ADHD is a common and disabling disorder, with an increased risk for coexisting disorders, substance abuse and delinquency. In the present study, we aimed at exploring ADHD and criminality. We estimated the prevalence of ADHD among longer-term prison inmates, described symptoms and cognitive functioning, and compared findings with ADHD among psychiatric outpatients and healthy controls.At Norrtälje Prison, we approached 315 male inmates for screening of childhood ADHD by the Wender Utah Rating Scale (WURS-25) and for present ADHD by the Adult ADHD Self-Report Screener (ASRS-Screener). The response rate was 62%. Further, we assessed 34 inmates for ADHD and coexisting disorders. Finally, we compared findings with 20 adult males with ADHD, assessed at a psychiatric outpatient clinic and 18 healthy controls.The estimated prevalence of adult ADHD among longer-term inmates was 40%. Only 2 out of 30 prison inmates confirmed with ADHD had received a diagnosis of ADHD during childhood, despite most needed health services and educational support. All subjects reported lifetime substance use disorder (SUD) where amphetamine was the most common drug. Mood and anxiety disorders were present among half of subjects; autism spectrum disorder (ASD) among one fourth and psychopathy among one tenth. Personality disorders were common; almost all inmates presented conduct disorder (CD) before antisocial personality disorder (APD). Prison inmates reported more ADHD symptoms during both childhood and adulthood, compared with ADHD psychiatric outpatients. Further, analysis of executive functions after controlling for IQ showed both ADHD groups performed poorer than controls on working memory tests. Besides, on a continuous performance test, the ADHD prison group displayed poorer results compared with both other groups.This study suggested ADHD to be present among 40% of adult male longer-term prison inmates. Further, ADHD and coexisting disorders, such as SUD, ASD, personality disorders, mood- and anxiety disorders, severely affected prison inmates with ADHD. Besides, inmates showed poorer executive functions also when controlling for estimated IQ compared with ADHD among psychiatric outpatients and controls. Our findings imply the need for considering these severities when designing treatment programmes for prison inmates with ADHD. ADHD is a common, inherited and disabling developmental disorder with early onset. Most often ADHD persists across the life span, affecting 2-4% of adults . The corWe hypothesized that ADHD would be common among this group comprising mainly longer-term prison inmates, typically convicted of crimes because of violence and drugs. Also, we hypothesized that they would present more severe ADHD symptoms across the lifespan, more common coexisting psychiatric disorders, and poorer executive functions compared with the other groups.The present study included an estimation of the prevalence of ADHD among longer-term prison inmates. Further, it included a description of ADHD and executive functions among prison inmates compared with ADHD among psychiatric outpatients and healthy controls. The Regional Ethical Board in Stockholm approved the studies. Participants provided written informed consents before study procedures.Norrtälje Prison is a high-security prison placed outside Stockholm, Sweden, serving the entire country, hosting 200 adult male inmates. The prison holds mainly longer-term inmates, typically convicted of crimes because of drugs or violence.Figure Following the screening survey, we performed extensive diagnostic assessments for ADHD and coexisting disorders among a group of inmates. We selected subjects first according to their origin, as the Stockholm County Council funded the assessments as part of regular clinical practice. Thus, we invited all prison inmates marking adult ADHD by the screening, registered in the Stockholm County, with at least 14 months left to conditional release, and approved by the security officers to stay at the ADHD ward. By this pre-screening, we evaluated if subjects with ADHD would fulfil criteria for taking part in the following clinical trial with methylphenidate . Subjects with coexisting disorders, such as ASD, anxiety and depression could take part if considered stable by the investigator at the assessment. Further, the general cognitive functioning had to be above the level of mental retardation. In addition, subjects could continue stable pharmacological treatment for coexisting disorders if we did not suspect treatment interfering with methylphenidate. Additionally, subjects had to be free from serious medical illnesses. Thus, after meeting criteria for the following trial and providing a written informed consent, the subject could take part in the diagnostic evaluation.We considered 47 prison inmates for assessment. However, we excluded one subject because of an exclusion criterion, whereas six subjects denied taking part. Of 40 consented subjects, six dropped out during the assessments. Therefore, we finally assessed 34 subjects and could confirm ADHD among 30 of them Figure . When apThe psychiatric outpatient study group comprised 20 adult men with ADHD, 18 of them with ADHD of the combined type, and two with the predominantly inattentive subtype. We consecutively recruited these subjects to another study  between The control group  comprisenot at all or slightly, to 4 = very much. The subscale WURS-25 provides a total sum score (range 0-100) by summing those 25 items best discriminating between ADHD and controls [WURS is a 61-item self-administered scale for rating frequencies of ADHD childhood symptoms and behaviours retrospectively on a 5-point scale, from 0 = controls . Accordicontrols .The ASRS-Screener comprises the 6 out of 18 most predictive items of the Adult ADHD Self-Report Scale (ASRS)  for definever; to 4 = very often, providing a total sum score (range 0-72).Board certified psychiatrists and clinical psychologists well experienced in ADHD, conducted the clinical assessments. We confirmed ADHD in accordance to DSM-IV . The evaWhenever possible, we collected collateral information from parents or other significant others by questionnaires, before psychologists or psychiatrists performed interviews. The questionnaires included the Five to Fifteen (FTF) questionnaire ,27 and tThe Five to Fifteen (FTF) questionnaire [does not apply, to 2 = definitely applies.ionnaire ,27 eliciThe Conners' Brief Parent Rating Scale - Conners' Hyperactivity Index is validated in several countries. This scale describes ADHD and oppositional defiant symptoms and behaviours in children up to 10 years of age [s of age , comprisWechsler Adult Intelligence Scale-III subtests Vocabulary and Block Design, a dyadic short form correlating 0.92 with WAIS-III FSIQ [We collected additional collateral information by medical records from child- and adolescent psychiatry, school health services, adult psychiatry and forensic psychiatry. Further, we evaluated coexisting disorders by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID I) , the HarIII FSIQ ,34.The Conners' Continuous Performance Test II (CCPT) [basic reaction time, whereas Hit RT SE, Variability, Hit RT block change, Hit SE block change, Hit RT ISI change, Hit SE ISI change and Perseverations reflect variability dependent measures. Finally, Omission errors, Commission errors, Detectability (d'), and Response style (â) reflect accuracy dependent measures.Digit Span  measuresI (CCPT) . The CCPThe diagnostic evaluation comprising neuropsychological tests was similar as among prison inmates. However, we did not assess SCID I, SCID II PQ, or PCL-R among ADHD psychiatric outpatients. Case files provided information on psychiatric comorbidity. Besides, the self-rated Beck Depression Inventory ,38, the We interviewed controls for confirming the absence of learning difficulties or psychiatric problems during childhood and the study, respectively. Further, we used the same self-rating scales for present psychiatric symptoms as among the psychiatric outpatients. Finally, the neuropsychological tests were similar as for the other groups.U-test for continuous measures, and chi-square test or Fisher's exact test for categorical measures. Further, for comparing between groups on neuropsychological measures, we performed a series of analysis of variance (ANOVA) with Bonferroni corrected post hoc comparisons, whenever main analyses reached significance. In addition, we aimed to control for IQ differences. Thus, we reanalysed measures of executive functions  by performing a series of ANCOVA with the dyadic estimated IQ entered as a covariate. By these analyses, we evaluated if lower IQ among prison inmates could explain their executive dysfunctions. We present statistics from both ANOVAs and ANCOVAs, as most measures of executive functions did not co-vary with IQ. We set the alpha-level at p = .05. Finally, we performed all statistical analyses by SPSS 17.0 and 18.0, respectively.Descriptive statistics summarised demographic data and clinical characteristics of subjects. We carried out inferential statistics by analyses of variance (ANOVA), Student's t-test or Mann-Whitney Figure This study included an extensive diagnostic evaluation of ADHD and coexisting disorders among a group of prison inmates Figure . Table 2As depicted in Table The ADHD-prison group rated more ADHD related symptoms and behaviours during both childhood and adulthood, compared with the ADHD-psychiatry group Table . By contF = 14.76, p < .001, ηp2 = .341) because of different inclusion criteria. In fact, only the ADHD-prison group included subjects with IQ between 70 and 85. As a result, 10% (3/30) of prison inmates presented estimated dyadic IQ within this range, specifically between 78 and 85. Therefore, we excluded those three inmates with IQ < 85 for making inclusion criteria homogenous. However, the ADHD-prison group still showed lower estimated IQ after performing this procedure, compared with both other groups .The dyadic estimation of IQ displayed similar IQ for controls and the ADHD-psychiatry group; , range 97 - 132); , range 89 - 132). On the other hand, IQ was substantially lower among ADHD prison inmates; (M = 95.18 (± 9.99), range 78 - 113). The ADHD-prison group (n = 22) had missing data for eight subjects. We expected significant differences between groups on estimated IQ  and visuo-spatial working memory (SB). On the other hand, the ADHD-psychiatry group outperformed the ADHD-prison group on the same measures. However, when controlling for IQ, the differences in working memory between ADHD groups no longer remained, but controls still outperformed both ADHD groups. Thus, both working memory tests showed executive dysfunctions associated with ADHD, also when controlling for IQ.accuracy dependent measures, and in three out of seven variability dependent measures, respectively. On