limit the generalizability of our findings. Last, while metrics such as the n-6:n-3 offer a more comprehensive picture of fatty acid status than absolute values of n-3s or n-6s, the n-6:n-3 is also not a perfect or complete measure of fatty acid status. For example, trans fatty acids interfere with the desaturation and elongation of both omega-6 and omega-3 fatty acids . Future This study found that, on average, pregnant individuals with heightened ADHD symptoms had higher plasma n-6:n-3s and higher TNF-α concentrations in plasma relative to controls. The heightened ADHD symptoms and control groups did not differ statistically on self-reported dietary intake , nor on essential fatty acid concentrations in blood. Though not conclusive, these findings are consistent with a picture of altered fatty acid metabolism in ADHD.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.All study procedures were reviewed and approved by the Oregon Health & Science University Institutional Review Board. Written informed consent to participate in this study was provided by the participants.ES and JN conceived the project. HG, ES, JN, and JL designed the research. HG, ES, and JL analyzed the data. AM data created the plots. HG and ES wrote the manuscript, with contributions from JN, JL, GD, AM, and KH. All authors discussed the data. All authors contributed to the article and approved the submitted version.Research reported in this publication was supported by the Abracadabra Foundation, the Bob and Charlee Moore Institute for Nutrition and Wellness, and by the National Institutes of Health under National Institute of Mental Health award numbers R3759105 (JN), R01MH117177 and R01MH124824 (ES and JN), K01MH120507 (HG), and R01MH117177-S1 (ES and JN). This material is the result of work supported with resources and the use of facilities at the VA Portland Health Care System and OHSU, Portland, OR.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.


Overall, the SnTe‐Bi2S3 nanocomposites exhibit peak z T up to 1.3 at 873 K and an average z T of ≈0.6 at 300–873 K, which is among the highest reported for solution‐processed SnTe.The broad implementation of thermoelectricity requires high‐performance and low‐cost materials. One possibility is employing surfactant‐free solution synthesis to produce nanopowders. We propose the strategy of functionalizing “naked” particles’ surface by inorganic molecules to control the nanostructure and, consequently, thermoelectric performance. In particular, we use bismuth thiolates to functionalize surfactant‐free SnTe particles’ surfaces. Upon thermal processing, bismuth thiolates decomposition renders SnTe‐Bi 2S3 nanocomposites with synergistic functions to enhance thermoelectric performance.A novel strategy of functionalizing the surface of “naked” particles by using inorganic molecules is proposed. In particular, bismuth thiolate were used to functionalize surfactant‐free SnTe particles’ surfaces. Upon thermal processing, bismuth thiolates decomposition renders SnTe‐Bi During the last century, material scientists have tried to maximize materials’ z T to enhance conversion efficiency. However, the complex and predominantly counterproductive relationships between the parameters determining z T make it challenging.Thermoelectric materials directly and reversibly transform heat and electricity. Considering heat as the most common form of waste energy, this phenomenon has been explored as a potential source of clean, non‐fossil energy.z Ts in different material systems, e.g. PbTe, SnTe, or SiGe.The most successful strategies to enhance performance have been based on refining the materials’ band structures and scattering centers simultaneously, which require superb control over the material structural properties.Alternatively, in the last decade, solution processing methods have been explored to reduce material production costs. Solution syntheses commonly use low‐cost reagents, low temperatures, and short reaction time to produce powders. The most widely used method to produce powders in solution for thermoelectric materials is the so‐called surfactant‐free since it has high reaction yields and renders particles without insulating long‐chain organic molecules, typically found when surfactants are used.From particles to dense materials, sintering is necessary.2S3 nanocomposites. Depending on the precursors used to prepare the bismuth thiolates, different decomposition products are obtained, resulting in nanocomposites with distinct structural properties. The produced SnTe‐Bi2S3 nanocomposites exhibit peak z T up to 1.3 at 873 K and an average z T of ≈0.6 at 300–873 K, which is among the highest reported for SnTe.One possibility, barely explored, is the particle surface functionalization with different organic or inorganic molecules. However, the high temperatures employed, usually above 400 °C, will decompose those surface species. While this can be seen as a hurdle, it also represents an opportunity. The decomposition products can be used to control the matrix composition or even to form different types of secondary phases. Herein, we demonstrate that adding surface molecules to “naked” particles and tailoring their decomposition is a powerful tool for precisely controlling nanocomposite structural and thermoelectric properties in SnTe. In particular, we prepare bismuth thiolates in a thiol‐amine mixture. These molecular solutes are then used to functionalize surfactant‐free SnTe particles’ surfaces. The surface‐modified SnTe particles are then subjected to various thermal processes that yield dense SnTe‐Bi2 and Te as precursors. This synthetic method was chosen due to its simplicity and uses very inexpensive precursors. The resulting SnTe NPs have an irregular shape with dimensions of 20–50 nm . The as‐synthesized SnTe NPs were purified from the reaction byproducts by precipitation, rinsing with ethanol and acetone. The washed NPs were then dried under vacuum overnight at room temperature, annealed in forming gas (95 % N2+5 % H2), and consolidated into pellets under vacuum using the spark plasma sintering technique. Further details of the entire process can be found in the Supporting Information.Ligand‐free SnTe nanoparticles (NPs) were prepared in water at ambient pressure using SnCl2S3 nanocomposites, SnTe NPs were dispersed in N‐methyl formamide, then different amounts (x mol %) of dissolved Bi2O3 or Bi2S3 in a thiol‐amine solution  were added. The mixtures were vigorously stirred at room temperature in an N2 filled glovebox for 24 h. The treated SnTe NPs were then precipitated from the solution, washed with acetone thoroughly, and dried under vacuum for further processing into pellets following the same steps as for the bare SnTe NPs, resulting in dense SnTe‐Bi2S3 nanocomposites . In the case of treating SnTe NPs with the Bi2O3 solution, the lattice parameter of SnTe increased with the Bi2O3 molar content used to treat the SnTe NPs  mixtures of EDT and en at room temperature and ambient pressure. In particular, we performed direct‐injection electrospray ionization mass spectrometry (ESI‐MS) using a liquid chromatography quadrupole time‐of‐flight mass spectrometer (LC/Q‐TOF‐MS) and UV/Vis spectroscopy measurements. Figure S3 shows the negative ion mode mass spectra for Bi2O3 and Bi2S3 solutions, respectively. The three most abundant peaks at m/z=272.9, 332.9, and 392.9 match well with the calculated values for [BiS2]−, [BiS(C2H4S2)]− (or BiS(EDT)−), and [Bi(C2H4S2)2]− (or Bi(EDT)2−), respectively, for both samples with the other peaks matching to those of the solvent blank  that is assigned to a ligand‐to‐metal charge transfer band (LMCT), consistent with other experimentally observed and computationally predicted bismuth(III) thiolate complexes.2O3 and Bi2S3 yield similar bismuth thiolate solutes upon dissolution, corroborating the conclusions drawn from ESI‐MS measurements.The X‐ray diffraction (XRD) patterns of the consolidated SnTe‐Bi2O3 solution transforms into a biphasic Bi2S3 and metallic Bi mixture, whereas the Bi2S3 solution yields phase‐pure Bi2S3  point to mostly identical solutes resulting from the two precursors, we found distinct differences after recrystallizing them by annealing under vacuum at 300 °C. The XRD patterns reveal that Bi2O3 and Bi2S3 solutions are constituted of the same molecular species ]− and [Bi(C2H4S2)2]−.Transmission electron microscopy (TEM) related analysis of the surface‐treated NPs showed a ca. 10 nm amorphous shell around the SnTe NPs constituted of homogeneously distributed Bi and S atoms Figures a, b. We 2S3 pellet was thinned to electron transparency by Ar+ polishing to produce a self‐suspended lamella. Figure 2S3 secondary phases because of the low solubility of Bi into SnTe.2S3 is mostly located along the grain boundaries forming grain boundary complexions and in the form of Bi2S3 nanodots .Grains grow through atomic diffusion across the grain boundaries, which can be envisioned as grain boundary movement.g Figure d.