This study investigated whether treatment naïve adults with Attention Deficit Hyperactivity Disorder  differed from healthy controls  in behavioral performance, event-related potential (ERP) indices of preparatory attention (CueP3 and late CNV), and reactive response control  derived from a visual cued Go/NoGo task. On several critical measures, Cue P3, late CNV, and NoGo N2, there were no significant differences between the groups. This indicated normal preparatory processes and conflict monitoring in ADHD patients. However, the patients had attenuated Go P3 and NoGoP3 amplitudes relative to controls, suggesting reduced allocation of attentional resources to processes involved in response control. The patients also had a higher rate of Go signal omission errors, but no other performance decrements compared with controls. Reduced Go P3 and NoGo P3 amplitudes were associated with poorer task performance, particularly in the ADHD group. Notably, the ERPs were not associated with self-reported mood or anxiety. The results provide electrophysiological evidence for reduced effortful engagement of attentional resources to both Go and NoGo signals when reactive response control is needed. The absence of group differences in ERP components indexing proactive control points to impairments in specific aspects of cognitive processes in an untreated adult ADHD cohort. The associations between ERPs and task performance provided additional support for the altered electrophysiological responses. Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent early-onset, neurodevelopmental syndrome characterized by severe and developmentally inappropriate levels of inattention, hyperactivity, and impulsivity . The core behavioral features of ADHD persist into adulthood in a substantial number of individuals and are associated with significant social, academic, vocational, and financial burden .Neuropsychological studies report reduced performance in a variety of cognitive tasks, including tasks demanding selective and sustained attention, motor response inhibition, working memory, and timing control, as well as more behaviorally complex executive functions such as planning and decision-making –11. A coFindings from functional neuroimaging studies have revealed altered hemodynamic response patterns in fronto-striatal and fronto-parietal circuits of individuals with ADHD during both resting state and cognitive tasks , 15, 16,The capacities to allocate attentional resources, anticipate and prepare for upcoming events, and suppress inappropriate responses are critical cognitive control functions that are prerequisites for complex goal-directed behavior. Deficits in any of these basic control functions may contribute to difficulties with flexible and timely behavioral adjustment to changing environmental demands, as is typically seen in individuals with ADHD –35.An inherent limitation of behavioral methods for assessing covert cognitive control functions, such as preparation for- or inhibition of action, is that the rapid neural processes subserving them can only be indirectly inferred from the presence or absence of behavioral responses. However, stages of neural information flow evoked by an event can be captured with millisecond time resolution by examining event-related brain potentials (ERPs) extracted from ongoing electroencephalographic (EEG) activity recorded from the scalp. ERPs have been particularly successful for understanding the neural basis of attentional processes , 35–43, may require a response. When cues are mostly valid signals for Go stimuli, they evoke increased motor preparation processes facilitating speeded reactions. However, preparation for fast responding leads to an augmented need for abortion of the prepared response whenever a NoGo stimulus occurs [after detection of errors or high interference events such as NoGo signals. Proactive control, in contrast is triggered by contextual cues occurring in advance of goal-relevant events, and convey information to promote appropriate behavioral responses [In a cued Go/NoGo task, a defined cue (S1) signals that the subsequent stimulus (S2: Go or NoGo) s occurs . Thus, tesponses .An electrophysiological correlate of attentional preparatory processes is a broad positive-polarity deflection starting about 300 ms after cue (S1) onset. It is denoted Cue P3andhasa maximum over centro-parietal electrode sites , 59. It The presentation of an S2, defined as the target, generates positive-polarityGoP3 potentials that have partially overlapping central-parietal distributions . The ampCancellation of the prepared response is required when S2 occasionally constitutes a NoGo signal. The NoGo signal evokes two succeeding ERPs called NoGo N2 and NoGo P3. Both have a fronto-central distribution, where NoGo N2 has a pronounced negativity 200–300 ms after the onset of S2 , 76, andThe NoGo P3 , 85, 86 Regardless of the exact functional meaning of the ERP components generated to the cued Go/NoGo task, they can be viewed as indices of proactive  and reactive  cognitive control processes. The present study aimed at examining ERP markers of proactive and reactive attentional control in unmedicated adult ADHD patients.Despite the focus on altered P3 as a possible endophenotype for childhood ADHD  there arUsing variants of cued Go/NoGo tasks, the few studies of adult ADHD found reduced P3 to cues , and theThis study is unique in that we report data from ADHD patients with clinically significant difficulties who were examined prior to initiation of pharmacological treatment . This avoids the effects on brain function of any prior pharmacological treatment , 100. AcBased on the previous ERP literature on childhood ADHD, and the limited literature on adult ADHD, we proposed the following main hypotheses. The amplitudes of the Cue P3 and late CNV would be attenuated in the ADHD group relative to the healthy age-matched control group. We further predicted that the P3 to Go signals, and the N2 and P3 to NoGo signals would be diminished in the ADHD group. Behavioral concomitants of the electrophysiological parameters were also examined. Increased reaction time variability to Go signals is one of the most stable behavioral markers of ADHD in both childhood , 103 andBecause cognitive ERPs can be impaired in clinical disorders involving depression –108, anxThe initial study samples had 36 ADHD patients and 35 healthy controls. However, 2 patients and 4 controls had excessive noise (mainly movement artifacts) in the electrophysiological recordings and/or lack of behavioral response registration and were therefore excluded from the study. In addition, 1 ADHD patient was excluded due to excessive commission errors (6 times that of the patient with the next highest error rate). In the following, we report the results of a group of 33 treatment-naive adults with newly diagnosed ADHD , and a comparison group of 31 healthy controls . The ADHD participants were recruited from a consecutive series of patients referred to the Department of Neuropsychology, Helgeland Hospital in the time period from 2008 to 2011. All patients were referred from specialist mental health services or primary care physicians for a second opinion evaluation of suspected ADHD. None had received stimulant medications prior to or during participation in the study, primarily because the ADHD diagnosis was not confirmed. Three patients with ADHD were treated with antidepressant medication at the time of study. All had taken the prescribed dose on the day before- but not on the day of assessment. Inclusion in the ADHD group was based on the DSM-IV criteria for ADHD  assessedHealthy controls were recruited from three medium-size companies in the Helgeland area. Controls were selected based on the matching criteria sex, age, and years of education. From lists of all employees in the companies, those who fulfilled the matching criteria were asked to participate. In cases where more than one employee met the matching criteria for a patient, a random draw was conducted. In addition, healthy control participants underwent the diagnostic assessment. None fulfilled the DSM-IV diagnostic criteria for ADHD.All participants were questioned about their past and present somatic and psychological health. Criteria for exclusion were: a) history of mild to severe traumatic brain injury, b) neurological disorder, c) history of severe memory problems, d) diabetes, e) metabolic disorder, f) psychotic symptoms, g) alcohol and/or substance abuse requiring treatment, and h) visual or auditory sensory loss. Prior to inclusion in the study, all participants were tested for auditory (audiometry test) and vision (optometry test) deficits. Participants had either normal acuity or vision corrected by optical lenses. None had impaired hearing. The participants were right-handed except for 1 in each group who was left-handed.The participants were further evaluated for general IQ with the Wechsler Adult Intelligence Scale (WAIS-III) . The patThe cued Go/NoGo task consisted of three categories of visual stimuli: 20 different images of animals, 20 different images of plants, and 20 different images of humans. The centrally presented stimuli subtended an approximate visual angle of 3°.In order to maintain alertness and arousal in a long-lasting repetitive task , 116 novThe participants were instructed to press a button with their dominant index finger to S2 in all Go trials. They were told not to press the button to S2 in NoGo trials and Irrelevant trials. The total duration of the task was approximately 20 minutes with a 2 minutes break mid-way when 200 trials had elapsed . In the Omission errors, defined as not responding to S2 in Go trials, and commission errors, defined as responding to S2 in NoGo trials, were calculated separately for each participant across trials. A button press was defined as a response and recorded if it occurred in the time interval from 200 ms to 1000 ms after presentation ofS2. Mean reaction time (RT) and standard deviation of reaction time (RT SD) were calculated across trials for each participant.Event-related potentials (ERP): Electroencephalogram (EEG) was recorded using a Mitsar  19-channel EEG system. Electrodes were placed according to the International 10–20 system, using an electrode cap with tin-electrodes . Impedance was kept below 5 kOhm. The input signals referenced to the linked ears were filtered between 0.3–50 Hz, and digitalized at a sampling rate of 250 Hz. EEG data were computed using Win EEG software  in common average montage. ERPs for each individual were computed for Go, NoGo and Irrelevant trials without errors. Error trials were automatically excluded from averaging. Eye blink artifacts were corrected by zeroing the activation curves of individual independent components corresponding to eye blinks. Epochs of the filtered EEG with excessive absolute amplitude (>100 uV), and/or slow (> 50 uV in the 0 to 1 Hz band), and excessive fast (> 35 uV in the 20 to 35 Hz band) frequency activity were automatically excluded from further analysis.The ERP components were scored as mean amplitude at electrodes where the components of interest are known to be clearly present to reduce noise and increase the statistical power . The CueThe Go P3 was measured 280–380 ms after the onset of S2 in the Go condition at the Cz and Pz electrodes. The mean number of artifact-free trials used to compute the Go P3 was 83.3  for the ADHD group, and 89.7  for the healthy control group. In the NoGo condition, the NoGo N2 was measured at the Fz and Cz electrodes, 200–300 ms after the presentation of S2, and the NoGo P3 was measured in the time interval 300–480 ms after onset of S2 