the other hand, there were no significant differences in reaction time between groups (Table On the Conners' Continuous Performance Test II (CCPT), controls and the ADHD-psychiatry group showed similar results. However, at least one of the other groups outperformed the ADHD-prison group on all four ps Table . Notablyps Table .The present study included an estimation of ADHD prevalence among adult male longer-term prison inmates from a high-security Swedish prison. Further, we evaluated ADHD and executive functions among prison inmates and then compared results with ADHD psychiatric outpatients and healthy controls. We estimated a prevalence rate as high as 40% among these prison inmates. Further, those inmates we later confirmed with ADHD were severely affected and disabled from ADHD and coexisting disorders, such as SUD, ASD, personality disorders, mood- and anxiety disorders. Previous studies reported increased frequencies of major mental disorders, personality disorders, and early adjustment problems among prison inmates, regardless of ADHD . The preAlthough ADHD is common among prison inmates, prevalence rates are inconsistent, probably because of different used criteria among different prison populations -9. FurthTo our best knowledge, this study is the first to report a screening survey for ADHD, followed by extensive evaluations of ADHD and coexisting disorders among adult male longer-term prison inmates. The evaluations incorporated both self-reports and confirming collateral information from parents, medical records and school reports. Additionally, evaluations included a physical examination and neuropsychological assessments. Further, we compared ADHD prison inmates with ADHD psychiatric outpatients and controls for ADHD symptom load, coexisting disorders and executive functions.As hypothesized, ADHD was prevalent among these adult male longer-term prison inmates with a median age of 31 years. We estimated the prevalence as high as 40%, compared with previous findings by Rösler et al  who repoThis study only partially supported our hypothesis that ADHD prison inmates would present more severe ADHD symptoms across the lifespan, compared with ADHD psychiatric outpatients. The ADHD-prison group reported more ADHD symptoms and behaviours during both childhood and adulthood. However, collateral information from parents on childhood symptoms did not reveal any differences between groups. As a result, subjects rated more childhood symptoms retrospectively compared with parental ratings. This observation contradicts previous findings by Barkley  who dispTo summarise, our findings imply the importance of recognising ADHD early and offering effective treatment immediately. Prospective studies should evaluate if treatment will reduce the risk for serious outcomes.As hypothesized, coexisting disorders were common among our prison inmates. In fact, all subjects reported a lifetime history of SUD, with amphetamine as the most preferred drug of choice. Besides, abuse and antisocial behaviour had an early onset, consistent with previous findings . AdditioPrevious studies reported that personality disorders are common among different ADHD populations, such as prison inmates . Recentlaccuracy dependent measures, and on several variability dependent measures, respectively. On the other hand, reaction time was comparable between groups, thus implying slow reaction time not to be a concern among adult ADHD. Summarising, these findings are in line with theories of ADHD as an executive disorder [The present study supported our hypothesis that ADHD prison inmates would present poorer cognitive abilities compared with ADHD psychiatric outpatients and healthy controls. As expected, the ADHD-prison group showed lower estimated IQ. However, different inclusion criteria could not explain the observed IQ differences between groups, as differences remained when excluding prison inmates with IQ < 85. As presented, both ADHD groups displayed poorer executive functions compared with controls, also when adjusting for IQ. Working memory functions were similar between ADHD groups when adjusting for IQ. Considering the CCPT results overall, controls and the ADHD-psychiatry group showed similar results. Further, at least one of them outperformed ADHD prison inmates on all disorder . In addidisorder ,49 who sdisorder -52, as wdisorder . Howeverdisorder ,51 suggedisorder , as he sdisorder , Newman disorder ,57 respeWe have to consider several limitations of this study. As the attrition rate of the screening survey was 38%, we must interpret the results with caution. However, we imply that we not exaggerated the prevalence rate of ADHD. Further, both rating scales used for screening lack Swedish validations. Nevertheless, these scales are used as standard tools in clinical practice. Besides, this study included only male longer-term prison inmates, why results can not extend to female inmates or to inmates serving shorter-term convicts. Further, there might have been selection bias when recruiting for the screening survey, mainly at the end of the study period when the study was commonly known in the Swedish Prison and Probation service. It might be that some inmates recognised themselves as suffering from ADHD and therefore applied for serving conviction at Norrtälje Prison in hope for treatment. However, as we screened the majority at the beginning of the study period, we imply this potential bias as minor important. Further, there might have been selection bias because of different inclusion criteria between groups. Therefore, it implies a selection of subjects among ADHD psychiatric outpatients, functioning better than average, as treatment for coexisting disorders excluded for the present study. Actually, in clinical practice, adults with ADHD often receive treatment for common coexisting disorders. On the other hand, the ADHD-psychiatry group may better reflect ADHD among the general population, as considered presenting less severe symptoms and severities compared with psychiatric outpatients. Additionally, there may have been a selection bias when recruiting prison inmates for diagnostic assessments. We noticed a few prison inmates denied taking part in the study in lack of motivation for changing their behaviour, or resistance to stay at the ADHD ward. The ward was apart from other wards for reducing the risk of exposing inmates to illicit drugs. As a result, study subjects received less time for physical exercise and restricted access to some prison programmes, as long as they stayed at the ADHD ward. Therefore, a selection bias towards more motivated prison inmates could have been present. If so, the bias probably worked towards better performances and higher functioning, than the reverse. Finally, the study samples were small. However, results were statistically significant despite small sample sizes. Notably, the strength of this study was the extensive clinical description of ADHD, coexisting disorders and executive functioning among prison inmates, as well as comparisons with ADHD psychiatric outpatients and controls. The extensive diagnostic evaluation included self-reported information, collection of collateral information, physical examination, structured diagnostic interviews and neuropsychological assessments. To our best knowledge, such extensive evaluations of longer-term prison inmates have not previously been reported. We infer our reported findings of ADHD symptom severity, coexisting disorders and executive functioning among prison inmates, are clinical important and relevant. We need to consider these severities when adjusting existing, or designing new ADHD treatment programmes for prison inmates. Further, these extensive evaluations might provide helpful insight for addressing future research on ADHD endophenotypes. Knowledge on endophenotypes may promote individually tailored treatments by identifying who will benefit from treatment. Finally, we will report effects of methylphenidate treatment among these ADHD prison inmates in another paper .This study suggested ADHD to be present among 40% of adult male longer-term prison inmates. Diagnostic evaluations for ADHD among 30 inmates showed them severely disabled from ADHD and coexisting disorders, such as SUD, ASD, personality disorders, mood- and anxiety disorders. Further, these ADHD prison inmates displayed poorer executive functions, also when controlling for estimated IQ, compared with ADHD psychiatric outpatients and healthy controls. We infer the reported findings of ADHD symptom severity, coexisting disorders and executive functioning among prison inmates, are clinical important and relevant. These findings imply the need for considering these severities when introducing ADHD treatment programmes for prison inmates.YG has been on the speaker's bureau and consultant for Janssen-Cilag, Novartis and Lundbeck A/S. YG has been the principal investigator of two clinical trials sponsored by Janssen-Cilag. NL has been the investigator of a clinical trial sponsored by Janssen-Cilag. TH declares no conflicts of interest.YG designed the study in collaboration with NL and TH, applied to the Ethical Board in collaboration with NL, prepared the Case Report Forms, conducted clinical assessments, collected data, planned and executed the analyses, interpreted the results in collaboration with TH and NL, and prepared all drafts of the manuscript in collaboration with TH. NL revised the manuscripts critically. TH was responsible for assessments and analyses of the psychiatric outpatients and controls. All authors read, commented on and approved the final manuscript.1 Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden, 2 Karolinska Institutet Center of Neurodevelopmental Disorders, Stockholm, Sweden, 3 Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/10/112/prepub


