Although it is well established that cognitive performance in children with attention-deficit/hyperactivity disorder (ADHD) is affected by reward and that key deficits associated with the disorder may thereby be attenuated or even compensated, this phenomenon in adults with ADHD has thus far not been addressed. Therefore, the aim of the present study was to examine the motivating effect of financial reward on task performance in adults with ADHD by focusing on the domains of executive functioning, attention, time perception, and delay aversion.We examined male and female adults aged 18–40 years with ADHD (n = 38) along with a matched control group (n = 40) using six well-established experimental paradigms.Impaired performance in the ADHD group was observed for stop-signal omission errors, n-back accuracy, reaction time variability in the continuous performance task, and time reproduction accuracy, and reward normalized time reproduction accuracy. Furthermore, when rewarded, subjects with ADHD exhibited longer reaction times and fewer false positives in the continuous performance task, which suggests the use of strategies to prevent impulsivity errors.Taken together, our results support the existence of both cognitive and motivational mechanisms for the disorder, which is in line with current models of ADHD. Furthermore, our data suggest cognitive strategies of “stopping and thinking” as a possible underlying mechanism for task improvement that seems to be mediated by reward, which highlights the importance of the interaction between motivation and cognition in adult ADHD. Attention-deficit/hyperactivity disorder is a multidimensional disorder that is characterized by developmentally inappropriate levels of activity, impulsivity, and inattentive behavior. ADHD affects 5–10% of school-aged children One of the most influential models at present, the dual-pathway model activation  and arousal  influence individual task performance. According to this model, effective cognitive functioning relies on an optimal energetic state wherein arousal and activation are optimally adjusted to actual task demands. When the adjustment is suboptimal, i.e., when under- or overactivation occurs, performance deficits are predicted to occur. Adjustments to the actual task demands are provided by the effort pool, which increases or decreases activation and arousal. In subjects with ADHD, deficient functioning of the effort pool is assumed to cause energetic maladjustment and, as a consequence, impaired task performance. Support for the cognitive-energetic model has been largely derived from the literature on event rate effects, i.e., the speed with which stimuli are presented  or a composite measurement . Using the n-back task, two studies found performance accuracy to be unimpaired in adults with ADHD The term working memory refers to a temporally and quantitatively limited storage mechanism in which information is actively processed  to provide complex goal-directed behavior. In adults with ADHD, meta-analyses have revealed working memory deficits The term sustained attention denotes the maintenance of attention allocation over a longer period of time. One of the most typically applied tasks in the domain of sustained attention is the continuous performance task (CPT), which requires the patient to detect a target sequence that is embedded in randomly presented visual stimuli. Variables of interest include measurements of performance accuracy, omission errors, RT, and SDRT. Four meta-analyses addressed CPT performance in adults with ADHD and consistently found that subjects with ADHD performed less accurately and exhibited a higher number of omission errors and higher SDRT, whereas no RT differences were observed between the groups Time discrimination tasks evaluate the ability of a patient to discriminate between stimuli that differ in their presentation time for only several milliseconds. Dependent variables of interest include the performance quality , and the time needed to make a decision. Discriminatory deficits have been consistently observed in children and adolescents with ADHD In this type of task, stimuli are presented for a defined time interval , and participants have to infer the duration of stimulus presentation and indicate this time interval by pressing a button. Absolute discrepancy scores , which reflect the overall magnitude of error regardless of its direction, and accuracy coefficient scores , which reflect the under- and over-reproductions, are used as dependent variables. Compared with controls, children and adolescents with ADHD seem to overestimate short time intervals and underestimate long time intervals As outlined above, the term delay aversion denotes a motivational tendency to avoid delays over time, with a preference for the immediate delivery of consequences to reduce waiting. The Choice Delay Task To summarize, the inhibitory deficit in adults with ADHD appears to be most prominent in terms of an abnormally prolonged stopping process, and sustained attention appears to be most affected in terms of impaired performance accuracy. Furthermore, both domains are characterized by increased reaction time variability, whereas reaction time itself appears largely unaffected. For the remaining domains in focus, the body of literature is less substantial. Research on working memory performance using the n-back task is deficient in the fact that most studies report measures of either performance accuracy or speed, complicating the interpretation of heterogeneous findings; however, both speed and accuracy measures were found to be impaired. In time discrimination tasks, adults with ADHD appear to perform less accurate but performance strategies of slowing might help the subjects to overcome their deficits, and in time reproduction tasks, they seem to underreproduce especially long time intervals which results in decreased reproduction accuracy. Furthermore, adults with ADHD seem to prefer small immediate over large delayed rewards.Although there are no pre-data on rewarded task performance in adults with ADHD, a performance-enhancing effect of reward contingencies has been found in studies in children and adolescents with ADHD see . SummariDelay aversion has extensively been examined within reward paradigms, but no study thus far has compared rewarded and non-rewarded conditions directly. Studies in which children received physical rewards  Taken together, several studies on the influence of reward contingencies on cognitive task performance in children and adolescents with ADHD are available, and these studies suggest that parameters of response speed and homogeneity The aim of the current study was (1) to identify core cognitive deficits in adult ADHD that have been repeatedly reported in children and adolescents with ADHD and (2) to use well-established paradigms for these domains to examine the influence of financial reward contingencies as potentially motivating factors for relevant performance parameters in adults with ADHD. We followed a task-oriented approach, which allowed the direct comparison of rewarded task performance patterns in children and adults with ADHD. Simultaneously, implementing a substantial number of tasks across several key domains of cognitive functioning allowed us to follow a parameter-oriented approach; we were able to determine which task parameters are the most susceptible to motivational incentives across domains. With regard to the dependent variables, we therefore considered a holistic approach and incorporated parameters of accuracy, speed, and reaction time variability. We are convinced that this approach best reflects the possible patterns of task performance , as well as the possible changes in task performance strategies that may be induced by incentives . Based on the literature described above, the cognitive domains of interest for this study incorporate executive functioning (inhibition and working memory), attention (sustained attention), time perception (time discrimination and time reproduction), and delay aversion.We hypothesized that subjects with ADHD in the non-rewarded condition would exhibit deficits in all cognitive domains examined and that they would demonstrate improved stop-signal task performance, CPT performance, and time reproduction performance in anticipation of a reward. Because group × condition interaction effects have been demonstrated for stop-signal task parameters and time reproduction parameters as outlined above, thus demonstrating that children with ADHD benefit more from rewards than controls, we anticipated that the performance improvements would be most pronounced for the stop-signal task and the time reproduction task. To the best of our knowledge, no study thus far has examined the influence of reward on working memory, time discrimination and delay aversion, but we anticipate the performance-improving effect of rewards to be present in these tasks as well.We examined males and females with ADHD who were aged 18–40 years, together with gender-, age-, and IQ-matched controls. Patients were recruited from the ADHD outpatient service of the Department of Psychiatry and Psychotherapy, University of Rostock. Patients were screened for exclusion criteria by telephone before being invited to participate in the study. The detailed diagnostic procedure included German versions of the Barkley Interview Fifty-one subjects with a clinical diagnosis of ADHD and 43 controls were screened for participation in the study. According to the exclusion criteria, eight subjects with borderline personality disorder, one subject with epilepsy and tic disorder, and four subjects with subclinical symptom severity were excluded from the ADHD group. From the control group, one subject with epilepsy was excluded, and two additional subjects were excluded as a result of the age- and IQ-matching procedure. The final sample consisted of 38 subjects with ADHD  and 40 controls . With respect to ADHD subtypes, 30 subjects met the criteria for the combined subtype, seven subjects were primarily inattentive, and one subject was primarily hyperactive-impulsive. Eighteen ADHD subjects were drug-naïve; the others had previously taken methylphenidate but were free of any medication for a minimum of 72 h prior to testing. Within the ADHD group, the following comorbidities were present: two subjects with recurrent depressive disorders, currently remitted; one subject with an adjustment disorder; two subjects with a binge-eating disorder; and nine subjects with personality disorders (except for BPD). Within the control group, no psychiatric or personality disorders were observed. Subjects with ADHD were older but did not differ from the controls in terms of IQ. It should be noted that the relatively high IQ values could have resulted from the use of the short version of the WAIS, which