The results showed that, the as-prepared hierarchical Bi2S3/In2S3 core/shell heterostructure exhibits significant visible light photocatalytic activity for degradation of 2, 4-dichlorophenol. The introduction of Bi2S3 core can not only improve charge transport and enhance the electron-hole separation, but also broaden the visible light response. The hierarchical porous folwer-like shell of In2S3 could increase the specific surface area and remarkably enhanced the chemical stability of Bi2S3 against oxidation.Core/shell heterostructure composite has great potential applications in photocatalytic field because the introduction of core can remarkably improve charge transport and enhance the electron-hole separation. Herein, hierarchical Bi Recently, the design and synthesis of core/shell materials from nanoscale to microscale size have attracted much attention due to their unique structure-induced properties1245782S3 nanostructure, a III-VI group sulfide, is known to crystallize in three polymorphic forms: α-In2S3, β-In2S3, and γ- In2S3. Of these, β- In2S3 is a n-type semiconductor with a band gap of 2.0–2.3 eV and is a potential candidate for photocatalytic applications because of its proper band gap for solar energy conversion102S3 with a narrow bandgap (~1.3 eV) can be a good candidate semiconductor12142S3/Bi2S3 core/shell heterostructure composite, which can efficiently promote charge separation and lead to enhanced activity. So the combination of In2S3 and Bi2S3 in a single core/shell composite could hold possible applications in energy conversion for the photodegradation reaction, which has not been reported yet.Metal sulfides have been extensively investigated and proven to be a group of highly efficient catalysts for photochemical reactions. Typically, InIn all cases to date, general synthesis strategies used to fabricate core/shell structures involve two main steps. The core powders are first prepared, and then coated with other materials (shell) to form a core–shell structure. It is difficult to achieve uniform coating with well-defined morphologies due to compatibility issues between the core and desired shell materials. Therefore, how to construct hierarchical heterogeneous core/shell structures via a facile one-spot route is still a significant challenge to material scientists.2S3/In2S3 core/shell microspheres via a hydrothermal process. In this process, consecutive reactions of the sole sulfur source of L-cysteine with Bi and In salts lead to the formation of Bi2S3/In2S3 core/shell structures due to their significantly different reaction rate. The as-prepared core/shell hybrid has an interesting structure with uniform size consisting of a Bi2S3 sphere core and a nanosheet-based In2S3 shell. The special hierarchical structure, high light-harvesting capacity and the microscale core/shell heterostructure make it to be an excellent candidate for the degradation of 2, 4-dichlorophenol with enhanced photostability and photocatalytic efficiency.Herein, we reported a facile route for growth rate controlled synthesis of hierarchical Bi2S3 is composed of nanospheres with an average diameter of 100–200 nm  and cubic β-In2S3 (JCPDS Card No. 32-0456). For hierarchical core/shell spherical superstructure (Line c in 2S3 match with the reflections from the cubic β-In2S3 lattice planes of (311), (400) and (440), making it easy to reveal the presence of In2S3 phase. In contrast, other diffraction peaks can be attributed to orthorhombic phase Bi2S3. All the above results suggest that the intercrossed In2S3 nanosheet shell could in situ grow on the surface of Bi2S3 core.The morphology and the crystal phase information of the final products were investigated by SEM and XRD analysis, as shown in 0–200 nm . As for nosheets . Interesurements . The X-r2S3/In2S3 composite was revealed using TEM and HRTEM. As shown in 2S3, while 0.27 nm corresponds to the (400) plane of cubic β-In2S3, which implying the formation of Bi2S3/In2S3 heterostructure. The selected area electron diffraction pattern (SAED) image in 2S3/In2S3 core/shell spheres have a small diameter and the constituent nanosheets are very thin, which would contribute to the light-harvesting in the photocatalytic reaction.Additionally, the more detailed structural information of the hierarchical Bi2S3/In2S3 spheres  line scans on single submicrosphere  was carried out on Bi spheres . The EDS spheres . The S e spheres  confirms spheres  than tha spheres , which crosphere  show tha2S3/In2S3 core/shell composite were further characterized by XPS. 3/2, Bi4f7/2, and In3d5/2167/2 and Bi 4f5/2 peaks (5.30 eV), S2p3/2 and S2p1/2 peaks (1.25 eV) (5/2 and In 3d3/2 peaks (7.5 eV)  , and In (7.5 eV)  suggest 2S3, In2S3 and the hierarchical Bi2S3/In2S3 core/shell composite are displayed in the 2S3 and In2S3 present the photoresponse property from UV light region to visible light region. Compared with bare Bi2S3, the light absorption ability of the core/shell material is enhanced after In2S3 was introduced, which has strong absorption in nearly the whole range of visible light. This can be attributed to the small band gap and synergistic affect of the two compositions. Taking into account the efficient use of visible light in a large part of the solar spectrum, we believe that this photocatalyst, with its long wavelength absorption band, is an attractive photocatalyst for pollutant degradation.For highly efficient photocatalyst, light absorption range and intensity are important. The optical absorption properties of Bi2S3/In2S3 core/shell spheres, samples prepared at different reaction times were collected and investigated by SEM. As shown in 2S3 under hydrothermal condition. By prolonging the reaction time to 1 h, small nanoparticles congregated into compact submicrospheres  patterns  show theas short , but the for 3 h , and the for 3 h . Further the SEM  and EDS  the SEM  observat2S3/In2S3 core/shell spheres is illustrated in 2S and thioacetamide) used in the synthesis of semiconductor metal sulfides2− in solution during the hydrothermal process. In the L-cysteine molecule, there are many functional groups, such as -NH2, -COOH, and -SH, which have a strong tendency to coordinate with inorganic cations and metals2S3/In2S3 core/shell spheres structure with small size. Our contrast experiment (2S3/In2S3 core/shell spheres (In-Bi-30). Notably, there were different morphologies in the final product, which indicated that In2S3 and Bi2S3 can't grow intimately to form core/shell structure. Therefore, under the help of mutual coordination between PSS and L-cysteine, Bi3+ and In3+ can coordinate with L-cysteine to form initial precursor complexes on the long chain structure of PSS252S with the assistance of water. Because the Ksp of Bi2S3 (1.0 × 10−97) is much smaller than that of In2S3 (5.7 × 10−73)2S3 will preferentially deposit and form crystal seeds along the PSS chain before In2S3  could make the nanosheets much thicker and radius much larger . This can be attributed to its smaller particle size, ultrathin nanosheets and the presence of large quantity of mesoporous. The large surface area for heterogeneous photocatalysis can provide more surface active sites for the adsorption of reactant molecules, which will make the photocatalytic process more efficient2S3/In2S3 core/shell hybrid to increase bulk combination in In2S3 or Bi2S3, which are not beneficial for the photocatalytic reaction. So we predicted that the hierarchical flower-like core/shell Bi2S3/In2S3 (In-Bi-30) with heterostructure and ultrathin nanosheets will have higher photocatalytic ability than other samples.Compared to the conventional synthetic methods, this one-spot synthetic route is simple and easy to achieve uniform coating with hierarchical nanosheets due to compatibility issues between the Bi smaller  than the smaller , indicath larger , which wh larger . The porh larger  of the simproved , especia2S3/In2S3 core/shell nanostructures by the degradation of 2, 4-dichlorophenol under visible light irradiation in an aqueous solution, together with that of Bi2S3 and In2S3 for the purpose of comparison. Before the photocatalytic reaction, the dark adsorption experiments were performed. As shown in 2S3 and In-Bi-30 were high, which associate with their high BET surface areas. After irradiation, the plots for the concentration changes of 2, 4-dichlorophenol determined from its characteristic absorption peak over different catalysts are altered. It can be seen that all the In2S3/Bi2S3 core/shell composites show higher photocatalytic activities than individual Bi2S3 and In2S3 under identical experimental conditions. As discussed above, the hierarchical core/shell structure of the In2S3/Bi2S3 composites improves the light absorption and facilitates the efficient separation of photogenerated carriers, which can be considered as main reasons for the enhancement of photocatalytic activities. The photocatalytic mechanism was shown in 2S3. Because the CB of In2S3 is slightly higher than that of Bi2S3, the photoexcited electrons in the CB of In2S3 can be transferred to Bi2S3 in the core/shell hybrid nanostructure easily, creating positive holes in the VB of In2S3. Importantly, the In2S3 shell is made up of ultrathin nanosheets with intersection, there exist lots of porous channels, the oxygen could permeate through the shell to the core of Bi2S3. Since the ECB potential of Bi2S3 (−0.76 eV vs NHE) is more negative than E0 (O2/·O2-) (−0.046 eV vs NHE), the electrons left on the ECB of Bi2S3 could reduce O2 to ·O2- through one-electron reducing reaction2O or OH− in the solution, generating hydroxyl (·OH) radicals adsorbed at the surface322S3 has obvious influence on the photocatalytic ability in the present material system (2S3 is relatively low (In-Bi-10), the small surface area of Bi2S3/In2S3 core/shell nanostructure provides relatively low surface active sites for the adsorption of reactant molecules. Increase the amount of In2S3, hierarchical core–shell structure was formed (In-Bi-30), the degradation rates of 2, 4-dichlorophenol reached the maximum value  can allow multiple reflections of visible light, which enhances light-harvesting and thus increases the quantity of photogenerated electrons and holes available to