Christina Stadler

Abnormal neural responses to emotional visual stimuli in adolescents with conduct disorder

BACKGROUND It is widely held that aggression and antisocial behavior arise as a consequence of a deficiency in responding to emotional cues in the social environment. We asked whether neural responses evoked by affect-laden pictures would be abnormal in adolescents with conduct disorder (CD). METHODS Functional magnetic resonance imaging during passive viewing of pictures with neutral or strong negative affective valence was performed in 13 male adolescents with severe CD aged 9 to 15 years and in 14 healthy age-matched control subjects. RESULTS Main effects for negative-neutral affective valence included activations in the amygdala and hippocampus, ventral extrastriate visual cortex, and intraparietal sulcus bilaterally. There was a significant group-by-condition interaction in the right dorsal anterior cingulate cortex that was due to a pronounced deactivation in the patient group during viewing of negative pictures. When correcting for anxiety and depressive symptoms, we additionally found a reduced responsiveness of the left amygdala to negative pictures in patients compared with control subjects. CONCLUSIONS We suggest that these findings reflect an impairment of both the recognition of emotional stimuli and the cognitive control of emotional behavior in patients with CD, resulting in a propensity for aggressive behavior.

A structural neural deficit in adolescents with conduct disorder and its association with lack of empathy

The goal of this study was to determine whether brain regions implicated in emotion processing show structural alterations in adolescents with conduct disorder (CD). Using an optimized voxel-based morphometry protocol, we compared grey matter volume in 12 patients with CD and 12 age-, sex-, and intelligence-matched control subjects. Grey matter volume in bilateral anterior insular cortex and the left amygdala was significantly reduced in CD patients compared to healthy control subjects. The insular grey matter abnormalities could be attributed to aggressive behaviour. Moreover, bilateral anterior insular grey matter volume in CD patients correlated significantly with empathy scores. These novel findings point at a joint neuroanatomical substrate underpinning aggressive behaviour and impaired capacity of empathy and suggest a critical role for the anterior insula in regulating social behaviour.

Neuroimaging of aggressive and violent behaviour in children and adolescents

In recent years, a number of functional and structural neuroimaging studies have investigated the neural bases of aggressive and violent behaviour in children and adolescents. Most functional neuroimaging studies have persued the hypothesis that pathological aggression is a consequence of deficits in the neural circuits involved in emotion processing. There is converging evidence for abnormal neural responses to emotional stimuli in youths with a propensity towards aggressive behaviour. In addition, recent neuroimaging work has suggested that aggressive behaviour is also associated with abnormalities in neural processes that subserve both the inhibitory control of behaviour and the flexible adaptation of behaviour in accord with reinforcement information. Structural neuroimaging studies in children and adolescents with conduct problems are still scarce, but point to deficits in brain structures in volved in the processing of social information and in the regulation of social and goal-directed behaviour. The indisputable progress that this research field has made in recent years notwithstanding, the overall picture is still rather patchy and there are inconsistencies between studies that await clarification. Despite this, we attempt to provide an integrated view on the neural abnormalities that may contribute to various forms of juvenile aggression and violence, and discuss research strategies that may help to provide a more profound understanding of these important issues in the future.

Cortisol reactivity in boys with attention-deficit/hyperactivity disorder and disruptive behavior problems: the impact of callous unemotional traits.

There is a body of literature demonstrating an association between altered hypothalamic pituitary adrenal (HPA) axis reactivity and aggressive behavior. Aggressive and disruptive behavior also is highly prevalent in children with attention deficit/hyperactivity disorder (ADHD). Findings on HPA-axis reactivity in ADHD, however, are rather inconsistent. Specific temperamental risk factors previously were associated with a specific subtype of severe disruptive behavior. These traits might also be characterized by a distinct neurobiological profile across ADHD and disruptive behavior disorders. In this study we focus on psychopathic traits, notably callous unemotional (CU) traits. The main objective of the present study was to investigate whether two groups of ADHD patients with high or low CU traits differed in cortisol reactivity. Subjects were 36 boys with ADHD and disruptive behavior symptoms aged 8 to 14 years. Salivary cortisol probes were taken before and repeatedly after an experimental standardized stress test. Patients scoring high on CU traits showed a blunted HPA axis reactivity to the experimentally induced stress. Results underscore the need to consider specific personality traits in investigating neurobiological correlates in ADHD with disruptive behavior problems.

Spezifische Wirksamkeit von Neurofeedback auf die Impulsivität bei ADHS

Fur das Neurofeedback (NF), ein verhaltenstherapeutisches Verfahren, das uber die Modifikation von EEG-Parametern eine Verbesserung von ADHS-Kernsymptomen anstrebt, hat sich die Evidenzbasis in den vergangenen Jahren verbessert. Die Arbeit gibt einen Uberblick uber die vorliegenden Befunde. Die durch NF erreichten kurzfristigen Verbesserungen entsprachen in mehreren Studien denen einer pharmakotherapeutischen Stimulanzien-Behandlung. Untersuchungen zur Wirkdauer der Effekte sind ermutigend. In einer eigenen Pilotstudie wurden 34 Kinder mit ADHS zufallig einer Neurofeedback-Behandlung oder einem computergestutzten Aufmerksamkeitstraining zugeteilt. Die Zahl der Impulsivitatsfehler in einem Stopp-Signal-Paradigma reduzierte sich durch Neurofeedback signifikant, wahrend sich im Elternurteil keine differenziellen Effekte fanden. Eine weitgehende Normalisierung hirnelektrischer Korrelate von Hemmungskontrolle fand sich nur in der NF-Gruppe. Neurofeedback ist ein vielversprechender Ansatz in der ADHS-Behandlung...