utilizes relatively old German norms. We did not examine a group of only well-educated subjects; rather, educational and occupational levels were mixed in both experimental groups. Basic demographic and clinical sample characteristics are provided in χ2 = 1.09, p = .78, ns . The ADHD subtype distribution and medication status was as follows: ADHD, non-reward condition: 13 combined, 4 inattentive, 1 hyperactive-impulsive, and 11 drug-naïve; ADHD, reward condition: 17 combined, 3 inattentive, and 7 drug-naïve.All subjects were randomly assigned to the reward conditions . Gender was equally distributed in the resulting four experimental groups, The stop-signal task was designed based on the task of Carter et al. Altogether, 12 n-back blocks  were randomly presented. Each block contained 14 letters  and was preceded by the numbers “1” or “2”, which indicated the respective n-back condition. The trial length was 3,000 ms. After 1,250 ms had elapsed, the n-back letter was presented for 500 ms. Consequently, subjects had a time window of 1,750 ms to respond. All subjects performed two 1-back and two 2-back practice trials prior to the task. The reaction time for correctly identified targets (RT) and performance accuracy (d′) served as dependent variables. Performance accuracy was analyzed based on signal detection theory, in which individual discrimination indices were calculated as follows: [d′  =  z (hits/number of targets) − z ].In this task, 525 letters are randomly presented on the screen, and the participants have to press the left mouse button as fast as possible if the letter “X” appears subsequent to the letter “A”. The task comprised 52 target-sequences (“A–X”) and 20 “A” without “X” to measure omission errors. Each letter was presented for 250 ms, and the inter-stimulus interval was 1,500 ms. The task was preceded by a practice trial that contained 30 letters and three targets. False positives (FP), omission errors, MDRT for correctly identified targets and SDRT served as dependent variables.Participants were shown a red circle and a green circle in quick succession that barely differed in presentation duration. The participants were then required to decide which of the circles was presented for a longer duration. One of the circles was always presented for 1,000 ms; the other circle was initially presented for 1,300 ms. Correct answers were followed by a 15-ms reduction in the presentation duration, whereas incorrect answers were followed by an increase of 15 ms. For task details, see Smith et al. The ability to estimate a several-second interval of time was assessed using a time reproduction paradigm The applied delay aversion task was a modified version of the continuous delay aversion test introduced by Müller et al. The QCM is an 18-item questionnaire that was designed to assess current motivational aspects regarding task completion, including the dimensions of task interest, perceived challenge, mastery confidence, and incompetence fear, according to the cognitive-motivational process model The study was conducted at the Department of Psychiatry and Psychotherapy, University of Rostock. After explaining the general study purpose , the study procedure was explained, and the subjects underwent IQ testing. Subsequently, the subjects were seated in a quiet and dimmed experimental room and worked on the experimental tasks in the following order: delay aversion task, time reproduction task, n-back task, stop-signal task, time discrimination task, and CPT. For all tasks, a global instruction asked the subjects to perform the computerized tasks as fast and as accurately as possible. Each subsequent task was introduced by practice trials.Additionally, subjects who participated in the reward condition were given the opportunity to earn extra money, depending on their performance quality. In doing so, reward conditions for each single task were explained after the subjects had performed the practice trials and after they had indicated their task-specific motivational ratings. The design of the reward options was guided by the aim of distributing overall gains homogeneously across tasks. In this way, we intended to prevent differences in the degree of reward-induced motivation between tasks. For three tasks, a response-cost option was used . The reward conditions for the remaining tasks were as follows: time discrimination task, +0.10 € for each correct answer; delay aversion task, +0.10 € for trial duration ≥60 s, +0.08 € for ≥50 s, +0.06 € for ≥40 s, and +0.04 € for ≥30 s; time reproduction task, +0.10 € if the deviation between the demanded and the reproduced time interval was ≤20%. Assuming perfect performance, a maximum of 13.97 € could be gained across all tasks. Subjects in the reward condition were provided feedback on their earnings at the end of the task  or they were provided trial-based feedback in addition to feedback at the end of the task . The reward feedback was contingent on the subject's task performance.The tasks were projected onto a white screen using a Sanyo LCD Z2 projector. The subject's distance to the screen was approximately 138 inches, and the screen was 51 inches wide. The visual angle was 21 degrees. The experimental paradigm was presented using Presentation software , which was installed on a desktop PC . The total duration of the tests was approximately 2.5 hours.The study was performed in accordance with the latest version of the Declaration of Helsinki. The ethics committee of the Faculty of Medicine of the University of Rostock specifically approved this study, and written informed consent was received from all participants. At the beginning of the study, all of the subjects were told that they would be compensated for their time and expense with 20 €. Additionally, the subjects in the reward condition were told that they could earn extra money depending on the quality of their performance. To show equal appreciation for the effort of all subjects, however, all subjects received 30 € after finishing the study, irrespective of their performance quality. This procedure was already applied by other authors ηp2) is reported as a measurement of effect size. Prior to analysis, raw data were z-transformed to identify extreme outliers (z>3.0), which were replaced by the respective group mean. The data are available at hpps://www.researchgate.net/profile/Ivo_Marx/.Data were analyzed using SPSS version 17 . Group comparisons for sociodemographic and clinical data were performed using univariate analyses of variance (ANOVAs). Because of significant group differences in age, age was included as a covariate in all statistical analyses. Group comparisons for task-related motivations were also performed using univariate ANCOVAs. Group differences in the dependent variables were analyzed using univariate analyses of covariance (time discrimination task), multivariate analyses of covariance , and repeated-measures ANCOVAs with the diagnostic group and motivational condition as between-subject factors and the n-back level (n-back task), the seven time intervals (time reproduction task), and the first and second half of the test (delay aversion task) as within-subject factors. For repeated measurement analyses, tests for significance were performed using Pillai's trace statistic, and in case of significant main or interaction effects, post-hoc comparisons were performed by two-tailed univariate ANCOVAs, as well as independent-sample and paired-sample t-tests. The significance level for all tests was p≤0.05. The partial eta-squared  = 7.10, p = .009) and the reward condition  = 7.05, p = .01) for the n-back task. The controls exhibited higher QCM-scores than the ADHD subjects, and the subjects in the non-reward condition exhibited higher QCM-scores than the subjects in the reward condition. Therefore, individual QCM-scores were included as covariates in n-back analyses. In all other tasks, no significant effects emerged (p>.05). QCM-scores for the initial task motivations are presented in The initial task motivation for the six different tasks ranged from 3.71 to 5.13, which reflects an intermediate motivational baseline across the four experimental groups. Univariate ANCOVAs revealed a significant effect for the diagnostic group  = 2.34, p = 0.05), and univariate post-hoc ANCOVAS revealed a significant between-subjects effect for the number of omission errors  = 7.39, p = .008, ηp2 = 0.10), which was elevated in the ADHD subjects . No further significant effects emerged (p>.05). A post-hoc analysis was conducted to explore whether SSRT was abnormally prolonged relative to RT in the ADHD group, but no significant effects emerged (p>.05). Incentives did not affect performance in the stop-signal task (p>.05).MANCOVA revealed a global effect for the diagnostic group  = 20.04, p<.001, ηp2 = 0.22), with ADHD subjects impaired in both the 1-back  = 12.35, p = .001, ηp2 = 0.15) and the 2-back condition  = 11.84, p = .001, ηp2 = 0.14). Incentives did not affect performance in the n-back task (p>.05).A significant between-subjects effect for d′ emerged  = 4.21, p = .004), and univariate post-hoc ANCOVAs exhibited elevated SDRT in the ADHD subjects  = 5.30, p = .02, ηp2 = 0.07). Furthermore, we observed a global diagnostic group × reward condition interaction  = 3.02, p = .02), which was significant for FP  = 5.40, p = .02, ηp2 = 0.07) and MDRT  = 4.38, p = .04, ηp2 = 0.06). Post-hoc ANCOVAs revealed a higher prevalence of FP in the non-reward condition in ADHD subjects compared with the controls  = 6.89, p = .01, ηp2 = 0.16), whereas no group differences were observed in the reward condition  = 0.06, p = .81, ns). With regard to MDRT, subjects with ADHD exhibited prolonged MDRT in the reward condition than in the non-reward condition (t(36) = 2.00, p = .05), but no such effect was observed in the controls (t(38) = 0.70, p = .49, ns).MANCOVA revealed a global effect for the diagnostic group (p>.05). To determine whether performance accuracy in the ADHD group was correlated with slower and more variable reaction times, which could be interpreted as the need for an additional effort to make correct decisions F = 7.72, p = .007, ηp2 = .10) and SDRT  = 11.57, p = .001, ηp2 = .14); all subjects were faster and less variable in their decision times in the reward condition compared with the non-reward condition . Overall, no differences emerged between the experimental groups (p>.05); the incentives affected task performance for all subjects.No significant effects emerged for the sensitivity threshold  = 14.66, p<.001, ηp2 = 0.17). Absolute discrepancy scores increased as the time interval to be reproduced increased in length  = 3.57, p = .002, ηp2 = .05). Furthermore, the absolute discrepancy scores increased more in the ADHD group  = 5.49, p<.001, ηp2 = .07), and there was a significant interaction among the