[14] σ decreasing with rising temperatures  reduces from 1.4×1021 cm−3 to 3.0×1019 cm−3. Such electrical conductivity and carrier concentration changes are associated with Bi‐doping, which acts as an electron donor, reducing the overall hole concentration. The nanocomposite prepared with 1 mol % Bi2S3 solution referred to as SnTe‐1 %*Bi2S3* is also presented for comparison. As expected, σ in SnTe‐1 %*Bi2S3* is much higher than SnTe‐1 % Bi2S3 due to the absence of Bi doping evidenced by the lattice parameters. The data corresponding to all the SnTe‐x %*Bi2S3* nanocomposites can be found in Figures S16.All samples exhibit heavily doped semiconductor behavior, with s Figure a. SnTe ix %Bi2S3 nanocomposites have a positive S, which increases with temperature  in SnTe‐Bi2S3 nanocomposites . We calculated m* of all SnTe‐Bi2S3 nanocomposites, according to m*≈me(μw/μH)2/3 ,m* in SnTe‐Bi2S3 nanocomposites is higher than that of bare SnTe. Apart from the energy filtering effect, the potential barrier is also responsible for the carrier concentration reduction since low energy charge carriers are trapped in the potential well, which is confirmed in SnTe‐*Bi2S3* nanocomposites where carrier concentration still decrease without Bi doping (Table S2).To get an insight into the high s Figure d.[16] PF, the surface functionalization with bismuth thiolates also provides effective means to reduce κ. Figure κtot) and lattice thermal conductivity (κlat) as a function of temperature  model with acoustic phonon scattering, which is also discussed in Supporting Information). The room‐temperature κtot of bare SnTe is ≈7 W m−1 K−1, arising from the undesirable high κele. Using Bi2O3 solutions can significantly suppress the high κele by reducing pH (Table S2) and introduce additional scattering sources.Aside from the enlarged κlat according to the Wiedemann–Franz relationship (κlat=κtot−LσT)  Figure a. κlat κlat in SnTe‐Bi2S3 nanocomposites .κlat of SnTe‐x %Bi2S3 nanocomposites and the simulated by the Klemens model as a function of x. As for the Klemens model, κlat reveals an apparent decrease due to the point defects introduced by Bi2S3, assuming Bi2S3 is fully alloyed with SnTe. However, the experimental κlat values in SnTe‐Bi2S3 nanocomposites are much lower than the calculated values, indicating other potential phonon scattering sources. We attribute the significant discrepancy between experimental and predicted values to the combined phonon scattering at the grain boundaries, Bi2S3 rich grain boundary complexion, and Bi2S3 nanoprecipitates. These accumulated defects, ranging from nanometers to micrometers, scatter phonons with corresponding mean free paths effectively. Together with the phonon scattering at the atomic scale, the surface treatment allows producing nanocomposites with scattering features at all length scales, which is well‐known as all‐scale hierarchical phonon scattering.We carried out Klemens model simulations to evaluate the origin of the low κtot and κlat at ≈673 K in bare SnTe prepared by the melting method are indicative of the bipolar effect onset.κ values of all SnTe‐Bi2S3 nanocomposites decrease monotonically in the whole temperature range , same as bare SnTe synthesized by melting method shown with a continuous black line.κtot−κele of bare SnTe and SnTe‐Bi2S3 nanocomposites in this work continue to decrease upon 673 K  should be addressed to the authors.Supporting InformationClick here for additional data file.


John Fitzgerald Kennedy (JFK), the 35th President of the USA, had chronic low back pain deemed to be centralized pain. Reportedly, attention‐deficit/hyperactivity disorder (ADHD) could associate with centralized pain. Based on his biographies, JFK could have had ADHD, a plausible cause of pain that afflicted him. Patients who tend to be hyperactive, like JFK, have centralized pain, such as chronic low back pain, and may also have comorbid ADHD. Clinicians should screen for ADHD because chronic centralized pain can improve with ADHD medications. JFK's biographies are filled with tales of the President's inattention and hyperactivity. In recent years, ADHD has been associated with centralized pain and chronic LBP.2John Fitzgerald Kennedy was depicted as a lively man, full of energy; he forced himself to act this way. In reality, he suffered from poor health; the details of his ailments remained a secret until 2001 (at the request of the Kennedy family), when the medical archives of the Kennedy library were opened for public scrutiny.The Impact of Illness on World Leaders,Kennedy's biographer Robert Dallek chose Dr. Jeffrey Kelman, a specialist in internal medicine and physiology, to accompany him, along with Dr. Bert E Park, a neurosurgeon and the author of James MacGregor Burns was a Democratic nominee in Massachusetts's first congressional district who published a biography of JFK in 1959 to determine whether JFK had the qualifications of a president.3According to the diagnostic criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5),3.1Several factors indicate that JFK experienced problems with attention, including inattention related to work‐related activities (DSM‐5 inattention criterion a), difficulty in sustaining attention to tasks (criterion b), being dreamy or preoccupied (criterion c), not following through on instructions in the workplace (criterion d), having difficulty keeping belongings in order and poor time management (criterion e), avoiding tasks requiring sustained mental effort (criterion f), often losing things (criterion g), and frequent forgetfulness (criterion i). Several examples can be quoted as follows: JFK's thesis had “many typographical errors and was English diction defective” (a).Other descriptions indicate that he also had characteristics of hyperactivity and impulsivity, including often fidgeting with his hands (a), often leaving his place or seeking fast‐paced activity (b), often running about or feeling restless (c), always “on the go” acting as if “driven by a motor” (e), and difficulty in waiting patiently (h). Specifically, as he talked with visitors in his office, Kennedy would fidget with a pencil.Considering the above descriptions of JFK (some of which indicate his mannerisms even before 12 years of age), we believe that JFK met several diagnostic criteria for ADHD outlined in the DSM‐5; these included 8/9 items  from the subcategory “Inattention” and 5/9 items  from the subcategory “Hyperactivity/impulsivity” in item A of the ADHD section in DSM‐5. This could be considered ADHD of the combined type.4To the best of our knowledge, this study is the first report to investigate the possibility of JFK's diagnosis of ADHD in line with valid diagnostic criteria. However, ADHD did not prevent JFK from achieving success because he was able to surround himself with competent, detail‐oriented people , and he was willing to delegate to them both responsibility and authority.Thus, adult ADHD is less likely to manifest functional impairment when occupational and social demands are met by internal resources, such as intellectual ability and self‐control, and external resources, such as support from family members.As JFK was also called a dynamo, his “overactivity”, “action‐proneness”, and “ergomania”, which have been described as typical behavioral traits of patients with chronic pain in the previous literature,Pinals et al.In addition to pain disorders, conditions such as fibromyalgia, IBS, celiac disease, insomnia, malabsorption, hypothyroidism, and allergies, which were present in JFK, are all physical disorders associated with ADHD.Although the concept of ADHD had not existed during his lifetime, JFK preferred the central stimulant amphetamine for pain management,Additionally, Kennedy's son was diagnosed with ADHD,Furthermore, behind JFK's success, his continued anxiety and fear of rejection from his father, who forced him to become a politician like a surrogate doll, was one of the main conflicts in JFK's life.The limitation of this study is that the ADHD diagnosis of JFK is a hypothetical diagnosis based on the description in the published literature, as the authors did not directly examine JFK.The President's Panel on Mental Retardation,SK and KM conceived the study. SK and NS collected and organized the literature information. SK wrote the manuscript. S‐IN assisted in writing the manuscript. All authors have approved the final manuscript for submission.This study was funded by the Japan Society for the Promotion of Science KAKENHI (Grant Number: JP20K07755). The sponsor has no role other than funding.The authors declare that there is no conflict of interest.None.Informed consent for patient information to be published in this article was not obtained because we have dealt with only already published historical data in this case report. There is nothing in this paper that would harm the human rights of the patient.