at Fz, Cz, and Pz. The ERPs for NoGo N2 and P3 were computed from a mean of 89.0  trials for the ADHD group, and 90.4  for the healthy controls. Baseline was adjusted to the mean voltage average 100 ms before stimulus presentation relative to S1 for the Cue P3 and late CNV, and relative to S2 for Go P3, NoGo N2, and NoGo P3.All participants were interviewed by a senior neuropsychologist using the semi-structured Adult Interview , and filPrior to EEG recording and testing, all participants had been instructed to forgo taking any nicotine or alcohol, or psychoactive medication in line with physician recommendation, and starting no later than 6 pm the day before the assessment. On the morning of the EEG recording and testing, participants were evaluated related to testability and inquired about food intake, last night sleep, alcohol/nicotine use, and other drugs or conditions that could influence their cognitive performance. None had issues that prevented participation.For all participants, the experimental session was conducted before noon, in a room without environmental distractions. It was individually administered in accordance with the general task requirements. The participants sat in a comfortable chair with a distance of 1.5 meters (4.92 feet) from a 17-inch computer screen. The EEG recording session started with two resting state sessions (eyes closed and eyes open). Next, participants were shown the different visual stimuli to be used in the cued Go/NoGo task and underwent a formal practice session prior to the actual task. The task instructions were given by a test technician who was present during the whole session.Statistical Product and Service Solutions for Windows  was usedBased on the general hypothesis that all investigated ERP components would have reduced amplitudes in the ADHD compared with the healthy control group, power estimates were conducted based on previous studies indicating group differences in that direction. For the ERP components where the highest number of participants were needed, it was estimated that at least 27 participants per group would be required to achieve a power of .80 . The NoG2) and partial ƞ2(ƞp2). Significant interaction effects were decomposed using One-Way ANOVA. Tukey corrected p-values are reported in post hoc analyses. Pearson product-moment correlation coefficients (two-tailed test) were used to test within-group relationships of electrophysiological data , and of performance scores on the cued Go/NoGo task, and ASEBA ASR DSM scale scores.Group differences in ERP amplitudes and topographies were analyzed using multivariate analyses of variances (MANOVA). Multivariate analyses were performed instead of the more commonly used repeated measures (RM) ANOVA, as the RM ANOVA assumption of sphericity is often violated in ERP-data . The anaAlpha for statistical analyses was set at p ≤ .05, except for the correlation analyses where the more conservative significance level of ≤ .001 was chosen due to the large number of tests conducted.t(60) = -.14, p = .891,ƞ2 = .02) or reaction time variability (RT SD) (t(60) = 1.33, p = .188, ƞ2 = .34) to detected Go-signals. The ADHD group had significantly more Go trial omission errors (t(60) = 2.13, p = .037, ƞ2 = .27), and a tendency for more NoGo trial commission errors (t(60) = 1.88, p = .065, ƞ2 = .24) compared to the control group. Note that commission errors were seen in a minority of participants in both groups . For omission error, the incidence was high in both groups . None of the participants had more than 23% omission errors, and none had more than 4% commission errors.p values ranging from .361 to .885).The mean amplitudes of the Cue P3 and late CNV to the relevant S1 signal , P3 to the Go S2 signal , and N2 and P3 to the NoGo S2 signal (S2 = Plant or Human) are presented  MANOVA showed significant main effects of Condition  = 82.95, p = .001, ƞp2 = .57), and Electrode  = 134.04, p = .001, ƞp2 = .68), reflecting that the Cue P3 amplitude was larger for relevant compared to irrelevant cues across groups. There was no significant main effect of Group  = 1.79, p = .185, ƞp2 = .03), or interactions involving Group  = 0.20, p = .654, Wilks’ Lambda = .997, ƞp2 = .00); Group x Condition:  = .42, p = .519, Wilks’ Lambda = .993, ƞp2 = .01); Group x Electrode x Condition:  = .61, p = .438, Wilks’ Lambda = .990, ƞp2 = .01).Late CNV: The 3 x 2 x 2 (Electrode x Condition x Group) MANOVA showed significant main effects of Condition  = 130.76, p = .001, ƞp2 = .68), and Electrode  = 49.10, p = .001, ƞp2 = .62), which reflected that the late CNV amplitudes were generally larger for relevant than for irrelevant cues. The analyses showed no significant main effect of Group  = 0.18, p = .674, ƞp2 = .00), or interactions of Group and other factors  = 1.48, p = .236, Wilks’ Lambda = .954, ƞp2 = .05); Group x Condition:  = 0.02, p = .891, Wilks’ Lambda = 1.00, ƞp2 = .00); Group x Electrode x Condition:  = 1.11, p = .335, Wilks’ Lambda = .965, ƞp2 = .04). See Go P3: F = 4.31, p = .042, ƞp2 = .07), and Electrode  = 15.42, p = .001, Wilks’ Lambda = .801, ƞp2 = .20), that were modified by a marginally significant interaction of Group and Electrode  = 3.97, p = .051, Wilks’ Lambda = .940, ƞp2 = .06). Post hoc testing of the interaction effect showed that the ADHD patients had significantly smaller Go P3 at Cz relative to the controls  = 7.25, p = .009, ƞp2 = .11).NoGo N2: The 2 x 2 (Electrode x Group) MANOVA revealed a significant main effect of Electrode for the NoGo N2  = 141.83, p = .001, Wilks’ Lambda = .304, ƞp2 = .70), in that its amplitude was largest at Fz across groups. There was no significant main effect of group  = 0.00, p = .995, ƞp2 = .00), or interaction of Group and Electrode  = 0.59, p = .444, Wilks’ Lambda = .991, ƞp2 = .01). See NoGo P3: The 3 x 2 (Electrode x Group) MANOVA for the NoGo P3 resulted in significant main effects of Electrode  = 76.81, p = .001, Wilks’ Lambda = .284, ƞp2 = .72), and Group  = 5.02, p = .029, ƞp2 = .08), that were modified by a significant Group by Electrode interaction  = 5.30, p = .008, Wilks’ Lambda = .852, ƞp2 = .15).F = 8.19, p = .006, ƞ2 = .73). ƞp2 = .12).Post hoc tests revealed that the group differed significantly at Cz only (t(60) = 11.04, p = .001), the Depression scale (t(60) = 9.41, p = .001), the Anxiety scale (t(60) = 6.41, p = .001), and the Antisocial Personality Problems scale (t(52) = 5.73, p = .001) of the ASEBA ASR DSM self-report , as well as ensuing processes associated with conflict monitoring and response control . We further predicted that indices of altered neural response patterns would be accompanied by reduced task performance. The hypotheses were partly confirmed, and we also observed some discrepancy between behavioral and electrophysiological indices of cognitive control. ADHD patients had more Go-signal omission errors than their healthy counterparts, but performed comparably to controls on reaction time measures. ERP responses did not uniformly differ from those of controls, but key measures of reactive attention and response control were diminished. Specifically, the Cue P3 and late CNV, as well as the NoGo N2 did not distinguish the groups, but the Go P3 and NoGo P3 amplitudes were significantly attenuated in the ADHD patients. Both groups showed moderate associations between ERPs and task performance. The general pattern was that reduced ERP amplitudes were moderately correlated to inferior performance, but not with depressed mood, anxiety, or antisocial personality problems. The results are discussed in relation to findings of previous studies, and how joint sampling of electrophysiological and behavioral measures provide complementary data for detailed analysis of cognitive control processes in adult ADHD.The ADHD patients performed similarly to healthy controls on measures of response speed and consistency, and the commission error rate only differed at a trend-level. In line with other adult ADHD studies , 93, theThe cued Go/NoGo paradigm employed in the present study was also used in an adult ADHD study by Muller and colleagues . They reReaction time instability , togetheThus, behavioral measures in the present task may not be as sensitive to the inattention and inhibitory control deficits often reported in patients with ADHD doing typical CPTs without the midway break . HoweverThe Cue P3 and late CNV were investigated as electrophysiological indices of processes related to relevance evaluation, sustained anticipation and motor preparation for potential Go signals (S2) succeeding the cues (S1). Inspection of the Cue P3 and the late CNV at centro-parietal sites  suggestsThe hypothesized reduction of P3 amplitudes was found for the ADHD group with both the Go P3 and the NoGo P3 amplitudes decreased relative to the control group. Attenuated P3 ERPs have been reported in children and adolescents , 60, 127The low rate of commission errors accompanied by the diminished NoGo P3 in the adult ADHD group, and the lack of significant correlation between them, might fit with the view that NoGo P3 is not an index of the inhibitory process itself, but alternatively reflects evaluation of the inhibitory process or its outcome . In caseThe magnitude of the N2 preceding the P3 in NoGo trials did not distinguish patients from controls. The results are in line with findings in a study of male adults with ADHD who showed no change in NoGo N2compared to age-matched healthy controls , and a sAs in the present study, electrophysiological and behavioral parameters often show negligible or only modest correlations , 131. ThThe magnitude of the ERP components were not significantly associated with self-reported mood, anxiety, or antisocial behavior. The results indicate that some elevation of emotional distress and social problems in the ADHD group  did not The present patient cohort was unique in the sense that patients were previously undiagnosed and had no history of central stimulation medication. Long-term effects of medications on brain neurobiology have been reported –134, andThe sizes of the study samples were modest. Thus, the suggestive findings reported here await replication in future studies with larger cohorts. The broad age range of the samples may hide potential different aging trajectories in the patient and the control group. Future studies should aim to include larger samples covering the full length of the adult life span in order to address this issue as well as potential gender differences.Our cohort of treatment-naive adults with ADHD had similar performance and ERP metrics to controls. Moreover, the topographic distributions and morphologies of the waveforms elicited by S1 and S2 were similar across groups both in the Go, NoGo, and Irrelevant task conditions. At the physiological level, this indicates that the neural generators of the waveforms operated in an analogous manner across groups. At the cognitive level, the results suggest that the two groups assigned task relevance to the stimuli in similar ways.The most striking group difference was the attenuation of Go P3 and NoGo P3amplitudes in the ADHD group. The attenuated P3s were accompanied by a higher rate of Go-signal omission errors. We suggest that the P3 amplitude reductions may be related to deficits in effortful allocation of attentional resources to task stimuli demanding reactive response control. The association of NoGo P3 amplitude to prolonged Go signal response speed only seen in the control group supports this interpretation. The electrophysiological results highlight specific information processing deficits in the adult ADHD population in that late reactive-, but not proactive cognitive processes were altered.