absolute discrepancy score increase, block order, and the reward condition  = 2.49, p = .02, ηp2 = .03). However, post-hoc repeated measures ANCOVAs revealed no significant interactions between the increase in absolute discrepancy score and block order under both reward conditions (p>.05). Additionally, we observed a significant increase in the absolute discrepancy score with the diagnostic group and the reward condition  = 3.58, p = .002, ηp2 = .05). Post-hoc repeated measures ANCOVAs revealed larger absolute discrepancy score increases in the ADHD group than in the control group in the non-reward condition  = 6.35, p<.001, ηp2 = .16) but not in the reward condition  = 0.94, p = .47, ns). Consequently, the mean absolute discrepancy score across all time intervals differed significantly between the groups in the non-reward condition  = 19.00, p<.001, ηp2 = .36) but not in the reward condition  = 1.80, p = .19, ns).Absolute discrepancy scores were elevated in subjects with ADHD  = 4.81, p = .03, ηp2 = .06). Furthermore, there was a significant interaction between the diagnostic group and block order  = 4.91, p = .03, ηp2 = .06), and post-hoc analyses revealed a decrease in accuracy coefficient scores in the second task block compared with the first task block in ADHD subjects (t(37) = 2.71, p = .01) but not in controls (t(38) = 0.22, p = .82, ns).The accuracy coefficient scores were lower in the reward condition than in the non-reward condition  = 10.73, p = .002, ηp2 = .13) and reward condition  = 8.92, p = .004, ηp2 = .11), with ADHD subjects and subjects in the non-reward condition exhibiting shorter time intervals. Univariate ANCOVA with post-hoc comparisons revealed that ADHD subjects in the reward condition did not demonstrate different performance compared with controls in the non-reward condition  = 6.76, p<.001, ADHD, reward condition vs. CON, non-reward condition: p = 1.00, ns). Repeated-measures ANCOVA revealed no effect of imposing post-trial delays of different lengths on subsequent interval lengths (p>.05).The overall mean trial duration differed significantly depending on the diagnostic group (p>0.05). The means and standard deviations for all dependent measures can be derived from No further between- and within-subject main effects or interaction effects were observed  than ADHD subjects , but this difference was not significant  = 2.04, p = .16, ns).Across all tasks, controls gained slightly more money  and time perception (time reproduction task).As expected, impaired performance was observed across several cognitive domains in subjects with ADHD, including stop-signal task omission errors, n-back accuracy, reaction time variability in the CPT, and time reproduction accuracy. Moreover, subjects with ADHD demonstrated shorter time intervals in the delay aversion task. However, although our data are consistent with recent findings of increased delay aversion in adults with ADHD With regard to the domains that were impaired in subjects with ADHD in the present study, reward affected the task performance in different ways. Whereas stop-signal omission errors, n-back accuracy and response time variability in the CPT were not affected by rewards, a differential group effect was observed for time reproduction. Subjects with ADHD exhibited higher absolute discrepancy scores with increasing time interval lengths and, as a consequence, a higher overall absolute discrepancy score only in the non-reward condition but not in the reward condition. Thus, reward minimized absolute discrepancy score increases in subjects with ADHD and equalized the performance between the groups. Likewise, McInerney and colleagues Furthermore, reward affected task performance in cognitive domains where subjects with ADHD were not impaired. A differential group effect was observed for CPT performance; subjects with ADHD exhibited longer reaction times in the reward condition than in the non-reward condition, whereas controls did not. In addition, ADHD subjects exhibited a higher number of false positives in the non-reward condition but not in the reward condition. Thus, it may be concluded that subjects with ADHD, when rewarded, take more time to make their decisions, which results in a lower number of impulsivity errors as measured by false positives. Similarly, a speed-accuracy trade-off for the stop-signal task was reported by Scheres et al. In accordance with recently conducted studies, we determined that subjects with ADHD were not impaired with respect to the number of successful inhibitions In line with the literature, we further found decreased performance accuracy in the CPT in the absence of reward Furthermore, although studies in children and adolescents Our results provide support for current models of ADHD that incorporate motivational pathways to the disorder. First, the cognitive-energetic model With regard to the dual-pathway-model of ADHD There are some limitations of our study. First, we examined subjects who visited the ADHD outpatient service of our outpatient clinic. As indicated by the symptom severity scores, the ADHD symptom severity was rather moderate. The relatively low symptom severity and the low rate of comorbid disorders could indicate that we included rather moderately affected subjects in our study. In addition, one of the tasks used (the delay aversion task) appears to display a ceiling effect. Therefore, the presence of group differences between subjects with and without ADHD in some of the domains, namely, response inhibition and time discrimination, should be replicated in samples with higher symptom severity. In addition, a more challenging task for delay aversion may be needed so that the resultant findings can be interpreted in terms of marked delay aversion. Second, it is possible that the 20 € compensation for study participation increased the initial degree of motivation such that the additional reward produced a performance increase in addition to this effect. For this reason, it is possible that the motivational power of financial reward was not as strong as it could have been with non-compensated study participation or if larger rewards were used. Third, as the order of experiments in our study was not randomized, order effects cannot be ruled out. Fourth, we implemented reward and response cost options, which makes it difficult to directly compare the performance-increasing effect of both contingencies. Because there is some evidence that both contingencies may be differentially effective By implementing a large test battery that covered different key domains of cognitive functioning associated with ADHD, the current study succeeded in reproducing cognitive dysfunctions typical of children and adults with ADHD and demonstrated for the first time that the cognitive functioning of adults with ADHD is susceptible to reward. Forging a bridge to current models of ADHD, our results suggest the existence of primarily motivational deficits in delay aversion and time reproduction, with rewards equalizing the performance of subjects with and without ADHD. Furthermore, our data suggest cognitive strategies of “stopping and thinking” as possible underlying mechanisms for performance improvements that seem to be mediated by reward (CPT), thereby highlighting the interaction between motivation and cognition in ADHD.Future studies are needed to identify domains that may be influenced by reward , the extent to which influence is possible (effect size of reward), and finally, the quality and amount of reinforcement necessary to achieve maximum performance in subjects with ADHD (improvement vs. compensation). In addition to theoretical model specifications, this knowledge may help to determine which therapeutic interventions are most effective in different settings associated with different cognitive demands .


In previous studies, we found a strong reduction in contrast perception and retinal contrast gain in patients with major depression, which normalized after remission of depression. We also identified a possible role of the dopaminergic system in this effect, because visual contrast perception depends on dopaminergic neurotransmission. Dopamine is also known to play an important role in the pathogenesis of attention deficit hyperactivity disorder (ADHD). Therefore, in order to explore the specificity of retinal contrast gain as a marker of depression in comparison with other psychiatric diseases, we recorded the pattern electroretinogram (PERG) in patients with ADHD. Twenty patients diagnosed with ADHD and 20 matched healthy subjects were studied. Visual pattern electroretinograms were recorded from both eyes. The contrast gain of the patients with attention deficit disorder (ADD) did not differ from the control group, nor did the contrast gain of any ADHD subgroup (predominantly inattentive or combined patients). In the healthy subjects, a significant correlation between depression score and contrast gain was found. As the contrast gain in an earlier study clearly separated the patients with depression from the controls, we assume that retinal contrast gain might be a specific marker in depression. Increasing evidence points to abnormalities in vision in depressive disorder Very similar findings in contrast sensitivity and retinal contrast processing have been reported in patients with Parkinson's disease (PD). In earlier studies, we found that contrast sensitivity is reduced in PD, whereas contrast adaptation is not affected Against this background, we assessed the specificity of reduced retinal contrast gain in depression with respect to other neuropsychiatric disorders with a link to dopaminergic dysfunction, namely, attention deficit hyperactivity disorder (ADHD).ADHD is well known in child and adolescent psychiatry, and its lifelong persistence is making an increasing impact on psychiatry in general Given the hypothesis that retinal contrast perception is modulated by the dopaminergic system, we chose ADHD as the first psychiatric condition in which we wanted to test the specificity of our findings of reduced retinal contrast gain in major depressive disorder. Thus, the aim of the present study was to investigate a possible dysfunction of visual contrast processing at the level of the retina in patients with ADHD by assessing their retinal contrast gain. Given that retinal contrast gain is reduced in patients with depression, the study tested the specificity of that finding.Patients were recruited at the Department of Psychiatry of the University Hospital of Freiburg. They gave written informed consent to participate in the study, which was approved by the ethics committee of the Albert-Ludwigs-Universität Freiburg. The participants met the DSM-IV criteria for attention deficit disorder (ADD), classified as either ADHD of the combined type or predominantly inattentive or hyperactive type (DSM-IV: 