The purpose of this study was to investigate the association between the ionotropic and glutamate receptors, N-methyl D-asparate 2A (GRIN2A) and 2B (GRIN2B), and the metabotropic glutamate receptor mGluR7 (GRM7) gene polymorphisms and attention-deficit hyperactivity disorder (ADHD) in Korean population.We conducted a case–control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 149 trios, and compared scores from the continuous performance test (CPT), the Children’s Depression Inventory (CDI), and the State-Trait Anxiety Inventory for Children (STAIC) according to the genotype of the glutamate receptor genes.There were no significant differences in the genotype or allele frequencies of the GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphisms between the ADHD and control groups. For 148 ADHD trios, the TDT analysis also showed no preferential transmission of the GRIN2A rs8049651 or GRIN2B rs2284411 polymorphisms. However, the TDT analysis of the GRM7 rs3792452 polymorphism showed biased transmission of the G allele . In the ADHD probands, the subjects with GG genotype in the GRM7 rs37952452 polymorphism had higher mean T-scores for omission errors on the CPT than did those with the GA or AA genotype . In addition, the ADHD subjects who were homozygous for the G allele in the GRM7 rs37952452 polymorphism had higher STAIC-T  and STAIC-S  scores than did those with the GA or AA genotype.These results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population. Attention-deficit hyperactivity disorder (ADHD) is a disorder primarily characterized by inattention, impulsivity, and hyperactivity and has a worldwide prevalence of 5.3% . It has Although the exact etiology of ADHD is unknown, one theory posits that the dysregulation of neurotransmitter systems underlies the pathogenesis and associated cognitive and locomotor deficits of this disorder . PreviouGlutamate is the primary excitatory neurotransmitter in the brain and is found as a neurotransmitter in approximately 60% of brain neurons, including almost all cortical pyramidal neurons. Glutamate receptors are responsible for the majority of excitatory synaptic transmissions and plasticity in the central nervous system . BecauseThe NMDAR subunits GRIN2A and GRIN2B play essential roles in memory and learning by regulating key aspects of synaptic plasticity . Mice lacking the NMDAR 2A subunit gene GluRε1 (the mouse homolog of the GRIN2A gene in humans) show increased spontaneous locomotor activity in novel environments, impaired latent learning associated with selective attention  and defiIt is of particular interest that the metabotropic glutamate receptor mGluR7 (GRM7) gene is widely expressed in the cerebral cortex, hippocampus, and cerebellum, and studies have established a relationship between structural differences in these areas and ADHD ,26. FurtThe above-mentioned evidence suggests that GRIN2A, GRIN2B, and GRM7 represent candidate genes for ADHD or certain phenotypes of ADHD. However, the few association studies investigating glutamate genes have yielded mixed results, and all of the above-mentioned studies were conducted on Caucasian populations. Therefore, the purpose of this study was to examine the relationship between ADHD and three glutamate genes: SNPs-GRIN2A exon 5 gene SNP (rs8049651), GRIN2B gene SNP (rs2284411), and GRM7 gene SNP (rs3792452). We conducted a case–control and family-based association study and compared the results of a continuous performance test and clinical scale according to each genotype. We selected these three glutamate genes because of their historical prevalence in the literature examining glutamate genes in relation to ADHD.We recruited children with ADHD from three child psychiatric clinics at university hospitals in Korea: Seoul National, Kyungpook National, and Chungbuk National Hospitals. Inclusion criteria were (1) diagnosis of ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) ; (2) a sIn addition, we recruited control group subjects from five different administrative regions in Korea: Seoul, Seongnam, Incheon, Ulsan, and Yeoncheon. The children were selected for the control group based on the following criteria: (1) did not meet the criteria for a DSM-IV diagnosis of ADHD according to the Korean version of the Diagnostic Interview Schedule for Children Version-IV (DISC-IV) ,37; (2) Subjects were excluded from the study if they had one or more of the following: (1) past and/or current history of any neurological disorder, including a seizure disorder or brain damage; and (2) presence of a comorbid psychosis, Tourette's, bipolar, communication, learning, or pervasive developmental disorder. In the ADHD subjects, ADHD and comorbid disorders were diagnosed using the Korean version of the Kiddle Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version ,39.The study was approved by the institutional review board (IRB) for human subjects at the Seoul National University Hospital and other hospitals. Parents/guardians provided written informed consent, and the children or adolescents provided verbal assent regarding participation in this study.We used a computerized continuous performance test (CPT)  to measuADHD children’s emotional symptoms were measured using the Korean versions of the Children’s Depression Inventory (CDI) and the State-Trait Anxiety Inventory for Children (STAIC). The CDI consists of 27 self-report questions along a Likert scale ranging from 0 (not present) to 2 (present and marked), and the total scores on the CDI can range from 0 to 54 ,43. The homogeneous Mass Extend (hME) reactions were designed using Assay Designer 3.1 (Sequenom) .Genomic DNA was extracted from whole blood lymphocytes using a G-DEXTM II Genomic DNA Extraction Kit . The detection of a single nucleotide polymorphism was based on an analysis of primer extension products generated from previously amplified genomic DNA using a chip-based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform . Primers in the PCR and All data analyses were performed using the Statistical Package for Social Sciences . For all data from 202 patients with ADHD and 159 controls, allele frequencies were calculated, and the occurrence of Hardy–Weinberg equilibrium was established by way of goodness-of-fit χ2 tests. Genotype distribution for each polymorphism was in agreement with the expected values of the Hardy-Weinberg equilibrium (p > 0.05). A family-based study was performed to assess genetic association by transmission disequilibrium test (TDT) statistics.2 test or Fisher’s exact test. The significance level was set at p = 0.05 (two-tailed).Subjects with ADHD were divided into genotype groups on the basis of their GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphism. Due to the small number of individuals having two rare alleles, subjects were dichotomized according to whether they possessed the rare A allele (recessive model). Group differences in the continuous clinical variables were examined using an independent two sample t-test. Between-group comparisons with categorical data were assessed using the χThe case–control analysis included 202 ADHD subjects with a mean age of 9.0 +/− 2.5 years and 159 controls with a mean age of 9.0 +/− 2.7 years. The mean ages of the two groups were not significantly different (p = 0.924). However, the gender distribution of the two groups differed significantly, as 174 ADHD subjects (86.1%) and 111 controls (69.8%) were boys . Oppositional defiant disorder was the most common (14.4%) comorbid diagnosis, followed by anxiety disorder (6.5%), enuresis (5.5%), and depressive disorder (3.5%) (Table The genotype distribution of the three SNPs did not deviate from expectation based on the Hardy–Weinberg equilibrium (p > 0.05). There were no significant differences in the genotype or allele frequencies of the GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphisms between the ADHD and control groups .In this study, the case–control and family-based association analyses of the GRIN2A rs8049651 and GRIN2B rs2284411 polymorphisms found no significant association of these two polymorphisms with ADHD in Korean subjects. Previously, Turic et al.  reportedThe negative results in our study of these loci that had been previously reported as associated with ADHD could be interpreted in several ways. First, if the GRIN2A rs8049651 and GRIN2B rs2284411 polymorphisms are uncommon disease loci or ones of small effect, then our power to detect a gene would be reduced, and the failure to demonstrate a significant association in our case–control analysis might reflect false negative results stemming from the limited sample size and the resulting lower statistical power. Because susceptibility genes for ADHD are likely to have a small effect size , more inWith regard to the GRM7 rs37952452 polymorphism, this is the first study to report an association between the GRM7 polymorphism and ADHD using case–control and family-based analyses. The biased transmission of the G allele in the TDT analysis of our ADHD trios suggests a possible role of this allele in the development of ADHD. However, we found no association between the GRM7 rs37952452 polymorphism and ADHD using the case–control approach. As reviewed by Bobb et al. , a relatIn this study, the GRM7 rs37952452 polymorphism was associated with omission errors on the CPT. Numerous studies using neuropsychological tests in individuals with ADHD have found deficits in selective attention , and conAlthough the frequency of a comorbid anxiety disorder did not significantly differ according to the GRM7 rs37952452 genotype, it is notable that the GG genotype of the GRM7 rs37952452 polymorphism was associated with higher state and trait anxiety scores even after excluding the subjects with comorbid anxiety disorders. An association between GRM7 and anxiety has been previously reported. Animal studies, for example, have shown that mGluR7 ablation can cause deficits in fear response , and mGlSeveral limitations of this study should be noted. First, the patient group included all subtypes of ADHD, which might have contributed to clinical heterogeneity. Second, although the genotype distribution was not different according to ADHD subtypes, when we compared the CPT, CDI, and STAI-C results according to the genotypes, the subtypes might have acted as potential confounders. Third, because of the relatively small sample size, the samples of this study would have limited power to detect genes of small effect. Finally, we genotyped only one specific SNP of GRIN2A, GRIN2B, or GRM7, and this may have been insufficient to fully address the association between these glutamate genes and ADHD.These results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population. Further studies, including a replication of these findings with more SNPs in a larger sample, are warranted to evaluate the association of glutamate genes and complex phenotypes of ADHD.ADHD: Attention-deficit hyperactivity disorder; NMDA: N-methyl-D –aspartate; NMDAR: N-methyl-D-aspartate receptor; mGluR: Metabotropic glutamate receptor; GRM7: Metabotropic glutamate receptor mGluR7 gene; DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision; ARS: ADHD Rating Scale-IV; CBCL: Child Behavior Checklist; IQ: Intelligent quotient; DISC-IV: Diagnostic Interview Schedule for Children Version-IV; CPT: Computerized continuous performance test; CDI: Children’s Depression Inventory; STAIC: State-Trait Anxiety Inventory for Children.None of the authors have any financial interest in the study, or any other competing interest.SWJ, SCC, JWK, HJY, USC, JWS, and HWK participated in data collection. DYC and SWJ analyzed the data. SWJ prepared the first draft of the report. SCC and MSS supervised the statistical analysis. SP and BNK interpreted the results. SP wrote the final report with input from all the authors. All authors read and approved the final manuscript.