To evaluate the mediating/moderating effects of common internalizing /externalizing disorders on the association between ADHD and adolescent substance use disorders (SUD) in a population-based birth cohort.Among 5718 children in the birth cohort, 343 ADHD incident cases and 712 matched controls were identified. Psychiatric diagnoses prior to age 19 were classified into DSM-IV categories. The association between ADHD and SUD was summarized (hazard ratios (HR), 95% CI). The effect of depression, CD/ODD, anxiety was evaluated separately.Assessment of the joint effects of ADHD and each psychiatric disorder did not support a moderating effect of these disorders on SUD on additive scale. However, the association between ADHD and SUD was partially explained by a mediating role of these psychiatric disorders.For clinicians our results emphasize that depression (or CD/ODD) confers greater risk for SUD than ADHD alone. Early detection/treatment of SUD among adolescents with depression (or CD/ODD) is crucial regardless of ADHD. Attention deficit/hyperactivity disorder (ADHD), characterized by developmentally inappropriate levels of inattentiveness, impulsivity, and/or hyperactivity, is often accompanied by psychiatric disorders, such as mood disorders, anxiety disorders, conduct disorder (CD), and oppositional defiant disorder (ODD) –4. In a A recent meta-analytic review emphasized that the association between ADHD and SUD cannot be adequately addressed unless comorbidity with CD/ODD is considered . FurtherThere are some epidemiological studies evaluating the clinical associations between externalizing disorders and ADHD on SUD ,16, but Given the serious burden of SUD on society, families, and adolescents’ quality of life (QOL) , early dThis study was conducted in Rochester, Minnesota, located 90 miles southeast of Minneapolis-St Paul, the closest major urban center. According to 1990 census data, when subjects in our study were school-aged children, Rochester had 70,745 residents: 96% white, 72% ≤45 years of age, and primarily middle class. The demographic characteristics of Olmsted County  residents resembled those of the US white population during the timeframe relevant to this study .The capacity for population-based epidemiologic research on psychiatric comorbidities of ADHD in Rochester is the result of a unique set of circumstances. First, Rochester is relatively isolated in southeastern Minnesota, and as a result, virtually all medical care is provided locally by Mayo Clinic (MC) and Olmsted Medical Center (OMC) and their three affiliated hospitals. Through the Rochester Epidemiology Project, which includes a unique medical record-linkage system of Rochester and Olmsted County residents, all diagnoses and surgical procedures recorded at Rochester medical facilities are continuously indexed for automated retrieval , 22. The) from birth until the occurrence of either death or last clinical follow-up until 19 years of age). The steps and resources used for identification and follow-up of this birth cohort, and analysis of potential influence of migration bias, have been reported [Our birth cohort consisted of all children born between January 1, 1976 and December 31, 1982 to mothers residing in the townships comprising Minnesota Independent School District No. 535 (n = 8548). The target population consisted of 5718 children (2956 boys and 2762 girls) who still lived in Rochester at or after the age of five years , 24, whoreported .Our strategy in identifying ADHD incidence cases consisted of several steps, used multiple sources of information and relied on recorded history of symptoms, individual test results, and treatment. The details of this process were previously described . In shorIdentification of ADHD incidence cases consisted of applying research criteria to the 1961 children from our birth cohort who had any recorded behavioral or learning concerns. Subjects were defined as research-identified ADHD incidence cases if their school and/or medical records included various combinations of the following three different categories of information: 1) met DSM-IV criteria for ADHD, 2) positive ADHD questionnaire results, 3) clinical diagnosis of ADHD documented. Details of information regarding those criteria as well as identification process of ADHD cases were described elsewhere . ThroughFor each of the 379 ADHD incident cases, two control subjects were selected from the birth cohort. The controls were matched individually on gender and date of birth (±6 months) using an optimal matching algorithm applied to the values of the two matching factors . None ofThe procedure employed to identify all comorbid psychiatric disorders among ADHD cases and controls prior to 19 years of age consisted of a systematic, multi-staged process, utilizing detailed, routinely collected data as part of the Rochester Epidemiology Project resources . First, These 299 psychiatric diagnoses were collapsed into 10 categories based on their classification in the DSM-IV (comparable terms remain in DSM-5) . Thus, wAnalyses were performed using the SAS version 9.3 software . For each subject the duration of follow-up was calculated from birth until SUD diagnosis prior to 19 years of age; otherwise, for subjects without an SUD diagnosis prior to 19 years of age, their follow-up duration was censored at the date of last clinical follow-up if the subject was last seen prior to 19 years of age, or at age 19 if last seen after age 19. The association between ADHD case status and SUD was evaluated using Cox proportional hazards models; the association was summarized using the hazard ratio (HR) and corresponding 95% confidence interval (CI) derived from the parameters estimates. Separate analyses were performed to evaluate the moderating and mediating effect of each of three psychiatric disorders  on the association between ADHD and SUD. The presence or absence of each psychiatric disorder was handled using a time-dependent covariate and the start/stop counting process style of the Cox model ; therefoAB−HRA−HRB +1, where HRAB, HRA, and HRB are the corresponding HRs for those with both ADHD and the psychiatric disorder, ADHD only, and the psychiatric disorder only, respectively [First, an assessment of a moderating or interaction effect of the psychiatric disorder on an additive scale was performed by evaluating the joint effects of ADHD and the psychiatric disorder in a Cox model using the methods outlined by Li and Chambless . The relectively . In the Among the 5718 subjects in the birth cohort, 19 children with severe intellectual disability were excluded, leaving 5699 subjects. A total of 379 children fulfilled the research criteria for ADHD at a mean (SD) age of 10.4 (3.6) years (median 9.8 years). The study initially included 1137 subjects: 379 ADHD cases each with two gender and age matched controls (n = 758). However, 36 cases and 46 controls were excluded from the analysis because they denied access to their medical records for research purposes. The analyses herein are based on the remaining 343 ADHD cases and 712 non-ADHD controls. A comparison of demographic and perinatal factors between cases and controls has been previously described [The same statistical analyses were conducted for CD/ODD and results are shown in In the same manner, Population-based, non-referred samples of adolescents with ADHD and SUD are of critical importance in order to increase our understanding of the natural history of the comorbidity between ADHD and SUD. The core of this epidemiologic study is the population-based sample of carefully defined, research-identified ADHD cases and non-ADHD controls, as well as the standardized procedures for ascertaining SUD and the three common internalizing and externalizing psychiatric disorders. Our previous report, using multivariate analyses, from this population-based birth cohort clearly indicates a strong association between ADHD and SUD . HoweverTo better understand the clinical implications of the three common psychiatric comorbid conditions, we evaluated the effect of depression, CD/ODD and anxiety on the association between ADHD and SUD. Molina and Pelham  showed tAnalyses based on moderating and mediating models have been shown to be important tools in developmental and behavioral pediatric research . CompareWe found that depression was also more strongly associated with an increased risk of SUD than ADHD alone. Major depression or dysthymia was reported by Williams et al. to be more strongly associated with substance use than ADHD (odds ratio = 4.0 vs. 2.7) among adolescents of whom 66% were HIV positive, consistent with our findings .Unexpectedly, we found that adolescents with both depression (or CD/ODD) and ADHD were not at much greater risk to develop SUD than those with depression only (or CD/ODD only). Depression may motivate affected individuals to use substances, and CD/ODD is linked with delinquency, which in turn is strongly associated with the substance use that our results demonstrated. These disorders themselves might be strong risk factors leading to SUD compared to ADHD . Consequ2 = 55%), it might be difficult to compare these results directly with our findings. The authors of this meta-analysis also reported that the failure to detect a significant association might be due to statistical power issues stemming from small numbers of ADHD cases in each study [Our further analyses showed that the association between ADHD and SUD is only slightly mediated by such comorbid disorders. Other studies have reported the mediating effects of CD/ODD on the association between ADHD and SUD. For example, in the meta-analysis by Serra-Pinheiro et al. , 15 studch study . In addich study , 41 alsoLimitations should be considered when interpreting the present results. First, this is a retrospective cohort study dependent on retrospective review of medical and school records; therefore, the precise age of onset of ADHD could not be determined. Since the etiology of ADHD is determined by complex effects of prenatal, perinatal, and genetic factors , ADHD stIn conclusion, while our current findings confirmed our previous work and work of others showing a significant association between ADHD and substance-related disorders in adolescents , 45, our