314.00-01). The exclusion criteria were the presence of any other DSM-IV first-axis psychiatric disorder, any other general neurological or medical condition, or any eye disease, except for correctable refractive errors. The ADHD diagnosis was assessed by senior consultant psychiatrists on the basis of a detailed psychiatric interview that integrated common psychiatric and somatic differential diagnoses and the patients' medical histories. In addition, since ADHD is not included in the SCID-I, the investigator rated 18 items corresponding to the current DSM-IV-criteria for ADHD adapted for the special needs for adults as proposed by the German Medical Association (ADHD Checklist) Eleven patients fulfilled the criteria for ADHD of the combined type (DSM-IV: 314.01) and nine for the predominantly inattentive type (DSM-IV: 314.00). The control group consisted of 20 age- and gender-matched healthy subjects without a history of neurological or mental disorders, all of whom scored in the normal range on CAARS and the ADHD Checklist. All subjects had a visual acuity above 20/25 wearing appropriate correction at the distance used for visual stimulation 2. For illustration, see Stimulation, recording, and analysis were performed by the EP2000 system To quantify the PERG-based contrast gain, a sequence of five checkerboard stimuli with 0.8° check size, contrast-reversing at 12 reversals per second, was presented with Michelson contrasts of 3.2%, 7.3%, 16.2%, 36%, and 80%. Each contrast level was presented for 10 s, and then the next contrast was applied, finally recycling to the first contrast level. This interleaved sequence was repeated until 80 artifact-free sweeps per contrast  were accumulated. The interleaved blocking ensured that any sequential effects  were distributed equally across all contrast values. The sequence was repeated once, and further analysis was based on the vector average of each recording pair.The PERG signals were recorded simultaneously from both eyes, using DTL electrodes placed at the lower limbus of each eye The potentials were amplified, filtered (first order 0.5–100 Hz), and digitized at 1 kHz with 16-bit resolution. To prevent temporal aliasing, all timing  was related to the stimulus monitor frame rate Off-line, all traces were Fourier-analyzed to calculate the magnitude spectrum. From this, a noise-free response estimate was extracted The total duration of the recording was approximately one hour per subject.We tested for statistical significance on contrast gain and contrast and interaction using a 2-factorial ANOVA. Post-hoc analysis was performed to test the effects of type of diagnosis.Correlations between contrast gain and the score on CAARS and the ADHD Checklist were calculated. Given our earlier reports of significant correlations between the extent of depression as measured with the Beck depression inventory (BDI) We measured the PERG-based contrast gain in 20 unmedicated patients with a current diagnosis of ADD .Eleven of our patients met the DSM-IV criteria for ADHD of the combined type and nine for the predominantly inattentive type. In the post-hoc comparison, no significant difference was seen .The number of artifacts is a quality estimate of patient cooperation. For example, when the participants are particularly restless, or execute frequent eye movements or blinks, the number of artifacts rises. The number of artifacts did not differ significantly between the two groups. The control group presented a mean 116 (SE = 92) sum of all recorded artifacts, compared to 102 (SE = 79) in the patient group .As in our earlier reports, we found a significant correlation between the BDI and retinal contrast in the control group , despite the low variability of BDI ratings. We did not find such a relationship in the patient group. None of the patients had been clinically diagnosed with depression .There was no correlation between any CAARS rating scale  or the ADHD Checklist  and contrast gain.The results demonstrate that the pattern electroretinogram, which was reduced in patients with major depression in previous studies With respect to depression, we replicated our earlier finding of a significant correlation between BDI scores and contrast gain in the healthy control group . This isTherefore, with this study, we found some specificity of retinal contrast gain as a marker of major depression, at least in comparison to ADHD in adulthood. Of course, specificity to other neuropsychiatric disorders, such as schizophrenia, schizoaffective, or bipolar disorder, needs to be examined as well, and a direct comparison between different disorders must be carried out.We assumed that reduced retinal contrast gain in major depression reflects a systemic dopaminergic dysfunction, objectively measurable at the level of the retina. Thus, it might be surprising that retinal contrast gain was not altered in patients with ADHD, since retinal contrast is modulated by dopamine and dopamine plays an important role in ADHD 2-receptor family, rather than, for example, in the D1-receptor 2-receptor family has been proposed 1-receptor family is discussed as one target element in ADHD 1-receptor function are best detected there Our primary goal was to test the specificity of retinal contrast gain abnormalities for major depression. Therefore, we used the identical paradigm as in our previous study. In this context, one has to consider that different stimulation and testing paradigms analyze different aspects of retinal function. Generally, contrast stimuli with high spatial frequency  are sensitive to changes in the DSome further limitations must be taken into account. Patients with ADHD obviously suffer from attention problems, and these might have hampered our results. Could it be that inattention led to a reduction in contrast gain that would have been detected otherwise or could have camouflaged reduced contrast gain in the ADHD group? In the present approach, we minimized a confounding effect of attention, since we used an electrophysiological task that is largely independent of attentional processes. The patients just viewed a computer screen displaying checkerboard patterns of different contrasts. We ensured that the participants fixated and focused by asking them to read out randomly presented digits from the screen center. The correct responses and artifacts did not differ between the two groups. In addition, the 12-Hz signal recorded from the retina illustrates that the subject looked at the grating, since no 12-Hz signal would have been produced otherwise see .Another issue is the moderate sample size of 40 subjects (20 ADHD and 20 control subjects). A larger sample might have picked up a more subtle difference in signal; thus, our result could be a false negative due to an underpowered sample. However, the size of this sample relates well to that of other similar pilot studies, and on the basis of our earlier study of patients with depression, we know that such a sample can produce very strong and clear difference signals None of the patients in the ADHD group had a clinical diagnosis of depression; nevertheless, some of our patients presented high BDI ratings. In this case, the BDI is not a good measure for the severity of depression In summary, in this study, we reported some specificity with respect to our earlier report of reduced retinal contrast gain as an objective marker of major depression: in the adult patients with ADHD, retinal contrast gain was normal. We replicated the previous finding of a significant correlation between contrast gain and BDI in the healthy subjects, but not in the subjects with ADHD. Thus, the measurement of contrast processing with this stimulus paradigm might be helpful in the differential diagnosis of patients with ADHD and major depression.


Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders, affecting an estimated 5 to 12% of school-aged children worldwide. From 15 to 19 million Chinese children suffer from ADHD. The aim of this study was to investigate the association between family-environmental factors and ADHD in a sample of Chinese children.A pair-matched, case-control study was conducted with 161 ADHD children and 161 non-ADHD children of matching age and sex, all from 5–18 years of age. The ADHD subjects and the normal controls were all evaluated via structured diagnostic interviews. We examined the association between family-environmental factors and ADHD using the conditional multiple logistic regression with backward stepwise selection to predict the associated factors of ADHD.Having experienced emotional abuse and being a single child were both significant factors associated with children diagnosed with ADHD. ADHD subjects were more likely to have suffered from emotional abuse  and have been a single child in the family  when compared to normal controls. The results were not modified by other confounding factors.Our findings provide evidence that family-environmental factors are associated with ADHD among children in China. These findings, if confirmed by future research, may help to decrease ADHD by increasing the awareness of the effects of childhood emotional abuse. Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders occurring during childhood and adolescence, affecting an estimated 5 to 12% of school-aged children worldwide Family structure, such as being a single child in a family with either two biological parents or with a single parent/step-parent, may play a role in child psychiatric disorders since these factors affect material resources and emotional strain in families A 3 year panel study in Taiwan This study was designed as a pair matching case-control study and conducted from July 2009 to May 2010. ADHD subjects were recruited from the Beijing Children and Adolescents Mental Health Center at Beijing An Ding Hospital of Capital Medical University in Beijing, China. All ADHD  subjects were children of Chinese Han nationality and between 5 to 18 years old at the time of the investigation. All ADHD participants were evaluated by child psychiatrists and fully met DSM-IV-TR criteria for ADHD (any subtype) Normal controls were children between 5 to 18 years old randomly selected from local elementary and middle/high schools during the same study period and from the same district in Beijing as the ADHD subjects. Using the pair-matched test design, each ADHD subject and normal control had the same sex and the same age (difference between birthdays within 6 months). The same exclusion criteria applied to the ADHD subjects was applied to the normal controls.The study was approved by the institutional review boards of An Ding Hospital of Capital Medical University and Mercer University, and complied with all applicable requirements of the United States. Written informed consent was obtained from each of the parents after the purpose and