participate in the photocatalytic degradation of 2, 4-dichlorophenolConsidering the core/shell architectures with special hierarchical nanocomposites are advantageous to photocatalytic application, we investigate the photocatalytic properties of as-prepared hierarchical Bil system . When thlue 95%, . Further•OH reacts with terephthalic acid (TA) in basic solution to generate 2-hydroxy-terephthalic acid (TAOH), which emits a unique fluorescence signal with the peak centered at 426 nm·OH produced on the surface of photocatalysts. The maximum emission intensity in fluorescence spectra was recorded at 425 nm by the excitation at 315 nm, and the results are shown in •OH radicals. Obviously, the maximum number of •OH radicals is formed by using the Bi2S3/In2S3 core/shell photocatalyst (In-Bi-30) in the photoreaction process, this result is in good agreement with the result of photodegradation of 2, 4-dichlorophenol. Hence, the photocatalytic activity has a positive correlation with the formation rate of •OH radicals·OH and ·O2-, respectively2S3/In2S3 core/shell nanostructure (In-Bi-30) with 30 min irradiation. It can be seen that the addition of IPA and BQ in the reaction solution both have apparent effect on the photocatalytic activity, suggesting that •OH and ·O2- are the main oxygen active species involved in the 2, 4-dichlorophenol photocatalytic process under visible light irradiation. All of the above results could well support the proposed photocatalytic mechanism in To further prove the mechanism of the photocatalysis, the formation of OH on the surface of photocatalysts was detected by the fluorescence technique using terephthalic acid (TA) as a probe molecule. It is well known that 2S3/In2S3 core/shell structure (In-Bi-30) and pure Bi2S3 and In2S3 were evaluated by performing the cycling experiments under the same conditions  does not exhibit evident loss of activity, indicating the better stability of this Bi2S3/In2S3 core/shell composite. The high stability of the Bi2S3/In2S3 core/shell structure is attributed to the close interaction between Bi2S3 and In2S3 solid solution, which favors the transfer of the photogenerated electrons from the conduction band (CB) of In2S3 to Bi2S3 conduction band (CB), as shown in 3+ and Bi3+.Metal sulfides are usually not stable during the photocatalytic reaction and subjected to photocorrosion38nditions . After f2S3/In2S3 core/shell microspheres according to the different growth rate of the two kinds of sulphides. Moreover, their performance studies indicated the hierarchical Bi2S3/In2S3 core/shell microspheres exhibit higher photocatalytic activity than the pure Bi2S3 and In2S3 for the degradation of 2, 4-dichlorophenol due to the efficient synergistic effect resulted from the interaction between Bi2S3 core and hierarchical In2S3 shell. The synergistic activity was also investigated through the measurement of •OH and ·O2- radicals produced by Bi2S3/In2S3 core/shell microspheres. It is considered that this facile and promising synthetic strategy can be extended to prepare a wide variety of functional nanohybrids for potential applications in waste water treatment, solar cells and so on.In summary, we demonstrated a facile one-pot hydrothermal method to synthesize hierarchical Bi3)3·5H2O, 0.15 g poly (sodium-p-styrenesul-fonate) (PSS), a specified quality of In(NO3)3·4.5H2O and L-cysteine were added into 25 mL distilled water and stirred for 30 min at room temperature. Then, the obtained yellow solution was transferred to a 50 mL Teflon-lined stainless steel autoclave, which was heated to 150°C and maintained for 9 h. After cooling, the as-synthesized brown products were rinsed with distilled water, absolute ethanol, respectively, and dried at 60°C overnight. The molar ratios of In3+ to Bi3+ were 10%, 30%, and 50%, and the resulting samples were labeled as In-Bi-10, In-Bi-30 and In-Bi-50, respectively. For comparison, bare In2S3 and Bi2S3 were obtained under the same experimental conditions in the absence of Bi(NO3)3·5H2O and In(NO3)3·4.5H2O, respectively.In a typical experiment, 0.3 g Bi, SEM-EDS analyses were carried out with a Hitachi S-4800 SEM equipped with an EDAX energy dispersive X-ray analyzer. Transmission electron microscopy , and powder X-ray diffraction . The UV-visible diffuse reflectance spectra of films were obtained using a UV-visible spectrophotometer (Shimadzu UV-2550). The electronic states of elements in the sample were analyzed using X-ray photoelectron spectroscopy . The specific surface areas of the materials were calculated using the Brunauer–Emmett–Teller (BET) method.λ ≥ 420 nm). Prior to light irradiation, the suspension was kept in the dark under stirring for 30 min to ensure the establishing of an adsorption/desorption equilibrium. Oxygen flow was employed in all experiments as oxidant. Adequate aliquots (5 mL) of the sample were withdrawn after periodic interval of irradiation, and centrifuged at 10000 rpm for 5 min, then filtered through a Milipore filter (pore size 0.22 μm) to remove the residual catalyst particulates for analysis. The filtrates were analyzed using a UV-vis spectrophotometer (Shimadzu UV-2550).The photodegradation experiments were performed in a slurry reactor containing 100 mL of 50 mg/L 2, 4-dichlorophenol and 0.05 g of catalyst. An 150 W xenon lamp  was used as the solar-simulated light source, and visible light was achieved by utilizing a UV cut filter (•OH) radicals produced by the photocatalysts under visible light irradiation were measured by the fluorescence method on a Fluoromax-4 Spectrophotometer (Horiba Jobin Yvon) using terephthalic acid (TA) as a probe molecule. The •OH radical trapping experiments were carried out using the following procedure: A 5 mg portion of the sample was dispersed in 30 mL of a 5 × 10−4 M TA aqueous solution in a diluted NaOH aqueous solution (2 × 10−3 M). The resulting suspension was then exposed to visible light irradiation for 15 min. 2 mL of the suspension was collected and centrifuged to measure the maximum fluorescence emission intensity with an excitation wavelength of 315 nm. Besides, isopropanol , and benzoquinone  were added into the 2, 4-dichlorophenol solution to capture hydroxyl radicals (·OH) and the superoxide radicals (·O2-), respectively, followed by the photocatalytic activity test.In order to detect the active species during the photocatalytic reaction, hydroxyl (J.Z. performed synthesis experiments, G.H.T. and H.G.F. designed the experiment. Y.J.C. and Y.H.S. contributed in material characterization and discussion. C.G.T. and K.P. carried out photocatalytic evaluation and discussion. J.Z. and G.H.T. wrote the manuscript.dataset 1


Objective: Attention-deficit/hyperactivity disorder (ADHD) is a common mental disorder in adults that was under-diagnosed until recently. Due to probable consequences of ADHD such as occupational and educational dysfunctions and substance use, this disorder is becoming more and more of a concern. This study aimed to investigate ADHD symptoms among students of Zahedan University of medical sciences, Iran.Methods: This cross-sectional study was performed in Zahedan University of Medical Sciences from 2008 to 2009. Our sample included 1500 individuals who were chosen using simple sampling method. Considering the goal of the investigation, two questionnaires were distributed among students including demographic information form and the Conners' Adult ADHD Rating Scales–Self Report . Data analysis was done using descriptive and analytical statistics in SPSS software. Results: Out of 1500 questionnaires distributed among students, 913 were completed. 589 students (64.5%) were female and 324 (35.5%) were male. The Mean age of participants was 21.7 ± 3.2 years. ADHD symptoms were defined based on the Conner’s adult test. Based on CAARS-S: SV, inattention/memory, hyperactivity/restlessness, impulsiveness/emotional lability, and problems with self-concept subscale symptoms were found in 107 (11.7%), 109 (12%), 121 (13.2%), and 30 (3.3%) respondents, respectively. These findings were significantly higher than average.Conclusions: According to our results, it seems that the prevalence of ADHD is high among students. Thus, more screening is required in this population in order to diagnose and treat the disorder earlier and prevent its consequences, such as substance abuse. Declaration of interest: None. Attention deficit hyperactivity disorder (ADHD) is a developmental-nervous-behavioral disorder mostly diagnosed in childhood. Its prominent features are attention deficit, hyperactivity, and impulsiveness, which can cause poor occupational, academic, and social performance in the future . The preADHD is a mental disorder in adults and in spite of many published studies from mid-1970 until recently, it was rarely diagnosed in adults. About 30-70% of children who suffer from ADHD will suffer from the same disorder during puberty, so that the physicians prescribe ongoing treatment for them .This disorder was described previously as a disorder pertaining to children and youth, but Cohort studies following up on children with ADHD showed that the disease conditions continue noticeably until adulthood depending on the disease intensity. Studies have shown poor mental results for patients in their adulthood, sometimes with high percentage of educational deficiency, drug abuse, personality disorder, and etcetera , 10.ADHD is prevalent among 30-50% of patients with psychiatric problems suffering from drug abuse , 11-13.According to the results of a study carried out in Iran in 2004 on 409 students the prevalence of disorders due to hyperactivity-attention deficit was reported to be 3.7% .Characteristic clinical features of ADHD in adults include hyperactivity, attention deficit, intense emotional response, low provocation threshold, sudden and intense anger, impulsiveness, instability in interpersonal relations, occupational and educational frustration, and alcohol abuse . AttentiThe incidence of ADHD in adults is unclear, but it is more than what was imagined before. It is increasingly diagnosed nowadays, and still requires more investigation. Other symptoms in adults include impulsiveness and attention deficit. Failure to diagnose and/or treat this