Attention-deficit/hyperactivity disorder (ADHD) is a widely studied neurodevelopmental disorder. It is a highly heterogeneous condition, encompassing different types of expression. The predominantly inattentive type is the most prevalent and the most stable over the lifetime, yet it is the least-studied presentation. To increase understanding of its cognitive profile, 29 children with attention-deficit/hyperactivity disorder of predominantly inattentive type (ADHD-I) and 29 matched controls, aged 7–15 years, had their attentional abilities assessed through the Conners’ continuous performance test. Diffusion tensor imaging data were collected for all of the participants using a 3.0-T MRI system. Fractional anisotropy (FA) values were obtained for 20 fiber tracts, and brain-behavior correlations were calculated for 42 of the children. The ADHD-I children differed significantly from the typically developing (TD) children with respect to attentional measures, such as the ability to maintain response-time consistency throughout the task (Hit RT SE and Variability), vigilance (Hit RT ISI and Hit RT ISI SE), processing speed (Hit RT), selective attention (Omissions), sustained attention (Hit RT Block Change), error profile (Response Style), and inhibitory control (Perseverations). Evidence of significant differences between the ADHD-I and the TD participants was not found with respect to the mean FA values in the fiber tracts analyzed. Moderate and strong correlations between performance on the attention indicators and the tract-average FA values were found for the ADHD-I group. Our results contribute to a better characterization of the attentional profile of ADHD-I individuals and suggest that in children and adolescents with ADHD-I, attentional performance is mainly associated with the white matter structure of the long associative fibers that connect anterior–posterior brain areas. Many studies have aimed to investigate cognitive and behavioral differences among the attention-deficit/hyperactivity disorder (ADHD) types, mainly between the combined (ADHD-C) and inattentive (ADHD-I) presentations –4. AlthoTherefore, the findings suggest that ADHD-I and ADHD-C individuals have different patterns of attentional deficits. The continuous performance test (CPT) is the most common neuropsychological instrument used for the evaluation of attention skills, and its indicators have been shown to be sensitive to the identification of attentional deficits in ADHD , 8. DiffIn addition to differences in attentional patterns, ADHD-C and ADHD-I also differ with respect to the age of onset and referral. Symptoms frequently occur several years later for ADHD-I , 19. AltDevelopmental, cognitive, and behavioral differences between the types mentioned above confirm the clinical validity of the types, thereby suggesting the existence of phenotypic manifestations that, in turn, indicates possible underlying neurobiological differences .Attention-deficit/hyperactivity disorders precise etiology is still unclear, but many structural and functional neuroimaging studies have investigated brain alterations  and havein vivo the white matter fiber architecture  or to increased membrane permeability , 32. HigTo the best of our knowledge, to date, only two recent DTI studies have considered ADHD types in their analysis , 34. IndAlterations in neural circuits that connect regions of the prefrontal cortex and the striatum have been associated with cognitive control deficits, which have been suggested to account for the inattention symptoms in ADHD –37. NoneA few studies have already searched for associations between white matter fiber structure and attentional functioning, as measured by the CPT –42. AgaiThus, the present study aimed to compare individuals with ADHD-I and typically developing (TD) individuals with respect to attentional functioning as well as with respect to white matter measures (FA) to contribute to the characterization of individuals with this type. We also intended to investigate possible correlations between the attentional variables (CCPT) and the white matter measures (FA).The sample of the present study was composed of 29 ADHD-I children, aged 7–15 years, and 29 TD children matched for age, sex, and type of school (public or private). Participants were recruited using a purposive sampling method, from 2010 to 2014.The ADHD-I participants were referred from public and private centers, where they had their diagnosis made by an ADHD clinician expert (neuropaediatrician or child and adolescent psychiatrist) based on the DSM-IV parameters. The ADHD individuals must have presented six or more inattention symptoms and up to five hyperactivity/impulsivity symptoms to be classified as with the inattentive type. All of the TD children were enrolled from the community.The exclusion criteria included an estimated intelligence quotient (IQ) of 85 or lower, neurological disease, sensory deficits, or another condition that would prevent participation in the procedures.Only three of the ADHD-I children were using methyl- phenidate, and the use was for a few months  until assessment time. They were without medication at least 24 h before testing.Seven children from the TD group and nine children from the ADHD-I group were excluded from imaging analysis due to excessive motion during imaging or to artifacts. Thus, 22 TD and 20 ADHD-I images met the quality criteria for processing and comprised this stage of the analysis. Only two of the three children who were using methylphenidate had their images analyzed due to quality criteria.This study was approved by the Ethics Committee of the Federal University of São Paulo. The parents provided written informed consent for all of the participants. The children provided verbal or written informed assent.All of the subjects were subjected to a neuropsychological protocol, as described here. To identify the presence of possible exclusion criteria, the level of intellectual functioning was assessed through the Block Design and Vocabulary subtests of the abbreviated version of the Wechsler intelligence scale for children, third edition (WISC-III) . Both suAll of the participants were subjected to a neuropsychological evaluation, which included an examination of the subject’s intellectual level, a computerized attention test, and tests of working memory, visual constructive functions and visual memory, verbal fluency, decision making, facial emotion recognition, and academic performance. This evaluation was used to exclude other diagnostic conditions.Attention was evaluated through the response to the standard version of the CCPT-II . Twelve b = 1000 m/s2, thickness = 4 mm with the gap between slices = 0.8 mm, yielding 30 slices) was acquired using a 3.0-T, 43 mT/m gradient MR system  in all of the subjects. All of the images were checked for quality, which was rated based on an initial visual inspection. This procedure was followed by inspection for and the detection of artifacts, such as geometrical distortions, susceptibility effects, and motion.A 2D MR-DTI sequence .Nifti images were processed using the FSL platform , followiWe then used the 4D skeletonized FA image, with all of the projected mean skeletons of each subject, and the skeleton mask of the group to run an automated region of interest (ROI) extraction, using R project 3.0.3. The extraction of the tracts was based on the 20 tracts of the JHU (John Hopkins University) DTI white matter tractography atlas , 48, rest-test and chi-square tests . To minimize the age effect, the raw neuropsychological measures were standardized into z-score measures, adopting the Brazilian population norms . It was calculated the minimum effect size (based on Cohen’s d) for a 58 subjects sample (2 groups of 29) so that it would have the power to detect an 80% of difference expected in population. Statically significant differences were considered to have an observable effect in the population with 80% of power when the d value was >0.67 .The power calculation was performed based on the collected sample size of 58 participants , but the mean estimation of intellectual functioning was above the average range in both groups. Based on the recommendations of Dennis et al.  was under 0.67, the current sample size does not have the power to assume that these differences are observable in the population . Thus the differences regarding these indicators should be taken cautiously.Hit RT Block Change, Response style, and Perseverations indicators were statistically different between groups but since their effect size . First, a TFCE statistical analysis was run in TBSS to compare the ADHD-I group and the TD group. Differences were found between the groups at z-scores. As presented in Table Then, the ADHD-I and TD groups were compared with respect to the mean FA values of 20 tracts. The FA values were standardized as Comparative analysis excluding the two ADHD-I participants who were in use of methylphenidate were possible since groups remained not differing statistically in respect to mean age or sex distribution. Results revealed similar results .Pearson’s correlations were calculated for the ADHD-I group to identify possible associations between attentional functioning (measured by performance on the CCPT indicators) and the neurobiological data  in the individuals with ADHD-I. Standardized measures of attentional performance and the neuroimaging data were adopted in this analysis, and some of the correlations were found to be statistically significant for the ADHD-I group Table . Correlap-value was 0.06, what indicates an almost significant tendency.The very same Pearson’s correlations (comprising the same variables) were run excluding the two ADHD-I subjects who were in use of methylphenidate. The same results were found, with the exception of the correlation between the right corticospinal tract (CST R) and the Detectability indicator. Although CST R and Detectability correlation were not statistically significant for the analysis without the two medicated children, its Taking into account that results were very much similar in the analyses with and without the medicated participants and that the time of use of the methylphenidate was short for both children (2 and 13 months), discussion will be conducted considering the findings of the analysis that comprised all participants.The participants in the ADHD-I group showed significantly lower mean IQ scores than the participants in the TD group, but previous studies have concluded that ADHD children exhibit lower IQ scores when compared with their peers , 53, posWith respect to attentional functioning, which was measured by performance on the CCPT indicators, the ADHD-I group showed worse performance than the TD group on the measures related to the ability to maintain a consistent response time throughout the task (Hit RT SE and Variability), vigilance , processing speed (Hit RT), selective attention (Omissions), sustained attention (Hit RT Block Change), and inhibitory control (Response Style and Perseverations).The Hit RT SE and Variability indicators, as mentioned above, evaluate the ability to maintain a stable response time throughout the test. Intra-individual variability, as assessed by a variety of speed-based reaction-time (RT) tasks, is one of the most consistent manifestations among ADHD individuals. This “moment-to-moment” variability and inconsistency in performance is considered a core feature of the disorder , 54, 55.Our results also showed that the ADHD-I group presented lower scores on Hit RT ISI and Hit RT ISI SE, which are measures of vigilance. These measures evaluate the ability to adapt performance (or reaction time) in accordance to the different intervals in which stimuli are presented . Thus, our results suggest that ADHD-I individuals have more difficult in rapidly adapt their performance based on changes in the environment. Among the previous studies that investigated the performance of ADHD individuals with different types on the CPT, Egeland et al.  and RiveIn addition to vigilance deficits, the ADHD-I participants exhibited slower processing speed as well. The ADHD-I group performed significantly worse than the TD group with respect to the Hit RT measure. This finding is in line with the results from previous studies , 14, in Studies that compared the performance of patients with ADHD on the CCPT to the performance of normal controls have frequently concluded that the number of Omissions is a measure that is impaired in ADHD individuals , 56–58. The Hit RT BC indicator is a measure of the change in reaction time to stimuli