procedure of the study was explained. Parents and teachers of the ADHD subjects completed the questionnaire with a participation rate of 97.5%, and parents and teachers of the normal controls completed the questionnaire with a participation rate of 100%.To address important confounding factors, such as the male sex and younger ages being associated with an increased prevalence of ADHD The variable of maternal stress during pregnancy was provided by the biological mothers of both the ADHD and normal subjects. The mothers were asked whether or not they had experienced any of 10 major life stress events selected from a broader list of life stress events In the questionnaire, the parents were required to provide information about familial factors present during the child’s lifetime. Maternal and paternal education was assigned as being either compulsory education (≤9 years), high school education (9–12 years), or some college or advanced training (≥12 years) Altogether, seven lifestyle variables were included in this study. Parents were asked about their children’s exposure to domestic tobacco smoke and domestic alcohol consumption. Study factors were defined as binary variables - that is, domestic tobacco smoke (yes/no) and domestic alcohol consumption (yes/no) Statistical analyses were performed by SAS, version 9.2 . To assess the impact of the associated factors on the dependent variable-ADHD, we performed multivariate logistic regression analysis with all factors simultaneously included in the same model to adjust each other. The following independent variables were included in the model: age, sex, biological factors, family-environmental factors, and lifestyle factors. Finally, we performed a conditional logistic regression analysis with backward stepwise procedures based on the maximum partial likelihood estimates to construct a final best fit logistic regression model to identify the predictors of risk for ADHD among all factors. This specifies the significance level at p 0.05 for entering an explanatory variable into the model in the backward stepwise method. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for differing levels of exposure. All statistical tests were considered to be significant at an alpha level of 0.05 on a two-tailed test.The analysis included 161 ADHD cases and 161 non-ADHD control subjects matched by age and sex. There were 113 boys and 48 girls included in the case group and control group of this study. There was no statistical age difference between the two groups (mean age of 12.89±2.96 in the case group and mean age of 12.91±2.81 in the control group).General information in demographic and distribution of biological factors is shown in ORs for ADHD cases and controls by family-environmental factors are presented in In The remaining variables in our analysis were not associated with ADHD status , 2, 3.To eliminate multivariable interaction and multicollinearity, we performed a backward stepwise logistic regression based on the maximum partial likelihood estimates. In the final best-fit model, the associations between ADHD and maternal stress during pregnancy, maternal age at childbirth, paternal education, family conflicts, and physical activity which were once significant , 2, 3 haIn contrast, the ORs  for the In this study, we examined the effects of family-environmental factors in pair-matched ADHD cases and normal controls in a population of Chinese children, 5 to18 years of age. The results show that having suffered emotional abuse and being a single child were likely to have strong associations with ADHD. The ADHD subjects were 11 times more likely to suffer from emotional abuse as compared to the normal controls.Recently, family-environmental factors such as abnormal intra-familial relationships, lack of emotional warmth towards the child, child maltreatment , frequent arguments and fights between adults in the family, ambiguous communication patterns, parental separation/divorce and isolated family units, showed a trend towards an increasing risk for having a child with ADHD-related disorders, as reported previously in numerous studies. Poor parenting and conditions such as negative, inconsistent and detached parenting have been repeatedly reported as a risk factor for ADHD children There is a growing body of literature that supports the claim that psychological mistreatment is just as damaging as physical or sexual abuse, and child neglect Since the 1970s, China has had a one-child policy and family planning program. Today the total fertility rate is 1.6, which releases 24% more resources for the family and national investments Previous studies have found that family-environmental factor such as family conflicts Previous reports have indicated that the biological factor of maternal stress during pregnancy is associated with ADHD Previous studies also found that physical inactivity is associated with increased ADHD diagnosis in children Further investigations are needed before definitive conclusions can be made about the possible effects of these potential factors on ADHD.Several limitations should be considered in interpreting the results of this study. First, case-control studies offer only hints about causal models leading to the development of ADHD. The use of terms such as “prediction” and “risk” are not meant to imply causal or temporal relationships. Second, retrospective self-reporting of prenatal complications or family environment and lifestyle factors may be susceptible to recall bias. Observational measures of parent-child interactions may be necessary to understand moment-to-moment relationships between parent and child behavior patterns. Other variables such as in utero tobacco and alcohol exposure may be also susceptible to recall bias. Third, this study lacks of a comparison of the differences between ADHD subgroups. Future research may focus the relationship between family-environmental factors and ADHD subgroups, especially on the difference between subgroups. Fourth, all of our subjects were Chinese Han; the cohort was not a random sample of the Chinese population so potential selection biases cannot be fully ruled out. In addition, children living in foster families were not included, so the results of this study may not generalize to children with different socioeconomic or ethnic backgrounds. Future studies may be proposed to address these limitations.This hospital-based case-control study identified that emotional abuse and single child status are associated with ADHD children in China. The families and health care providers of children with ADHD should be aware of the implications of existing emotional abuse and the associated risks to these children. Appropriate parenting skills, such as proper supervision and prevention by increasing knowledge, need to be addressed for parents of children with ADHD, particular of single child families. Further investigations based on prospective, longitudinal birth cohorts are needed to explain the causal relationships between family-environmental factors and ADHD. Future studies may help to form the basis for successful intervention to prevent ADHD through reduction of family risk factors.


This retrospective database analysis used data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) to examine common primary diagnoses among children and adolescents hospitalized with a secondary diagnosis of attention- deficit/hyperactivity disorder (ADHD) and assessed the burden of ADHD.Hospitalized children (aged 6-11 years) and adolescents (aged 12-17 years) with a secondary diagnosis of ADHD were identified. The 10 most common primary diagnoses (using the first 3 digits of the ICD-9-CM code) were reported for each age group. Patients with 1 of these conditions were selected to analyze demographics, length of stay (LOS), and costs. Control patients were selected if they had 1 of the 10 primary diagnoses and no secondary ADHD diagnosis. Patient and hospital characteristics were reported by cohort , and LOS and costs were reported by primary diagnosis. Multivariable linear regression analyses were undertaken to adjust LOS and costs based on patient and hospital characteristics.A total of 126,056 children and 204,176 adolescents were identified as having a secondary diagnosis of ADHD. Among children and adolescents with ADHD, the most common diagnoses tended to be mental health related . Other common diagnoses included general symptoms, asthma (in children only), and acute appendicitis. Among patients with ADHD, a higher percentage were male, white, and covered by Medicaid. LOS and costs were higher among children with ADHD and a primary diagnosis of affective psychoses (by 0.61 days and $51), adjustment reaction (by 1.71 days and $940), or depressive disorder (by 0.41 days and $124) versus controls. LOS and costs were higher among adolescents with ADHD and a primary diagnosis of affective psychoses (by 1.04 days and $352), depressive disorder (by 0.94 days and $517), conduct disturbances , emotional disturbances , adjustment reaction (by 1.25 days and $702), and neurotic disorders (by 1.60 days and $541) versus controls.Clinicians and health care decision makers should be aware of the potential impact of ADHD on hospitalized children and adolescents. Attention-deficit/hyperactivity disorder (ADHD) is a neurobiological disorder that affects children, adolescents, and adults. It is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than typically observed in patients at a comparable stage of development. ADHD has been associated with a wide range of lifelong complications, including academic underachievement, conflicting interactions with peers and family members, and low self-esteem, all of which have far-reaching and long-term consequences for individuals . FurtherPatients with ADHD often suffer from comorbid mood and conduct disorders, which may further complicate treatment. Biederman and colleagues estimated that approximately 30% of pediatric patients with ADHD also had major depression, while Kessler and colleagues found that almost 19% of adult patients with ADHD also had major depression ,5. PreviADHD has been shown to have serious economic implications for children, families, and society. Patients with ADHD often need long-term care, resulting in significant medical expenditures for prescription drugs and psychotherapy. Previous studies have estimated that children with ADHD have annual health care expenditures that are between US $775 and US $1,330 greater than children without ADHD -17. It iDespite substantial literature on the costs and economic implications of ADHD, there have been few studies that investigate the impact of ADHD on comorbid conditions and limited studies on the economics of ADHD in the inpatient setting. This study sought to identify the most common primary diagnoses among hospitalized children