disorder is accompanied by many complications, such as secondary depression and low self-esteem , which can influence occupational and social functions. Pharmacotherapy includes amphetamine (5-60 mg daily) or methylphenidate (5-60 mg daily) , 16. SimThese two disorders are interrelated in some ways. Patients suffering from ADHD may begin to abuse drugs at an early age and show a more frequent intense model of abuse .Researchers using factor analysis have consistently found support for an inattention factor both in children and adults. Findings have been mixed regarding whether hyperactivity and impulsiveness reflect one or two dimensions . ADHD paThese patients may need to select some special types of occupation to enable them to adapt continuously with previous conditions. They usually have many problems with their colleagues and employers such as being late, absent, and careless .Other findings support the results that ADHD is associated with greater disruptive behaviors, substance abuse, mood and anxiety disorders, early onset of major depression, dysthymia, oppositional defiant disorder, and conduct disorder. Males had a higher risk of disruptive behavior disorders. Females with oppositional defiant disorder also have a high risk of depression and anxiety . According to previous studies, ADHD control is important in order to prevent one of its most dangerous consequences; drug abuse . ADHD yoDue to what was stated about this disorder and future social, familial, and educational damages, and the limited number of studies about adults' ADHD, we decided to do this study. The aim of this study was to determine the prevalence of ADHD in students.This descriptive study included all students of Zahedan University of Medical Sciences, Zahedan (in the southeast of Iran). Two questionnaires were used; one included demographic, educational, and medical history, and the other one was the Conners' Adult ADHD Rating Scales–Self Report: Screening Version (CAARS-S:SV) . The queAll students were assured regarding the confidentiality of their information. Students were asked to fill out the questionnaires at the beginning of their classes. Comprehensive information and enough time were provided by researchers. All questionnaires were collected by researchers after being answered by the students. It should be noted that the CAARS-S:SV is applied to screen adults for ADHD, and clinical interview is necessary in order to confirm the diagnosis of this disorder.CAARS-S:SV has an approved reliability and validity. It includes 30 items with 0 to 3 points which can assess the following four subscales : A: Inattention/memory problemB: Restlessness/hyperactivityC: Emotional instability/impulsiveness D: Problems concerning general self-image This scale has been normalized in the Iranian population by Arabgol et al. on 20 students of Shahid Beheshti University of Medical Sciences, Iran, and its content validity and reliability has been reported by Chronbach's alpha (0.81) . The raw score of each subscale was changed to T-scores by appropriate norm tables (T-scores had the mean (± standard deviation) of 50 (± 10)). Scores higher than 65 were considered as clinically significant; therefore, T-scores of 66-77 were higher than the mean. Scores over 70 were much higher than the mean. Furthermore, scores higher than 80 indicated sever pathological disorders and exaggerated bad symptoms . Statistical significance was evaluated with an alpha level of 0.05.Of 1,700 students in all fields of study 913 students answered the questionnaires completely. 589 respondents (64.5%) were female and 324 (35.5%) were male. They were 18-44 years old with the mean age of 21.7 (± 3.2). Based on CAARS-S:SV, inattention/memory, hyperactivity/restlessness, impulsiveness/emotional lability, and problems with self-concept subscale symptoms were found in 107 (11.7%), 109 (12%), 121 (13.2%), and 30 (3.3%) respondents, respectively. They were significantly higher than average.To determine the severity of the disease, the raw score of each subscale was changed to T-scores by appropriate norm tables. As is shown in Regarding the frequency of ADHD symptoms inattention/memory problems, hyperactivity/restlessness, impulsivity/emotional lability, and problems in self-concept subscale scores were higher or much higher than the mean in both sexes .Most of the respondents (25.7%) were paramedical students. ADHD symptoms in A, B, C, and D subscales are given in Students' T-scores average of the respondents regarding inattention, hyperactivity, impulsiveness, and self-concept disorder subscales based on their gender showed that the mean in males was higher than that in females in all subscales except for self-concept disorder. According to these results a significant difference was observed between the inattention, hyperactivity, and impulsiveness scores of male and female respondents (p ≤ 0.001), but not in the self-concept score (p = 0.679) .Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health condition exhibited by the difficulty to maintain attention, hyperactivity, and impulsive behavior , 8. In our investigation, 15.4% of the respondents had ADHD symptoms. It was reported as 0.3 to 6% in other studies , 9. FernFayyad et al. administered a similar study in ten countries in the Americas, Europe, and the Middle East on 11422 respondents aged 18-44 years. Adult ADHD average prevalence was reported to be 3.4% (1.2–7.3%). This research showed that socio-economic status influences the prevalence of this disorder. In this cross-national study, different prevalence rates were reported in low-income countries (1.9%) compared with high-income countries (4.2%) .Other studies have shown different results according to different methodological methods and estimated a prevalence ranging from 3.7% to 8.9% . These rFinally, Polanczyk et al. have undertaken a systematic review and stated that the worldwide prevalence of ADHD was 5.29%. This suggests that geographic conditions play a limited role in ADHD/HD prevalence estimates worldwide .Some evidences demonstrate that cultural and contextual aspects  are predisposing risk factors . In otheThe prevalence of ADHD in our study was higher than that in other recent studies -31. ThisIt is also noteworthy that 557 participants were eliminated from our study due to not completing the questionnaires. They might have also been suffering from ADHD disorder. Therefore, a higher prevalence rate was also possible among students. These symptoms can disturb students’ academic efficiency, lengthen their study, and even disturb their development , 2. ADHDIn addition, impulsiveness can disturb interpersonal and marital relationships, and occupational functions .In this study, 21% of participants of both sexes had impulsiveness index higher or much higher than mean. Few studies have investigated the ADHD adulthood prevalence rate and its consequences in Iran. In a study performed in Tehran, 4.9% of the study participants had impulsiveness index higher or much higher than mean . The lowAnother study showed that the maximum rate was related to subscale B (7.8% for hyperactivity-restlessness) and the minimum rate (2%) was related to subscales D  and A (Low attention–memory) . HoweverAs various researches have shown, rate of ADHD symptoms in different countries is varied due to geographic aria, race, and psychosocial adversity. Moreover, its rate is believed to be higher in high-income countries; these cases were not examined in the present study.Recent studies have also showed a significant difference between the male and female inattention, hyperactivity, and impulsiveness symptoms (p ≤ 0.001), but not self-concept. DuPaul et al. have performed a cross-gender and cross-national prevalence study among university students which did not find a significant difference between the two sexes . These rAccording to another study performed in Tehran the maximum and minimum ADHD symptoms were related to the impulsiveness subscale (13.2%) and self-concept subscale (3.3%), respectively. According to the study performed by Arabgol et al., the maximum and minimum rates were related to hyperactivity (7.8%) and self-concept problem subscales (2%), respectively. These results confirm our results. Furthermore, symptoms intensity in subscales A, B, and C were mostly related to the intensity much higher than mean. Symptoms intensity percentage was higher than mean only in self-concept problems .Another study about ADHD symptoms on 1,209 university students from three countries  reported that inattention and hyperactivity-impulsiveness among Italian students were significantly higher than that in the students from the United States. However, inattention symptoms in the students of New Zealand were reported to be higher than that in the students from the United States .Some studies have tried to address the consequences of this disorder and the importance of early diagnosis. This disorder is associated with a higher risk of antisocial personality (10 times more than the control group) and substance and alcohol abuse (4-5 times more than the control group). Adults’ ADHD increases mood disorders (2-6 times), anxiety (2-4 times), communication disorders (2 times), and learning disorders compared with the control group .Other researches have confirmed the above results and emphasized that ADHD, alone and in combination with other psychiatric problems, is a risk factor for the development of substance use disorder (SUDs) in youths. These studies reported that approximately one fifth of adults with SUDs have ADHD -38. People with ADHD symptoms, particularly attention deficit disorders, have difficulty in communication and conversation . In addiDue to the high prevalence of ADHD in adults and the importance of its early diagnosis and treatment, there is a need for more frequent screening.On the other hand, applied approaches such as students’ psychological assessment during primary enrollment, informing counselors and paying more attention to this disorder in university counseling centers, on time referral of patients to psychiatrists, and finding patients are necessary in order to decrease the unfavorable effects of ADHD on their occupational, educational, and familial lives.