throughout the task. Impaired performance on this indicator would suggest slower reaction times across the test, and thus a deficit in sustaining attention. Our findings demonstrated worse performance of the ADHD-I individuals on this measure, and this result is in accordance with the findings of Egeland et al. . These aResponse style is an indicator that intends to identify the style of response during the test: either a more conservative or a more free-responding profile. The individuals with ADHD-I presented significantly higher scores on these measures, which suggest a tendency to respond in more cautious way, choosing to respond infrequently to guarantee that the responses given are correct. A previous study that compared ADHD-I, ADHD-C, and controls on this measure did not find significant differences , 16. NonIn our results, the ADHD-I group presented a higher frequency of perseverative (anticipated) responses than the TD group. This higher number of Perseverations is indicative of greater impulsiveness . Althougn = 17) did not find evidence of statistically significant differences between the groups with respect to FA values. Widespread differences were obtained through MD and AD measures  is a hook-shaped bundle of fibers that bidirectionally connects the lower surfaces of the frontal lobe to structures in the anterior temporal lobe, such as the hippocampus and amygdala . Our finThe forceps minor is a commissural tract that connects the medial and lateral surfaces of the frontal lobes . The resThe Hit RT ISI indicator, which is a measure of vigilance, evaluates the ability to change response speeds across the different inter-stimulus intervals of the CCPT. This indicator was positively and moderately associated with the FA values of the left anterior thalamic radiation (ATR) and the right inferior fronto-occipital fasciculus (IFOF). A previous study found that the majority of the processing speed clusters projected on the ATR and the forceps minor , highligThe right IFOF was also moderately associated with a measure of perseveration, indicating that the higher the FA value, the less frequent the perseverative errors on the CCPT. As discussed previously, perseverations are errors that are influenced by impulsivity – or poor inhibitory control – and thus it is possible to infer that a higher FA of the IFOF, which is a tract associated with attentional control, may exert an expressive influence on the control of impulsive responses. This measure of perseverative errors was also positively associated with the hippocampal portion of the right cingulum (CGH). A previous study also identified that the integrity of the CGH bundle is associated, among other functions, with inhibition performance in both ADHD and control individuals, which is in line with our findings .The FA values of the right IFOF, along with the left CST and the forceps major, were also associated with another CCPT measure, the Response Style indicator. According to our results, the FA values of the forceps major, the right IFOF and the left CS were associated with the ability to adequately discriminate between target and non-target stimuli. The forceps major consists of the splenium of the corpus callosum and the associated white matter radiations that interconnect the occipital lobes , thus efFinally, detectability, which is a measure of the individual’s ability to distinguish and detect target from non-target stimuli, demonstrated a negative correlation with the right CST. Curiously, this measure was the only one to present a negative correlation with the FA values of a fiber tract, namely the right CST. On the other hand, the left CST was positively associated with the ability to inhibit motor responses to non-target stimuli (Response Style indicator). It is possible to assume that in the ADHD-I individuals, better stimulus discrimination indicates a reduced requirement for these motor fibers on the right side, which occurs through hemispheric compensation, with these functions taken on by the left CST.We can conclude that our findings suggest that compared to matched TD individuals, the ADHD-I attentional profile is characterized by more variable performance, difficulty in rapidly adapting performance in accordance with environmental requirements, slower processing speed, less efficient responses (higher number of Omissions), and reduced duration of the engagement of focus on tasks. In the ADHD-I group, attentional measures  were associated with the associative, projection, and commissural tracts but mainly with the long associative fibers that connect posterior cortical and subcortical areas to the frontal lobe. These findings indicate that attention is a complex cognitive function that depends on the integration of multiple brain areas and, more intensively, on the adequate development of frontal regions. Previous studies also concluded that circuits that connect the prefrontal cortex and motor areas exert an important influence on the inattention deficits of ADHD individuals , 36.This study contributes to a better delineation of the attentional profile of ADHD-I individuals and the association of their deficits with structural white matter particularities. We highlighted the extensive involvement of the long associative fibers that connect anterior–posterior brain areas, as the IFOF, in attentional functioning in children and adolescents with ADHD-I.d = 0.067. Thus, part of the findings regarding the attentional measures could not be extrapolated to the population.The limitations of this study include the use of attentional measures extracted from only one attentional test. Three of the participants in the ADHD-I group were using methylphenidate for approximately up to a year, which may have had a minimal impact on the brain microstructural properties. The small size of our sample prevented some generalization of our findings. Our sample size just allowed us to affirm that a finding would be representative enough to consider it as an observable effect in the population (at 80% of power) when it had an effect size greater than Future studies should replicate the present procedures, including ADHD-C individuals as a third group in addition to the ADHD-I and TD individuals, to allow individuals from different types to be compared with respect to the same variables. So far, the studies performed to investigate attentional performance associations with white matter structure in ADHD have either grouped different type individuals into the same group or selected one type of the disorder to better analyze, as done here. Nonetheless, comparisons across studies are limited because the methods and procedures are variable. Thus, we suggest that further studies utilize larger samples in their cognitive-brain structure analysis and include, in addition to TD individuals, the other presentations of the disorder, i.e., the restrictive inattention (proposed by the DSM V), inattentive, combined, and hyperactive–impulsive-presentations, to allow increased understanding of these different manifestations of the disorder.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This study examines beliefs about depression as a function of ethnic background (British Bangladeshis vs. British Whites) and age. A total of 364 participants completed a 65-item questionnaire, containing general questions regarding depression and anti-depressive behaviour; the causes of depression, and treatments for depression. The hypotheses were broadly supported; there were significant interactions between ethnicity and age, which generally revealed an increasingly negative attitude towards depression with increasing age amongst British Bangladeshis. Older British Bangladeshis believed depression was an illness that brought a sense of shame and loss of dignity to the individual and his or her family, and they also favoured a lay referral system for sufferers. They also had more superstitious beliefs about depression than both younger British Bangladeshis and British Whites. A pattern of increasing negativity with increasing age was not evident amongst the British Whites, but older individuals in both groups tended to believe that depression was not helped by psychological intervention. The attitudes towards depression in the young was similar  in both ethnic groups. These findings highlight the necessity to provide more culturally sensitive and accessible services for migrant communities – particularly amongst older individuals. This study concerns cultural differences in beliefs about depression which is a topic that has been extensively explored e.g., . It alsoThe Southeast Asian community views depression as “self-indulgent” and there is little tolerance for cognitions of the self . Karasz more frequent visits to their general practitioners than the British Whites, they are less likely to have their psychological difficulties (and particularly depression) identified ; however there is evidence for traditional cultural beliefs to be more deeply embedded and structured than those that exist in the Western culture . In Western countries the public attribute depression mainly to social-environmental factors, and biological causes are viewed as less important . This suIn non-Western cultures, there is a tendency to attribute a supernatural force, such as black magic and possession by evil spirits as the underlying cause for mental illness . The useA number of studies have demonstrated the impact cultural conceptions of mental illness have on help-seeking and the way in which the mentally ill are treated by health professionals and the public . Asian cThe Asian culture has a tendency to conceal mental illness from the wider community, as the reputation of the family is at stake . Asian cThe present study explores the attitudes of both the young and older generation of British Bangladeshis compared to British Whites, and will further develop our understanding of cultural differences. It is hypothesised that overall, the British Bangladeshis will have more conservative and negative attitudes towards depression than British Whites but this effect will be moderated by age; the younger British Bangladeshis will have similar beliefs and attitudes towards depression as British Whites. It was also predicted that Older British Bangladeshis will be more inclined to seek help from their family and to make use of “lay referral systems” than British Whites, and that British Bangladeshis will have more superstitious beliefs about depression than the British Whites.A total of 364 participants completed the questionnaire, of which 190 were British Bangladeshis living in East London, and 174 were British Whites. The majority of the younger participants were recruited from University of London and others through personal contact. The majority of the older participants were recruited from two local community centres (British Bangladeshis from the Bromley-by-Bow Community Centre (London borough of Tower Hamlets) and British Whites from the Froud Community Centre (London borough of Newham). The remainder of the participants were recruited via the local libraries in the London borough of Newham, and a small number through personal contact. Most of the questionnaires were completed in the presence of one of the researchers, but a number were distributed and then collected after completion. Participation in the study was entirely voluntary, and each participant gave verbal consent prior