ADHD is the most common mental disorder in school-aged children. In France, methylphenidate is the only drug authorized for ADHD. Here, we describe the pattern of ADHD diagnosis and methylphenidate prescription to children and adolescents from 2010 to 2019.We conducted a retrospective cohort study of all beneficiaries of the French general health insurance scheme . We extracted information for all children and adolescents aged 0–17 years who received: (1) A diagnosis of ADHD . (2) At least one methylphenidate prescription . We analyzed the clinical, demographic, institutional, and social parameters associated with ADHD diagnosis and methylphenidate consumption in France.The ADHD diagnosis among children and adolescents increased by 96% between 2010 and 2019. ADHD diagnosis affects more boys than girls. About 50.6% of children hospitalized with a diagnosis of ADHD in 2017 also had another psychiatric diagnosis. The rate of children hospitalized with an ADHD diagnosis and treated with MPH varied between 56.4 and 60.1%. The median duration of MPH treatment for a 6-year-old ADHD child initiated in 2011 is 7.1 years. In 2018, 62% of ADHD children were receiving at least one psychotropic medication. Between 2010 and 2019, methylphenidate prescription increased by +56% for incidence and +116% for prevalence. The prevalence of methylphenidate prescription reached between 0.61 and 0.75% in 2019. Boys are predominantly medicated. The median duration of treatment among 6-year-olds in 2011 was 5.5 years. The youngest children received the longest treatment duration. Diagnoses associated with methylphenidate prescription did not always correspond to the marketing authorization. Among children receiving the first prescription of methylphenidate, 22.8% also received one or more other psychotropic drugs during the same year. A quarter of initiations and half of renewals were made outside governmental recommendations. Educational and psychotherapeutic follow-up decreased from 4.1% in 2010 to 0.8% in 2019. French children and adolescents, who were the youngest in their class were more likely to be diagnosed (55%) and prescribed methylphenidate (54%). Children from disadvantaged families had an increased risk of ADHD diagnosis (41.4% in 2019) and methylphenidate medication (25.7% in 2019). Attention Deficit Hyperactivity Disorder (ADHD) is considered the most common mental disorder in school-aged children . For thiDespite decades of intensive research, there are currently no neurological markers, genetic markers, or biological tests to identify or confirm the diagnosis of hyperactivity –8.Thus, the description of ADHD relies exclusively on evaluating behavioral symptoms, namely, an attention deficit with or without motor impulsivity and hyperactivity. For this reason, the prevalence of ADHD is intensely debated at the international level, with significant variations depending on countries, regions, and the survey methods used. A systematic review of more than 150 prevalence studies shows significant variations ranging from 0.4 to 16.6% of school-aged children , 10. BeySimilarly, treatment recommendations vary considerably between countries . In NortOtherwise, numerous studies have shown the influence of the school system on the diagnosis and medication of children with ADHD. For example, in one city in the state of Virginia, 63% of school children who were 1 year ahead of their peers were treated with psychostimulants . In the Similarly, many environmental and social risk factors have been identified. These include exposure to toxic levels of lead , prematuUnfortunately, this type of study is lacking in France, meaning that questions concerning the prevalence of ADHD, drug prescription, and the influence of academic and social factors on diagnosis and prescription are still the object of much controversy.Indeed, the only prevalence study currently available in France was financed by the drug industry. It reports a high prevalence of ADHD (3.5–5.6% of children) based on a telephone survey entrusted to a polling institute and carried out by non-specialist operators trained on the fly . This st®) and a delayed form . MPH is recommended for children aged 6 years and over “when psychological, educational, social, and family corrective measures alone are insufficient”  or Psychiatric (PSY) hospitalization between 2010 and 2019 ;The pattern of MPH prescription to children in France in the same period;The influence of the school system and social inequalities on ADHD diagnosis and psychostimulant prescription.This article presents unpublished data on the evolution of ADHD diagnosis in France and represents by far the most comprehensive and robust analysis of the multiple clinical, demographic, institutional, and social variables concerning MPH prescription in that country.We conducted a retrospective cohort study of all beneficiaries of the general health insurance scheme, including local mutual health insurance companies, i.e., nearly 87% of the French population, more than 58 million people.We extracted information for all children and adolescents aged 0–17 years who received:1) A diagnosis of ADHD/hyperkinetic disorder during an MCO or PSY hospitalization  between 2010 and 2019 (F.90 and subtypes);Anatomical Therapeutic Chemical Classification System)].2) At least one MPH prescription during the period 2010–2019. For each patient, the date of inclusion in the cohort was defined as the date of the initial delivery of MPH  or complementary health insurance (CMU-C), or complementary health insurance payment aid .- Among the children in our two cohorts, we looked for those whose families benefited from the French universal health coverage , aripiprazole , valproic acid , midazolam (Hypnovel® derivatives and/or generics−2.6%), sertraline , Diazepam , and tropatepine .The main drugs used the year fallowing an hospitalization in 2018 were MPH  and 82.5% (in 2010).As explained above, the duration of treatment was calculated only for patients who received their initial prescription in 2011 . The medThus, the median duration of MPH consumption among 6-year-old children in 2011 was 5.5 years and up to more than 8 years for 25% of them . The tabWhile the data collected do not allow us to give a precise idea of the evolution of the duration of treatment between 2011 and 2019, the comparison between prevalence and incidence sheds some light. Indeed, between 2010 and 2019, the prevalence of MPH prescription increased more than its incidence. This indication suggests that treatment durations increased between 2011 and 2019. To support this interpretation, we examined the MPH deliveries for each patient. Haute Autorité de Santé, or HAS) are not always followed, given that according to the HAS, MPH prescription should be reserved for children diagnosed with ADHD.We were only able to examine the diagnosis associated with the MPH prescription for 3,965 children who started treatment in 2017. Of these, two-thirds (65.4%) were diagnosed with ADHD. In the remaining third, we found various psychiatric pathologies including mood disorder (8.4%), mental disabilities (7.7%), psychotic disorders (1%), and various other child psychiatric disorders (17.5%) . These very partial data must be considered with caution. However, they show that the recommendations of the French National Authority for Health , anxiolytics (35.5%), antidepressants (16.2%), antiepileptics (11%), hypnotics (4.8%), and antiparkinsonians (3%).