Meta-analysis: Altered Perceptual Timing Abilities in Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: We meta-analyzed studies comparing perceptual timing abilities in the range of milliseconds to several seconds in persons with attention-deficit/hyperactivity disorder (ADHD) and neurotypical participants, using the well-established time discrimination, time estimation, time production, and time reproduction paradigms. METHOD: We searched PubMed, OVID databases, and Web of Knowledge through September 17, 2020. From 2,266 records, 55 studies were retained and meta-analyzed with random effects models. We conducted meta-regression analyses to explore moderating effects of task parameters and neuropsychological measures of working memory, attention, and inhibition on timing performance. RESULTS: Compared with persons without ADHD, those with ADHD had significantly more severe difficulties in discriminating stimuli of very brief durations, especially in the sub-second range. They also had more variability in estimating the duration of stimuli lasting several seconds. Moreover, they showed deficits in time estimation and time production accuracy, indicative of an accelerated internal clock. Additional deficits in persons with ADHD were also found in the time reproduction paradigm, involving attentional (slower counting at short time intervals due to distraction) and motivational (faster counting at long time intervals due to increased delay aversion) functions. CONCLUSION: There is meta-analytic evidence of a broad range of timing deficits in persons with ADHD. Results have implications for advancing our knowledge in the field (eg, for refinement of recent timing models in ADHD) and clinical practice (eg, testing timing functions to characterize the clinical phenotype of the patient and implementation of interventions to improve timing abilities).

Brain Arousal as Measured by EEG-Assessment Differs Between Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Depression.

Objective: Disturbed regulation of vigilance in the wake state seems to play a key role in the development of mental disorders. It is assumed that hyperactivity in adult ADHD is an attempt to increase a general low vigilance level via external stimulation in order to avoid drowsiness. For depression, the avoidance of stimulation is interpreted as a reaction to a tonic increased vigilance state. Although ADHD is assumed to start during childhood, this vigilance model has been barely tested with children diagnosed for ADHD so far. Methods: Resting-state EEG (8 min) measures from two groups of children diagnosed with either ADHD [N = 76 (16 female, 60 male), age: (mean/SD) 118/33 months] or depression [N = 94 (73 female, 21 male), age: 184/23 months] were analyzed. Using the VIGALL toolbox, EEG patterns of vigilance level, and regulation were derived and compared between both groups. In correlation analysis, the relations between vigilance measures, attentional test performance (alertness and inhibition), and mental health symptoms were analyzed. Results: Children with ADHD differed from children with most prominent depressive symptoms in brain arousal regulation and level, but EEG vigilance was not related to behavior problems and not related to the attentional test performance. Brain arousal was dependent on the age of the participant in the whole sample; younger children showed lower vigilance stages than teenagers; this effect was not present when analyzed separately for each diagnostic group. EEG assessment time and received medication had no effect on the EEG vigilance. Discussion: Although based on a small sample, this explorative research revealed that EEG vigilance level is different between children with ADHD and with depression. Moreover, even the standard procedure of the clinical routine EEG (resting state) can be used to differentiate brain arousal states between participants with ADHD and depression. Because routine EEG is not specialized to vigilance assessment, it may not be sufficiently sensitive to find vigilance-symptomatology associations. Further research should address developmental changes in EEG measurements in children and use bigger samples of participants within the same age range.

ADHD and the Choice of Small Immediate Over Larger Delayed Rewards: A Comparative Meta-Analysis of Performance on Simple Choice-Delay and Temporal Discounting Paradigms.

Objective: Impulsive choices can lead to suboptimal decision making, a tendency which is especially marked in individuals with ADHD. We compared two different paradigms assessing impulsive choice: the simple choice paradigm (SCP) and the temporal discounting paradigm (TDP). Method: Random effects meta-analyses on 37 group comparisons (22 SCP; 15 TDP) consisting of 3.763 participants (53% ADHD). Results: Small-to-medium effect sizes emerged for both paradigms, confirming that participants with ADHD choose small immediate over large delayed rewards more frequently than controls. Moderation analyses show that offering real rewards in the SCP almost doubled the odds ratio for participants with ADHD. Conclusion: We suggest that a stronger than normal aversion toward delay interacts with a demotivating effect of hypothetical rewards, both factors promoting impulsive choice in participants with ADHD. Furthermore, we suggest the SCP as the paradigm of choice due to its larger ecological validity, contextual sensitivity, and reliability.