The questionnaire-children with difficulties (QCD) is a parent-assessed questionnaire designed to evaluate a child’s difficulties in functioning during specific time periods of the day. In this study, the QCD was applied to determine the time periods of the day that are concerning for the parents of children with attention deficit hyperactivity disorder (ADHD). The results were compared with those for a community sample.Elementary and junior high school students with ADHD  and a community sample of children  were enrolled in this study. Their behaviors were assessed by the QCD, the ADHD-rating scale (ADHD-RS), and the Oppositional Defiant Behavior Inventory (ODBI). The effects of gender (boy/girl) and diagnosis (ADHD/community sample) on the total QCD score were analyzed across each school grade (elementary/junior high school). Correlation coefficients between QCD and ADHD-RS/ODBI scores were analyzed.The QCD score for the ADHD group was significantly lower than that for the community sample (P < 0.001). There were significantly strong correlations between “evening” and ADHD-RS and ODBI scores for all children with ADHD  and between “night” and inattention and oppositional symptoms for the girls with ADHD .Parents reported that children with ADHD faced greater difficulties in completing basic daily activities compared with the community controls, particularly in the evening. Furthermore, these difficulties were related to the severity of ADHD symptoms. The parents’ perceptions depended on the gender, ADHD and oppositional symptoms, and the time period of the day. This study determined that children with ADHD face greater difficulties in daily functioning compared with community sample children, that these difficulties are time-dependent, and that these difficulties were particularly experienced in the evening. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with core symptoms of hyperactivity, impulsiveness, and inattention. These symptoms are continuously recognized throughout the daytime from childhood to adulthood -4. It haEvaluation of a child’s functioning across various periods of the day and a trial of appropriate treatment are important from the perspective of the long-term prognosis of ADHD in children and family burden . CertainThe Questionnaire-Children with Difficulties (QCD) has been widely used to evaluate a parent’s perceptions of their child’s daily behaviors during specific periods of the day, such as morning, during school, after school, evening, and night -17. The However, no study has used the QCD to examine difficulties in daily functioning in children with ADHD compared with those in typically developing children. The use of the QCD in children with ADHD enables one to elucidate ADHD symptom-associated difficulties in daily functioning during different time periods of the day.In this study, we aimed to use the QCD to evaluate difficulties in daily functioning associated with ADHD during different time periods of the day. A major hypothesis of this study was that the QCD scores of children with ADHD exhibit significantly strong correlations with ADHD symptoms reported during all time periods of the day. Because boys have more severe ADHD symptoms compared with girls as per the ADHD-rating scale (ADHD-RS) score, a minor hypothesis of this study was that boys with ADHD exhibit significantly lower QCD scores compared with girls with ADHD. This hypothesis indicated that the family burden was more severe on boys than on girls with ADHD.ADHD is often comorbid with other neuropsychiatric disorders ,21, one This study was a survey administered as a paper questionnaire. The Kohnodai Hospital is located in Ichikawa City in the eastern part of the Tokyo metropolitan area. No real data was available regarding the socioeconomic status of the citizens of Ichikawa City. The city has fully developed into a residential area and center for education with an estimated population of 468,275 (as of February 2013), making it the fourth largest city in the prefecture.The ethical committee of the National Center for Global Health and Medicine approved this study. Using the QCD, we performed a case–control study of the relationship between ADHD symptoms and parents’ perceptions. There were two subject groups of elementary school and junior high school students in this study: an ADHD group and a community control sample of typically developing children. All 298 individuals in the ADHD group  were examined and diagnosed with the combined subtype of ADHD according to the DSM-IV-TR by psychiatrists with specialization in child and adolescent psychiatry at the Department of Child and Adolescent Psychiatry, Kohnodai Hospital, National Center for Global Health and Medicine between September 4, 2008 and March 31, 2012. Seventy-six ADHD patients diagnosed with the inattentive type and 34 diagnosed with the hyperactivity–impulsivity type were excluded, as were patients with coexisting mental disorders such as intellectual disability, pervasive developmental disorders, eating disorders, mood disorders, oppositional defiant disorder, and conduct disorder. All children in the ADHD group were outpatients and drug-naive. To minimize confounding factors, we selected only the combined subtype of ADHD without coexisting disorders.The ADHD group completed the QCD, ADHD-RS, and Oppositional Defiant Behavior Inventory (ODBI) as routine screening tools during the initial examination at the child and adolescent psychiatry outpatient clinic of the Kohnodai Hospital. Researchers as well as all staff members of our hospital had access to the ADHD-RS, ODBI, and other clinical data from the patient’s medical records. Data pertaining to the QCD, ADHD-RS, and ODBI for the ADHD group were obtained from the patients’ clinical records. Along with documented informed consent from each patient, the guardians also provided informed consent for participation. The ethical committee of the National Center for Global Health and Medicine approved this consent procedure.　The community sample was surveyed in cooperation with the Board of Education in Ichikawa City . The QCDFirst, the survey method was explained to the principals of all schools by the Education Committee of Ichikawa City. Next, the teachers distributed a letter written by the Education Committee to explain the survey to all children and their parents. The letter clearly stated that completion of the consent form by a parent would be considered provision of consent to the survey from both the parents and students. The letter also specified that the results would be published as a medical paper in a format that individual is not specified. This consent procedure was approved by the ethical committee of the National Center for Global Health and Medicine.QCD data for the community sample was obtained from 1,803 parents who provided informed consent to the mailed survey. Of these, 1,136 questionnaires that were completely filled out were analyzed. We discussed this QCD and ADHD-RS data in a previous study . ChildreThe QCD comprises 20 questions related to activities that occur during specific periods of the day: questions 1–4, early morning/before going to school; questions 5–7, during school; questions 8–10, after school; questions 11–14, evening; questions 15–18, at night; and questions 19 and 20, overall behavior (Appendix). Each question is scored on the basis of the following four grades: 0 = completely disagree, 1 = somewhat  agree, 2 = mostly agree, and 3 = completely agree. The QCD comprises the total score and six subscales . Higher scores indicate higher life function and less difficulty in daily activities during specific periods of the day. The questionnaire is composed of practical and easy-to-understand questions regarding basic daily activities such as face washing, brushing teeth, and dressing. These subscales of the QCD were revised by Yamashita to match the daily life of Japanese children without using factor analysis .The ADHD-RS comprises 18 questions about hyperactivity, impulsiveness, and inattention. Four possible responses are recorded for each question: “generally none,” “usually none,” “usually exists,” or “always exists”, scored as 0, 1, 2, or 3 points, respectively. The total score is used for evaluation. Higher scores indicate multiple and more severe symptoms. The ADHD-RS is widely used in Japanese clinical practice and clinical research . Harada and colleagues developed and standardized theODBI . The ODBScores for the questions in each of the 6 subcategories and the total QCD score were all determined separately. Six subscores and the total QCD score were statistically compared between the ADHD group and the community sample using an unpaired t-test. These effect sizes were calculated.The effects of gender and diagnosis  on the total QCD score were analyzed using two-way analysis of variance. The significance threshold was defined as P < 0.0071, which corresponds to the Bonferroni-adjusted P < 0.05 corrected for the number of subscales (N = 7). Spearman’s correlation coefficient was calculated to examine whether the total QCD score and subscores correlated with the hyperactivity/impulsiveness score and the attention deficit score on the ADHD-RS and the ODBI score. The significance threshold for correlations of QCD subscale scores with ADHD-RS and ODBI scores was defined as P < 0.0012, which corresponds to the Bonferroni-adjusted P < 0.05 corrected for the number of tests performed All statistical tests were two-tailed, and P < 0.0071 or P < 0.0012 indicated statistical significance. Analyses were performed using PASW Statistics 18.0 statistical software (IBM Japan Inc.). The raw data used for the analyses described in this manuscript are available upon request.QCDs that were filled out completely were collected from the parents of the children in the ADHD group and the community sample . The 6 QThe average total QCD score and QCD subscores were compared within each gender . The totCorrelations of the total QCD score and subscores with the hyperactivity/impulsiveness score and the inattention score of the ADHD-RS or the total ODBI score are shown in This study is the first, as per our knowledge, to examine QCD scores in relation to ADHD-RS and OBDI scores in a community sample of children as well as children with ADHD during various time periods of the day. Regardless of the gender, we found that the QCD scores were significantly lower for the ADHD group than for the community sample during every time period; furthermore, they were associated with ADHD-RS and ODBI scores. These results indicate that ADHD children face difficulties in daily functioning, which are associated with ADHD and ODBI symptoms. Correlations were comparatively higher in the evening, suggesting that the QCD reflects difficulties at home that may be associated with family burden. When parents answered the QCD, they reported that they were more concerned to care for their children with ADHD in the evening. Particularly after they returned home, children with ADHD did their homework with greater difficulties and did not enjoy family time because of constant quarreling with others. Therefore, the parents felt uncomfortable in spending time with the child while engaging in evening activities. Considering the results, the hypothesis that the family burden was more severe on boys with ADHD was rejected. However, functional problems of girls with ADHD are more strongly correlated with their ADHD and oppositional symptoms during the night-time compared with those of boys. The results indicated that the family burden for children with ADHD is related to gender, ADHD symptoms, oppositional symptoms and the time period.  These findings have implications for treatment planning. The children in the study were not yet on medication. Nevertheless, comprehensive treatment consisting of parent training based on learning principles and behavioral therapy, psychotherapy, social therapy, and medication is recommended in the guidelines for the treatment of ADHD in Japan. MedicatThis study has some limitations that need to be considered. Children in the ADHD group were diagnosed with the combined subtype of ADHD. Furthermore, we have excluded children with ADHD and actual comorbid diagnoses. This study did not evaluate difficulties in daily functioning that are related to the inattention subtype or the hyperactivity–impulsivity subtype of ADHD. This result showed the relationship between oppositional behavior as reported in a questionnaire and ADHD symptoms, but the ability to examine this is constrained by excluding children diagnosed with ADHD and ODD.The subjects were recruited from the general population of one district and a population of children with ADHD in one national center in Japan. That national center was located in the same district; however, outpatients from the center were children from different districts. Therefore, the present findings should be carefully generalized to populations at large. Also, children in the community sample did not undergo psychiatric evaluation; therefore, the presence of mental disorders could not be determined in these children. Such factors must be taken into account when determining reference values and cutoff scores. Future studies should include participants from different districts to minimize the effects of district-specific factors. This study demonstrated that the family burden for girls with ADHD during the night time was more severe and ADHD and sleep problems are highly interrelated, both bing impacted by medications . HoweverIn summary, this study determined that children with ADHD face more difficulties in daily functioning compared with community sample children. These difficulties are dependent on gender and time period, and parents experience them particularly in the evening. Use of the QCD enables clinicians to inform parents about specific time periods during which their children experience ADHD-related difficulties and oppositional defiant symptoms in their daily life. Appendix S1Questionnaire-Children with Difficulties (English version*). To prevent misinterpretation and biases, two Japanese psychiatrists with a good command of English, who understood the background and objectives of the evaluation scale, independently carried out forward translation of the QCD into English. Then, the two translators discussed and integrated the two translated versions into one. Another psychiatrist did back translation to Japanese, the original language. The back-translated version was examined by the author of the original version and it was confirmed that the intent of the author was accurately translated. After the final proofreading, construction of the QCD English version was completed.(DOCX)Click here for additional data file.