The aim of this review was to gain insight into the relationship between Attention deficit hyperactivity disorder (ADHD) and risky performance in gambling tasks and to identify any potential alternate explanatory factors.PsycINFO, PubMed, and Web of Knowledge were searched for relevant literature comparing individuals with ADHD to normal controls (NCs) in relation to their risky performance on a gambling task. In total, fourteen studies in children/adolescents and eleven studies in adults were included in the review.Half of the studies looking at children/adolescents with ADHD found evidence that they run more risks on gambling tasks when compared to NCs. Only a minority of the studies on adults with ADHD reported aberrant risky behavior. The effect sizes ranged from small to large for both age groups and the outcome pattern did not differ between studies that applied an implicit or explicit gambling task. Two studies demonstrated that comorbid oppositional defiant disorder (ODD) and conduct disorder (CD) increased risky behavior in ADHD. Limited and/or inconsistent evidence was found that comorbid internalizing disorders (IDs), ADHD subtype, methylphenidate use, and different forms of reward influenced the outcomes.The evidence for increased risky performance of individuals with ADHD on gambling tasks is mixed, but is stronger for children/adolescents with ADHD than for adults with ADHD, which may point to developmental changes in reward and/or penalty sensitivity or a publication bias for positive findings in children/adolescents. The literature suggests that comorbid ODD/CD is a risk factor in ADHD for increased risky behavior. Comorbid IDs, ADHD subtype, methylphenidate use, and the form of reward received may affect risky performance in gambling tasks; however, these factors need further examination. Finally, the implications of the findings for ADHD models and the ecological validity of gambling tasks are discussed. Attention deficit hyperactivity disorder (ADHD) is characterized by attentional problems, hyperactivity, and impulsivity In general, individuals with ADHD tend to be involved in a greater proportion of risky situations and behaviors in everyday life than individuals without ADHD. Specifically, those with ADHD tend to demonstrate more dangerous driving behavior The relationship between ADHD and risky behavior may be explained by executive dysfunctioning, in particular inhibition deficits, that for many years have been the focus of ADHD models To gain more insight into the relationship between ADHD and risky behavior, cognitive tasks with a gambling component can be used to investigate the risky behavior of individuals with ADHD. In gambling tasks, participants can usually choose between several options that differ in the chance for a reward or penalty. The exact probability distribution of the outcome can be evident for the participant (explicit) or not (implicit). Examples of implicit gambling tasks are the Balloon Analogue Risk Task (BART) Implicit and explicit gambling tasks aim to measure different types of decision-making. Implicit gambling tasks are thought to depend on ‘hot’ decision-making involving emotional and affective responses to the options of choice as well as on ‘cold’ decision-making involving the rational and cognitive determinations of risks and benefits associated with the options in the later stages of the task Studies on the gambling task performance of individuals with ADHD show mixed results, which may be caused by the use of different task paradigms and/or by sample characteristics. Therefore, the aim of this review is to gain more insight into the relationship between ADHD and risky decision-making on gambling tasks in existing research, and to identify any alternate explanatory factors that could have influenced the outcomes presented in the literature. Based on the increased sensitivity to immediate rewards and decreased sensitivity to penalties predicted by motivational models of ADHD, it is hypothesized that individuals with ADHD will display more risky behavior in gambling tasks than individuals without ADHD. Specifically, purely motivational models The literature was searched for studies that compared individuals with ADHD to normal controls (NCs) concerning their risky performance on a gambling task. A neuropsychological approach was taken by only including studies using standardized tasks and experimentally controlled methods. Furthermore, non-experimental studies that examined decision-making in everyday life were outside the scope of this review. The studies included were searched for the following alternate explanatory variables: the type of gambling task, comorbidity (ODD/CD and IDs), methylphenidate (MPH) use, the form of reward used, and the demographic characteristics of the participants .This systematic literature review was carried out according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) The Card Playing Task (CPT)  and Door Opening Task (DOT)The Iowa Gambling Task (IOWA)The Cambridge Gambling Task (CGT)In the Game of Dice Task (GDT)The The Make-a-Match Game (MMG) Probabilistic Discounting Task (PD)The The results in We identified several potential alternate explanatory variables in the literature, which were age, sex, intelligence and/or education level, ODD/CD, IDs, ADHD subtype, MPH use, and the form of reward used. The potential influences of these alternate explanatory variables are addressed in a separate section, in which a comparison was made between studies in which differences in risky behavior were found between individuals with ADHD and NCs (positive findings) and studies that did not find any group differences (null findings). A rather conservative strategy was adopted for allocating studies to the positive findings category in order to maximize generalizability. As such, studies that only found group differences for specific aspects or parts of a gambling task were allocated to the null findings category. In cases where more than one ADHD group was compared to NCs only the results of the ADHD group with the least comorbidity were used for the classification. A potential alternate explanatory variable was regarded as controlled for when the ADHD and NC samples were matched or did not differ on this variable, when statistics showed that this variable did not correlate with the performance on a particular gambling task, or when an appropriate statistical correction was carried out for the variable in question.Ten studies investigated the performance of children/adolescents with ADHD on an implicit gambling task. Six studies used the IGT or a IGT variant Six studies investigated the performance of children/adolescents with ADHD on the IGT or a variant of the IGT Luman et al. Three studies found no abnormalities in the degree of risk-taking on the IGT in children/adolescents with ADHD As mentioned above, Garon et al. Three studies investigated the performance of children/adolescents with ADHD on the DOT with comorbid ODD ran more risks by pumping up the balloons more than the ADHD group without comorbid ODD, who did, however, still pump the balloons more than the NCs. Contrary to expectations, the children with ADHD and comorbid ODD were most sensitive to punishment, in that they pumped the balloon less in trials after having just been penalized with a balloon pop, followed by the NCs, and then the children with ADHD without ODD, who were the least sensitive to punishment. The authors therefore assumed that children with ADHD and comorbid ODD are characterized by poor affect regulation, which makes them too reactive and/or unable to cope adequately with punishment. The authors further hypothesized that this caused children with ADHD and comorbid ODD to perform inconsistently on the gambling task, thereby demonstrating an increase in risky behavior and an increase in the frequency of impulsive adjustments of behavior after receiving penalties.Humphreys & Lee Four studies investigated the performance of children/adolescents with ADHD in explicit gambling tasks. All of which made use of a different task paradigm  DeVito et al. Drechsler et al. Drechsler et al. Scheres et al. implicit gambling task, of which five studies (5/10 = 50%) found clear evidence that children/adolescents with ADHD displayed more risky behavior than NCs explicit gambling task and two studies (2/4 = 50%) found that children/adolescents with ADHD performed in a more risky fashion than NCs Fourteen studies investigated the performance of children/adolescents with ADHD on various gambling tasks. The effect sizes of the group differences in these studies ranged from a Cohen’s d of 0.04 to a d of 1.32. Ten studies used an With regard to the sensitivity to rewards and penalties (feedback use) in children/adolescents, one study found significantly less T-patterns that included penalties in the IGT in children with ADHD compared to NCs Eight studies investigated the performance of adults with ADHD on implicit gambling tasks. Six of these studies used the IGT or a variant of the IGT Of the six studies investigating the performance of adults with ADHD on the IGT Conversely, Agay et al. without working memory problems and NCs both with and without working memory problems (1.94<Cohen’s d<2.04).Much like Agay et al. Two studies investigated the performance of adults with ADHD on the BART and neither study revealed significant differences in risky performance between adults with ADHD and NCs with a comorbid CD, however, played longer (persevered) compared to adults with persistent or remittent ADHD without a comorbid CD (Cohen’s d = 0.43).Only one study assessed the performance of adults with ADHD on the CT Three studies investigated the performance of adults with ADHD using an explicit gambling task, the GDT Of the three studies assessing the GDT in adults with ADHD implicit gambling tasks, of which two studies (2/8 = 25%) provided clear evidence that adults with ADHD performed in a more risky fashion than NCs explicit gambling task (GDT) was examined in three studies. While one study observed (1/3 = 33%) increased risky behavior in adults with ADHD In total, eleven studies examined the performance of adults with ADHD on various gambling tasks. The effect sizes of the group differences between adults with ADHD and NCs in these studies ranged from Cohen’s d 0.01 to 2.04. Eight studies used In terms of the impact of feedback, only one two-part study investigated feedback use in adults with ADHD. In their first study, Matthies et al. [67)] , ADHD subtype, MPH use, the form of the reward received, and demographic factors .In this section, studies that provide evidence for more risky performance of individuals with ADHD in comparison to NCs, i.e. studies with positive findings, will be contrasted with regard to the aforementioned alternate explanatory variables, with studies that failed to find such evidence, i.e. studies with null findings. We made a broad categorization of studies with positive findings age of the participants, see The first potential alternate explanatory factor is the sex of the participants. Twenty-one out of the 25 studies examined matched their samples on sex or had equal sex ratios in the ADHD and control groups. Of the remaining studies, one study included sex as a covariate A second potential alternate explanatory factor is the intelligence/education level of the participants. Eleven out of 25 studies reported no differences in IQ scores between the ADHD and control groups. Of the remaining studies, three studies entered IQ as a covariate in the