and adolescents with a secondary diagnosis of ADHD. Patients with these most common primary diagnoses and a secondary diagnosis of ADHD were compared with patients with the same set of primary diagnoses who did not have a secondary ADHD diagnosis to assess differences in patient characteristics, length of hospital stay, and associated costs.Data for this analysis were taken from the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS), a nationally representative inpatient database sponsored by the Agency for Healthcare Research and Quality (AHRQ) . This anInternational Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 314.00 and 314.01) were extracted. The 10 most frequent primary diagnoses, based on the first 3 digits of the ICD-9-CM code, were reported for each age group  and adolescents (aged 12-17 years) with a secondary diagnosis of ADHD , admission source , admission type , discharge disposition , and year discharged, while hospital characteristics included geographic region , location , teaching status, and bed size. LOS and costs were reported by cohort for each primary diagnosis. Costs were converted from charges, using hospital-specific cost-to-charge ratios, and were updated to 2008 US dollars using the medical care component of the Consumer Price Index.All data management and analyses were carried out using SAS (version 9.1), Stata (version 11), and SUDAAN (version 9). To account for the complex sampling design of the NIS, appropriate survey-based statistical procedures were employed . Descriptive analyses entailed the tabular display of the mean values, medians, ranges, and standard errors (SEs) of continuous variables of interest  and frequency distributions for categorical variables . Students' t-tests and chi-square tests were used to assess the statistical significance of differences across study measures between the study groups.In addition to descriptive analyses, we conducted multivariable linear regression analyses to estimate the incremental effect of ADHD on LOS and costs. Regressions were estimated for each primary diagnosis within each age group. The use of regression models to analyze cohort differences in LOS and costs allowed us to control for confounding factors that might not otherwise be accounted for .LOS and cost models were estimated using a generalized linear model (GLM) with a log-link function and a gamma distribution for the error term to resolve the issue of skewed cost and LOS distributions ,21. In aEach estimated model included a dichotomous indicator variable, equal to 1 if the patient was in the ADHD cohort and equal to 0 if the patient was not in the ADHD cohort, as well as a vector of underlying patient characteristics . Once a regression model was estimated, predicted values were generated for each patient by cohort. Mean adjusted values were reported, with differences in mean predicted values assessed with t-tests.A total of 126,056 children with a secondary diagnosis of ADHD and 204,176 adolescents with a secondary diagnosis of ADHD were identified . This higher rate in the ADHD cohort was found to be true for all mental health-related hospitalizations, including emotional disturbances , conduct disturbances , adjustment reaction , and depressive disorder . A similar percentage of patients were hospitalized with appendicitis in both cohorts; however, a much higher percentage of ADHD children and a slightly higher percentage of ADHD adolescents were hospitalized with a diagnosis of general symptoms compared with controls . Similarly, a slightly higher percentage of ADHD children had diagnoses of asthma or epilepsy compared with controls . Approximately the same percentages of children in the ADHD and control populations were hospitalized with a primary diagnosis of pneumonia (1.78% of ADHD children vs. 1.75% of control children). In adolescents, a slightly higher percentage of patients with ADHD were hospitalized with diagnoses of neurotic disorders or poisoning by psychotropic agents compared with controls . A similar percentage of adolescents in both cohorts were hospitalized with a primary diagnosis of diabetes mellitus (1.84% of ADHD adolescents vs. 1.53% of control adolescents).A total of 74,438 children with ADHD and 785,229 children without ADHD had 1 of the 10 most frequent primary diagnoses among ADHD children . Compared with control adolescents, a significantly higher percentage of ADHD adolescents were male  or white . Additionally, a significantly smaller percentage of ADHD children were admitted to the hospital from the emergency room compared with control children (42.41% of ADHD children vs. 54.47% of control children P = .006). Correspondingly, a significantly smaller percentage of ADHD children had their admission type labeled as emergency compared with control children . In both cohorts, most discharges were labeled as routine (90.67% of ADHD children vs. 92.24% of control children), and patients were fairly evenly distributed over the 4 geographical regions. Additionally, in both cohorts, the majority of children were treated in urban locations (92.65% of ADHD children vs. 89.54% of control children), and more than half were treated in teaching hospitals (54.67% of ADHD children vs. 52.47% of control children) and large bed-size hospitals (66.96% of ADHD children vs. 63.12% of control children). Furthermore, in both cohorts, the distribution of patients was fairly even across all years of admission.Unadjusted LOS was significantly greater (significant defined as P < .05) for children with ADHD with a primary diagnosis of adjustment reaction  compared to children without ADHD Table . While nUnadjusted LOSs were significantly greater for adolescents with ADHD with a primary diagnosis of affective psychoses , depressive disorder , emotional disturbances , adjustment reaction , and neurotic disorders . While not statistically significant, unadjusted LOS tended to be greater for adolescents with ADHD with a primary diagnosis of conduct disturbances  compared to adolescents without ADHD. Unadjusted costs were significantly greater for adolescents with ADHD with a primary diagnosis of affective psychoses  and emotional disturbances . While not statistically significant, unadjusted costs tended to be greater for adolescents with ADHD with a primary diagnosis of depressive disorder , conduct disturbances , adjustment reaction , and neurotic disorders  compared to adolescents without ADHD.Adjusted LOSs were significantly greater for children with ADHD with a primary diagnosis of affective psychoses , adjustment reaction , and epilepsy  Table . While nAdjusted LOSs were significantly greater for adolescents with ADHD with a primary diagnosis of affective psychoses , depressive disorder , emotional disturbances , adjustment reaction , and neurotic disorders . While not statistically significant, adjusted LOSs tended to be greater for adolescents with ADHD with a primary diagnosis of conduct disturbances  and diabetes mellitus  compared to adolescents without ADHD. Additionally, while not statistically significant, adjusted costs tended to be greater for adolescents with ADHD with a primary diagnosis of affective psychoses , depressive disorder , conduct disturbances , emotional disturbances , and adjustment reaction  compared to adolescents without ADHD.This retrospective database analysis examined demographics, hospital characteristics, LOS, and costs among children and adolescents hospitalized in the United States with a secondary diagnosis of ADHD. The most common primary diagnoses among children and adolescents were identified. Patients with a secondary diagnosis of ADHD were compared with patients without ADHD, using the most commonly observed primary diagnoses. We found that a higher percentage of children and adolescents in the ADHD cohort were male compared with the control cohort and that a lower percentage of children and adolescents in the ADHD group were admitted to the hospital from the emergency room compared with the control cohort. Additionally, a higher percentage of children and adolescents with ADHD had Medicaid listed as their primary expected payer compared with patients without ADHD.We found that children with ADHD with a primary diagnosis of affective psychoses, adjustment reaction, and depressive disorder had longer LOSs and higher costs compared with children without ADHD. Similarly, adolescents with ADHD with a primary diagnosis of affective psychoses, depressive disorder, conduct disturbances, emotional disturbances, adjustment reaction, and neurotic disorders also had longer LOSs and greater costs compared with adolescents without ADHD. These findings could suggest that children and adolescents with ADHD who are hospitalized for mental disorders may be more difficult to treat compared with children and adolescents without ADHD.Our study has several limitations common to most retrospective database analyses. First, physician charts were not available to confirm ADHD or other conditions; hospitalizations were identified from diagnosis codes, which, if recorded inaccurately, may cause misidentification of events of interest. Additionally, this study examined only US hospitals; thus, results may not be relevant outside the US setting. Also, only inpatient stays were examined, so results of this analysis may not be generalizable to other care settings.A number of other studies have used methods similar to those employed in our analysis. Trasande and colleagues studied the burden of obesity on pregnant women and found that obesity was associated with an additional 0.55 inpatient days and an additional US $1,805 in costs . In a stIn summary, this study examined common primary diagnoses among children and adolescents with ADHD in an inpatient setting. Patients with a secondary diagnosis of ADHD were compared with patients without ADHD, using the most commonly observed primary diagnoses. Both children and adolescents with ADHD and a primary diagnosis of affective psychoses, adjustment reaction, or depressive disorder had longer LOSs and higher costs compared with patients without ADHD. Additionally, adolescents with ADHD with a primary diagnosis of conduct disturbances, emotional disturbances, and neurotic disorders were found to have longer LOSs and higher costs compared with adolescents without ADHD. Clinicians and other health care decision makers should be aware of the impact that ADHD appears to have on inpatient LOS and costs, when pediatric patients with ADHD present with comorbid conditions in a hospital setting.This study was funded by Eli Lilly and Company.This study was conceived by PC and LW. All authors contributed to the study design and coordination. Database analyses were conducted by SC and JM. The study manuscript was drafted by JM and SC with input from PC and LW. All authors have read and approved the final manuscript.