It is unclear whether the association between Attention Deficit/Hyperactivity Disorder (ADHD) and violence is explained by ADHD symptoms or co-existing psychopathology. We investigated associations of ADHD and its symptom domains of hyperactivity and inattention, among individuals reporting violence in the UK population.We report data from the Adult Psychiatric Morbidity Survey (2007), a representative sample of the household population of England. A randomly selected sample of 7,369 completed the Adult Self-Report Scale for ADHD and the self-reported violence module, including repetition, injury, minor violence, victims and location of incidents. All models were weighted to account for non-response and carefully adjusted for demography and clinical predictors of violence: antisocial personality, substance misuse and anxiety disorders.p = .01). Hyperactivity, but not inattention was associated with several indicators of violence in the domestic context . Mild and moderate ADHD symptoms were significantly associated with violence repetition, but not severe ADHD where the association was explained by co-existing disorders. Stratified analyses further indicated that most violence reports are associated with co-occurring psychopathology.ADHD was moderately associated with violence after adjustments (OR 1.75, The direct effect of ADHD on violence is only moderate at the population level, driven by hyperactivity, and involving intimate partners and close persons. Because violence associated with severe ADHD is explained by co-existing psychopathology, interventions should primarily target co-existing disorders. Attention deficit-hyperactivity disorder (ADHD) is associated with criminality , includiNevertheless, a more complex association is suggested by longitudinal studies showing that childhood ADHD is a risk factor for a wide range of adverse psychiatric outcomes in adulthood associated with violence, including addictive, mood and anxiety disorders, and antisocial personality disorder (ASPD) ,16,17. CBecause violence is increasingly recognized as a major public health problem  requirinThe Adult Psychiatric Morbidity Survey 2007  recruited adults aged 16 and over living in private households in England. Field work was carried out between October 2006 and December 2007 and detailed information is published elsewhere . A multiEthical approval for the Adult Psychiatry Morbidity Survey (APMS 2007) was obtained from the Royal Free Hospital and Medical School Research Ethics Committee , one of the Research Ethics Committees of the National Research Ethics Service for non-clinical populations.Consent for participation was obtained in written form by participants. The APMS 2007 was designed to study the English adult population, and individuals aged 16-17 can legally consent as adults for medical and research purposes in the UK .The 6- item version of the Adult Self Report Scale (ASRS)  based onCommon mental disorders were assessed using the Clinical Interview Schedule-Revised (CIS-R) . This meASPD was measured using the self-report version of the Structured Clinical Interview for DSM-IV Axis II disorders ,32. The Alcohol dependence was examined using the Severity of Alcohol Dependence Questionnaire (SADQ) , which ePositive psychotic disorder classification was assessed via the Psychosis Screening Questionnaire (PSQ), which includes 5 main and secondary items covering mania, thought insertion, paranoia and hallucinations in the past year .Social class was based on the UK Registrar General’s Classification  which usParticipants were asked about violent behaviour in the section which assessed ASPD. The first question was: “Have you been in a physical fight or deliberately hit anyone in the past 5 years?” Additional questions then included information on violence severity, including: repetition (5 or more incidents), violent when intoxicated, victim or perpetrator injured, police involvement, and minor violence (when none of the preceding occurred). Additional information included: victims and location of incidents .Weighted (N) frequencies and proportions were reported on all categorical variables. Group associations were established using binary logistic regression with Odds Ratios (OR) as a measure of magnitude. Multiple categorical predictor covariates were assigned a reference category against which other categories were contrasted.Two approaches examined the associations of ADHD with dependent binary measures of violence. In the first, the exposure was a binary measure of ADHD, based on a cut-off of 13 or more , and by When testing for number of violent incidents (count variable), the Negative Binomial Regression (NBR) was applied. This model is suited to account for observed and unobserved heterogeneity when using count variables by under fitting the dispersion . ADHD waConsidering the high levels of comorbidity of adult ADHD , and to All statistical analyses were adjusted by including covariates in each model simultaneously. Adjustments included demographic factors, ASPD, drug dependence, alcohol dependence and anxiety disorders. To adjust effects of selecting one individual per household and under-representation of certain subgroups, and to account for any deviation from selecting a simple random sample, all variance estimates were weighted. Details of the procedures used in weighting have previously been described . All modOf 7,369 respondents, 614 (8.4%) reported any violence in the past 5 years. Socio-demographic factors of male gender, marital status other than married, and social class lower than I & II were significantly associated with violence risk, whereas any age category above 34 years were protective. All clinical and personality covariates significantly contributed to violence after adjustments, with the exception of alcohol dependence with a weak association (P < 0.10) and screening positive for psychosis .Overall prevalence of ADHD in the sample was 5.7%. The older age group (55 or more) showed significantly lower rates of ADHD. Anxiety disorders, ASPD and alcohol dependence were significantly associated with ADHD, whilst drug dependence showed a weaker association (P < 0.10) in the adjusted covariates model for ADHD .When using four ADHD symptom strata with none or few symptoms (stratum I) as reference, strata II, III and IV all were significantly associated with any violence . Nevertheless, after fully adjusting for demography and psychopathology only those in stratum III had significant associations with violence .There were no significant associations between ADHD and either victims or locations of violent incidents following adjustments .To test independent contributions of hyperactivity and inattention, we developed adjusted models, replacing the ADHD binary variable with continuous scores of hyperactivity and inattention. Considering the correlation between the inattention and hyperactivity scales was 0.36 (P < 0.001), they were entered in models simultaneously . To explore the effect of ADHD on number of violent incidents, we used negative binomial regression (NBR) models. The association between ADHD symptom dimensions and number of violent incidents were also investigated. The adjusted NBR model for continuous scores of hyperactivity and inattention demonstrated a significant association with hyperactivity but not inattention .We performed logistic regression analyses stratified by comorbidities (presence/absence) in order to examine the impact of specific co-occurring disorders on the association of ADHD with reports of any violence. We found that categorically defined ADHD was only moderately associated with violence at the population level following adjustments for demographic factors and coexisting psychopathology. Furthermore, the association was only for minor violent incidents where no one was injured and the police were not involved. After separating ADHD into two continuous measures based on symptom dimensions, inattention demonstrated little or no impact on violence in the population and involved only minor incidents. However, hyperactivity was independently associated with violent incidents resulting in police involvement, with reports of victims in close relationships, taking place in the perpetrator’s or someone else’s home, as well as violence in pubs and bars. Hyperactivity, but not inattention, was additionally associated with repetition of violent incidents.Finally, we found a more complex relationship between increasing levels of severity of ADHD with any and repetitive violence. Unadjusted models demonstrated a linear relationship with severity of ADHD. Following adjustments, moderate levels of severity still demonstrated associations with violence, but at the most severe level (stratum IV) there were no direct associations. Further examination of our data suggests that the association with violence and its repetition among participants in stratum IV was entirely explained by coexisting conditions of ASPD, alcohol and drug dependence, and anxiety disorders, which were highly prevalent among participants with severe ADHD. We thereby conclude that repetitive violence among persons with severe ADHD is associated with multiple forms of coexisting psychopathology but not ADHD.Our findings are consistent with reports that the relationship between hyperactivity and serious violence  is mediated by ASPD  and otheSymptom onset of ADHD usually precedes CD and substance misuse, increases risk of developing these conditions, and frequently amplifies their severity ,40. HoweOur findings suggested that direct associations of ADHD are restricted to violence towards persons in intimate relationships, family members, and friends. A representative US longitudinal study demonstrated that ADHD is consistently associated with violence in intimate relationships . After cWe did not measure motivating factors or other qualitative characteristics such as whether violence was reactive or defensive to aggression initially directed towards the participant, or whether proactive, predatory, or instrumental. The latter characteristics are more common among individuals with ASPD ,48, resuOur findings also confirm the magnitude of the association of the hyperactivity construct with behavioural disturbance and impulsivity. Hyperactivity was recently linked to increased risk of aggression amongst adults . These aThe findings in this report should be interpreted in the context of several methodological limitations. Psychiatric diagnostic classification was derived from self-report scales and not by structured clinical diagnostic interviews. Interpretations regarding ADHD and co-occurring disorders should consider possible false positives in all estimates. Violence and psychiatric morbidity were not contrasted or corroborated against other sources of information, such as official offence records or collateral reports. Self-report in this aspect might have underestimated the prevalence for violence, partly due to social desirability. There is no information regarding childhood diagnosis of ADHD.Only 57% of all originally approached participated in the survey. It is likely that these differed from non-responders in a way that is not possible to evaluate. However our estimates were weighted to account for non-response based on differences from census data.Another limitation is related to temporal relation of our predictor and outcome assessments. Violence was assessed over a period over 5 years, and whilst ADHD assumes a stable trajectory of symptoms from childhood, certain diagnostic covariates were assessed over a shorter time span . Additionally, the cross-sectional design does not allow conclusions on causal associations between ADHD and violence, or the investigation of potential mediating effects of ASPD and/or substance misuse on these associations.High levels of comorbidity amongst individuals with ADHD, overlap of symptoms across co-occurring disorders, and overall heterogeneity of symptom presentation indicated limitations in assessing categorical adult ADHD, with potential confounding from dimensions of ADHD on the different associations with violence. Our findings indicate that ADHD should be investigated further from a dimensional perspective to gain better understanding into its underlying associations with co-occurring disorders, longitudinal development, and to inform targeted interventions ,55.ADHD is an impairing  lifelongNevertheless, our findings have two important implications for targeted interventions for persons with ADHD to reduce violence. Firstly, medication treatment may be important if the aim is to reduce minor violence experienced by close persons, including intimate partners, family, and friends. The burden of care resulting from even minor violence directed towards close persons should not be underestimated. Secondly, further trials of medication on violent behaviour should be extended to those with low and moderate levels of ADHD where we have shown that symptoms of hyperactivity have an independent effect. Lastly, psychological interventions with focus on the development of executive, regulatory techniques and coping skills may play a critical role in managing impulsive behaviour associated with ADHD and its common co-occurring disorders ,67.