statistical analyses A third potential alternate explanatory factor is the type of gambling task used, see A fourth potential alternate explanatory factor is the psychiatric comorbidity, such as ODD/CD , see A seventh potential alternate explanatory factor is the treatment of ADHD symptoms by using form of reward received by the participants, see An eighth potential alternate explanatory factor is the The aim of this review was to gain more insight into the relationship between ADHD and risky performance in gambling tasks and to identify potential alternate explanatory factors that may have also affected the outcome. In total, 25 studies were reviewed that examined the performance of children/adolescents (14 studies) and adults (11 studies) with ADHD on a gambling task. Ten of the 25 included studies, i.e. 40%, reported that individuals with ADHD displayed more risky behavior in gambling tasks, as indicated by significantly higher scores than NCs on outcome measures related to risk-taking. In terms of potential alternate explanatory factors, age appeared to play an important role in the relationship between ADHD and risky decision-making, as half of the studies in children/adolescents (50%), but only a minority of studies in adults (27%) reported greater risky performance in individuals with ADHD when compared to NCs. Across the studies with children/adolescents and adults effect sizes ranged from small to large, with no clear pattern related to age. The results of the studies examined did not differ between studies applying explicit gambling tasks, in which the exact probability distribution is evident for the participants , and implicit gambling tasks in which the exact probability distribution is not evident . This review therefore provides evidence that children/adolescents with ADHD appear to be likely to perform in a risky fashion in gambling tasks than NCs , whereas adults with ADHD are less likely to perform differently from NCs on gambling tasks. This finding holds for both age groups irrespective of the use of an implicit or explicit gambling task.However, as the results varied between studies it was investigated whether other alternate explanatory factors could also help explain these inconsistencies. Two studies showed consistently that the presence of comorbid ODD or CD increases the risky performance on implicit gambling tasks in children and adults with ADHD. Furthermore, two additional studies including only children with ADHD and a comorbid ODD/CD had positive findings. Children and adults with ADHD and comorbid ODD/CD could, therefore, be more prone to risky performance in implicit gambling tasks. Several other alternate explanatory factors have been reported in the literature, such as comorbid IDs, ADHD subtype, MPH use, and the form of reward used. The evidence for a substantial influence of these variables was limited and/or inconsistent. Future studies on risky behavior should therefore take these variables into account in the study design. The outcomes of this review are, however, not likely to be distorted by demographical differences between individuals with ADHD and NCs within the studies concerning age, sex, and intelligence/education, because a vast majority of studies controlled for these factors by means of group matching or statistical correction. It is unclear how limited power of the included studies may have contributed to the prevalence of null findings. The variability in effect sizes reported limits the possibility to compute the required sample size for reaching adequate power. Nevertheless, 17 of the 25 studies (68%) included ADHD samples that were smaller than n = 30, which are in general small sample sizes. Future studies should therefore include larger sample sizes to assure adequate power.The result that children/adolescents with ADHD may be more likely to perform in a more risky fashion on gambling tasks than NCs, irrespective of the use of explicit or implicit tasks, implies both altered ‘cold’ and ‘hot’ decision-making strategies. On the one hand, more risky behavior on explicit gambling tasks implies an impaired ‘cold’ decision-making strategy, which may be due to deficiencies in the cognitive control system that is comprised of the dorsal and ventral lateral prefrontal cortex and posterior parietal cortex frequent punishment With regard to motivational deficiencies, the motivational models and combined motivational and cognitive models have primarily focused on the stronger discounting of future over immediate rewards (delay aversion) in individuals with ADHD. The increased likelihood of children with ADHD to perform more risky on implicit gambling tasks found in the literature, however, could point to an additional aspect of a dysfunctional reward (or punishment) system, which is that children/adolescents with ADHD favor less probable large rewards over more probable smaller rewards, and risk higher penalties for those rewards. This is in somewhat in line with the prediction of motivational models that participants with ADHD would perform poorer under partial or discontinuous reinforcement schedules, because reinforcement during gambling tasks is by definition discontinuous, i.e. a behavioral response may lead to different outcomes . An important ability in the face of discontinuous reinforcement is the use of outcome feedback in order to subsequently adapt behavior or to change strategy. Only a few studies investigated the use of feedback and the findings were mixed. Some studies demonstrated aberrant feedback use in children/adolescents with ADHD, such as a reduced use of negative feedback The evidence for aberrant risk-taking performance on gambling tasks is stronger for children/adolescents with ADHD than for adults with ADHD, although is it still only present in around fifty percent of the reviewed studies in children/adolescents. A possible explanation for the higher proportion of positive studies in children/adolescents is the developmental trajectory of ADHD, which is characterized by a reduction of symptoms from childhood to adulthood (often accompanied with remission of ADHD). The prefrontal recovery hypothesis Even though MPH is the most prescribed pharmacological treatment for ADHD, only two studies investigated the effects of MPH on gambling task performance. One placebo-controlled study found that children with ADHD taking MPH bet fewer points in the CGT, indicating more conservative play. The other placebo-controlled study was carried out on adults and found no effects of MPH on performance on the IGT and FPGT in adults with ADHD or in NCs. Given the small number of studies and the inconsistent findings, no conclusions can be drawn about the effectiveness of MPH in reducing risky behavior in gambling tasks. Literature on the effects of MPH on risky behavior in the real-world, however, suggests that MPH has a beneficial effect. MPH has for example been demonstrated to reduce the risk for drug abuse Although there might be some association between risky performance on gambling tasks and childhood ADHD, little is known about the relationship between the performance on such tasks and behavior in real life. Some of the reviewed studies in children with ADHD suggest that there is an association between risky performance on gambling tasks and the severity of ADHD symptoms This systematic literature review on performance in gambling tasks of individuals with ADHD found mixed evidence for increased risky behavior. Specifically, in children with ADHD half of the studies showed increased risky performance when compared to NCs. In adults, the evidence was weaker, with only a minority of studies (27% of the studies in adults) finding any increase in risky behavior on gambling tasks in adults with ADHD. The effect sizes in these studies ranged from small to large for both age groups. Given this variability in effect sizes and the generally small sample sizes (n<30 in 68% of the included studies), it is unclear whether limited power has contributed to the mixed findings. It is possible that the age related difference is due to developmental changes occurring during the transition from childhood to adulthood. However, this age related pattern might also reflect a publication bias for positive findings in children/adolescents in the past twenty years of research.Concerning the gambling tasks themselves, the outcome did not differ between studies applying implicit or explicit gambling tasks, which implies that, in the cases where risky performance was observed, both ‘cold’ and ‘hot’ decision-making strategies may have been altered in children/adolescents with ADHD. This finding cannot solely be explained by motivational models, because also ‘cold’ decision-making appears to be deficient, but is in line with the predictions of cognitive and combined motivational and cognitive models of ADHD, such as the behavioral inhibition model With regard to potential alternate explanatory factors, the literature indicates that the presence of ODD/CD is a risk factor in ADHD that can result in increases in risky behavior in gambling tasks. Several other potential alternate explanatory factors have been reported in the literature, including comorbid IDs, ADHD subtype, use of MPH, and the form of reward used. The evidence for a substantial contribution of these variables to the relationship between ADHD and risky decision-making was limited and/or inconsistent, especially given the prevalence of null findings in the literature. However, the outcomes of this review are not likely distorted by age, sex or intelligence/educational differences between participants with ADHD and NCs, because the majority of studies controlled for these variables.The increased risky performance in some children/adolescents with ADHD in implicit gambling tasks provides some evidence that children/adolescents with ADHD do not only prefer immediate over future rewards, but also prefer less probable large rewards over more probable smaller rewards, and risk higher penalties for these larger rewards. However, there is also some evidence that with more frequent punishment that both children/adolescents with ADHD are better able to develop an advantageous strategy. It remains unclear, however, how increased risky behavior in gambling tasks relates to real-life decision-making, firstly because of the mixed findings in the area, but also because evidence for the ecological validity of the available gambling tasks is limited, especially in children/adolescents.Table S1Checklist of the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).(DOC)Click here for additional data file.Table S2Descriptives and results of studies considered in the review.(DOC)Click here for additional data file.