Diminished Serotonergic Functioning in Hostile Children with ADHD: Tryptophan Depletion Increases Behavioural Inhibition

INTRODUCTION Serotonergic (5-HT) functioning has been shown to account for a variety of behavioural characteristics, in particular aggressive and impulsive behaviour. This study explored the effects of rapid tryptophan depletion (RTD) and the ensuing reduction of brain 5-HT synthesis on behavioural inhibition in passive avoidance learning assessed in a computerized go/no-go task. METHODS 22 male patients with an ICD-10 diagnosis of ADHD were administered RTD within an amino acid drink lacking tryptophan, the natural precursor of 5-HT, thus lowering the central nervous 5-HT synthesis rate in a placebo-controlled double-blind within-subject crossover-design. 4 hours after RTD/placebo intake the patients were subjected to a go/no-go task for assessment of behavioural inhibition. RESULTS Highly hostile aggressive patients showed increased inhibition errors under RTD compared to placebo. Low hostile aggressive patients showed lower rates of inhibition errors and thus better performance under RTD compared to placebo. DISCUSSION The data suggest that in ADHD levels of trait-aggressive characteristics influence the susceptibility to changed behavioural inhibition after an acute 5-HT dysfunction. The detected influence of 5-HT could also be relevant as regards behavioural inhibition being subject to a developmental change in 5-HT functioning.

Comparative efficacy of once-a-day extended-release methylphenidate, two-times-daily immediate-release methylphenidate, and placebo in a laboratory school setting.

AbstractBackgroundGiven the dosing limitations of methylphenidate short–acting preparations in treating ADHD, galenics with longer release of the substance were developed mainly to avoid drug intake during school hours.ObjectivesThis investigation was conducted to assess the efficacy and the duration of action of a new extended-release formulation of methylphenidate (Medikinet® retard) as a once–daily treatment for children with attention–deficit hyperactivity disorder (ADHD).MethodThis was a randomized, double–blind, crossover multicentre study with three treatment conditions: once–daily extended–release methylphenidate, twice–daily immediate–release methylphenidate and placebo given to 79 children (8–14 years old) with ADHD. Daily assessments in an analogue classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained 5 times over an 8–hour period. Secondary measures included an ADHD rating scale, based on DSMIV/ ICD–10 separately rated for the morning and the afternoon.ResultsBoth active treatment conditions displayed significant time course effects and were superior to placebo in improving all efficacy measures. Once a day extended–release methylphenidate was not different from the same dose of twice daily immediate–release methylphenidate.ConclusionsThese data provide support for the benefit of this novel, once-daily methylphenidate preparation in the treatment of ADHD. The longer duration of action of Medikinet Retard has the potential to simplify psychostimulant treatment, thus reducing dose diversion and eliminating the need for in–school administration.

Influence of rapid tryptophan depletion on laboratory-provoked aggression in children with ADHD.

Background: The present study investigated the effects of rapid tryptophan depletion (RTD), and the ensuing reduction of central nervous system levels of serotonin (5-HT), upon reactive aggression in patients with attention deficit/hyperactivity disorder (ADHD). Furthermore, it was asked whether the relation between 5-HT function and behavioural aggression in patients is influenced by their age, the intensity of their attention problems or their comorbid symptoms. Methods: The study employed a double-blind, within-subject crossover design. On day 1, 22 male adolescent patients with ADHD were subjected to RTD and the subsequent reduction of central 5-HT levels. On day 2, they received a tryptophan-balanced amino acid mixture (BAL), which acted as a placebo. On both days, 4.5 h after the intake of the RTD/BAL amino acids, reactive aggressive behaviour was provoked using a competitive reaction time game, which consisted of both high and low provocation conditions. Results: The number of aggressive responses was significantly higher after low provocation during acute tryptophan depletion, in comparison to the placebo. Furthermore, this study provides evidence that neither age nor the intensity of attention symptoms in ADHD patients had an impact on the relation between 5-HT and reactive aggression. Conclusion: This study indicates that in children with ADHD, there is an inverse relationship between 5-HT and aggression.

The Heterogeneity of Disruptive Behavior Disorders – Implications for Neurobiological Research and Treatment

Disruptive behavior disorders (DBDs) are reflected by a great variety of symptoms ranging from impulsive-hot-tempered quarrels to purposeful and goal-directed acts of cruelty. A growing body of data indicates that there are neurobiological factors that increase the risk for developing DBDs. In this review, we give a broad overview of recent studies investigating physiological, neural, genetic factors, and specific neurotransmitter systems. We also discuss the impact of psychosocial risk and consider the effects of gene-environment interactions. Due to the heterogeneity of DBDs, it is concluded that specific subtypes of disruptive behavior should be considered both in terms their biological basis and in regard to specific treatment needs.

Electroencephalographic biofeedback for the treatment of attention-deficit hyperactivity disorder in childhood and adolescence

Considerable scientific effort has been directed at developing effective treatments for attention-deficit hyperactivity disorder (ADHD). Among alternative treatment approaches, electroencephalographic (EEG) biofeedback has gained promising empirical support in recent years. Short-term effects were shown to be comparable to those of stimulant medication at the behavioral and neuropsychological level, leading to significant decreases of inattention, hyperactivity and impulsivity. In addition, EEG biofeedback results in concomitant improvement of neurophysiological patterns. EEG biofeedback may already be used within a multimodal setting, providing affected children and adolescents with a means of learning to counterbalance their ADHD symptoms without side effects. However, there is still a strong need for more empirically and methodologically sound evaluation studies.