Background: Perfluorinated compounds (PFCs) are persistent environmental pollutants. Toxicology studies demonstrate the potential for perfluorooctanoic acid (PFOA) and other PFCs to affect human growth and development. Attention deficit/hyperactivity disorder (ADHD) is a developmental disorder with suspected environmental and genetic etiology.Objectives: We examined the cross-sectional association between serum PFC concentration and parent or self-report of doctor-diagnosed ADHD with and without current ADHD medication.Methods: We used data from the C8 Health Project, a 2005–2006 survey in a Mid-Ohio Valley community highly exposed to PFOA through contaminated drinking water, to study non-Hispanic white children 5–18 years of age. Logistic regression models were adjusted for age and sex.Results: Of the 10,546 eligible children, 12.4% reported ADHD and 5.1% reported ADHD plus ADHD medication use. We observed an inverted J-shaped association between PFOA and ADHD, with a small increase in prevalence for the second quartile of exposure compared with the lowest, and a decrease for the highest versus lowest quartile. The prevalence of ADHD plus medication increased with perfluorohexane sulfonate (PFHxS) levels, with an adjusted odds ratio of 1.59  comparing the highest quartile of exposure to the lowest. We observed a modest association between perfluorooctane sulfonate and ADHD with medication.Conclusions: The most notable finding for PFOA and ADHD, a reduction in prevalence at the highest exposure level, is unlikely to be causal, perhaps reflecting a spurious finding related to the geographic determination of PFOA exposure in this population or to unmeasured behavioral or physiologic correlates of exposure and outcome. Possible positive associations between other PFCs and ADHD, particularly PFHxS, warrant continued investigation. Perfluorooctanoic acid (PFOA) is a synthetic chemical that has been used in the manufacture of fluoropolymers since the 1950s [U.S. Environmental Protection Agency (EPA) 2009a] and may also result from the breakdown of a related group of chemicals called fluorinated telomers (U.S. EPA 2009b). Fluoropolymers are used in nonstick cookware and clothing made from waterproof, breathable fabric (U.S. EPA 2009b).PFOA and other perfluorinated compounds (PFCs) with comparable industrial uses—perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA)—are persistent environmental pollutants that have been detected worldwide in both wildlife and humans, with higher exposure closer to urbanized and industrialized regions . In the Toxicology studies highlight the potential for PFCs to affect fetal growth and development , early pregnancy plasma PFOA and PFOS levels were essentially unrelated to motor or mental development through 18 months of age, although there were weak associations between increased PFOS levels and sitting without assistance or using wordlike sounds to indicate wants  of PFCs used automated solid-phase extraction combined with reverse-phase high-performance liquid chromatography ?” We additionally constructed a second, more sensitive ADHD definition by combining report of ADHD diagnosis with current use of a medication commonly used to treat ADHD . Particiz-score based on the 2000 CDC growth charts of BMI for age , sex, race/ethnicity (non-Hispanic white vs. other), body mass index (BMI)  for age , and aveStatistical analysis. Analysis was performed using SAS software . Given the concern that PFCs may be hormonally active  to facilitate comparisons with other studies requiring adjustment for race/ethnicity. Because average household income was missing for 21.3% of participants, we compared odds ratios (ORs) adjusted for age, sex, and income with ORs adjusted for age and sex only. There was a < 10% change in ORs between the fully and partially adjusted models, so we excluded average household income from analysis, allowing us to retain a larger study population. We ran logistic regression models adjusted for age and sex to calculate the OR and 95% confidence intervals (CIs) for each PFC–outcome combination.y active , we firsion term . There w outcome . Neithera) For all 10,546 children, we ran each model, simultaneously adjusting all PFCs for one another to account for confounding. For instance, in the model for PFOA, we adjusted for age, sex, PFOS, PFHxS, and PFNA. b) Among the 6,523 children permitting use of identifying information, we restricted analysis to the 2,437 children who lived in the same PFOA-exposed water district their entire life. Because PFOA exposure is directly related to residential location, this residential restriction is more likely to maintain the same relative ranking of PFOA exposure distribution over time, potentially reducing exposure misclassification, particularly if there is an early-life critical developmental window of susceptibility to PFOA. c) To facilitate comparisons with the NHANES population  between PFOA and PFNA to the strongest ρ = 0.54 (p < 0.001) between PFOS and PFHxS. The mean ± SD age in the population was 13.1 ± 3.8 years, and 51.6% were male. Of the 6,532 children in the subset where residential history was available, 2,437 (37.4%) lived their entire life in a single PFOA-exposed water district.Of the 10,546 non-Hispanic white children 5–18 years of age in the C8 Health Project, 12.4% reported a diagnosis of ADHD and 12.1% a learning problem . Using tThe association between serum PFOA and ADHD followed an inverted J. We observed a small increase in prevalence for the second quartile of exposure compared with the lowest, and a somewhat larger decrease for the highest versus lowest quartile . For PFOWe observed small reductions in ORs comparing quartiles 2–4 with the lowest quartile for PFOA, PFOS, and PFNA and reported learning problems, but no dose–response gradient . The preSimultaneous adjustment for all PFCs tended to weaken positive ORs and strengthen negative ORs for ADHD. The exception was for PFHxS, where simultaneous adjustment for all PFCs strengthened all of the observed positive associations. For instance, for ADHD with medication, the OR comparing the highest and lowest exposure groups was 1.67  with simultaneous adjustment for all PFCs, compared with 1.59  without the additional adjustment. Overall, the changes to the results with adjustment for all PFCs were minor and did not alter interpretation of the estimates (data not shown).n = 2,437), the association between PFOA and ADHD was attenuated (data not shown). For ADHD with medication, the modest increased prevalence in quartile 2 remained the same while the reduced prevalence in quartile 4 relative to the first quartile was eliminated .Among the children living in a single PFOA-exposed water district where presumably the current level of exposure reflects long-term patterns , the patterns of association for ADHD alone and learning problems remained the same as for the full age range , for ADHD alone all ORs were near the null value and CIs were wide (data not shown). For ADHD with medication, we observed no reduction in prevalence for quartile 4 as we observed in the full population. Rather, the increase in prevalence observed when moving from the lowest quartile to quartile 2  remained consistent for quartile 3  and quartile 4 .When restricting the analysis to children with PFOA exposures below the median (Our sporadic positive associations between PFCs and ADHD contrast somewhat with the findings of The pattern of results for PFOA and ADHD in our full population, with a small increase then more notable decrease in prevalence, is unlikely to be causal and may reflect some unmeasured correlate of PFOA exposure. The diagnosis of ADHD requires that behavioral symptoms be present in two or more settings, such as at home and at school . If the We found support for a small, positive association between PFC exposure and report of learning problems only for PFHxS. Serum PFNA levels were associated with a modest decrease in the prevalence of a self-reported learning problem. However, this outcome was defined nonspecifically and may indicate disabilities in listening, speaking, basic reading skills, reading comprehension, written expression, mathematical calculation, or mathematical reasoning . Future A major limitation of this cross-sectional investigation is the reliance on parent or self-report for measurement of the outcome, although we also included the more stringent case definition of ADHD report with medication use . One stuWith only two studies, each with its own limitations, research on the developmental health effects of PFCs is at a very early stage. The suggestive findings of these cross-sectional studies examining PFCs as risk factors for ADHD call for a more thorough evaluation of the association.