A short note on the reliability of perceptual timing tasks as commonly used in research on developmental disorders.

OBJECTIVES: Perceptual timing tasks are frequently applied in research on developmental disorders, but information on their reliability is lacking in pediatric studies. We therefore aimed to assess the reliability of the four paradigms most frequently used, i.e., time discrimination, time estimation, time production, and time reproduction. METHODS: Based on the data from our recent longitudinal study by Marx et al. (Front Hum Neurosci 11:122, 2017), we estimated the internal consistency and test-retest reliability of these tasks in children with ADHD and typically developing children. Individual thresholds were used as dependent measures for the time discrimination task, whereas absolute error and accuracy coefficient scores were used for the other three tasks. RESULTS: Although less commonly used, the time estimation paradigm was the most robust measure of perceptual timing in terms of internal consistency and test-retest reliability in both ADHD and typically developing children, whereas the most frequently used paradigms showed poor internal consistency (time reproduction) and poor test-retest reliability (time discrimination). Compared to the absolute errors, accuracy coefficients showed almost exclusively higher internal consistency and test-retest reliability. CONCLUSIONS: Our findings call for more frequent use of the time estimation paradigm in studies of perceptual timing in ADHD. The time reproduction paradigm should be re-considered, avoiding pooling of a wide range of time intervals (2-48 s). The accuracy coefficient score is the more reliable and the more intuitive dependent variable and should be preferred in future timing research. To increase the reliability of the timing measurement, each experimental session should be performed twice, if possible.

Perceptual timing in children with attention-deficit/hyperactivity disorder (ADHD) as measured by computer-based experiments versus real-life tasks: protocol for a cross-sectional experimental study in an ambulatory setting.

INTRODUCTION: The goal of this study is to get a better understanding of the fundamentals of perceptual timing deficits, that is, difficulties with estimating durations of explicitly attended temporal intervals, in children with attention-deficit/hyperactivity disorder (ADHD). Whereas these deficits were repeatedly demonstrated in laboratory studies using computer-based timing tasks, we will additionally implement a more practical task reflecting real-life activity. In doing so, the research questions of the planned study follow a hierarchically structured path 'from lab to life': Are the timing abilities of children with ADHD really disturbed both in the range of milliseconds and in the range of seconds? What causes these deficits? Do children with ADHD rather display a global perceptual timing deficit, or do different 'timing types' exist? Are timing deficits present during real-life activities as well, and are they based on the same mechanisms as in computerised tasks? METHODS AND ANALYSES: A quasi-experimental study with two groups of male children aged 8-12 years (ADHD; controls) and with a cross-sectional design will be used to address our research questions. Statistical analyses of the dependent variables will comprise (repeated) measures analyses of variance, stepwise multiple regression analyses and latent class models. With an estimated dropout rate of 25%, power analysis indicated a sample size of 140 subjects (70 ADHD, 70 controls) to detect medium effect sizes. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethics committee of the Faculty of Medicine, University of Rostock. Results will be disseminated to researcher, clinician and patient communities in peer-reviewed journals and at scientific conferences, at a meeting of the local ADHD competence network and on our web page which will summarise the study results in an easily comprehensible manner. TRIAL REGISTRATION NUMBER: DRKS00015760.

Methylphenidate promotes the interaction between motor cortex facilitation and attention in healthy adults: A combined study using event-related potentials and transcranial magnetic stimulation.

OBJECTIVE: This study investigated simultaneously the impact of methylphenidate (MPH) on the interaction of inhibitory and facilitative pathways in regions processing motor and cognitive functions. METHOD: Neural markers of attention and response control (event-related potentials) and motor cortical excitability (transcranial magnetic stimulation) and their pharmacological modulation by MPH were measured simultaneously in a sample of healthy adults (n = 31) performing a cued choice reaction test. RESULTS: Methylphenidate modulated attentional gating and response preparation processes (increased contingent negative variation) and response inhibition (increased nogo P3). N1, cue- and go-P3 were not affected by MPH. Motor cortex facilitation, measured with long-interval cortical facilitation, was increased under MPH in the nogo condition and was positively correlated with the P3 amplitude. CONCLUSION: Methylphenidate seems particularly to enhance response preparation processes. The MPH-induced increased motor cortex facilitation during inhibitory task demands was accompanied by increased terminal response inhibition control, probably as a compensatory process.