®, derivatives and/or generics−10.6%), hydroxyzine , cyamemazine  aripiprazole , sertraline , valproic acid , and fluoxetine .The main drugs prescribed were risperidone , 20.8% received three psychotropic drugs, 8.5% received four, and 6.9% were prescribed five or more psychotropic drugs.Until September 2021, an initial MPH prescription was required to be given in a hospital. Yet, during the period studied, nearly a quarter of initial MPH prescriptions were made in private practice or private MCO facilities. The reports and reminders of prescribing conditions carried out by the ANSM in 2013 and 2017 had only a limited effect on this practice .In addition, French regulations required that the annual renewal of the MPH prescription be done during a specialized hospital consultation. To examine whether this requirement was met, we looked for the occurrence of a renewal of the MPH prescription in hospitals during the 14 months following the date of the initial prescription. For nearly half of the children (49.6%) having started treatment in 2015, 2016, and 2017, this was not the case. Even when accounting for the interruption of treatment within 1 year for some children, it appears that the annual on-site hospital refill requirement was not always met.This observation suggests that an increasing number of general practitioners prescribe MPH in France. Thus, in 2010, 15,318 general practitioners wrote 97,819 prescriptions. The number of general practitioners who prescribed MPH almost doubled in 2019 , while the number of their prescriptions increased by 221% . Moreover, 87% of MPH prescriptions outside of hospitals were given by general practitioners. This proportion remained stable between 2010 and 2019.However, it is noteworthy that nearly two-thirds of French general practitioners never prescribe MPH . Among prescribing physicians, practices are very heterogeneous, with large variations in the number of prescriptions per physician in 2019 . These results suggest that the majority of MPH prescriptions, as well as their increase between 2010 and 2019, were given by a minority of general practitioners.Such heterogeneous practices can also be observed in hospitals: across the country, 358 of the 1,356 French public health establishments carried out 78.8% of hospital prescriptionsInsofar as MPH is not a first-line treatment for ADHD in France and can only be used once appropriate psychological, educational, social, and family measures have been taken , we wereWe were also interested in the follow-up treatment of children in CMPPs. French CMPPs are the primary organizations providing psychosocial support for children and their families. The practices used in CMPPs represent, however, only a part of the care provided to children with ADHD. Although the raw values shown in The diagnosis of hyperactivity is systematically correlated with the child's month of birth, meaning that the youngest students in a class are most at risk of being diagnosed as hyperactive.Thus, in 2011, children with an ADHD diagnosis born in December (291) were significantly more numerous than those born in January (170). This observation was confirmed throughout the period studied, since in 2019, among the 4,337 children coded as having ADHD as a principal diagnosis in the PMSI MCO and PSY databases, 487 were born in December and 294 in January. Overall, children born in December were 55% more likely to be diagnosed with ADHD than their peers born in January  .French children and adolescents are 44 to 60% more likely to be prescribed a psychostimulant treatment if they were born in December than if they were born in January . In fact, the number of initial prescriptions increased progressively each year from January to December between 2010 and 2019, only to fall sharply in January of the following year .Between 2010 and 2019, 35.4–38.8% of children diagnosed with ADHD lived in families receiving CMU or CMU-C (attributed to 7.8% of the French population). An ADHD diagnosis is therefore much more frequent among children from the most disadvantaged families. If we also consider children with ADHD diagnosed at hospital as being socially disadvantaged, the percentage of children with social difficulties in the ADHD cohort varies between 39.8 and 42.6% over the period .In 2019, 21.7% of children receiving MPH lived in families receiving CMU or CMU-C. This rate was much higher than the allocation of these aids in the general population (7.8%), and this trend increased between 2010 and 2019. If we also consider children taking MPH with a diagnosis of social disadvantages, the percentage of children with social difficulties among children taking MPH reaches 25.7% .Although the data available concerning the ADHD cohort do not allow establishing a reliable diagnostic or prevalence rate for France, the information dedicated to methylphenidate consumption in the population of child patients leads to adopt a critical stance concerning the prevalence information currently available. Indeed, between 2008 and 2011, the pharmaceutical industry financed a study concluding that there was a high prevalence of ADHD in France—between 3.5 and 5.6% in 2008 . This prYet, a comparison of these data with MPH consumption rates listed in health databases shows clear exaggerations of the original study. In 2019, the prevalence of the consumption of MPH by children in France can be estimated at between 0.61 and 0.75% and has been steadily increasing since 2010. Previous publications, as well as the ANSM study published in 2017, estimated the prevalence of MPH use in 2008  at 0.2% of children –54. The Moreover, the telephone survey did not take into account the complexity of psychological and diagnostic situations specific to child psychiatry. It did not include situations of co-diagnosis and co-morbidities: indeed, 50.6% of children hospitalized with an ADHD diagnosis between 2010 and 2019 had also received at least one other psychiatric diagnosis. Furthermore, one-third of the children in the MPH cohort had received a psychiatric diagnosis other than ADHD. The present study also supports the influence of the school and social system on ADHD diagnosis.Previous international studies already reported such critical stance about ADHD prevalence estimations: serious studies have shown that the diagnosis of hyperactivity initially made in specialized centers was refuted in 62 to 78% of cases after re-evaluation , 14. SevAutorisation de mise sur le marché, or AMM). The duration of MPH treatment for these hospitalized ADHD children is particularly long (with a median of 7.1 years for children aged 6 in 2011). These long prescription durations and the massive use of co-prescriptions suggest that these children never get off the drug treatment and that MPH may be a gateway to medications that are not authorized for children in France.On the one hand, among hospitalized children diagnosed with ADHD in 2018, 51.4% used MPH and 62% used one or more psychotropic drugs, most of which did not respect the recommendations of the French marketing authorization  and even more so in prevalence (+116%). A similar increase had already been reported for the period 2003–2005   as well Two previous studies presented data regarding the duration of MPH prescription , 54. TheOur study shows that MPH prescription does not always comply with the recommendations of the AMM and the regulations.Contrary to the recommendations of the AMM, MPH is sometimes prescribed before the age of 6. Although these prescriptions concern a limited number of children , they involve particularly long treatment times. The prescription to children younger than 6 years has been previously reported –54.MPH prescription in France is not necessarily associated with an ADHD diagnosis, which is the only authorized psychiatric indication for this drug. Moreover, when a psychiatric diagnosis is made, it does not always correspond to the therapeutic indication defined by the AMM. Indeed, the summary of product characteristics states that “psychostimulants are not intended for [...] patients with other primary psychiatric pathologies [...]”Contrary to the regulation in force until 13 September 2021, 25% of initial prescriptions and 50% of annual renewals are not made by a hospital specialist. Knellwolf et al.  had alreMedical follow-up in the hospital services which initiated the treatment is not systematic (only 15.8–12.9% between 2011 and 2018). Consultations in CMPPs decline as the use of MPH increases, suggesting a progressive abandonment of the psychosocial treatment of ADHD. This treatment is nevertheless recommended as first-line treatment by the HAS.In 22.8% of children and adolescents, we observed that MPH was prescribed in combination with at least one other psychotropic medication. A previous study had already reported relatively high rates (28.8%) of multiple prescriptions . AccordiFrench and international studies, even recent ones, have supported the idea that the prevalence of the prescription of MPH to children in France was particularly low compared to other European countries. This view was presented in a recent review comparing the prevalence of MPH prescriptions in 13 countries . Our datOur study and that of Pauly et al.  show thaOther characteristics of MPH prescription in France have also been observed in many countries.First, MPH prescription concerns mainly boys . For exaSecond, our study points to poly-prescriptions and a systematic undermining of the marketing authorization and recommendations of French health authorities, concerning both the treatment of ADHD and the prescription of MPH. Such multiple psychotropic prescriptions