to completing the questionnaire. The study was granted ethical approval by the University College London Medical School.The questionnaire used in the study was constructed from questions used in three previous studies; . In addicentred so that the test between the intercepts of the regression lines would provide a test of the difference between the adjusted means for the two ethnic groups – even in the presence of a significant interaction. This method also avoids the loss of statistical power and other problems associated with the dichotomisation of the participants into young and old age groups  age and (ii) ethnicity on beliefs about, explanations for, and treatments of depression, multiple regressions were conducted on summated scores for each of the factors identified in the three sections of the questionnaire. Three predictors were used in each regression; age, ethnicity (indicator coded for British Bangladeshi and British White) and an interaction term (age × ethnicity). Prior to each analysis, the age variable was e groups . In caseA summary of the demographic information for the two samples is presented in p < .01). There were no significant differences between the two groups with respect to gender, employment, educational qualifications, and diagnosis of depression. There was a significant difference in marital status (p < 0.01) as more British Bangladeshis were married than British Whites, whereas more British Whites were cohabiting than British Bangladeshis. Significant differences in religion and piety existed between the two groups (both p's < 0.001). The majority of British Bangladeshi participants were Muslims whereas the majority of British Whites were Christian, and the British Bangladeshis reported being more pious than their British White counterparts. A significant difference was also found with respect to knowing other people who were suffering from depression (p < 0.01). A greater proportion of the British White participants than the British Bangladeshi participants reported knowing an individual suffering from depression.There was a small but significant difference between the mean age of the British Bangladeshis and British Whites  generated a seven-factor solution  and accounted for 56.5% of the total variance. The eigenvalues and variance accounted for by each factor are presented in Myths and Shame. All the items comprising this factor had high mean scores, indicating that participants did not believe that depression is associated with low socioeconomic status, or that the family of a depressed individual should feel shame and hide the depressed individual from the community. Overall, they did not believe that evil spirits cause depression. The second factor was labelled Loss of Dignity. Again, the items had relatively high mean scores indicating that the participants did not believe that there is a loss of dignity or respect for the depressive or their family, or that people would not wish to be associated with a depressed individual. The third factor was labelled Simplistic Notions. Participants did not think that depression was the same thing as being unhappy, or that simply suggesting that the depressed individual should go out to buy new clothes would be useful. They were more equivocal regarding the efficacy of talking to a family member rather than a friend. The fourth factor we labelled Depression as an Illness. Although participants believed that depression was a mental illness, they were more equivocal about the notion that depression runs in families. Perhaps surprisingly, that were also equivocal about the notion that seeking help from a psychiatrist was better than trying to deal with the problem oneself. The next factor contained just two items, and was labelled Negative Approach. The mean ratings indicate that in general, the participants felt that talking to a mental health professional would be useful, and that something could be done to help the depressed individual. The sixth factor was labelled Helplessness. Participants believed that depressed people lose control over important things in their lives, but also thought that it would be helpful for the depressed person to engage in an activity that he/she enjoyed. The final factor was Sympathy. An inspection of the mean scores indicates that participants thought that one could sympathise with a depressed person, and they believed that the risk of depression was reduced if an individual discussed their problems with someone. However, they were more equivocal with regard to the sympathy shown towards depressed individuals by the community.The first factor was labelled Life-events and Illness. This factor comprised a wide range of items all of which had low mean scores, indicating that participants believed that social factors, financial stresses, traumatic experiences and physical illness could all lead to the onset of depression. Scores for the items making up the second factor, labelled Psychological Stress, suggest that the participants believed psychological stress as a result of social isolation, loss of occupation or general social pressure could lead to depression. The third factor, Biological Explanation, had mean scores relatively close to the centre of the 6-point scale. Thus participants seemed equivocal with respect to the notions that depression is caused either by an imbalance of chemicals or hormones in the body, or that people become depressed for no apparent reason. The fourth factor, Environment and Aging, also had mean scores close to the middle of the scale. Participants adopted a neutral position with respect to the role of society, the weather, and aging as causes of depression. The fifth factor, Genetics and Substance Abuse, indicates that participants believed that substance abuse could be a source of depression, but rejected the association of blood-ties with depression. The final factor, Non-Biological Explanations, indicated that participants did not believe that depression had a supernatural origin, but were equivocal with respect to depression resulting from a boring, mundane lifestyle.The factor analysis conducted on the second section of the questionnaire  produced a six-factor solution , and accounted for 57.2% of the total variance. The eigenvalues and variance accounted for by each factor are presented in Religion and Culture. Participants generally believed the family, friends, and religion were important factors in the treatment of depression. Moreover, the participants believed the society and self-help could also play a role in relieving depression. They were far less sure that trying to think positively or focusing attention elsewhere would cure depression. The second factor was labelled Counselling and Therapy. The means scores on the questions making up this factor indicate that the participants generally believed that psychological intervention  was useful in the treatment of depression. The third factor was Medical Treatment. The mean scores suggested that participants were rather equivocal with respect to the role of physicians and antidepressants in the treatment of depression. The means scores for the fourth factor, Institutionalisation, indicated that participants were again equivocal with respect to the stigmatising and negative effects of mental institutes on patients. The fifth factor, Historical Cures contained just two items. Participants did not believe that faith healers could cure depression, nor did they think that the mentally ill should be kept in hospital until they completely recover. The last factor, Failure of Psychological Intervention, contained a single item. Participants indicated that they were unsure that a psychological intervention could cure depression.The factor analysis on the third section of the questionnaire (treating depression) again generated a six-factor solution  and accounted for 57.0% of the total variance. The eigenvalues and variance accounted for by each factor are presented in The regression results for the first section of the questionnaire, beliefs about depression, are presented in Myths and Shame, there was a significant effect of age, ethnicity, and the interaction between these two variables. The British Bangladeshi group had a lower adjusted mean score on this factor than the British Whites, indicating that the British Bangladeshi participants were more likely to believe that there is a sense of shame associated with depression, that depression is more common in the lower socioeconomic classes, and that a depressed individual may be possessed by evil. However, it should be noted that both adjusted means are well above the mid-point of the 6-point Likert-like scale. The simple regressions revealed a significant negative relationship between age and summated score for the British Bangladeshi participants, β = −.34, p < .001, indicating that beliefs concerning shame, socioeconomic status, and evil spirits were more prevalent with increasing age within this group. There was no age effect for the British White participants, β = .04, p = .614. For the second factor, Loss of Dignity, there was again an effect of age and ethnicity, and an age × ethnicity interaction. The British Bangladeshi participants had a significantly lower adjusted mean score than the British White participants on this factor, indicating that they were more likely than the British Whites to believe that a depressed individual and his or her family lose respect and dignity. However, the mean scores for both groups were above the mid-point of the scale. The simple regressions revealed that within the British Bangladeshis, a belief in loss of dignity was stronger with increasing age, β = −.44, p < .001, but no such trend was found within the British White group, β = −.09, p = .245. For the third factor, Simplistic Notions, there was a significant effect of both age and ethnicity – and a significant age × ethnicity interaction. The adjusted mean score for the British Bangladeshi group was significantly lower than for the British White group. Thus the British Bangladeshi participants were more likely than the British Whites to believe that being depressed is the same as being unhappy, that talking to family members can help, and that the depressed individual can be helped by simply going out to buy new clothes. A simple regression showed that within the British Bangladeshi group, increasing age was associated with stronger beliefs in the simplistic notions making up this factor, β = −.28, p < .001. This trend was not evident in the British White group, β = −.12, p = .106. For the fourth factor, Depression as an Illness, there was a significant effect of age, ethnicity and a significant interaction. The adjusted mean score on this factor for the British Whites was significantly lower than for the British Bangladeshis. Thus, overall, the British Whites were more likely to view depression as being an illness than were the British Bangladeshi participants. However, the simple regressions reveal that within the British Bangladeshi group, older participants were more likely to view depression as an illness, β = −.23, p = .002, whereas within the British White group, older participants were less likely to view depression as an illness, β = .18, p = .018. For the fifth factor, Negative Approach, there were significant effects of both age and ethnicity, but no interaction. Older participants were more likely to believe that depression is not helped by