Living in the Fast Lane: Evidence for a Global Perceptual Timing Deficit in Childhood ADHD Caused by Distinct but Partially Overlapping Task-Dependent Cognitive Mechanisms.

Dysfunctions in perceptual timing have been reported in children with ADHD, but so far only from studies that have not used the whole set of timing paradigms available from the literature, with the diversity of findings complicating the development of a unified model of timing dysfunctions and its determinants in ADHD. Therefore, we employed a comprehensive set of paradigms (time discrimination, time estimation, time production, and time reproduction) in order to explore the perceptual timing deficit profile in our ADHD sample. Moreover, we aimed to detect predictors responsible for timing task performance deficits in children with ADHD and how the timing deficits might be positively affected by methylphenidate. Male children with ADHD and healthy control children, all aged between 8 and 13 years, participated in this longitudinal study with three experimental sessions, where children with ADHD were medicated with methylphenidate at the second session but discontinued their medication at the remaining sessions. The results of our study reveal that children with ADHD were impaired in all timing tasks, arguing for a general perceptual timing deficit in ADHD. In doing so, our predictor analyses support the notion that distinct but partially overlapping cognitive mechanisms might exist for discriminating, estimating/producing, and reproducing time intervals. In this sense, working memory deficits in terms of an abnormally fast internal counting process might be common to dysfunctions in the time estimation/time production tasks and in the time reproduction task, with attention deficits (e.g., in terms of disruptions of the counting process) additionally contributing to time estimation/time production deficits and motivational alterations additionally contributing to time reproduction deficits. Methylphenidate did not significantly alter performance of the ADHD sample, presumably due to limited statistical power of our study. The findings of our study demonstrate a pivotal role of disturbed working memory processes in perceptual timing task performance in childhood ADHD, at the same time broadening the view for additional attentional and motivational determinants of impaired task performance.

Attentional control of emotional interference in children with ADHD and typically developing children: An emotional N-back study.

Emotional interference control refers to the ability to remain focused on goal-oriented processes when confronted with disrupting but irrelevant emotional stimuli, a process that may be impaired in children and adults with attention deficit/hyperactivity disorder (ADHD). However, emotional interference levels are known to be associated with trait anxiety, and patients with ADHD often display elevated levels of trait anxiety, such as these may have confounded previous findings of decreased emotional interference control in this population. In the present study, male and female 8-13 years old (mean =11.0 years) children with ADHD (n=33) and typically developing (TD) children (n=24) performed a visual emotional working memory (n-back) task with 2 memory loads and three different background pictures (neutral/positive/negative), and trait anxiety measures were obtained. Children with ADHD performed less well, and displayed increased emotional interference in the presence of aversive distractors when compared with TD children. Contrary to our expectations, trait anxiety did not mediate the association between diagnostic group membership and the degree of emotional interference control; however, co-morbid ODD was associated with decreased levels of emotional interference in ADHD. Future research should aim at characterizing the mechanisms subtending decreased emotional interference control in the ADHD population.

Altered serum fatty acid composition in geriatric depression.

Fatty acids (FA), mainly polyunsaturated (PUFA) of n-3 or n-6 types, may influence neuropsychobiological processes. Decreased levels of n-3 PUFA have been shown to be related to major depression and supplementation of n-3 PUFA seems to contribute to improved depression treatment outcome. The profiles of serum FA profiles in patients with geriatric depression have not been thoroughly studied yet. The present study investigated the FA profiles of patients with geriatric depression and of mentally healthy elderly individuals. Serum FA profiles of 36 inpatients with geriatric depression who fulfilled DSM-IV criteria for unipolar major depression were compared with those of 37 control subjects. Patients with geriatric depression, irrespective of gender, exhibited lower total FAs, as well as significantly lower concentrations of total n-3 PUFA and eicosapentaenoic acid, though the groups did not differ with regard to Body Mass Index. The findings of the present study point to an association between lower FA serum levels and geriatric depression. Further investigations with larger samples and dietetic interventions may provide deeper insights into the role of eicosapentaenoic acid and total n-3 PUFA in the development and treatment of geriatric depression.