However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine  along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD—the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)—and one ‘control' region—the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal ‘control' region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate–glutamine levels are not explained by use of stimulant medication.There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine,  ADHD leads to significant functional impairments and economic burden.2 ADHD in adults has historically been underdiagnosed and has received less research attention than childhood ADHD, but its importance is becoming more widely recognised.3Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome with childhood onset that affects ~5% of children and 2.5% of adults.4 and perhaps especially in dopamine neurotransmission6 within the prefrontal cortex (PFC) and the basal ganglia—areas known to be involved in both attention and the regulation of behaviour.There is substantial evidence that individuals with ADHD have abnormalities in brain anatomy and function,7One line of evidence in favour of the ‘dopamine hypothesis' of ADHD comes from the efficacy of cathecholaminergic stimulant drugs, such as methylphenidate and amphetamine, in relieving ADHD symptoms. Stimulants enhance synaptic dopamine  levels by blocking dopamine reuptake transporters (DAT) and, in the case of amphetamine, by promoting dopamine release from presynaptic neurons.8 they are not effective in all cases. For instance, it is estimated that stimulants produce complete remission in ~30% of cases, with substantial but partial improvement in another 40%, and little or no benefit in 30%.9 Hence, deficient dopamine neurotransmission seems unlikely to be responsible for all cases of this heterogeneous disorder. In order to develop effective treatments for ADHD cases refractory to current medications, therefore, it may be necessary to look beyond dopamine.However, although stimulants are superior to placebo in improving ADHD symptoms in the short term,10 Glutamate is an amino acid involved in excitatory neurotransmission.11 Further, glutamate and dopamine interact, with glutamate modulating dopamine release in corticostriatal pathways and vice versa.12Impaired glutamate signalling is another possible underlying abnormalities in (some cases of) ADHD, and an emerging treatment target.13 Further, some animal models suggest that altered glutamate regulation of the dopamine system14 underpins the functional deficits associated with ADHD. Until relatively recently, however, it was impractical to measure human brain glutamate in vivo.There is some—albeit preliminary—evidence to suggest glutamatergic involvement in ADHD. For example, genetic studies have reported an association between ADHD and a number of glutamate receptor gene variants.N-acetylaspartate (NAA). It is generally accepted that Cr is involved in phosphate metabolism and reflects energy use and storage by neurons, whereas Cho is a measure of membrane synthesis and turnover, and NAA is a marker of neuronal density and/or mitochondrial function.15Proton magnetic resonance spectroscopy ([1H]MRS) can be used to quantify the combination of glutamate and its metabolic product glutamine  in addition to other metabolites of potential clinical importance, such as choline (Cho) containing compounds, creatine (Cr) and phosphocreatine , and 17 (see the Discussion for details) have reported mixed findings. For example, some reported increases in Glx,18 whereas others found decreases.19 These studies were valuable first steps. However, they suffered from a number of limitations, for instance, most did not control for possible effects of prior use of ADHD medication (which has been shown to affect Glx and other metabolite levels.20)Prior [1H]MRS studies of Glx and other metabolites in adults with ADHDTherefore, we investigated differences in brain glutamate/glutamine and other key neurometabolites in adults with ADHD and controls. In addition, we recruited both treatment-naive and stimulant-medicated ADHD individuals in order to allow us to ascertain whether any differences observed were associated with pharmacological confounds.21 Moreover, these two selected areas are known to be involved in processes relevant to the symptoms of ADHD: the caudate/striatum is responsible for the regulation of attention,23 whereas the DLPFC is a key part of the executive control network in the brain.25We acquired spectra from three [1H]MRS voxels, with the following locations: the caudate nucleus/striatum , the dorsolateral PFC (DLPFC) and the medial parietal cortex. The caudate/striatum and the DLPFC were chosen on the grounds that abnormalities in both of these interconnected regions have been previously implicated in ADHD.We selected the third area, the medial parietal cortex, as a ‘control' region, as the structure and neurochemistry of this area have not previously been linked to ADHD. This was included as we wished to investigate whether any abnormalities seen in these disease-linked areas reflected specific local changes, or more widespread differences in metabolite levels.We included 60 adults: 40 with ADHD and 20 matched healthy controls . The ADHADHD participants were recruited from the Adult ADHD Service at the Maudsley Hospital in London, a specialist clinic providing diagnostic assessment and treatment for adults with ADHD referred from across the United Kingdom.26Diagnosis was performed by a consultant psychiatrist specialising in adult ADHD. Diagnosis was informed by pre-assessment questionnaires and by an in-depth clinical interview based around the ‘Conners Adult ADHD Diagnostic Interview DSM-IV', a structured clinical interview based on DSM-IV  criteria.Using Part II of ‘Conners Adult ADHD Diagnostic Interview DSM-IV', the ‘Diagnostic Criteria Interview for DSM-IV', information was gathered on current symptoms as well as on the age of onset, pervasiveness and level of impairment for each symptom present. Diagnosis was made if there was clear evidence of clinically significant impairment in more than two domains  in accordance with DSM-IV criteria. Therefore, all 40 participants with ADHD meet the DSM-IV diagnostic criteria for ADHD. In terms of clinical subtypes, these, 22 individuals meet the criteria for Combined Type ADHD and 18 individuals for inattentive type; none met criteria for hyperactive type. However, it is noteworthy that we have not conducted subgroup analyses, as we believe that correlational analysis using dimensional symptom measures is more appropriate.27, which provides both self- and informant assessment for (a) adulthood and (b) childhood symptoms.The assessment also included obtaining a detailed account of past psychiatric history, developmental history, medical history and a mental state examination. Information regarding past psychiatric history was also provided by the referring clinician. Pre-assessment questionnaires included the Barkley ScalesExclusion criteria for the ADHD group included the current presence of any other DSM-IV Axis I psychiatric disorder; an autistic spectrum disorder; a tic disorder; past or current substance abuse; significant medical or neurological illness affecting brain function; and the use of any psychotropic medication, other than stimulants, in the previous 6 months.Although we included ADHD patients only if they had no current psychiatric comorbidity, 22 out of the 40 ADHD participants had a prior history of a psychiatric disorder(s) other than ADHD, including depression, anxiety and personality disorder. Furthermore, 14 ADHD patients had been exposed to psychotropic medication other than stimulants in the past, mainly antidepressants.Healthy controls had no history of any psychiatric disorder, and were naive to psychoactive medication.Ethical approval for this study was provided by South London and Maudsley/Institute of Psychiatry (SLaM/IoP) National Health Service Research Ethics Committee, study reference 1997/087. After complete description of the study to the subjects, written informed consent was obtained.[1H]MRS data were acquired on a 1.5T GE HDx Magnetic Resonance Imaging (MRI) scanner  equipped with TwinSpeed gradients.3 voxels. Full Scale IQ was measured using the Wechsler Abbreviated Scale of Intelligence.The scanning protocol included a structural MRI scan for the localisation of the spectroscopy voxels in each participant, namely a three-dimensional fast inversion-recovery prepared spoiled gradient echo (SPGR) acquisition with number of slices=146, slice thickness=1.2 mm, inversion time=300 ms, repetition time=11 ms, echo time=5 ms, field of view=310 mm, flip angle=18°, matrix=256 × 160 over a 310 × 194 mm field of view, giving 1.20 × 1.20 × 1.20 mmThree single voxel [1H]MRS spectra were then acquired, using a point-resolved spectroscopy sequence. Point-resolved spectroscopy parameters were: repetition time=3000 ms and echo time=30 ms. A total of 72  or 104  repeat observations were averaged to produce the final spectrum. In addition to this, eight observations without water suppression were averaged and used for absolute water scaling.3) was placed in the left medial parietal lobe. The second voxel (20x20 × 15 mm3) was positioned in left basal ganglia to include parts of the head of the caudate, the anterior putamen and the internal capsule. The last voxel (16x24 × 20 mm3) was placed in the left DLPFC. See The first voxel  structural MRI, (2) parietal voxel, (3) basal ganglia voxel, (4) DLPFC voxel and (5) phantom. The total scan time was ~45 min.in vitro to analyse the major resonances of in vivo spectra. In this case, a basis set of alanine, aspartate, Cr, gamma-aminobutyric acid, glutamine, glutamate, glycerophosphocholine, myo-inositol, lactate, NAA, N-acetyl-aspartylglutamate , scyllo-inositol and taurine, together with a baseline function were used for analysis.[1H]MRS spectra were processed using LCModel software version 6–1–0 . LCModel uses a linear combination of model spectra of metabolite solutions Metabolite concentrations for NAA, Cr, Glx and Cho were calculated, in institutional units, as follows. Raw estimates (LCModel output) were corrected by reference to calibration data from a phantom containing an aqueous solution of known NAA concentration. A phantom [1H]MRS spectrum was acquired at the end of each scanning session. The ratio of the known concentration of NAA in the phantom to the observed NAA phantom concentration was used to derive a correction factor that was applied to calibrate the metabolite concentrations into molar units. This served to control for possible scanner ‘drift' in raw [1H]MRS estimates. See spm_segment, part of the Statistical Parametric Mapping software package (http://www.fil.ion.ucl.ac.uk/spm/).To guard against partial volume confounds  in the [1H]MRS voxels), we also corrected the metabolite concentrations for voxel composition. We first determined the percentage of grey matter, white matter and CSF within each [1H]MRS voxel for each participant by segmenting the SPGR structural volume, using an automated procedure, CSF), where ProportionCSF could range from 0 to 1.The position of each individual [1H]MRS voxel relative to the corresponding structural image was determined using positional coordinates embedded in the spectra data files. The % grey, white and CSF composition of each voxel was then calculated automatically from the segmented images using in-house software. Finally, metabolite concentrations were corrected for voxel % (CSF) by multiplying values by an individual correction factor=1/(1−Proportioncorrected=Metaboliteraw × (PhantomNAAknown/PhantomNAAobserved) × (1/(1–ProportionCSF)).In summary, MetaboliteAll statistical analysis was performed using SPSS 15.0 .