for ADHD and co-prescriptions of other psychotropic medications in combination with MPH have already been observed at the international level, particularly in the United States . Among tThird, we show for the first time in France that school pressure contributes to the prevalence of MPH prescriptions. Indeed, children born in December receive this prescription more frequently than those born in January of the same year. This effect of schooling had already been observed in 13 countries .Fourth, our data show that MPH prescription is more common among children from the most disadvantaged families and that this trend increased between 2010 and 2019. Similarly, US children whose families are insured by Medicaid are more often prescribed a psychostimulant than those whose more affluent families are insured by private companies, and this gap increased between 2001 and 2010 .MPH in France obtained its AMM in 1995. Between 1995 and 2001–2002, the prescription rate was very low . Since tThe comparison between our ADHD hospitalized children and MPH cohorts suggests that the increase in MPH prescription in France is the result of the greater frequency of ADHD diagnosis. This may be due either to better recognition of ADHD or to a true increase in the frequency of ADHD in children. This second hypothesis is often rejected by proponents of a biological and a neuro-essentialist view of ADHD , but sevThe fact that ADHD diagnosis is becoming more and more frequent in France is also the result of a societal evolution partly driven by the mass media. Since the beginning of the 2000s, television programs and websites dedicated to ADHD have proliferated in France. The vast majority of them support an organic cause for ADHD and present the drug treatment in an excessively favorable light , 72. TheThe pharmaceutical industry also played a role by funding the only ADHD prevalence study available in France, concluding a high prevalence rate (between 3.5 and 5.6% in 2008) , even thFinally, the increase in the prescription of MPH could also result from a change in practices. In France, psychotherapy treatment, and educative and social interventions are recommended as first-line treatment for ADHD. When MPH is prescribed, it remains desirable to combine it with psychosocial treatment. This recommendation is in line with the main clinical guidelines, which recommend a multimodal approach . Our datOur study shows that, concerning ADHD medication and the prescription of MPH to children, it is no longer possible to point to a French specificity. The prevalence of MPH prescription in France is now much higher than in Italy and has surpassed that of Great Britain. If the current progression continues at the same pace, France will soon catch up with Germany and Denmark. Indeed, in all countries comparable to France, there has been a stabilization of MPH prescription since the end of the 2000s. However, there is a concern that the current progression in France may accelerate given the 2021 authorization of initial out-of-hospital prescriptions. A large number of placebo-controlled studies have shown that MPH can reduce ADHD symptoms in most children. However, these are all short-term studies, and there is no evidence that the beneficial effects last more than a few months , 75. If Our study highlights an academic and social influence on ADHD diagnoses and MPH prescription. There is a proven risk of children being diagnosed and medicated as a function of their age or social origins. These discriminations compound unbridled breaches of prescription regulations that are supposed to underpin the democratic pact of confidence between citizens and their health care system. Faced with this situation, neither the AMM, nor the recommendations and reminder letters from the ANSM, nor warnings from researchers or health professionals who for many years have been denouncing these abuses seem to have been heard .What benefits can we expect from the increasing medication of children's behaviors and from a progressive deregulation of the prescription of psychostimulants or even psychotropic drugs to child patients? Can children, adolescents, and their families find better support? Can the help provided to patients and care practices be improved? Can the link between the population, practitioners, and health services be strengthened?These questions challenge the regulatory capacities of the medical community, health agencies, and public authorities, but they also touch on societal choices: what practices and what model of care do we want for our children and the next generations? These are sensitive and complex issues that at the very least deserve to be seriously debated by scientists, political authorities, and citizens themselves. This is all the more crucial as France is characterized by a culture of psychanalytic and psychologic care, educational practices, and social intervention which have proved their worth in the clinic and constitute a specificity of French psychiatry and psychopathology . It is oThe original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author.The study protocol has been validated by the Scientific Expertise Committee for Research, Studies, and Evaluations in the field of Health , case SNDS TPS 1190830 validated on 29-12-2019. It has also been validated by the French National Commission for Information Technology and Civil Liberties (CNIL) and an agreement with the National Health Insurance Fund (CNAM).SP obtained the funding, designed the study, contributed to the analysis of the data, and wrote the article. BT designed the study and analyzed the data. Both authors commented on the manuscript and approved its final version.This study was conducted with the financial support of the EOVI MCD Mutual Foundation (AP-EOV-18-002), in partnership with the Fondation de l'Avenir.SP declares that his research is conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. SP le CIRNEF and the université de Rouen Normandie are responsible for this research. BT as founder and CEO of Median Conseil, has worked with several clients tied to the healthcare or nutrition domains, namely: Grunenthal, Lundbeck, Octapharma, Kiowa, Baxter, Physidia, Nestlé, Alexion, Amgen, Ipsen, Mallinkrodt, Merck, Pharma Mar, Takeda, Thea, 3M, Urgo. None of the studies conducted for these clients dealt with child psychiatry or psychotropic medications. BT and Median Conseil were responsible for processing the data for this research.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Despite overlaps in clinical symptomatology, autism and ADHD may be associated with opposite autonomic arousal profiles which might partly explain altered cognitive and global functioning. We investigated autonomic arousal in 106 children/adolescents with autism, ADHD, co-occurring autism/ADHD, and neurotypical controls. Heart rate variability was recorded during resting-state, a ‘passive’ auditory oddball task and an ‘active’ response conflict task. Autistic children showed hyper-arousal during the active task, while those with ADHD showed hypo-arousal during resting-state and the passive task. Irrespective of diagnosis, children characterised by hyper-arousal showed more severe autistic symptomatology, increased anxiety and reduced global functioning than those displaying hypo-arousal, suggesting the importance of considering individual autonomic arousal profiles for differential diagnosis of autism/ADHD and when developing personalised interventions.The online version contains supplementary material available at 10.1007/s10803-021-05244-w. Autism Spectrum Disorder  and Attention Deficit/ Hyperactivity Disorder (ADHD) are neurodevelopmental conditions that typically manifest in early childhood. While ADHD is mainly characterised by inattention and hyperactivity/impulsivity, autism is defined by social communication and interaction difficulties, and restricted and repetitive behaviours, interests or activities . Conversely, the PNS is active (and predominant over the sympathetic branch) when energetic resources should be preserved for a period of time, including those situations that require sustained attention or rest-digest behavioural responses .A domain which might differentiate ADHD from autism is arousal regulation, namely the physiological mechanisms that characterise alertness, wakefulness, and reactivity to the environment Lacey, . SynergiAtypical functioning or regulation of one or both branches of the ANS, leading to reduced or heightened arousal, are likely to negatively impact performance on cognitive