Effects of task-irrelevant emotional stimuli on working memory processes in mild cognitive impairment.

BACKGROUND: Research suggests generally impaired cognitive control functions in working memory (WM) processes in amnestic mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). Little is known how emotional salience of task-irrelevant stimuli may modulate cognitive control of WM performance and neurofunctional activation in MCI and AD individuals. OBJECTIVE: We investigated the impact of emotional task-irrelevant visual stimuli on cortical activation during verbal WM. METHODS: Twelve AD/MCI individuals and 12 age-matched healthy individuals performed a verbal WM (nback-) task with task-irrelevant emotionally neutral and emotionally negative background pictures during fMRI measurement. RESULTS: AD/MCI individuals showed decreased WM performance compared with controls; both AD/MCI and control groups reacted slower during presentation of negative pictures, regardless of WM difficulty. The AD/MCI group showed increased activation in the left hemispheric prefrontal network, higher amygdala and less cerebellar activation with increasing WM task difficulty compared to healthy controls. Correlation analysis between neurofunctional activation and WM performance revealed a negative correlation between task sensitivity and activation in the dorsal anterior cingulum for the healthy controls but not for the AD/MCI group. CONCLUSION: Our data suggest compensatory activation in prefrontal cortex and amygdala, but also dysfunctional inhibition of distracting information in the AD/MCI group during higher WM task difficulty. Additionally, attentional processes affecting the correlation between WM performance and neurofunctional activation seem to be different between incipient AD and healthy aging.

Dissociable patterns in the control of emotional interference in adults with attention-deficit/hyperactivity disorder (ADHD) and in adults with alcohol dependence.

OBJECTIVES: To effectively manage current task demands, attention must be focused on task-relevant information while task-irrelevant information is rejected. However, in everyday life, people must cope with emotions, which may interfere with actual task demands and may challenge functional attention allocation. Control of interfering emotions has been associated with the proper functioning of the dorsolateral prefrontal cortex (DLPFC). As DLPFC dysfunction is evident in subjects with ADHD and in subjects with alcohol dependence, the current study sought to examine the bottom-up effect of emotional distraction on task performance in both disorders. METHODS: Male adults with ADHD (n = 22), male adults with alcohol dependence (n = 16), and healthy controls (n = 30) performed an emotional working memory task (n-back task). In the background of the task, we presented neutral and negative stimuli that varied in emotional saliency. RESULTS: In both clinical groups, a working memory deficit was evident. Moreover, both clinical groups displayed deficient emotional interference control. The n-back performance of the controls was not affected by the emotional distractors, whereas that of subjects with ADHD deteriorated in the presence of low salient distractors, and that of alcoholics did not deteriorate until high salient distractors were presented. Subsequent to task performance, subjects with ADHD accurately recognized more distractors than did alcoholics and controls. In alcoholics, picture recognition accuracy was negatively associated with n-back performance, suggesting a functional association between the ability to suppress emotional distractors and successful task performance. In subjects with ADHD, performance accuracy was negatively associated with ADHD inattentive symptoms, suggesting that inattention contributes to the performance deficit. CONCLUSIONS: Subjects with ADHD and alcoholics both display an emotional interference control deficit, which is especially pronounced in subjects with ADHD. Beyond dysfunctional attention allocation processes, a more general attention deficit seems to contribute to the more pronounced performance deficit pattern in ADHD.

Minor cognitive disturbances in X-linked spinal and bulbar muscular atrophy, Kennedy's disease.

Spinal and bulbar muscular atrophy (SBMA), Kennedy's disease, is an adult-onset hereditary neurodegenerative disorder, associated predominantly with a lower motor neuron syndrome and eventually endocrine and sensory disturbances. In contrast to other motor neuron diseases such as amyotrophic lateral sclerosis (ALS), the impairment of cognition in SBMA is not well documented. We conducted a systematic cross-sectional neuropsychological study in order to investigate cognition in SBMA patients more thoroughly. We investigated 20 genetically proven SBMA patients compared to 20 age- and education-matched control subjects using a comprehensive neuropsychological test battery, measuring executive functioning, attention, memory and visuospatial abilities. The SBMA patients performed significantly worse than healthy controls in three sub-tests in the executive and attention domains. This low performance was in the working memory (digit span backward task), verbal fluency category (single letter fluency task) and memory storage capacity (digit span forward task). No disturbances were detected in other cognitive domains. The impairments were subclinical and not relevant to the patients' everyday functioning. In addition, no correlations were found between cognitive scores and the CAG repeat length. In conclusion, we found minor cognitive disturbances in patients with SBMA, which could indicate subtle frontal lobe dysfunction. These findings extend our neurobiological understanding of SBMA.