Methylphenidate (MPH), a psycho-stimulant, is the most widely administered drug for the pharmacological management of patients with attention deficit hyperactivity disorder (ADHD). This study attempts to determine whether sustainable improvements occur in neurocognitive function among ADHD patients following 12-month treatment with MPH, at drug-free status. Whether age groups, gender or ADHD subtypes differ in neurocognitive performance during MPH treatment is also examined.Study participants consisted of 103 ADHD patients (mean age: 9.1 ± 1.9 years old) who were drug naïve or drug free for at least 6 months. The patients were prescribed oral short-acting MPH at each dose range of 0.3–1.0 mg/kg daily. During 12 months of the study, the patients underwent the test of variables of attention (TOVA) at the baseline, month 6 and month12. Patients were instructed to not intake MPH for one week before the second and the third TOVA.Seventy five patients completed the study. Results of this study indicated that although commission errors and response sensitivity (d’) significantly improved during MPH treatment for 12 months, omission errors, response time, response time variability and ADHD score did not. While younger ADHD patients (<9 y/o) performed better in response time, response time variability, d’ and ADHD score than older ones (≥9 y/o), the latter more significantly improved in response time than the former during 12 months of treatment. Additionally, boys improved more than girls in omission error and d’. Moreover, although ADHD subtypes significantly differed in ADHD score during the treatment, MPH treatment and ADHD subtypes did not interact with each other for all TOVA indices.ADHD patients significantly improved in impulsivity and perceptual sensitivity, determined as TOVA, during MPH treatment for 12 months. Age and gender, yet not ADHD subtypes, appear to influence the MPH treatment effects in some indices of TOVA. A future study containing a comparison group is suggested to confirm whether the neurocognitive improvements are attributed to long-term effects of MPH or natural maturation of patients. Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder among children and adolescents, affecting 3% to 10% of all school-age children . The curet al. demonstrated that children with ADHD did not substantially improve in executive control performance after long-term MPH treatment [et al. noted that intelligence quotient of ADHD patients significantly increased after 6 months of MPH treatment [Methylphenidate (MPH), a psycho-stimulant, is the most widely administered drug for the pharmacological management of ADHD patients . The phareatment . Howeverreatment . In sum,The treatment effects are diverse among ADHD patients, with some studies attempting to determine the predictors of treatment outcome ,20. ExacTherefore, this study attempts to determine whether neurocognitive function among ADHD patients improve in a sustainable manner during 12 months of treatment with MPH, at drug-free status. In addition to the main purpose, we also conduct an explorative analysis to examine whether age groups, gender or ADHD subtypes differ in neurocognitive performance during MPH treatment.ADHD patients between ages of 6 and 16 years old were recruited from the out-patient Child Psychiatry Department at Chang Gung Children’s Hospital . The study received approval from the Institutional Review Board of Chang Gung Memorial Hospital. Written informed consent was obtained from the parents of the patients. ADHD and comorbid disorders were diagnosed by two senior child psychiatrists, based on the DSM-IV criteria  after stNeurocognitive function of ADHD patients was assessed using the test of variables of attention (TOVA)-Visual , which iThe TOVA stimuli are coloured squares with a small black square within, which is adjacent to either the top or the bottom edge. The squares with a small inner square near the top edge are designated targets, and the ones with the small squares near the bottom edge are non-targets. The stimuli appear individually and are presented randomly, based on a determined ratio. The tested subject was instructed to immediately press a button after seeing a target and does not respond when a non-target is presented. The test lasted 22.6 minutes and is preceded by a practice session for 2.5 minutes. Two visual stimuli appeared 648 times. The TOVA was reported to achieve satisfactory levels of reliability and concurrent validity in Taiwanese children with ADHD . The indOmission errors: this score is evaluated as the failure to respond to the target stimulus. Omission error scores are presented as percentages and are considered to be a measure of inattention.Commission errors: this score is measured as an inappropriate response to the non-target stimulus. Commission error scores are presented as percentages and are considered to reflect impulsivity or disinhibition.Response time (in msec): this score is determined as the average of the correct response times. This score denotes response latency in information processing and motor response speed.Response time variability: this score is evaluated as the standard deviation of the mean of correct response times. It is a measure of the subject’s inconsistency in response times.Response sensitivity (d’): this score is a response sensitivity score reflecting the ratio of the hit rate to false alarm rate. This score refers to the accuracy of target and non-target discrimination and is interpreted as a measure of perceptual sensitivity.ADHD score: this score is a composite score generated by the TOVA program. The score is calculated by comparing an individual’s performance on the TOVA to those of an ADHD sample collected by the authors of the TOVA. The score describes how similar an individual’s performance is to the ADHD profile.Each subject performed the TOVA 3 times. At the first TOVA (month 0), all subjects were drug naïve or had not taken medication for ADHD during the previous 6 months or longer. Subsequently, ADHD patients were prescribed oral short-acting methylphenidate (MPH) twice or three times daily at each dose range of 0.3–1.0 mg/kg, based on the severity of their clinical symptoms as well as their age, height, and body weight. Concomitant medications were prohibited. Patient care was performed based on their usual practice at the out-patient services of the child psychiatry department. There was no additional behavioral therapy or family therapy provided during the period of study. Drug compliance at each visit was confirmed according to the reports of patients’ caregivers.th and 12th month after treatment with MPH, respectively. Patients were instructed to not intake MPH for one week before the second and the third TOVA. The TOVA tests were compared before treatment, 6 months and 12 months after MPH treatment.The second and third TOVA were performed at the 6Data were analyzed using the statistical software package SPSS, version 16.0 . Variables are presented as either the mean (standard deviation) or frequency. Two-tailed p values of <0.05 were considered statistically significant.th and 12th months were accounted for by using the method of last observation carried forward (LOCF). The longitudinal data were analyzed using a linear mixed model, with the maximum likelihood estimation method and auto-regression covariance matrix, as the primary analytic strategy. To examine the trends of neuro-cognitive function under MPH treatment within 12 months, the dependent variables were set as the indices in TOVA. The age of patients was divided into a categorical variable based on the median age of 9. This study also investigated the extent of the differences in changes of performance in TOVA between age groups, gender and ADHD subtypes, also by the linear mixed model. The hypothesis that a differential change occurs in dependent measures over 12 months is supported by significant interactions of MPH treatment × age, gender or ADHD subtypes.The TOVA results were reported as standard deviations, which indicated the extent of deviation from the norm. Variables between ADHD subtypes at baseline were compared using the Fisher’s Exact Test and Kruskal Wallis Test. Missing data at the 6This study recruited 103 ADHD patients (mean age: 9.1 ± 1.9 years). Of the 103 patients, 82 (79.6%) were male and 21 (20.4%) were female. Fifty-four of them were inattentive type; 5 were hyperactive-impulsive type; and 44 were combined type. The three ADHD subtypes identified at month 0 (pretreatment) did not significantly differ in age, gender, and indices in TOVA  and performances in TOVA  : t = −0.68, p = 0.496; ADHD score: t = −1.25, p = 0.215).Among the 103 ADHD patients at the initial visit, 75 patients remained in the study at month 6 and month 12. The mean dose of MPH of the 75 patients at the endpoint is 19.8 ± 13.2 mg. Among the 28 drop-out patients, 10 patients withdrawal of consent, and 18 patients lost of follow up. Comparing the remaining patients with the drop-out patients, there were no significant differences in demographic characteristics  and d’  were significantly improved during 12 months of treatment by MPH in a clinical setting. Table Table This study demonstrates that commission errors and d’ significantly improved during MPH treatment, while the other indices of TOVA did not. This finding suggests that ADHD patients have an improved ability of impulse control and perceptual sensitivity, but not sustained attention or response speed, under long-term MPH treatment. Our previous study has established that one dose of MPH produced more effects on impulsivity than on inattention in children with ADHD . A previet al. demonstrated that non-medicated ADHD patients have a more pervasive pattern of cognitive deficits than medicated ADHD ones [Results of this study also suggest that the effects of MPH on two TOVA indices can be sustained for at least 12 months, even when ADHD patients are tested at drug-free status. These results support the conclusion of a recent review that MPH is continuously effective for an extended period . Some loDHD ones . In contDHD ones , the earDHD ones . TherefoThis study also examines whether differences occur in neurocognitive performance between age, gender and ADHD subtypes during MPH treatment. Analytical results indicate that older patients (≥9 y/o) performed worse in many indices of TOVA than younger ones (<9 y/o), and the older patients more significantly improved in response time during treatment. However, there were differences in some indices of TOVA at baseline between age groups (data not shown). The effect of age in neurocognitive performance is not necessarily implying that older patients gained more from MPH treatment than younger ones, and might be just a regression to the mean. Moreover, male patients more significantly improved in omission error and d’ than female ones during MPH treatment. Despite similar findings found in a previous study on the acute effects of MPH on TOVA performance , a recenResults of this study further demonstrate that patients with ADHD-inattentive type had a higher ADHD composite score in TOVA than patients with hyperactive-impulsive or combined type. Meanwhile, MPH treatment and ADHD subtypes did not interact with each other in all TOVA indices. Subjects with hyperactive or combined type of ADHD show more significantly improve in commission errors than those with inattentive ADHD after one dose of MPH . HoweverDespite its contributions, this study has certain limitations. First, a comparison group was absent. Exactly how age-related decline in ADHD-symptoms and social and environmental influence affects TOVA performance could thus not be controlled. Longitudinal studies have shown that there is a natural decline of symptoms with age, particularly the symptom of hyperactivity and impulsivity, in children with ADHD . TherefoUsing TOVA as a neuropsychological assessment scheme revealed that impulsivity and perceptual sensitivity in ADHD patients significantly improved during MPH treatment for 12 months. Age and gender, yet not ADHD subtypes, appear to influence the MPH treatment effects in some indices of TOVA. A future study containing a comparison group is suggested to confirm whether the neurocognitive improvements are attributed to long-term effects of MPH or natural maturation of patients.The authors report no competing of interest.YSH and LJW are joint first authors and contribute equally to this manuscript. YSH conceived the study and recruited the participants. LJW analyzed the data and wrote the paper. CKC carried out the literature search and helped to draft the manuscript. 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/12/194/prepub