tasks  less stimulating and less challenging experimental contexts might trigger hypo-arousal in individuals with ADHD, ii) at least a subgroup of autistic individuals might display a profile of hyper-arousal during more cognitively demanding tasks and iii) another subgroup of autistic individuals might be characterised by hypo-arousal. The autonomic arousal profiles of individuals with co-occurring autism and ADHD (those who meet the diagnostic criteria for both conditions) have not been investigated previously, to our knowledge.additive model of comorbidity) or if it is independent from those groups, reflecting a unique profile (interactive model).The first aim of the present study was to investigate differences in autonomic arousal between individuals with autism, ADHD and neurotypical children, in different experimental contexts. Further, we investigated the autonomic arousal profile of individuals with co-occurring autism and ADHD, to determine whether this phenotype is associated with the same atypicalities found in those with a single diagnosis of autism or ADHD  has been proposed to reflect the overall activity of the SNS and PNS but, more specifically, to be primarily influenced by parasympathetic activity and top-down control of the PNS .In addition, using data from the same study, we used cluster analysis to determine whether transdiagnostic sub-groups could be identified based on their autonomic profile. This approach was informed by the RDoC framework , or local special educational needs teams in both mainstream and special schools. Neurotypical participants were recruited from local schools and from a database of volunteers held by the School of Psychology, University of Nottingham UK. The study was advertised on social media platforms and information about the study was shared on an online blog published by the Association for Child and Adolescent Mental Health (ACAMH). Children under pharmacological treatment for ADHD with stimulants were required to withdraw their medication for at least 24 h before the testing session. Potential participants were excluded if they had any neurological conditions; if they were on non-stimulant medication ; if they or their parent/legal guardians were unhappy with stimulant medication being withdrawn for 24 h prior the testing session; or if they did not speak fluent English. Children were not excluded if they had a co-occurring diagnosis of mental health or behavioural conditions , or intellectual disability . Children recruited as neurotypical controls were not included in the study if they were siblings of a child with a pre-existing diagnosis of autism, ADHD or any other ICD-10/DSM-5 psychiatric diagnoses.Symptoms of ADHD and autism were evaluated for all participants using parent- and teacher-report Conners’ Rating Scales  eye-tracking and (b) EEG. The present paper is focused on measures collected during the EEG battery only, which comprised a 3-min resting-state period, a ‘passive’ auditory oddball task and an ‘active’ response conflict task. A detailed description of the EEG setup, data collection and analyses (not presented in this paper) can be found in Bellato et al. , where wAt the beginning of the EEG battery, a 3-min resting-state period measurement was obtained. During this time, children watched a silent movie (“Despicable Me”) and were asked to relax and sit still.http://www.asel.udel.edu/speech/tutorials/synthesis/vowels.html) or non-social . The type of deviant  was manipulated due to evidence that autistic individuals might demonstrate reduced salience for social information , alternated by less frequent stimuli (‘deviant’), was presented at an inter-stimulus interval of 700 ms. Deviant tones were either social , but that they would not exhibit parasympathetic activation (indexed by no changes in CVI between breaks and task blocks) since no demands were placed on attention or response preparation. We predicted that individuals with ADHD would demonstrate a sympathetic hypo-arousal profile and will exhibit a diminished sympathetic response to auditory stimuli . We did not expect group level differences in autistic participants in this task, in line with the literature and the predicted heterogeneous autonomic arousal profiles in autistic participants when cognitive demand is low.After the oddball task, we presented an adapted version of the Preparing to Overcome Prepotency task  was recorded from two free electrodes placed on participants’ wrists. Raw HR signal was processed to obtain non-linear measures of HRV, the Cardiac Sympathetic Index (CSI) and the Cardiac Vagal Index (CVI). To derive these measures, heart rate signal was band-pass filtered (8–20 Hz) to minimise the impact of artifacts and high frequency noise Fedotov, , before The effects of ADHD and autism were investigated using the binomial between-subjects factors of ADHD and Autism  reflecting the presence (or absence) of a diagnosis of ADHD or autism. In this way, we could compare children with and without ADHD , and those with or without autism , to test specific effects of each condition on the outcome measures. Moreover, we could investigate the impact of co-occurring autism and ADHD by following up significant interactions between the ADHD and Autism factors or the co-presence of significant main effects of ADHD and Autism. When following-up significant interactions between ADHD and Autism factors, we calculated p-values adjusted for multiple comparisons using the Benjamini-Hochberg (BH) method . In this way, we could also maximise the number of participants included in each of these analyses . However, we also conducted a secondary set of analyses to compare groups of participants across the three experimental contexts .To compare between-subject effects of ADHD and Autism on resting-state HRV, we carried out separate one-way ANOVAs on CSI and CVI calculated for the 3-min resting-state period, with ADHD and Autism as between-subject factors. Next, we conducted separate mixed ANOVAs on CSI and CVI measured during the passive oddball task to investigate between-subject effects of ADHD and Autism. We also controlled for possible differences between the first and second task blocks by modelling a within-subjects factor Time , and we evaluated the presence of any differences between the breaks and the task blocks by modelling a second within-subjects factor Block Type . Thirdly, we conducted separate mixed ANOVAs on CSI and CVI for the POP task, with ADHD and Autism included as between-subject factors. We investigated differences between the breaks and the task blocks by modelling the within-subject factor Block Type , and we controlled for any time-related differences between the first and second task half, and between each block of the task, by modelling Task Half  and Block Number  as within-subject factors. In all models, we controlled for the effects of age, gender, verbal IQ and performance IQ.To replicate previous studies indicating an inverse relationship between CSI and CVI  on measures of ADHD  and autistic symptomatology ; psychopathology , and conduct disorder (CD), measured through the DAWBA); and global functioning (CGAS), controlling for gender, verbal and performance IQ, and age, and using the newly created clusters as the between-subject factor. Statistically significant univariate ANOVAs were followed up by analysing pairwise comparisons, for which p-values were adjusted to control for multiple comparisons (using the Benjamini-Hochberg/FDR method described above).106 children and adolescents were included in the final database of participants . Among these, 31 children were assigned to the control group of neurotypical (NT) participants; 18 had a diagnosis of autism (but not ADHD), 33 met criteria for co-occurring autism and ADHD (Autism + ADHD), while 24 children had a diagnosis of ADHD without autism. Table 1,69 = 8.687; p = 0.004; ηp2 = 0.112). No other main effects or interactions were statistically significant.Children with ADHD (ADHD-only and autism + ADHD) had significantly lower CSI than those without ADHD  during the 3-min-long resting-state period . Children with ADHD (ADHD-only and autism + ADHD) had reduced CSI compared to children without ADHD (NT and autism-only). In addition, there was a significant interaction between Block Type, Autism and ADHD factors , reflecting that children with ADHD-only had significantly reduced CSI specifically during the 30-s breaks compared to the other groups, including neurotypical controls , children with autism-only  and children with co-occurring