Following the agreements on the reformulating and revising of ADHD diagnostic criteria, recently, the proposed revision for ADHD added 4 new symptoms to the hyperactivity and Impulsivity aspect in DSM-V. This study investigates the psychometric properties of the proposed ADHD diagnostic criteria.ADHD diagnosis was made according to DSM-IV. The parents completed the screening test of ADHD checklist of Child Symptom Inventory-4 and the 4 items describing the new proposed symptoms in DSM-V.The confirmatory factor analysis of the ADHD DSM-V derived items supports the loading of two factors including inattentiveness and hyperactivity/impulsivity. There is a sufficient reliability for the items. However, confirmatory factor analysis showed that the three-factor model is better fitted than the two-factor one. Moreover, the results of the exploratory analysis raised some concerns about the factor loading of the four new items.The current results support the two-factor model of the DSM-V ADHD diagnostic criteria including inattentiveness and hyperactivity/impulsivity. However, the four new items can be considered as a third factor. Attention-deficit/hyperactivity disorder (ADHD) is one of the most common behavioral disorders in children and adolescents. Its rate in community samples is variably reported. A study reported the rate of 5.29% . MeanwhiThere has been a recent significant argument or controversy regarding the necessity of reformulating and revising ADHD criteria ,4,5. ForGiven that the proposed DSM-V criteria for ADHD are available and would be implemented in the near future , it is aDSM-IV defines ADHD as a cluster of symptoms; the patient must have at least six or more out of the 9 symptoms of inattention and/or six or more out of the 9 symptoms of hyperactivity/impulsivity . The proThe aim of this study was to investigate the psychometric properties of the proposed ADHD symptoms in DSM-V. In the first step, factor analyses were conducted to assess the loadings for the symptoms. Then, the convergent and discriminative validity of the categories of inattentiveness and hyperactivity-impulsivity of DSM-V ADHD symptoms were assessed. Finally, the internal reliability of the inattentiveness and hyperactivity- impulsivity was calculated.106 children, who were consecutive referrals to a university affiliated Child and Adolescent Psychiatry Clinic in Shiraz, Iran, participated in this study. All of the children and adolescents were interviewed face to face by a board certified Child and Adolescent psychiatrist. In addition, at least one of their parents or caregivers was interviewed face to face as a collateral information resource.The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, DSM-IV diagnostic criteria was used to make psychiatric diagnoses . InterviParents reported ADHD symptoms by completing the ADHD checklist of child symptom inventory-4 -16. The The four new items proposed by DSM-V to be added to ADHD diagnostic criteria were translated into Farsi and back translated into English by a bilingual child and adolescent psychiatrist and a psychologist. Every effort was made to preserve the concept of each symptom. After a pilot study on children referred to the clinic, the final version was used in the current study. The responses to these symptoms were in the Likert scale ranging from "never," "sometimes," "often," to "almost always".The children and parents or caregivers gave their assent or informed written consent for voluntary participation in this study. This study was approved by the Ethics Committee of Shiraz University of Medical Sciences.SPSS statistical software was used to analyze the data. A factor analysis with varimax rotation was conducted to examine the factor structure of the ADHD DSM-V symptoms. The Kaiser-Meyer-Olkin Measure and the Bartlett's test of sphericity were conducted. Internal consistency was examined using Cronbach's tests.One-, two-, three-factor models of confirmatory factor analysis were also conducted using LISREL 8.54 software. The convergent and discriminative validity of ADHD symptoms were analyzed using Pearson's r correlation coefficient.Another factor analysis was also conducted including the four newly proposed symptoms to examine item loading of the 13 symptoms of DSM-V derived hyperactivity- impulsivity symptoms. Here, the symptoms of inattentiveness were not included in the analysis. This analysis was conducted to examine whether the 13 items could be divided into two categories of hyperactivity and impulsivity.Another factor analysis was conducted including the DSM-IV derived inattentiveness symptoms and the four new symptoms proposed in DSM-V. The symptoms of hyperactivity-impulsivity of DSM-IV were not included.The sample included 84 (79.2%) boys and 22 (20.8%) girls. The age range of the children and adolescents was 5.5 to 17years. Their mean age was 9.1(SD = 2.5) years.The Kaiser-Meyer-Olkin Measure was 0.76. It shows the adequacy of sampling. The Bartlett's test of sphericity was less than 0.001. These results indicate that the data are suitable for factor analysis. The factor loading of the principal component analysis is indicated in Table In order to test which of the various models gives the best fit to the data, three confirmatory factor analyses were conducted. A one-factor model was not a good fit  = 0.098, Non-normed Fit index (NNFI) = 0.96, Comparative Fit index = 0.96.).A two-factor model fit well. The results of two-factor model confirmatory factor analysis showing the correlation between inattentiveness and hyperactivity/impulsivity factors that was .56 are displayed in Table However, a three-factor model of confirmatory factor analysis also fit well and it was better than the two-factor model Table .The factor loading of the second component analysis including only the symptoms of hyperactivity-impulsivity of DSM-V is displayed in Table The principal component analysis including the DSM-IV derived inattentiveness symptoms and the four new symptoms proposed in DSM-V indicated the two factor loading Table . This anThe convergent and discriminative validity for the whole 22 symptoms proposed for ADHD in DSM-V were calculated. The range of convergent validity for the symptoms of inattentiveness was from 0.504 to 0.772 and that of discriminative validity for the symptoms of inattentiveness was from 0.017 to 0.427. Also, the range of convergent validity for the symptoms of hyperactivity-impulsivity was from 0.42 to 0.770 and that of discriminative validity for the symptoms of hyperactivity-impulsivity was from 0.12 to 0.39.The alpha coefficient for the whole 24 symptoms of ADHD in DSM-V was 0.88. The alpha for the DSM-V hyperactivity-impulsivity was 0.87. It was 0.80 for DSM-IV inattention.To the best of the author's knowledge, this is the first study investigating psychometric and factor structure of ADHD DSM-V derived symptoms. So, it is not possible to compare the current results with those of other studies. Confirmatory factor analysis confirmed the proposed two-factor loading of inattentiveness and hyperactivity/impulsivity for the new ADHD DSM-V criteria. However, the three-factor model of confirmatory factor analysis showed that the four new items can be considered as the third factor.The results indicate that convergent and discriminative validity for ADHD DSM-V derived inattention symptoms are sufficient. Although the symptoms of hyperactivity- impulsivity are discriminated from inattentiveness symptoms, the convergent validity of the four newly proposed symptoms in DSM-V is not as high as that of the 9 symptoms derived from DSM-IV. The three new criteria for hyperactivity/impulsivity were loaded in inattentiveness factor rather than in hyperactivity-impulsivity factor. These may not support the fact that the 4 proposed symptoms for revision of ADHD exactly describe hyperactivity-impulsivity symptoms. However, the internal consistency and reliability of the inattentiveness and hyperactive/impulsivity symptoms are high.Considering the factor loading of the four newly proposed symptoms added to DSM-V, there is a concern that inattentiveness symptoms may falsely increase the diagnosis of ADHD-hyperactive/impulsive type or combined type of ADHD. It means that the symptoms which are loaded as inattentive symptoms may lead to subthreshold ADHD- hyperactive/impulsive type using DSM-IV, while fulfilling criteria of ADHD- hyperactive/impulsive type using DSM-V.With respect to the fact that the better diagnoses and classification of children with ADHD could lead to a better treatment, more discussion and justification about the new items are required. Probably, future studies should investigate the neuropsychological functioning of children with ADHD for the classification of the subtypes of ADHD. The current results indicated that continued research is required to reach accurate diagnostic criteria for making accurate ADHD diagnoses.There is some overlap between ADHD symptoms and ODD in DSM-IV . ODD symThere are some limitations in this study which need to be considered. This study was conducted on a clinical sample of children and adolescents with ADHD. Further studies with larger sample size including community sample with a wider age rage are recommended. The children and their parents were the sources of information. Including other informants such as teachers is also recommended. This study is based on one sample in a specific geographical area. In addition, the use of translation instead of the actual questionnaire is another limitation. A multi-site approach with a more limited age range would be required to appropriately assess the psychometric properties of the proposed items of a classification used worldwide.Despite the above-mentioned limitations, this is the first study that assesses psychometric properties of ADHD DSM-V derived symptoms. In addition, the children, adolescents and parents were interviewed face to face using a well known semi- structured interview. Moreover, all the interviews were conducted by a Board-certified child and adolescent psychiatrist.The findings of present study support the two-factor model of the DSM-V ADHD diagnostic criteria including inattentiveness and hyperactivity/impulsivity. Nevertheless, the four new items can be considered as a third factor.The authors declare that they have no competing interests.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/12/21/prepub


Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD.We used the Iowa gambling task (IGT), a task of rational decision-making under risk (RDMUR) and a rapid-decision gambling task (RDGT) which elicits behavioral measures as well as event-related potentials (ERPs: fERN and P3) in connection to the motivational impact of events. We did not observe between-group differences for decision-making under risk or ambiguity (RDMUR and IGT); however, there were significant differences for the ERP-assessed RDGT. Compared to controls, the ADHD group showed a pattern of impaired learning by feedback (fERN) and insensitivity to reward magnitude (P3). This ERP pattern (fERN and P3) was associated with impulsivity, hyperactivity, executive function and working memory. Compared to controls, the BD group showed fERN- and P3-enhanced responses to reward magnitude regardless of valence. This ERP pattern (fERN and P3) was associated with mood and inhibitory control. Consistent with the ERP findings, an analysis of source location revealed reduced responses of the cingulate cortex to the valence and magnitude of rewards in patients with ADHD and BD.Our data suggest that neurophysiological (ERPs) paradigms such as the RDGT are well suited to assess subclinical decision-making processes in patients with ADHD and BD as well as for linking the cingulate cortex with action monitoring systems. Decision-making is essential in our daily lives. We make many different decisions; some are based on risk and predictability, whereas others are based on uncertainty or emotional heuristics. Current research examining decision-making has assessed multiple processes engaged in this complex cognitive ability. Evidence from animals, healthy human volunteers and neuropsychiatric patients Bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) usually share clinical symptoms, present high rates of comorbidity and are challenging to differentiate from one another clinically We hypothesized that, given the distributed neural network involved in decision making, the comparisons among groups would disentangle the different processes with regard to separate subtasks. Moreover, if both disorders present impaired decision-making related to their specific symptomatology, decision making deficits may be associated with specific ADHD and BD clinical/neurocognitive profiles.This study assesses decision-making using the behavioral and neural correlates of different tasks in both ADHD and BD participants. We included affective, risky and rapid-decision gambling paradigms in order to test different aspect of decision making in patients. Specifically, we used an affective decision making task, the Iowa gambling task (IGT) Fifty participants  received a full clinical assessment and neurocognitive profile, and their ERPs were recorded. Patients in the BD and ADHD groups were selected from the outpatient population of the Institute of Cognitive Neurology using the following inclusion criteria: 1) aged between 18 and 54 years old; 2) diagnosed with Type II BD or adult ADHD according to the DSM-IV using the Structured Clinical Interview for DSM-IV (SCID); and 3) euthymia scores less than or equal to 8 points according to the Montgomery-Asberg Depression Rating Scale (MDRS) We recruited 25 healthy controls matched for sex, age, handedness, and