Saldula laticollis (Reuter). This shore bug is adapted to an intertidal environment and can survive short periods of submergence during high tides. The present study describes the nematode parasite and discusses aspects of its development, ecology and evolution.It is rare to find terrestrial nematode lineages parasitizing arthropods inhabiting the intertidal or littoral zone of the oceans. During an ecological study along the Oregon dunes, an allantonematid nematode (Tylenchomorpha: Allantonematidae) was discovered parasitizing the intertidal shore bug, S. laticollis  were collected from the high intertidal zone among clumps of Juncus L. (Juncaceae) plants at Waldport, Oregon on October 3, 2011. The bugs were dissected in 1% saline solution and the nematodes killed in 1% Ringers solution and immediately fixed in 5% formalin (at 20°C). Third stage juveniles removed from infected hosts were maintained in 1% saline solution until they matured to the adult stage, molted and mated.Adults and last instar nymphs of Halophilanema prolata n. gen., n. sp. (Nematoda: Allantonematidae) is described from last instar nymphs and adults of the intertidal bug, Saldula laticollis on the Oregon coast. The new genus can be distinguished from other genera in the Allantonematidae by a stylet lacking basal knobs in both sexes, an excretory pore located behind the nerve ring, ribbed spicules, a gubernaculum, the absence of a bursa and the elongate-tubular shape of the ovoviviparous parasitic females. Studies of the organogenesis of Halophilanema showed development to third stage juveniles in the uterus of parasitic females. Maturation to the free-living adults and mating occurred in the environment. The incidence of infection of S. laticollis ranged from 0% to 85% depending on the microhabitat in the intertidal zone.Halophilanema adapted a parasitic existence fairly recently, evolutionarily speaking. It was probably a free-living intertidal or shore nematode that fed on microorganisms, especially fungi, in the intertidal habitat and became parasitic after saldids entered the environment. Halophilanema represents the first described nematode parasite of an intertidal insect.Based on the habitat and morphological characters, it is proposed that  Thaumamermis zealandica Poinar, Latham & Poulin [Heterorhabditis Poinar are thought to have evolved in an intertidal habitat from free-living rhabditids [It is rare to find nematodes parasitizing arthropods inhabiting the intertidal or littoral zone of the oceans. This is an extremely harsh environment where the occupants are subjected to wave action, high salinity and open exposure. An exception is the mermithid, & Poulin  that parabditids . HoweverSaldula laticollis (Reuter), which possesses morphological and physiological attributes that enable it to survive along the open coastline, including the ability to endure short periods of submergence during high tides [S. laticollis collected along the Oregon coast were discovered to be parasitized by an undescribed allantonematid. The present study describes this nematode and discusses aspects of its development, ecology and evolution.Insects are uncommon in the intertidal habitat and only a small number are able to complete their entire development in this domain. One of these few is the shore bug, gh tides . Adults S. laticollis  were collected from the high intertidal zone among clumps of Juncus L. (Juncaceae) plants at Waldport, Oregon on October 3, 2011 , are in micrometers unless otherwise specified.Several hundred adults and last instar nymphs of S. laticollis occurred contained a mixture of bacteria, algae, fungi, protozoa and free-living nematodes, including stages of the allantonematid parasite. The body cavity of infected S. laticollis contained mature parasitic female nematodes and numerous third stage juveniles  to the adult stage in 5-7 days at 20°C  ribs; development to third stage juveniles occurs in uterus of parasitic females; free-living stages adapted to saline intertidal conditions.Halophilanema keys to couplet 9, which ends with Pratinema Chizhov & Sturhan, 1998 and Protylenchus Wachek, 1955. However Pratinema lacks a gubernaculum, the parasitic female is ventrally curved and the stylet is knobbed. Protylenchus is characterized by an obese, cylindrical straight parasitic female and a thick, knobbed stylet. Neither genus contains any members with ribbed spicules. Halophilanema cannot be placed in any existing genus in this family. It can be distinguished from all existing genera by the following combination of characters: a stylet lacking knobs in both free-living males and females, an excretory pore located behind the nerve ring, uterus without post-uterine extension, a distinct gubernaculum, no bursa, ribbed spicules and the elongate-tubular shape of the parasitic female.Comments: Based on the key to the genera of Allantonematidae presented by Siddiqi (2000) Halophilanema prolata Poinar, n. sp.Free-living female (n = 12)Figures , 5, 6: tBody elongate; cuticle smooth; lateral fields 2.5 wide, with 4 incisures; stylet distinct, lacking knobs; dorsal pharyngeal gland opening slightly less than one stylet length behind stylet base; subventral gland openings located approximately 1.5 stylet lengths behind head; pharyngeal glands long, subventral gland sometimes reaching anterior tip of ovary in fertilized females; excretory pore located behind nerve ring; vulva and anal openings faint; uterus without post-uterine extension; ovary outstretched; tail conoid, tip sometimes slightly angular.Free-living male Figures , 8, 9  rib shorter than dorsal (lower); gubernaculum short, prominent, straight, basal portion bearing lateral flanges; bursa absent; tail tip conoid with blunt tip.Mature parasitic female. Figures , 14, 15 Immature stages. . The adult hosts range in size from 4.0-5.0 mm.Host: The parasites occur in the body cavity of immature and adult Etymology: The generic epithet is taken from the Greek "halos" = sea salt, the Greek "philia" = fondness, and the Greek "nema" = thread. The specific epithet is taken from the Latin "prolata" for elongated, in reference to the long, slender free-living stages Figure .Holotype: Free-living male (USDANL # T-661t) and paratype  deposited in the USDA Nematode Laboratory, Beltsville, Maryland. Paratypes deposited in the author's collection.Locality: Waldport (Lane County), Oregon.H. prolata, the embryos [Halophilanema appear to be a unique character.Spicular ribs are rare in the Allantonematidae ,5 and wh (Goodey), the paiHalophilanema is essentially a terrestrial nematode that has entered a marine environment. It is evident that H. prolata has acquired a wide tolerance to osmotic and ionic stress from living in the intertidal zone. The free-living stages of Halophilanema must have a low cuticular permeability constant, since when they were placed directly in 70% alcohol or 5% formalin at 20°C, they remained active for 48 hours. These stages probably excrete salt through their gut, excretory system and anisotropic cuticle, similar to marine nematodes. A corresponding tolerance to osmotic change occurs with the intertidal rhabditid, Pellioditis marina , which has a terrestrial origin [Marine nematodes living permanently in the oceans are isotonic with sea water and experience little or no osmotic gradients , howeverS. laticollis ranged from 0% to 85% and were highest in the tinted sand area of the Juncus zone  in the tinted sand area were parasitized. Previous studies showed that S. laticollis hibernated from December to April [Halophilanema were found in the yellow-tinted sand, they would have to infect the remaining population of bugs before being washed away by wave action during winter storms.Infection rates of e Figure . Outsideto April  but the S. laticollis along the Oregon coast, there is a spring generation and two summer generations. The infected bugs collected on October 3 would correspond to the end of the second summer generation [Halophilanema. The nematodes probably overwinter inside the bugs and emerge in the spring during host oviposition. Since the reproductive organs of parasitized bugs were atrophied, there may be a mock oviposition where infected bugs expel nematodes instead of eggs.It is not known at what host stage infection occurs during the year, since only last stage nymphs and adults were present at this late date. Based on life cycle studies of Bradynema zur Strassen from each of the above hosts. While they are clearly members of the Allantonematidae, their placement in Bradynema is questionable. With the exception of a molting male of B. veliae Poisson, only the parasitic females of these three species were described and it is not possible to obtain a generic placement without free-living adults of both sexes. The molting juvenile male of B. veliae Poisson has long, narrow spicules and a slender tail. While these characters separate this species from Halophilanema, it is not typical for members of the genus Bradynema. The parasitic females of B. nepae and B. gerridis have the vulva positioned more anteriorly than that of Halophilanema. Whereas none of these species are similar to Halophilanema, they are the only records of allantonematids parasitizing freshwater hosts.This is the first description of a nematode infecting an intertidal insect and the first complete description of an allantonematid parasite of a hemipteran. The only previously known allantonematid parasites of hemipterans occurred in fresh water hosts of the families Veliidae, Nepididae and Gerridae . PoissonHalophilanema. Males have no use of a stylet or pharyngeal glands since they never enter a host. Nor do the third stage juvenile males  have a stylet strong enough to assist exiting the host. It is possible that the degree of male stylet development is correlated with the evolutionary period that the particular nematode clade has parasitized its host. Generic lineages containing males that have lost their stylets, such as Bradynema and Howardula Cobb, could have had a longer period of parasitism than clades like Halophilanema with males containing well-developed stylets. In other words, the presence of a male with a well-defined stylet with dorsal and ventral pharyngeal gland openings and atrophied glands as in Halophilonema indicates a fairly short period of parasitism, evolutionarily speaking, Halophilanema probably was a free-living intertidal or shore nematode that fed on microorganisms, especially fungi, in the intertidal habitat before becoming an insect parasite. This scenario implies that Halophilanema became parasitic when saldids entered the intertidal environment. This infers that the Allantonematidae is a polyphyletic group with different lineages adapting parasitism at different time periods. The earliest known allantonematid lineage occurs in Eocene Baltic amber [Within the Allantonematidae, there is a range of stylet development in the males. They can lack a stylet and gland openings completely or posses a well developed stylet with gland openings as in ic amber .Saldula pallipes Fabricius and Saldula saltatoria (L.), as well the North American Saldula laticollis [Halophilanema, since the latter can reach up to nearly 4 mm in length and superficially resemble mermithid nematodes (Figure There are also reports of mermithid nematodes infecting saldids . Mermithticollis . The latticollis  were nevticollis  were devs Figure .S. laticollis (Figure During the present study, cysts of a eugregarine parasite were encountered inside the body cavity of s Figure . These cIn accordance with section 8.6 of the ICZN's International Code of Zoological Nomenclature, copies of this article are deposited at the following five publicly accessible libraries: Natural History Museum, London, UK; American Museum of Natural History, New York, USA; Museum National d'Histoire Naturelle, Paris, France; Russian Academy of Sciences, Moscow, Russia; Academia Sinica, Taipei, Taiwan.The author declares that they have no competing interests.GP discovered the nematode, wrote the paper and supplied the figures.