autism and ADHD . We also found a significant interaction between Time * Block Type * Autism on CVI during the oddball task , which showed that children with autism (autism-only and autism + ADHD) had significantly reduced CVI in comparison to children without autism (NT and ADHD-only) during the initial 30-s pre-block break (p = 0.033) and during the second task block (p = 0.038). Across all participants, both CSI and CVI were greater during the blocks of the oddball task, in comparison to the breaks , and CSI was greater in the second block compared to the first . No other significant main effects or interactions were found.We found a significant main effect of ADHD on CSI measured during the oddball task , indicating that children with autism (autism-only and autism + ADHD) had reduced CVI during the entire task, compared to children without autism (NT and ADHD-only). Across all participants, CSI was increased during the breaks of the POP task compared to the task blocks . No other significant main effects or interactions were found.A significant main effect of Autism was found on CVI during the POP task .We investigated bivariate correlations between CSI and CVI, autistic and ADHD symptomatology, and global functioning measures, on the sub-sample of participants from the clinical groups . We found negative correlations between all indices of CSI and CVI, even when measured across different experimental conditions . We therefore decided to average CSI and CVI indices across the three experimental contexts and ran a correlation analysis between averaged CSI and CVI. Averaged CSI was highly negatively correlated with averaged CVI  indicating that children who had higher values on one of the HRV indices had lower values on the other index. As shown in Table The Two-step cluster analysis on averaged CSI and CVI produced two distinct clusters. The majority of clinical participants (39 children) were categorised in Cluster 1, while 15 participants were assigned to Cluster 2. When analysing the characteristics of these clusters, we found that CSI was lower in those assigned to Cluster 1  than in children assigned to Cluster 2 ; we therefore labelled Cluster 1 as “Low-CSI”. Moreover, since Cluster 2 had lower mean CVI  than Cluster 1 , we labelled Cluster 2 as “Low-CVI”. We also calculated the CVI/CSI ratio, to reflect the balance between activity in the PNS and the SNS, for each child. We found that Cluster 1 (“Low-CSI”) had a higher CVI/CSI ratio  than Cluster 2 .Almost all children with ADHD-only (16 out of 17) were assigned to Cluster 1, which was characterised by low CSI. Children with autism-only and children with co-occurring autism and ADHD did not show a predominant profile. In fact, some of these children were assigned to the ‘low-CSI’ group (8 out of 15 children with autism-only and 15 out of 22 children with autism + ADHD), while others showed an autonomic arousal profile characterised by low CVI and high CSI (7 out of 15 children with autism-only and 7 out of 22 children with autism + ADHD)  after controlling for age, gender, verbal IQ and performance IQ. Following up this main effect by investigating results of univariate ANOVAs showed significant between-cluster differences in measures of autistic symptomatology, including SCQ Total score , SCQ Social , SCQ Communication  but not SCQ Restricted and Repetitive Behaviours (RRBs) . We found significant between-cluster differences on CRS Hyperactivity/Impulsivity , but not on other measures of ADHD symptomatology . There were also significant differences between the two clusters on generalised anxiety , social anxiety  and global functioning . There was no statistically significant between-cluster difference on ODD  or CD symptoms .The MANOVA conducted to detect any between-cluster differences on measures of clinical symptomatology was overall significant , the Cardiac Sympathetic Index (CSI) and the Cardiac Vagal Index (CVI) between groups of children with autism, ADHD, co-occurring autism and ADHD, and neurotypical children; in three separate experimental tasks .As initially predicted, we found ADHD- and autism-specific effects on HRV, and these were dependent on experimental context. We found evidence of hyper-arousal in children with autism and hypo-arousal in children with ADHD, in line with the main hypotheses of the study. In children with autism, indices of hyper-arousal were found during both passive and active tasks (but not during resting-state) and were associated with reduced activity of the parasympathetic nervous system . Conversely, in children with ADHD indices of hypo-arousal (including reduced HR in those with ADHD-only) were found during the resting-state period and the passive auditory oddball task; and were more associated with reduced activity of the sympathetic nervous system . Children with co-occurring autism and ADHD did not display a unique profile distinct from autism- and ADHD-only but showed the same atypicalities found in children with ‘pure’ conditions, namely reduced CVI during the POP task and some sections of the passive oddball task (like children with autism-only) and reduced CSI during the initial resting-state period and the oddball task (like children with ADHD-only). These findings, at least in the domain of arousal dysregulation, support the additive model of autism/ADHD comorbidity.Across the whole sample of participants, we found increased sympathetic and parasympathetic activation during passive auditory stimulation  in comparison to the 30-s periods without sounds (pre-block break). This is partly in line with our hypotheses (we only expected to observe increased sympathetic activation but not parasympathetic activation in relation to task blocks versus breaks). In support of our hypotheses and previous studies that proposed a direct relationship between increased parasympathetic activation and sustained attention during tasks challenging executive function  framework  is likely to be characterised by reduced functioning of the SNS and hypo-arousal, especially during less stimulating situations , not every child completed all tasks. Specifically, several children completed the resting-state and the passive auditory oddball task but decided to not proceed with the active task because they were too tired or did not want to continue. This could indicate that arousal regulation was particularly challenging for these children and so their attrition from the study before the final task may have influenced the findings. Moreover, although we designed our study to include children with low intellectual or adaptive functioning or more severe clinical profiles , parents of these children reported that they did not consider the study suitable for their child. Therefore, our findings may not be generalizable to children with co-occurring intellectual disability, sensory difficulties, high levels of anxiety or reduced global functioning. Further research is needed to understand more fully the barriers faced by these children in participating in neuroscientific research so that experiments can be adapted to be more inclusive or can be conducted in settings where children feel more able to participate.Lastly, participants with ADHD on stimulant medication were required to withdraw their medication at least 24 h prior to the testing session (to avoid any confounding effect of medication on HRV). This meant that we could not include children on non-stimulant ADHD medication  because non-stimulants require a longer washout period and cannot be withdrawn easily. As a result, the findings may not be generalisable to children with ADHD (with or without ASD) who are prescribed non-stimulant medication possibly because they tolerate stimulants less well. Considering that autonomic side effects may be one reason why children with ADHD tolerate one class of medication better than another, differences between medications and their effects on arousal and cognition remains an important empirical question which should be addressed in future research.It would be also important to further investigate the associations between core domains of human functioning  and subgrouping individuals with different profiles based on such domains, might better explain heterogeneity in symptomatology, adaptive or global functioning, and interventional outcomes , which might affect adaptive, global and cognitive functioning and treatment response in autism and ADHD.Supplementary file1 (DOCX 88 KB)Supplementary file2 (DOCX 16 KB)Below is the link to the electronic supplementary material.