The impact of financial reward contingencies on cognitive function profiles in adult ADHD.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Enhanced emotional interference on working memory performance in adults with ADHD.

OBJECTIVES: Subjects with attention-deficit/hyperactivity disorder (ADHD) suffer from both executive dysfunction and deficits in emotion regulation. However, up to now, there has been no research demonstrating a clear impact of emotional dysregulation on cognitive performance in subjects with ADHD. METHODS: Male and female adults with ADHD (n=39) and gender- and IQ-matched control subjects (n=40) performed an emotional working memory task (n-back task). In the background of the task, we presented neutral and negative stimuli varied in emotional saliency (negative pictures with low saliency, negative pictures with high saliency), but subjects were instructed to ignore these pictures and to process the working memory task as quickly and as accurately as possible. RESULTS: Compared to control subjects, ADHD patients showed both a general working memory deficit and enhanced distractability by emotionally salient stimuli in terms of lower n-back performance accuracy. In particular, while controls showed impaired WM performance when presented with highly arousing negative background pictures, a comparable decrement was observed in the ADHD group already with lowly arousing pictures. CONCLUSIONS: Our results suggest that difficulties in suppressing attention towards emotionally laden stimuli might result from deficient executive control in ADHD.

Differential patterns of disordered eating in subjects with ADHD and overweight.

OBJECTIVES: Despite growing evidence for an association between overweight and attention-deficit/hyperactivity disorder (ADHD), still little is known about the mechanisms underlying this relationship. METHODS: Within a two (no ADHD, ADHD) × two (normal weight, overweight) factorial design (n = 94) we tested disordered eating behaviour in a laboratory breakfast procedure as well as delay aversion (DA) in male children aged 7-15 years. RESULTS: While children with ADHD tended to eat above the normal level particularly at the beginning of the meal, children with overweight tended to eat above the normal level throughout the whole meal. Furthermore, preference for immediately available food was predicted by parental ratings of inattention and neuropsychological measures of DA in overweight children, and by impulsivity in children with ADHD. CONCLUSIONS: Our results suggest distinct neuropsychopathological pathways to abnormal eating in ADHD and overweight. Thus, children with overweight might benefit more from specialized treatment programmes that aim at improving attention functions while in children with ADHD the treatment should focus on impulsivity.

Contextual influence of highly valued rewards and penalties on delay decisions in children with ADHD.

In this study, we examined the influence of both reward and penalty on delay decisions in subjects with ADHD. Eighteen 6- to 13-year-old boys with ADHD (combined or hyperactive-impulsive subtype) along with age- and IQ-matched control participants performed a memory game. If the children were successful at the game, they could choose between a small immediate reward (one white chip in exchange for 5 s of waiting) or a large delayed reward (two white chips in exchange for 60 s of waiting). If they failed, they could choose between a large immediate penalty (two black chips in exchange for 5 s of waiting) or a small delayed penalty (one black chip in exchange for 60 s of waiting). Subsequent to task completion, white chips were exchanged for video time and black chips were exchanged with completion of a written task. All of the participants, regardless of ADHD diagnosis, were motivated to complete the task and chose the delayed alternative most often. We conclude that under highly motivating conditions, children with ADHD are not more delay averse than children from the control group with respect to anticipation of reward and penalty.

Neurocognitive performance in children with ADHD and OCD.