years of education from a larger pool of volunteers who did not have a history of drug abuse or a family history of neurodegenerative or psychiatric disorders.All participants provided written informed consent in agreement with the Helsinki declaration. Although some of the participants have diagnosis of ADHD or bipolar conditions, any of those disorders implied a reduced capacity to consent. The Ethics Committee of the Institute of Cognitive Neurology approved this study.All participants completed a series of psychiatric and behavioral questionnaires to establish a clinical symptom profile that included depression, mania, impulsivity, anxiety, attention and hyperactivity/impulsivity scores. The Beck Depression Inventory II A general neuropsychology test evaluated participants' basic attention and memory processes. Several tests, including the INECO Frontal Screening The computerized version of the IGT In this deck, there are 10 cards. Nine cards are “good,” and one is “bad”. You will win one dollar for each good card you draw; however, if you draw the bad card, then you will lose everything, and the game will end. You will keep whatever money you win, so try to play as well as possible. Choose one card at a time by clicking on it.” We also told participants that the Joker was the bad card and that it was randomly placed within the set of ten cards. Finally, we told participants that they would play only once but could stop at any time to collect their prize. The task ended when participants stopped or drew the bad card. Using a mouse, participants could either select a face down card or stop the game by clicking the “check-out” box. Participants were unaware that any of the first 8 choices led to wins; in other words, the bad card was always the ninth card We designed a simplified computer gambling task based on a modified version of blackjack The RDGT allowed us to evaluate the motivational impact of events and the guiding choices of behavior EEG signals were sampled at 500 Hz from a Biosemi 128-channel system. The data were bandpass filtered online (0.1 to 100 Hz) and offline (0.3 to 30 Hz) to remove unwanted frequency components. We set the default reference as the link mastoids for recording. Two bipolar derivations monitored vertical and horizontal ocular movements (EOG). The EEG data that occurred 100 ms prior to, and 800 ms after, the stimulus onset were removed. Furthermore, we removed all segments with eye-movement artifacts from analysis using an automatic  and visual procedure. We averaged artifact-free EEG segments to obtain ERPs.Rather than using a single dipole model , we estimated the cortical current density mapping of fERN/P3 using a distributed model of 10000 current dipoles. Finally, we reported the activation of the cingulate cortex , the valence (wins minus losses) at fERN, and the magnitude  at P3. Orientation and dipole locations were fit to the Montreal Neurological Institute's standard brain model. Next, they were adapted to the standard geometry of the EEG sensor net (BrainSuite software). All subsequent processing  was obtained using BrainStorm software. An extension of the overlapping-spheres analytical model computed EEG forward modeling We separately analyzed regions of interest (ROIs) at the anterior, medial and posterior cingulate cortex  in both hemispheres using a Tzourio-Mazoyer partition X2) examined categorical variables . For the RDGT, we averaged accuracy and the ERP amplitudes for wins and losses  as well as for large and small values (magnitude factor). We included a between-subjects factor for the group . Offline processing and EEG data analysis were performed using Matlab. After a valence and electrode position analysis of the fERN An ANOVA and Tukey's HSD post-hoc comparisons (when appropriate) compared demographic, neuropsychological and reaction time data across all three groups. The chi square test  valence (fERN: wins minus losses) and (b) magnitude . Spearman's rank examined these global scores with regard to all clinical and neuropsychological tests after correcting for multiple correlations comparisons .X2We did not observe between-group differences with regard to age  = 3.56, p = 0.03). Posthoc comparisons  evidenced lower performance for the BD group compared with controls (p = 0.05). On abstraction capacity IFS subscale, significant differences between groups were observed  = 5.21, p = 0.01). Posthoc comparisons  showed lower performance in the ADHD group (p<0.01) compared with controls. On the Go-no go Task, accuracy on go trials  = 3.38, p = 0.04) and omission responses percentage  = 3.28, p = 0.05), yield between groups significant differences. Posthoc comparisons on accuracy  presented lower performance for the BD group compared with controls (p = 0.03). Also, post hoc comparisons  showed that BD had significantly higher omission responses percentage than did control subjects (p = 0.04). No differences were observed on either the commission responses percentage  = 2.17, p = 0.12) or the reaction time  = 2.63, p = 0.08).Regarding the other measures of executive functioning, the score on verbal Phonologic Fluency Task presented significant differences between groups  = 3.86, p = 0.02). Posthoc comparisons showed lower performance for the ADHD group compared with controls (p<0.01). The score on the Backward Digit Span evidenced a trend towards lower performance for the ADHD group  = 3.14, p = 0.05). In contrast, no differences were observed between groups on the TMT-B  = 1.12, p = 0.34), or the Letters and Numbers task  = 1.32, p = 0.28).In brief, the global score of the executive-function (IFS) showed significant differences between groups. Specifically, patients with BD had lower go/no-go IFS subscale scores compared to controls, and ADHD patients had lower abstraction capacity IFS subscale scores than controls. Furthermore, we observed impairments in patients with ADHD with regard to executive control and working memory.The IGT net score did not reveal a between-group difference F.A.When comparing RDMUR tasks  = 3.49, p<0.05). Post hoc comparison performed over this effect  evidenced that ADHD patients made longer responses  than controls (M = 650 ms SD = 84). No differences were observed between BD  and controls. No main effects or interactions of valence and magnitude were observed in reaction times.We did not observe main effects of valence  and depression  were negatively correlated with fERN win/loss discrimination. ADHD-RS-Inattention subscale scores were positively correlated with P3 amplitudes of magnitude discrimination . Working memory (backward digits span) was negatively correlated with P3 magnitude discrimination .Depression level  was negatively correlated with win/loss discrimination. Anxiety scores (STAI- Trait) were positively correlated with P3 magnitudes discrimination . Inhibitory control (incorrect responses on a go/no-go task) was positively correlated with fERN win/loss discrimination  and with P3 magnitude discrimination . Go/no-go reaction times were negatively correlated with fERN win/loss discrimination .Significantly high ADHD-RS-Inattention  and ADHD-RS- Hyperactivity-impulsivity subscale scores  were negatively correlated with fERN win/loss discrimination. With regard to executive functions, the IFS total score was positively correlated with fERN win/loss discrimination . Working memory  and attention  were also positively correlated with fERN win/loss discrimination.This study revealed that fERN and P3 markers were more sensitive than behavioral measures in showing that the decision-making brain process is impaired in both groups of patients. We did not observe group differences using the IGT  or the RDMUR task. Nevertheless, the RDGT showed an abnormal data pattern within the patient groups.Patients with ADHD presented a neural pattern indicative of deficient valence (fERN) and reward magnitude learning (P3). This pattern was associated with clinical evaluations of impulsivity, hyperactivity and inattention as well as impairments in executive function and working memory. Our data are consistent with the clinical features of ADHD with regard to decision-making: If the learning of valence and reward magnitude from the environment is impaired, then information concerning which decisions are most important will be reduced. Thus, decisions will be based on impulsivity or will not have a learned strategy.Patients with BD presented a pattern of cortical modulation based on the saliency of reward magnitudes regardless of learning via feedback. There was no fERN valence modulation; but reward magnitude affected this variable. The P3 presented enhanced reward magnitude discrimination. The ERP pattern of our data was associated with mood states and inhibitory control. Those results are consistent with the hypothesis that there is reduced sensitivity to emotional reward or punishment contexts in BD Finally, we found reduced activity in the cingulate cortex  in both patient groups compared to controls. This activity was especially reduced for patients with BD at the fERN  and those with ADHD at the P3 (magnitude). These results suggest that one of the main circuits associated with decision-making, the so called “action selection-monitoring system”, is impaired at neural level, for both groups but at different stages.To our knowledge, this study is the first to compare the decision-making profiles of adults with ADHD and those with BD. Our results are novel in numerous aspects. First, we found that the behavioral measures of affective and risky gambling tasks are not sensitive enough in small samples to assess these disorders' well-known deficits in decision-making (but see limitations section regarding sample size). Second, we found that both patient groups show an abnormal neural processing of valence and reward magnitudes but that this pattern was associated with different clinical and neuropsychological profiles. Finally, our data are consistent with the models of cingulate cortex activation to reward, action selection and action monitoring.The data of healthy volunteers confirms previous findings of fERN valence modulation Higher levels of inattention, hyperactivity and impulsivity were associated with reduced fERN win/loss discrimination in patients with ADHD, which confirms the association between impulsivity and decision-making in these patients We found that anxiety and mood levels were correlated with reduced P3 magnitude discriminations in patients with BD. Previous studies have revealed a relationship between poor decision-making and anxiety and mood Our multivariate analysis shows that psychopathological measures  and executive functions can affect the decision-making processes. This is consistent with the current literature that highlights the involvement of executive functions Previous IGT studies testing patients with euthymic BD reported normal decision-making abilities. Recently, our group Likewise, the results of the IGT studies that test adults with ADHD are in conflict. Mantyla et al The assessment of rational decision-making using ‘risky’ tasks is scarce in ADHD or those with BD. No reports have examined the former group, and previous results have found both impaired Finally, we found a neural pattern associated with reward magnitude and valence consistent with models of action selection monitoring As expected, patients with ADHD had higher inattention and hyperactivity/impulsivity scores than controls. Patients with ADHD also had higher levels of depression, which is common in this clinical population As we previously reported Mainly, and similar to previous studies, the number of patients was restricted, and therefore more subtle differences may have been missed due to a lack of statistical power, and multivariate comparisons require replication using a larger sample. However, the exclusion of patients with comorbidities and those receiving medications that might modify their electrophysiological responses accounts for the small size of our sample. Future research should explore the possible associations of the neural-level findings of decision-making with measures of social and vocational functioning as well as insight and compliance, which are clinical dimensions usually affected by both disorders. Possibly, low numbers of subjects may have impacted on the lack of differences found between groups on the IGT as well as the finding of no risky behavior in either patient group, something that was at some extent unexpected. For example, in one study of the IGT in ADHD Finally, as all previous reports comparing ADHD and BD patients, potential confounding effects of medication were not completely ruled out. As with almost all previous studies, BD patients in the current study were taking medications (but we did not include participants on antipsychotics). Although ADHD participants suspended the medication the day of recordings, long term effects of stimulants may have persistent effects on brain function. Therefore, we cannot discount the influence of these drugs on cognitive function. Assessing the same decision making task and comparing those effects in drug-naive participants (in order to avoid the possible long term effects of medication) would be additional steps.Our results reveal a clinical association between neural substrates and the well-known impairments of decision-making in patients with ADHD and those with BD. Neurophysiology may be able to examine brain abnormalities undetected by classic neuropsychology. The present results expand our previous work on decision-making from frontal diseases with clear structural damage At a theoretical level, our results highlight the role of monitoring systems and their relevance in decision and reward processing