talking to a psychologist or psychotherapist, and that there is probably little that depressed individuals can do about their condition. The ethnicity main effect indicates that these views were stronger in the British Bangladeshi group than in the British White group. For the sixth factor, Helplessness, the overall regression was significant, but of the individual predictors, only ethnicity reached significance. The British Bangladeshi participants were more likely to believe that depression is associated with helplessness and loss of control than the British White participants. For the seventh factor, Sympathy, neither the overall regression nor any of the individual predictors were significant.For the first factor, The regression results for the second section of the questionnaire, causal explanations for depression, are presented in Life Events and Illness. There was a significant age effect for this factor, but no significant effect of ethnicity and no interaction. The results indicate that older participants (in both groups) were less likely to believe that social factors, financial stresses, traumatic experiences and physical illness could lead to the onset of depression. However this effect was weak – accounting for only 2.8% of the total variance. For the second factor, Psychological stress, the overall regression was significant, but of the individual predictors, only ethnicity reached significance. The British Bangladeshis were more likely to believe that psychological stress could cause depression than were the British White participants. For the third factor, Biological Explanations, there was no effect of age, a highly significant effect of ethnicity, and no interaction. The adjusted mean score for the British White participants was significantly lower than for the British Bangladeshis. Thus the British Whites were more likely to believe in a biological explanation for depression than were the British Bangladeshi participants. For the fourth factor, Environment and Aging, there was a significant effect of age and ethnicity – but no interaction between these variables. The adjusted mean score for the British White participants was significantly lower than for the British Bangladeshi participants. These results suggest that British Bangladeshis were less likely than the British Whites to believe in an environmental cause for depression, such as the weather or society, or that aging per se can cause depression; and older participants were less likely to believe in these causes than younger participants. However, both effects were weak; the age effect accounted for only 1.4%, and the ethnicity effect 2.8%, of the total variance. For the fifth factor, Genetics and Substance Abuse, there was a significant effect of age, no effect of ethnicity, but a highly significant cross-over interaction between age and ethnicity. The simple regression for the British Bangladeshi group revealed that the older participants were more likely to believe that depression is caused by having blood relatives who are depressed and less likely to believe that depression is caused by drug abuse, β = .30, p < .001. The opposite pattern was found for the British White group; older participants were less likely to believe that a blood relationship was of importance, and were more likely to believe that depression could result from drug abuse, β = −.22, p = .004. The final factor in this section was Non-Biological Explanations. For this factor, there was a significant effect of ethnicity, but no effect of age and no interaction between age and ethnicity. The mean score on this factor for the British White participants was significantly lower than for the British Bangladeshi participants. Thus, the British Whites were less likely to believe that depression could result from black magic, or a mundane life, than were the British Bangladeshi participants.The first factor in this section was The regression results for the third section of the questionnaire, treating depression, are presented in Religion and Culture, there was a significant ethnicity effect but there was no effect of age and no interaction. The result indicates that British Bangladeshi participants placed greater importance on religion, family, friends, self-help and society in the treatment for depression than did the British White participants. The overall regression was significant for the second factor, Counselling and Therapy, but of the individual predictors, only ethnicity reached significance. This indicates that the British Bangladeshi group had less faith in the effectiveness of counselling and therapy in the treatment of depression than the British White group. For the third factor, Medical Treatment, there was a significant effect of age – no effect of ethnicity – but a significant age × ethnicity interaction. As with the Genetics and Substance Abuse factor in the second section of the questionnaire, the interaction was cross-over in nature. The simple regression for the British Bangladeshi group revealed that a belief in medical  treatment for depression increased with increasing age, β = −.32, p < .001, but there was no such trend in the British White group, β = −.10, p = .201.For the first factor in this section, Institutionalisation, there were weak but significant effects of age and ethnicity, but no interaction. The results indicate that older participants in both groups were less likely to think that being in a mental hospital is stigmatising and has as a negative effect on the patient than the younger participants, but overall these beliefs were stronger amongst British Whites than British Bangladeshis. However, age accounted for only 1.5%, and ethnic group for only 1.4%, of the total variance. For the fifth factor, Historical Cures, there was a significant effect of age, ethnicity, and an age × ethnicity interaction. The adjusted mean score for the British Bangladeshi group was significantly lower than for the British White group. A simple regression revealed a significant age effect for the British Bangladeshi participants, β = −.32, p < .001, indicating that older British Bangladeshis were more likely than younger British Bangladeshis to believe that patients should be kept in mental hospitals until they are cured, and that a faith healer can cure depression. There was no effect of age in the British White group, β = .01, p = .934. For the sixth and final factor in this section, Failure of Psychological Intervention, there were no effects of age or ethnicity, and no interaction.For the fourth factor, Overall, the findings suggest that there are differences in attitudes and beliefs about depression between British Bangladeshis and British Whites, and that these differences are often moderated by age – particularly within the Bangladeshi population. We note that there appears to be very little difference between the two cultures in the young age group with respect to knowledge of depression.The older British Bangladeshis generally tended to show more negative attitudes towards depression than younger British Bangladeshis and British Whites. Thus attitudes towards depression were moderated by age within the Bangladeshis but not within the British Whites, where both young and old generally demonstrated similar attitudes towards depression. The results are generally consistent with other studies in the area e.g., .general beliefs about depression, and unlike younger British Bangladeshis and British Whites, older British Bangladeshis associate depression with personal shame, and loss of respect and dignity for the family. This finding is consistent with the findings from the study by With respect to causal explanations for depression, older individuals in both groups are less likely to believe that depression can be caused by exogenous factors . However, British Bangladeshis are more likely to believe that depression can be caused by psychological stress and less likely to believe it can be caused by biological factors than British Whites. They are less likely to think that depression is caused by environmental factors or ageing per se, and more likely to believe it has a genetic basis than British Whites – although they are also more likely to believe that depression can have a supernatural aetiology – and that faith healing can cure depression. An interaction between cultural and age was found; within British Bangladeshis older participants are more likely to believe that depression has a genetic component and less likely to believe that depression is caused by drug abuse than younger individuals, whereas the opposite pattern is evident amongst the White British.With respect to treatment of depression, British Bangladeshis place greater importance on the role of religion, family and friends, and have less faith in the effectiveness of counselling and therapy than British Whites. This was expected, and highlights the importance of the family in the British Bangladeshi culture and supports the notion that Asians are more likely to use a lay referral system rather than seeking professional help. This may imply that the British Bangladeshis do not view depression to be such a serious illness, and the depressed individual can get help from the family rather than a health professional, but alternatively, it may indicate a fear of being stigmatised. Older British Bangladeshis are more likely to believe in the efficacy of medical as opposed to psychological intervention than younger British Bangladeshis or British Whites, but they are also willing to seek help from other sources such as faith healers. Finally, older individuals in both groups are less likely than younger individuals to think that being in a mental hospital is stigmatising, and older British Bangladeshis are more likely to believe that a stay in a mental hospital can cure depression.With respect to This study has implications for the provision of appropriate psychiatric facilities for migrant communities, whose values are influenced by traditional cultural norms. It is important not to over-generalise cultural stereotypes since there is distinct diversity in values and attitudes within these cultures. Age was found to have significant impacts on the general beliefs and attitudes towards depression. Presumably therefore an older Bangladeshi's pathway to treatment or advice/help that they may give others will be different from younger Bangladeshi's. This pattern may be equally true of other immigrant groups where older migrants are more representative of the culture from which they come than the younger generation who take on the predominant beliefs found in the majority host culture.The clinical implications are primarily concerned with the mental health literacy of older Bangladeshi's who may not recognise the signs and symptoms of various types of depression in themselves, family and acquaintances. It may be therefore, particularly important to target this group with information and assistance. Indeed it seems that Islamic religious leaders may play an important part in this, particularly when they are seen to support and agree with health care professionals. Whilst there seems to be tension between Islam and certain types of faith healers, the role of Islam in the early development of medicine could be emphasised so help older migrants accept the advice of health care professionals with respect to their and others symptoms of depression and they way to get effective help.