Attention-deficit/hyperactivity Disorder (ADHD) and obsessive-compulsive disorder (OCD) have both been linked to dysfunction in the cortico-striato-thalamo-cortical circuitry (CSTCC). However, the exact nature of neurocognitive deficits remains to be investigated in both disorders. We applied two neuropsychological tasks that tap into different functions associated with the CSTCC, namely a serial reaction time (SRT) task, developed to assess implicit sequence learning, and a delay aversion (DA) task in order to assess abnormal motivational processes. The performance data of boys with ADHD (n=20), OCD (n=20) and healthy controls (n=25), all aged 10-18 years, were compared. Subjects with ADHD less frequently chose the larger, more delayed reward compared to those with OCD and controls, while subjects with OCD showed impaired implicit learning. In contrast, the ADHD group was unimpaired in their implicit learning behavior and the OCD group was not characterized by a DA style. Within the OCD-group, severity of obsessions was associated with implicit learning deficits and impulsive symptoms with DA in the ADHD-group. This double dissociation highlights the distinct cognitive dysfunctions associated with ADHD and OCD and might possibly point to different neural abnormalities in both disorders.

Cross-sectional evaluation of cognitive functioning in children, adolescents and young adults with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, albeit with changes in clinical symptoms throughout the life span. Although effect sizes of neuropsychological deficits in ADHD are well established, developmental approaches have rarely been explored and little is yet known about age-dependent changes in cognitive dysfunction from childhood to adulthood. In this cross-sectional study, 20 male children (8-12 years), 20 adolescents (13-16 years), and 20 adults (18-40 years) with ADHD and a matched control group were investigated using six experimental paradigms tapping into different domains of cognitive dysfunction. Subjects with ADHD were more delay-aversive and showed deficits in time discrimination and time reproduction, but they were not impaired in working memory, interference control or time production. Independent of age, the most robust group differences were observed with respect to delay aversion and time reproduction, pointing to persistent dysfunction in the mesolimbic reward circuitry and in the frontal-striatal-cerebellar timing system in subjects with ADHD. Across all tasks, effect sizes were lowest for adolescents with ADHD compared to age-matched controls. Developmental dissociations were found only for simple stimuli comparison, which was particularly impaired in ADHD children. Thus, in line with current multiple-pathway approaches to ADHD, our data suggest that deficits in different cognitive domains are persistent across the lifespan, albeit less pronounced in adolescents with ADHD.

Emotional processing in male adolescents with childhood-onset conduct disorder.

BACKGROUND: Boys with early onset of conduct disorder (CD), most of whom also meet diagnostic criteria of a comorbid attention deficit hyperactivity disorder (ADHD), tend to exhibit high levels of aggression throughout development. While a number of functional neuroimaging studies on emotional processing have been performed in antisocial adults, little is known about how CD children process emotional information. METHOD: Functional magnetic resonance imaging data were analyzed in 22 male adolescents aged 12 to 17 years with childhood-onset CD (16 of them with comorbid ADHD) compared to 22 age-matched male healthy controls. In order to consider the likely confounding of results through ADHD comorbidity, we performed a supplementary study including 13 adolescent subjects with pure ADHD who were compared with healthy controls. To challenge emotional processing of stimuli, a passive viewing task was applied, presenting pictures of negative, positive or neutral valence. RESULTS: When comparing CD/combined disorder patients with healthy controls, we found enhanced left-sided amygdala activation in response to negative pictures as compared to neutral pictures in the patient group. In addition, these boys exhibited no reduced activation in the orbitofrontal, anterior cingulate and insular cortices. By contrast, children with pure ADHD did not show any abnormalities in amygdala activation but showed decreased neural activity in the insula only in response to negative pictures. CONCLUSIONS: Increased rather than reduced amygdala activation found in our study may indicate an enhanced response to environmental cues in adolescents with early-onset CD (most of whom also met the condition of ADHD), and is not consistent with the assumption of a reduced capacity to take note of affective information in the social environment. Further studies with an emphasis on developmental aspects of affect regulation are needed to clarify the relationship between CD and adult personality pathology associated with different modes of persistent antisocial behavior.

Morphometric brain abnormalities in boys with conduct disorder.

OBJECTIVE: Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. METHOD: Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. RESULTS: Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms and widespread gray matter abnormalities in the frontoparietal and temporal cortices. By contrast, CD symptoms correlated primarily with gray matter reductions in limbic brain structures. CONCLUSIONS: The data suggest that boys with CD and comorbid attention-deficit/hyperactivity disorder show brain abnormalities in frontolimbic areas that resemble structural brain deficits, which are typically observed in adults with antisocial behavior.