χ2 analyses and one-way analyses of variance across the three participant groups, namely, stimulant-naive ADHD participants, medicated ADHD participants and healthy controls.First, participant demographic information for the groups was compared using t-tests comparing participants with ADHD (n=40) with the healthy controls (n=20) for each of (i) grey matter, (ii) white matter and (iii) CSF in each voxel. We further compared the two ADHD groups, ADHD naive and ADHD medicated, with independent samples t-tests.Voxel tissue composition was compared using independent samples t-tests comparing all participants with ADHD (n=40) to the matched healthy controls (n=20), for each corrected metabolite value (four), in each voxel (three). As this analysis involved multiple (12) comparisons, we performed a Bonferroni correction raising the significance threshold for each comparison from P=0.05 to P=0.004. We report results both before and after the Bonferroni correction.The primary [1H]MRS analysis was a series of independent samples t-tests. We further compared metabolite values in those ADHD participants who had never been prescribed any prescribed psychoactive medication in the past to healthy controls to verify the absence of any possible medication confounds.In order to test for the possibility of medication effects on metabolites, we compared the two ADHD groups, ADHD naive and ADHD medicated, with independent samples P<0.05 Bonferroni corrected) different from controls, and self-reported total Barkley Scale Inattention and Hyperactivity symptom scores.We explored possible correlations between metabolite abnormalities and symptom severity in stimulant-naive participants with ADHD. We calculated bivariate Pearson's correlations between those metabolite concentrations that were significantly  for each metabolite for each voxel. Higher %CRLBs indicate greater uncertainty in metabolite estimation.P>0.05) across the participant groups. The two patient groups did not differ in mean symptom severity. The mean duration of stimulant treatment in the ADHD-medicated group (n=16) was 86 weeks at the time of scanning .Participant characteristics are given in ADHD participants had a significantly lower concentration of Glx, Cho, Cr and NAA with all except Cho surviving Bonferroni correction for multiple comparisons .Individuals with ADHD had significantly lower Glx, Cr and NAA; however, only the difference in Cr survived Bonferroni correction.Only NAA was altered in ADHD in this voxel; this did not survive Bonferroni correction.P<0.05) difference in % CSF only. Nevertheless, because all metabolite concentrations were corrected for voxel % CSF , this is unlikely to have affected our results. There were no differences between the ADHD-naive and ADHD-medicated groups in any region (P>0.35).There were no significant differences between the ADHD and control groups in the mean tissue composition of the [1H]MRS voxels for grey matter, white matter or CSF  in eitheP=0.004); here, the healthy controls had higher %CRLB, indicating worse data quality. As this was the only instance in which quality differed, and as the ADHD patients (the group with lower estimates) had better quality than the controls in this case, we are confident that our findings of reduced concentrations of various metabolites in ADHD patients are not an artefact of group differences in data quality leading to globally biased measures. See Across the three voxels and the four metabolites, analyses of variance revealed no significant group differences in % CRLB, except in Glx in the DLPFC voxel where they differed significantly (P>0.139), even without correcting for multiple comparisons (n=15), including stimulants or any other drug classes, with the healthy controls (n=20). The basal ganglia Glx, Cr and NAA, and DLPFC Cr, were still significantly reduced (P<0.05 uncorrected), confirming most findings despite a reduced sample size.There were no significant differences between ADHD-naive and ADHD-medicated participants in any metabolite value, in any region , with lower  Glx concentrations associated with more severe symptoms of inattention  or between basal ganglia Cr, basal ganglia NAA and DLPFC Cr, and any other symptoms .An exploratory analysis of symptom dimensions in stimulant-naive ADHD participants revealed that the concentration of Glx in the basal ganglia voxel was negatively correlated with total Barkley Scale Inattention score (ttention . Howevert-tests comparing ADHD-past-comorbid vs ADHD-never-comorbid patients for each of the four metabolites in the three regions (n=40). There was no significant difference on any MRS metabolite in any region .As specified above, 22 of the 40 ADHD patients reported at least one past psychiatric comorbidity (though none had a current comorbidity), whereas none of the controls did. To verify that psychiatric history did not influence our MRS findings, we ran a series of independent group We report significantly reduced concentrations of glutamate/glutamine (Glx) in the caudate/putamen of adults with ADHD, compared with matched healthy controls as measured using [1H]MRS. We also observed reductions in Cr and NAA in this region in the ADHD group, as well as reduced Cr in the DLPFC.It is likely that these reductions represent a primary correlate of ADHD, rather than being secondary to medication effects, because we observed no differences between ADHD patients who were receiving stimulant medication compared with those who were medication naive. Also, our findings are not accounted for by differences in voxel grey/white matter proportion or by participant age, sex and IQ.Furthermore, we are confident that our finding of reduced concentrations of certain metabolites in ADHD does not reflect group differences in data quality. Those metabolite levels that had differences that survived Bonferroni correction did not differ in precision as estimated with %CRLB, which suggests that our results cannot be explained as a result of, for instance, degraded spectra due to increased within-scanner motion in the ADHD group reflecting hyperkinesis or ‘fidgeting'.19 However, this reduction probably does not affect whole brain, because we observed no significant differences in the DLPFC or the parietal ‘control' region in the current study, and increased glutamate has previously been reported in the cerebellum of ADHD adults.18Our data therefore add to an emerging literature on neurochemical abnormalities in adults with ADHD. Our finding of reduced Glx in the caudate/putamen is complemented by other studies that reported reduced Glx in the anterior cingulate cortex and the medial PFC.33 and significant34 or nearly significant31 increases in the striatum .Therefore, reduced Glx in adults with ADHD is not a brain-wide phenomenon, but seems to be affecting particular neural circuits. The reduction in Glx may also be age dependent, as studies in ADHD children have reported increased Glx, including significant increases in the frontal cortex37 and also from animal models.38 This evidence has led to the development of glutamate modulatory drugs as potential treatments for ADHD, including the novel AMPA receptor-positive modulator Org26576, which was recently shown to be effective in a preliminary trial.10 Our data suggest that, at least in adults, the caudate/striatum may be the most important region implicated in glutamate dysfunction in ADHD.Our results thus add to emerging evidence that ADHD is associated with glutamate pathway abnormalities at least in some cases. This evidence includes the discovery of rare deleterious variants in metabotropic glutamate receptors and other related genes in a minority of ADHD cases16 and no differences in Glx16 or increased Glx:Cr ratio39 (with no absolute Glx reported) in the caudate and striatum. However, these two studies were small (n=5 (ref. 16) and 10 , as these areas are, similar to the basal ganglia, major targets of dopamine.Dopamine is also known to regulate glutamatergic cell firing and vice versa.42 Such an energy deficit would be in line with glucose metabolism studies in adults with ADHD that have shown reduction of metabolism in both hemispheres.43Another possibility is that differences in Glx might be secondary to abnormal cellular metabolism. For instance, we also observed significantly reduced concentrations of Cr and NAA, in the basal ganglia voxel and of Cr in the DLPFC. This could indicate decreased neuronal metabolism and energy use, as both Cr/PCr and N-acetylaspartate  are involved in neuronal energy metabolism.However, an alternative possible basis for reductions in Cr and NAA is reduced neuronal density. We did not observe differences in the voxel compositions of grey and white matter in the basal ganglia and DLPFC, showing that these metabolite differences were not simply partial volume effects caused by different proportions of brain tissue. However, it is possible that there were fewer (glutamatergic) neurons per unit of volume, leading to reduced estimates of these neuronal metabolites. Unfortunately, we are not aware of any studies that have examined neuronal density in the basal ganglia in ADHD.Our study has a number of limitations. We obtained [1H]MRS data at a relatively low field strength of 1.5 Tesla. This could have limited the signal-to-noise ratio of our measures and, hence, it is possible that there exist further metabolite differences beyond the ones that we detected. Furthermore, we are unable to say whether the reliability of this 1.5T MRS compares with that obtained at higher field strengths. However, we do not believe that this undermines the robustness of those differences we did observe, rather it suggests that those differences we found are likely to be meaningful, as they can be detected even at 1.5 Tesla.44 To understand the nature of the Glx abnormalities seen in ADHD, future work should therefore use higher field strength MRS (3 or 7 Tesla) to measure glutamate and glutamine separately.Another limitation arising from our use of 1.5 Tesla [1H]MRS is that we were unable to distinguish between the compounds that contribute to the ‘Glx' signal, that is, glutamate and glutamine, as their proton resonance signals overlap at low field strengths. Although glutamine is not directly involved in neurotransmission, it serves as an intermediate in the recycling of glutamate after its release and reuptake. Therefore, the glutamate:glutamine ratio may provide important information about the rate of glutamate synthesis and turnover.A further issue is that we were not able to directly investigate the effects of medication on neural metabolites in ADHD, because patients were not examined before and after their treatment. We do not think that medication effects influenced our results, because we found no differences between adults with ADHD currently taking medication as compared with medication-naive adults. It is possible, however, that effects on neurometabolites might be dose-dependent; however, we did not have access to information on the prescribed dosage in those individuals who were taking stimulants. Therefore, an additional limitation of our study is that we were unable to examine possible dose-related effects and we cannot exclude the possibility that treatment with high doses of stimulants does exert an effect.45 Thus, it may not be unrelated to the pathophysiology of the disorder. However, as we did not observe any (corrected) significant neurochemical differences in this area, the parietal data nonetheless support the regional specificity of the other findings.Finally, although our study included a ‘control' region, the medial parietal cortex, on the basis that it has not classically been implicated in ADHD, some recent functional imaging studies have reported alterations in activation in this area in ADHD.In conclusion, adults with ADHD have regionally specific reductions in glutamate/glutamine and the neuronal energy metabolites NAA and Cr. Also reduction in striatal glutamate/glutamine is associated with more severe symptoms of inattention in medication-naive individuals. Glutamate may be a tractable treatment target is some adults with ADHD.