Background: The association of attention-deficit/hyperactivity disorder (ADHD) and tic disorder (TD) is frequent and clinically important. Very few and inconclusive attempts have been made to clarify if and how the combination of ADHD+TD runs in families.Aim: To determine the first time in a large-scale ADHD sample whether ADHD+TD increases the risk of ADHD+TD in siblings and, also the first time, if this is independent of their psychopathological vulnerability in general.Methods: The study is based on the International Multicenter ADHD Genetics (IMAGE) study. The present sub-sample of 2815 individuals included ADHD-index patients with co-existing TD  and without TD  as well as their 1606 full siblings (n = 358 of the ADHD+TD index patients and n = 1248 of the ADHD-TD index patients). We assessed psychopathological symptoms in index patients and siblings by using the Strength and Difficulties Questionnaire (SDQ) and the parent and teacher Conners' long version Rating Scales (CRS). For disorder classification the Parental Account of Childhood Symptoms (PACS-Interview) was applied in n = 271 children. Odds ratio with the GENMOD procedure (PROCGENMOD) was used to test if the risk for ADHD, TD, and ADHD+TD in siblings was associated with the related index patients' diagnoses. In order to get an estimate for specificity we compared the four groups for general psychopathological symptoms.Results: Co-existing ADHD+TD in index patients increased the risk of both comorbid ADHD+TD and TD in the siblings of these index patients. These effects did not extend to general psychopathology.Interpretation: Co-existence of ADHD+TD may segregate in families. The same holds true for TD (without ADHD). Hence, the segregation of TD (included in both groups) seems to be the determining factor, independent of further behavioral problems. This close relationship between ADHD and TD supports the clinical approach to carefully assess ADHD in any case of TD. Attention-deficit/hyperactivity disorder (ADHD) with its problems of attention, general motor restlessness, and impulse control is a developmental disorder with a strong impact on the affected individual's life, including academic difficulties, impaired socialization, and strained parent-child relationships  it needs to be disentangled further. Therefore, it seems to be worthwhile elucidating the familiality of ADHD+TD. While taking an ADHD perspective, this study will extend the small empirical data base in order to better answer question (a) and add new knowledge to (b).Hence, we are running this study by analyzing for the first time a large sample of ADHD affected children and their  siblings, who took part in the IMAGE-study  and their full siblings (regardless of their possible ADHD-status) were recruited as part of the IMAGE  study. IMAGE is a collaborative study of twelve specialist centers in seven European Countries and Israel. It aims to identify genes that increase the risk of ADHD using linkage and association strategies. As inclusion criteria were used an age of 5–17 years, Caucasian descent, IQ ≥ 70, no diagnosis of autism, epilepsy, general learning difficulties, brain disorders and known genetic disorders. Parent and teacher questionnaires (see below) were applied to screen participants. In screening cases positive for a diagnosis of ADHD, the PACS interview (see below) was conducted. PACS interviewers  were trained at the London Institute of Psychiatry under supervision of Prof. E. Taylor. Inter-rater agreement for PACS was 0.88 (range 0.71–1.00).A detailed description of the IMAGE sample  has already been given in previous reports  were allocated to the group ADHD+TD (N = 262) if they fulfilled the criteria for both ADHD and TD; if TD-criteria were not fulfilled, they were classified as group ADHD-TD (N = 947).The siblings of index patients  were differentiated in those of index patients with ADHD–TD (N = 1248) and siblings of index patients with ADHD+TD (N = 358) regardless of their own diagnostic status. Further the 1606 siblings of index patients with ADHD  were screened themselves for ADHD with Conners' Rating Scales and SDQ. In case of scores indicative for a diagnosis of ADHD a PACS interview (see Assessment below) has been conducted and led to a diagnosis of ADHD in 131 siblings. Because the information about a TD diagnosis was taken from the PACS interview and this has been conducted only in those siblings for whom ADHD was assumed by screening, also the information about the occurrence of TD yes/no was available only for 271 siblings . Among those siblings 41 were identified as being affected with TD  for parents and teachers and the Strengths and Difficulties Questionnaires (SDQ) for parents and teachers. Scores were indicative for a diagnosis of ADHD if T-scores were ≥63 on the Conners' DSM-IV ADHD Total score and if the score on SDQ Hyperactivity scale exceeded the 90th percentile. In these cases the valid, standardized semi-structured interview PACS , since when these tics occurred and if the tics have been present in the absence of stimulant medication. According to PACS each DSM-criterion was coded as a dichotomous variable , hence an omnibus diagnosis of TD was given if the child fulfilled the TD criteria. Since TD should be seen along a continuum and to keep large enough TD-subgroups we did not specify for single DSM TD-categories.To assess the psychopathological profile of the children (index patients and their related siblings) parents and teachers had to complete the long versions of Conners' Rating Scales – Revised .familial occurrence for each of the three conditions under investigation  we calculated the relative risk of sibling's diagnoses in relation to both index patient-groups (ADHD-TD and ADHD+TD). The odds ratio served as a measure for the degree to which the relative risks of sibling's diagnosis differed between both patient-groups. The method used was PROC GENMOD.To analyze the psychopathological symptoms a mean score was calculated for each Conners' and SDQ scale named above. Because of some missing data from questionnaires and PACS interview the number of cases varied between the different psychopathological variables.To analyze the level of t-tests for descriptive purposes. For the case of inhomogeneous variances the degrees of freedom were approximated by the Welch-Satterthwaite equation. For comparison of the sibling-groups we used PROC GENMOD.An analysis of variances was conducted, including two factors: “proband-status” (index patients vs. siblings) and “disorder” (ADHD–TD vs. ADHD+TD). Index patients and siblings derived from the same families, so their data were partly dependent of each other. But they did not form a sample of matched pairs with one sibling being assigned to each index patient, because number of participating siblings per family varied. Therefore, we employed PROC GENMOD for generalized linear models—a SAS procedure able to handle partly dependent data. Additionally, follow-up comparisons analyzed patient-groups and sibling-groups separately. The comparison of both index patients groups was accomplished with p = 0.06). Additionally, there were no differences in IQ between the two groups . However, in the group of children with ADHD-TD the proportion of girls (14.5%) exceeded their proportion in the ADHD+TD-group .Patients having ADHD without TD (ADHD–TD: mean age 10.7 ± 2.8 years) did not differ in age from patients with ADHD+TD . Also, there was no significant difference in gender between both groups .Siblings of index patients with ADHD-TD had a mean age of 10.8 ± 3.4 years and a mean IQ of 101.7 ± 13.3. This did not differ from the mean age and IQ of the siblings whose related index patient suffered from ADHD+TD  and on three scales of the SDQ-P . In teacher ratings the interaction only reached significance on the CTRS-R-L DSM-IV total score . In other words, if TD is added to ADHD (in the ADHD+ TD groups) it does not seem to increase the risk to develop ADHD. It follows, that in this case ADHD is the leading vulnerability marker.our main finding, there was a significantly higher risk to present with ADHD+TD (and a tendency for TD without ADHD) among siblings of patients with ADHD+TD. This suggests that the familiality of ADHD+TD may exist and is probably driven by the factor TD, which is part of both groups, namely ADHD+TD and TD without ADHD.In contrast, and this is To our knowledge there is only one study which examined the occurrence of ADHD+TD in relatives of ADHD+TD-patients  was not supported on the basis of dimensional psychopathology.In affected children teachers' ratings were found somewhat opposite to parents' ratings. While parents rated affected index children with ADHD+TD (compared to ADHD–TD) higher, teacher tended to see more problems in the ADHD–TD than in the ADHD+TD group. Since the effect-sizes of both kinds of differences were small (0.05–0.32) this may underline that TD usually adds little to psychic problems when it co-exists with ADHD  TD was diagnosed by parent interview only, (b) the TD group was not differentiated for the known TD categories because there was no full formal assessment and resulted sample size would have been too small for statistical testing. However, percentage of TD (13 vs. 22%) in the respective for ADHD screen positive sib-groups corresponds with the usual frequency of TD in ADHD . In order to comment on more specific modes of familiality it would be necessary to additionally include a TD-only and a healthy control-group.Our results suggest that ADHD+TD may run in families and that the vulnerability for this might be related to TD. The TD-specificity of our finding is supported by the fact, that TD-only ran also in families and that general psychopathology did not show familiality effects. It remains to be clarified if this familial TD-effect holds in a TD-only group and if it may be influenced by obsessive-compulsive symptoms (which often exist together with ADHD as well as TD), because there is some evidence that association between TD and ADHD “may be due to a genetic association between OCD and ADHD and in part to shared environmental factors” (O'Rourke et al., AR, VR, and TB designed and wrote the article; they contributed equally and share main authorship. All authors are principal investigators of the IMAGE study and reviewed and approved the article.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.