The literature has described comorbidities among the symptoms of children with Attention Deficit and Hyperactivity Disorder (ADHD) and the auditory processing changes, and these symptoms have been overlooked in the assessment, and consequently, on the rehabilitation of these individuals.To compare the findings of the long latency auditory evoked potentials in children with and without ADHD.This is a historical cohort cross-sectional case-control study, in which we enrolled 30 children with and without ADHD, aged 8-12 years. We performed the long-latency auditory evoked potential test in two scanning procedures through passive and active tasks differing in frequency and duration (MMNf and MMNd) (P300f and P300D).When comparing the performance of children with and without ADHD in the electrophysiological test assessment of hearing, we found significant differences concerning the P2 amplitude in the LE - which was higher for the ADHD group; and concerning the N2 amplitude and latency - which were abnormal in the ADHD group.This study provided a greater understanding of the central auditory pathways of children with and without ADHD when evaluated from electrophysiological tests. Neuropsychological studies have reported that individuals with attention deficit and hyperactivity disorder (ADHD) have alterations in their prefrontal cortex and in subcortical structures, associated to frequent levels of inattention, impulsivity, hyperactivity, disorganization and social awkwardness, involving an inhibitory system deficit or in the working memory executive functionsThe literature has described comorbidities between symptoms of children with ADHD and auditory processing (AP) disorders, and such symptoms have been overlooked in the assessment and consequently the rehabilitation of these individualsAuditory processing disorder is common in children with ADHD and may be due to a deficit in the functioning of the auditory pathway, caused by changes in some of the central auditory nervous system (CANS) structures, or in the cerebral hemispheres, which can be observed by Long Latency Auditory Evoked Potentials (LLAEP), which assesses the auditory pathway integrity from the periphery all the way to the auditory cortexAccording to the DSM-IVMany studies have suggested that attention dysfunction is not the main cause of behavioral changes in individuals with ADHDGiven the above, this study aimed to compare the findings of the auditory evoked potential latencies in children with and without Attention Deficit and Hyperactivity Disorder (ADHD).This study project was submitted to the analysis and appreciation of the Ethics in Research Committee of this University and carried out after approval according to protocol number: 0094/2011. This historical cohort study was cross-sectional and of the case-control type.•Control Group (CG) - comprising 15 children with good academic performance, selected by the teachers following the criterion of satisfactory performance on two consecutive marking periods in a reading and writing assessment;•Study Group (SG) - composed of 15 children properly diagnosed with ADHD by a multidisciplinary team, which included speech and hearing, neurological, educational, neuropsychological and educational assessments, considering the presence of at least six (or more) symptoms of inattention and six (or more) symptoms of hyperactivity-impulsivity persisting for at least six months, according to the Diagnostic Criteria for Attention Deficit/Hyperactivity Disorder from the DSM-IV. We employed Instruments from the neuropsychological battery of tests: WISC-IIIThe study included 30 children of both genders aged 8-12 years, divided into:The children from both groups were evaluated after their guardians signed the Consent Form. All the children had chronological age between 8 and 12 years and were previously submitted to audiological, ophthalmological and psychological evaluations. Thus, we excluded from the study those individuals who did not have audiometric thresholds within the normal range (20 dB HL)& KaplanBasic audiological evaluation was performed in a soundproof booth. For pure tone audiometry we used the GSI 61 (ANSI 3.6-1989 and S3.43-1992 standards) audiometer with TDH-50 phones. Hearing thresholds were obtained by air conduction, in the sound frequencies of 250-8,000 Hz. The normality criterion used was the classification proposed by Lloyd Evaluation of the Long Latency Auditory Evoked Potential was performed using the Biologic Navigator Pro and recorded with five disposable electrodes positioned at Fz and Cz in reference to the right (A2) and left (A1) lobes, using the two recording channels of the equipment, the ground electrode was placed on Fpz. Impedance was maintained at a level below 5 KW.The components were surveyed in two sweeps, i.e., it was first elicited for tonal stimuli (tone burst) differing in frequency - MMNf and P300f , and later, for stimuli differing in duration - MMNd and P300D .Both stimuli differing in frequency and duration were randomly presented in an oddball paradigm, a rate of 1.1 stimuli per second, with a rare stimulus occurrence probability of 20% of the total 250 stimuli. The analysis time of the waves was 500 ms with a filter from 0.5 to 30 Hz and 50,000 mV sensitivity and alternating polarity.For the MMN recording, the patient performed a passive task and was instructed to remain seated and relaxed but awake and watching a video (without sound) to get distracted and not pay attention to the sound stimulus presented to him. As for the P300 recording, the patient should undertake an active task, paying attention and discriminating the stimuli naming them as “thin” during P300f and “short” in P300d.The stimulus presentation was randomized concerning the stimulated ear, alternating them to avoid result biases. Moreover, due to the difficulties inherent to the behavior of children with ADHD, we decided to replicate the test only when necessary, in routine use the Cz and Fz records, in order to verify and ensure data accuracy.For final result analysis, we chose to use the records obtained at Cz, since in this study this was the region where the records were better; in addition, the literature has consistently described it as the region with the best visualization of these potentials.& Colafêmina•Identification of the N1-P2-N2 complex - the first three waves that appear in the sequence and have negative - positive - negative polarity, respectively, occurring in the replication of the traces, frequent and rare, between 60 and 300 ms;•P3 identification - the largest positive wave - immediately after the N1-P2-N2 complex, occurring in tracing replication for rare stimulus, between 240 and 700 ms;•Latencies were marked on the highest peak, i.e. the point of maximum wave amplitude;•The amplitudes were marked from the peak of the wave to the base line, and in the case of the N2-P3 inter-amplitude;In order to identify the P300 wave, we used the criterion proposed by Junqueira To identify the MMN waves, we considered the biggest wave of negative polarity, between latency values from 100-300 ms, viewed by the subtraction of the rare stimulus tracing from that of the frequent stimulus tracingp-value, and the level of significance adopted was always 5% or 0.05 (p ≤ .05).The result was described as Upon assessing the electrophysiological evaluation of hearing during the active task with stimuli that varied on frequency, P300f, the right ear (RE) had statistically significant difference only in the N1 latency, while in the left ear (LE) there was no difference as to the level of significance in any of the variables.p-value of the N1, P2, N2, P3 amplitude and latency values; and N2-P3 inter-amplitude in the P300f assessment in both groups of RE and LE, respectively.In the P300 evaluation, when we stimulated with a stimulus that varied in duration, P300d, the RE had no statistically significant difference when the two groups were compared with and without ADHD; while for the LE it was significant when comparing the P2 and N2 amplitude and N2 latency.p-value of the N1, P2, N2 and P3 latency and amplitude variables; and P300d N2-P3 inter-amplitude for the RE and LE, respectively.Comparing the electrophysiological evaluation of passive listening with stimulation with varied frequency, MMNf, both ears showed no difference as to the level of significance when the two groups - with and without ADHD were compared.In assessing the MMN stimulation with varying stimulus for duration, MMNd, we did not find a statistically significant difference when comparing the two groups with and without ADHD in any of the variables in both ears.There are many studies that have evaluated the P300 in children with ADHD, but few have focused on the other LLAEP components: N1, P2 and N2Concerning the P300d assessment, the LE had better P2 amplitude for the SG when compared to the CG, which corroborates studiesThe higher P2 amplitude in the SG children can be justified by studiesIn evaluating the P300d for the LE, we found a significant difference for the N2 amplitude, in which the CG had higher negativity when compared to the SG, and in N2 latency - where the SG values were more elongated. These results corroborate other studiesWith regard to N2 latency, the LE also showed a statistically significant difference when the SG was compared to the CG, and we found longer latency values for the SG, corroborating other studiesIn this study, we observed that the N2 was the only component to show significant differences in terms of both latency and amplitude when children with ADHD were compared to those without it, which makes us consider that the ADHD children of our study had a decline in the efficiency of responses involving pre-attentional and discriminatory processesConcerning the P3 component findings, it is consistent with studiesA first explanation for not having significant differences between the P300 in children with and without ADHD in this study is that our sample was small, and this is a limiting factor vis-à-vis the specific discussion of these findings. Such a limitation in this study was described by BraynerAnother possible explanation is that children with ADHD have alterations in their pre-attentional and discriminatory processes - which was evident in the results found in the N2 wave; however, these children began to process this information in some way, which could be aided by other structures of the central nervous system and/or by interference of neural plasticity, in which sensory experiences bring about a better neural synchrony or a reorganization of the nerve cellsWith regard to the MMN, both the MMNf and the MMNd did not show statistical difference for any of the variables, either in amplitude or latency when comparing the two groups. This suggests that children with ADHD in our study have deficits when they need to performa a discrimination task, while keeping sustained attention, or maintain attention for an extended period of time. To obtain the MMN, we need pre-attentional processes that are independent of the subject's response; thus, these children did not need to perform any task, which contributed to the normal MMN results found in the present studyAccording to the specialized literatureIn this study, we also found that the larger number of altered results came from the LE stimulation, leading us to suggest that, just like the processing of nonverbal stimuli, and the stimuli varying according to duration, are first processed by the right hemisphereIn comparing the performance of children with and without ADHD in the electrophysiological assessment of hearing, there were significant differences vis-à-vis the P2 amplitude in the LE, which was higher for the group with ADHD and for N2 amplitude and latency of the LE, which were abnormal in the ADHD group.Regarding P300 and MMN, there were no significant differences when comparing both groups.This study provided a greater understanding of the central auditory pathways of children with and without ADHD when evaluated with electrophysiological tests; however, further studies are needed, especially in the national literature, to better understand the functioning of the auditory pathway of these populations.