ADD/ADHD is the most common and most studied neurodevelopmental problem. Recent statistics from the U.S. Center for Disease Control state that 11% or approximately one out of every nine children in the US and one in five high school boys are diagnosed with ADD/ADHD. This number is thought to be increasing at around 15–20% per year. The US National Institute of Mental Health’s Multi-modal Treatment Study has shown that medication has no long-term benefit for those with ADHD. To effectively address ADD/ADHD from within the framework of child public health, an interdisciplinary strategy is necessary that is based on a neuroeducational model that can be readily implemented on a large-scale within the educational system. This study is based on previous findings that ADD/ADHD children possess underactivity between sub-cortical and cortical regions. An imbalance of activity or arousal in one area can result in functional disconnections similar to that seen in split-brain patients. Since ADD/ADHD children exhibit deficient performance on tests developed to measure perceptual laterality, evidence of weak laterality or failure to develop laterality has been found across various modalities . This has reportedly resulted in abnormal cerebral organization and ineffective cortical specialization necessary for the development of language and non-language function. This pilot study examines groups of ADD/ADHD and control elementary school children all of whom were administered all of the subtests of the Wechsler Individual Achievement Tests, the Brown Parent Questionnaire, and given objective performance measures on tests of motor and sensory coordinative abilities. Results measured after a 12-week remediation program aimed at increasing the activity of the hypothesized underactive right hemisphere function, yielded significant improvement of greater than 2 years in grade level in all domains except in mathematical reasoning. The treated group also displayed a significant improvement in behavior with a reduction in Brown scale behavioral scores. Non-treated control participants did not exhibit significant differences during the same 12 week period in academic measurements. Controls were significantly different from treatment participants in all domains after a 12-week period. The non-treatment group also demonstrated an increase in behavioral scores and increased symptoms of ADD/ADHD over the same time period when compared to the treated group. Results are discussed in the context of the concept of functional disconnectivity in ADD/ADHD children. Public health issues surrounding Attention Deficit/Hyperactivity Disorders (ADD/ADHD) have not been thoroughly studied but for a few major published works on the subject , 2. Of cSince 1902 when George Still described the “lack of moral control among children without noted physical impairments,”  no singlIn summary, the fact that the constellation of behaviors labeled ADHD is considered a medical disorder conveys the expectation to parents, children, and teachers that behavior should be unchanging, constant, and made better only by medicine. In many ways, the diagnosis creates an expectation that manifests in the very symptoms it sets out to describe.Since Orton  in the 1Rabiner and Malone  have indTo examine this notion further, we conducted a pilot study evaluating ADD/ADHD elementary school children from first through sixth grade. All participants were administered tests of academic performance evaluating relevant cognitive abilities, motor and coordinative, and rudimentary literacy skills. ADD/ADHD children were tested both before and after participation in a hemisphere-specific remediation program. Significant improvement was noted with hemisphere-specific interventions as opposed to educational remediation techniques not tailored to the neurocognitive strengths and weaknesses of the child .The literature supports the notion that interventions for ADD/ADHD can be both individualized and administered on a large scale through hemisphere-specific regimens administered through the educational system that would produce a significant public health effect.This study examines an intervention that involves neurophysiologically specific treatment that is integrated with educational interventions that address the heterogeneity of symptoms of ADD/ADHD.The pool of participants for this study consisted of 122 children between 6 and 12.11 years of age diagnosed with Attention Deficit Disorder (ADD) or ADHD (ADD/ADHD) who had undergone an intervention program described below and a control group of ADD/ADHD children not having undergone such a program whose characteristics are described below. Informed consent was obtained from each parent/guardian and the project underwent IRB review and approval.The 122 participant children were randomly selected from a larger group of 181 children undergoing the treatment program; 59 were excluded for not meeting the criteria specified below. At the conclusion of the 12-week intervention program, all children were tested again using the same instruments. All the obtained percentile scores were converted to grade equivalent.The participants presented with inattention, hyperactivity, impulsivity, academic under-achievement, and/or behavior problems, and each met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,  and cleaA second group of children between the ages of 4–13 (SD = 8.94) were also studied. While all went through the same initial evaluation process, none underwent any of the interventions that the treatment group did, but were likewise re-tested after 12 weeks. Of the participants in the control group, 22 were male (59%) and 15 (41%) female. Each was diagnosed with ADD or ADHD (ADD/ADHD) and met the identical criteria specified above. The participating children came from clinics located in school districts in middle- to upper-middle-class school districts in various regions of the United States that included, St Louis, Missouri, Los Angeles, and San Francisco California, Tampa and Miami, Florida, Carey Indiana, Wake Forest, Illinois, Atlanta Georgia, and Minneapolis, Minnesota.Twenty-two of the children in the control group in the study were taking stimulant medication before, during, and at the conclusion of the study.Initial pre-treatment evaluations included the functional assessment of sensory and motor function and on a separate day, academic testing as described below. The combined testing allowed the clinicians to formulate a remediation program for participants in the treatment group. The program was designed to selectively stimulate skills that were significantly below age-or functional level for a given participant. Additionally, tasks were designed to stimulate the less efficiently performing hemisphere . Each paSynchronized metronome training (SMT) was employed. Participants in the treatment group wore a headphone and listened to a reoccurring metronomic beat. As they listened to the beat, they engaged in physical movements such as clapping hand-to-hand with a sensor on one palm as they matched their physical movement to the presentation of the beat . The training attempted to reduce the mean negative synchronization error during normal tracking of the regularly occurring metronome beat (clapping before or past the beat). During training, participants received feedback through an auditory guidance system as they progressed through the simple, interactive physical movements. Although feedback was also provided through visual stimuli, the auditory feedback guidance system was the primary feedback method. The auditory feedback system provided tonal stimuli that indicated whether the participant responded before, at, or past the regularly occurring auditory metronomic beat. The accuracy of participants’ expectancy response to the metronome beat was provided in milliseconds (ms), with different tones indicating far from, close to, or at the metronome beat. A visual reading of millisecond latency was also presented to the participants on a computer screen. These interventional procedures have been elsewhere reported to be effective in effective change in psychophysical signal detection capabilities , 25.The purpose of the training was to improve participants’ timing/rhythmicity by reducing the latency between the onset of the metronome beat and the participant’s expectancy response to the beat. At the completion of the treatment program, participants had engaged in approximately 25,000 motoric repetitions. The purpose of the procedure was to examine the relationship between improvements in domain-specific SMT-based intervention and domain general improvements in the areas of academics and ADD/ADHD functioning – more fully explained in , 24.All participating children in both treatment and control groups were given the Wechsler Individual Achievement Tests [WIAT-II] , includiThe WIAT reading tasks were chosen because they require the ability of the participant to correctly read a series of printed words, sentences, and paragraphs and to answer questions about what was read and to correctly apply phonetic decoding rules when reading a series of nonsense words.The Mathematical Reasoning Subtest of the WIAT was chosen because it assesses the ability of the participants to add, subtract, multiply, and divide one- to three-digit numbers and to understand number, consumer math concepts, geometric measurement, basic graphs, and solve one-step word problems.The Spelling (Written Language) subtest was chosen because it requires the participants to correctly spell verbally presented words and to generate words within a category, generate sentences to describe visual cues, combine sentences, and compose an organized paragraph. This subtest likely measures skills less related to attentional concerns and more to a direct measure of achievement.The WIAT Oral Language subtest was chosen as the tasks require the participants to identify a picture best representing an orally presented descriptor or to generate a word that matches the picture and to generate words within a category, to describe scenes and give directions. Whereas IQ subtests are largely tests of thinking and reasoning skills, the WIAT-II is a test of academic achievement. We were interested in examining whether hemispheric specific training would have an effect on unmasking the actual level of achievement with reduced attentional effects and whether we could conclude that the evidence is enough to warrant a clinical trial on the notion of hemisphere-specific training.t tests.Pre-Post treatment differences were examined by using correlated t = 5.25, df = 60, p < 0.000005) between pre- and post-treatment responses by parents of the ADD/ADHD children in the treatment group as reported on the parent completed BADD, 79% of the participants demonstrated a significant improvement on pre- as compared with post-testing and a 67% difference between the treatment and control group parental responses on the Brown scale . The non-treatment control group, however, demonstrated a significant 94% difference with the experimental treatment group .Pre-post sensory-motor measured performance changes were likewise significant for the treatment group. Rhythmic integrated eye-hand and eye-foot coordination revealed that in excess of 54% of those ADD/ADHD children tested demonstrated statistically significant improvement  but no significant differences between pre- and post-testing were observed with WIAT Mathematical Reasoning in the treatment group . Even so, significant differences were still reported in Mathematical Reasoning associated with hemisphere-specific training when comparing controls with the treatment group .In the measurement of academic performance on subtests of the WIAT, the results indicated significant changes in all domains measured that required a strong attentional component to test performance in the treatment but not in the non-treatment control group. Tasks like Mathematical Reasoning, which require greater academic skill and less attentional focus, were more resistant to change. For example, on the WIAT Word Reading subtest, 62% of participants demonstrated a significant improvement, defined for this study as greater than 2 years improvement in grade level  and Written Expression , respectively, a significant 82% positive change was noted in performance related to Listening Comprehension, a more heavily attentionally loaded task . In contrasting the treatment and non-treatment groups a significant 52% difference was noted for both Spelling  and Written Expression  respectively, both domains likely having a significant attentional load.On the other hand, although 52 and 76% of participants in the treatment group exhibited significant change of greater than two or more years increase in performance after the 12-week treatment program in Spelling  associated that is reflective of an increase in the reported symptoms of ADD/ADHD relative to the treatment group.We here examined if treatment that is preferentially aimed at an hypothesized underactive right hemisphere in ADD/ADHD children would have a positive effect on their sensory-motor performance, as well as on cognitive function related to attention focus. The results support further examination by means of a large-scale clinical trial of the notion that hemisphere-specific training will have a significant effect on attentional performance in children with ADD/ADHD.The approach is potentially useful as a child public health intervention without the use of drugs in the treatment of attentional problems of childhood. The clinical trials will have to examine the differential effects of medication and hemispheric specific treatment, as well as the effects of nutritional interventions on academic and on sensory, motor, attentional, and signal detection performance, not examined in this study.Additionally, epidemiology has been an underutilized methodology in ADD/ADHD research. This is true even evidence suggesting a biological basis for ADD/ADHD. The lack of a standardized case prevents effective program implementation. The study reported here attempts to address that first step and place the resolution squarely within the education system for remediation with the addition of a solid understanding of the nature of the development of neurodevelopmental pathways.The study was limited by the fact that there were no normal compared to ADD/ADHD participants who were both treated and not. Also the treatment and control groups were not matched even though the inclusion criteria were the same. Further study is necessary to address some of these concerns, to find better ways to implement interventions on a large scale.This study has demonstrated that by employing comprehensive treatment planning that involves many disciplines all focused on hemisphere-specific training, significant effects can be observed. These effects can be implemented to address a large-scale public health problem by engaging the educational system as a vehicle for administration of alternative but comprehensive approaches to the treatment of ADD/ADHD.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.