Swantje Matthies

Spectroscopic findings in attention-deficit/hyperactivity disorder: Review and meta-analysis

Objectives. The last decade has seen an increasing interest in the method of magnet resonance spectroscopy (MRS) since this is the only research tool that allows a non-invasive in vivo assessment of neurochemical aspects of ADHD without employing ionising radiation. In this paper we review published MRS results with respect to childhood, adolescence and adult ADHD. Method. We searched the Medline (Pub Med) database using the key words ADHD, attention-deficit/hyperactivity disorder, magnet resonance spectroscopy, MRS and spectroscopy. Citations of identified articles were also searched for relevant studies. Meta-analyses were performed for the measured metabolites and regions of assessment. Results. Sixteen studies could be identified that used MRS to investigate the neurobiology of ADHD. Two regions could be identified as the focus of spectroscopic investigations – the frontal lobe including anterior cingulate cortex and parts of prefrontal cortex and the basal ganglia, mostly striatum, alongside the fronto-striato-thalamo-frontal circuits. As for metabolites, in the majority of studies the ratios to creatine and not absolute concentrations of metabolites were estimated. Choline compounds, N-acetyl-aspartate and glutamate/glutamine (to creatine ratios) could be identified as being altered in several studies in ADHD. The meta-analysis showed increased choline compounds in several researched regions. Discussion. MRS is a promising tool for the non-invasive in vivo assessment of the cerebral neurochemistry in ADHD. More regions of interest (ROI) like amygdala, hippocampus, thalamus and cerebellum should be assessed in future studies. Further methodological improvements of MRS are desirable in order to assess the absolute metabolite concentration of several ROIs at the same time. Such developments will open novel perspectives in spectroscopic investigations of ADHD.

Effects of Group Psychotherapy, Individual Counseling, Methylphenidate, and Placebo in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial

IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence in adulthood. There is a recognized need to assess the efficacy of psychotherapy in adult ADHD. OBJECTIVE To evaluate the efficacy of cognitive behavioral group psychotherapy (GPT) compared with individual clinical management (CM) and that of methylphenidate hydrochloride compared with placebo. DESIGN, SETTING, AND PARTICIPANTS Prospective, multicenter, randomized clinical trial of 18- to 58-year-old outpatients with ADHD from 7 German study centers. Patients were recruited between January 2007 and August 2010, treatment was finalized in August 2011, and final follow-up assessments occurred in March 2013. INTERVENTIONS Sessions of GPT and CM were held weekly for the first 12 weeks and monthly thereafter (9 months). Patients received either methylphenidate or placebo for 1 year. MAIN OUTCOMES AND MEASURES The primary outcome was the change in the ADHD Index of the Conners Adult ADHD Rating Scale from baseline to the end of the 3-month intensive treatment (blinded observer ratings). Secondary outcomes included ADHD ratings after 1 year, blinded observer ratings using the Clinical Global Impression Scale, and self-ratings of depression. RESULTS Among 1480 prescreened patients, 518 were assessed for eligibility, 433 were centrally randomized, and 419 were analyzed as randomized. After 3 months, the ADHD Index all-group baseline mean of 20.6 improved to adjusted means of 17.6 for GPT and 16.5 for CM, with no significant difference between groups. Methylphenidate (adjusted mean, 16.2) was superior to placebo (adjusted mean, 17.9) (difference, -1.7; 97.5% CI, -3.0 to -0.4; P = .003). After 1 year, treatment effects remained essentially stable. Descriptive analyses showed that methylphenidate was superior to placebo in patients assigned to GPT (difference, -1.7; 95% CI, -3.2 to -0.1; P = .04) or CM (difference, -1.7; 95% CI, -3.3 to -0.2; P = .03). Regarding depression, no significant differences were found. In contrast, GPT was superior to CM for all visits in the Clinical Global Impression global assessment of effectiveness. CONCLUSION AND RELEVANCE Highly structured group intervention did not outperform individual CM with regard to the primary outcome. Psychological interventions resulted in better outcomes during a 1-year period when combined with methylphenidate as compared with placebo. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN54096201.

Risky decision making in adults with ADHD

BACKGROUND AND OBJECTIVES Risky decision making and disadvantageous choices constitute core characteristics of patients with attention-deficit/hyperactivity disorder (ADHD). Consequences include negative psychosocial and health-related outcomes. However, risky decision making and its interrelations with emotional states in ADHD are poorly understood. Therefore, the authors investigated risky decision making without and after boredom induction in adults with and without ADHD. METHODS In study 1, ADHD patients (n = 15) and age/education matched controls (CG; n = 16) were compared on the Game of Dice Task (GDT), an established task measuring decision making in unambiguous situations. In study 2, ADHD patients (n = 14) and CG (n = 13) underwent boredom induction prior to the GDT. RESULTS In study 1, ADHD patients selected the disadvantageous alternatives significantly more often than CG. In study 2, no significant group differences were found due to an increase in risky decision making in CG following the boredom induction. LIMITATIONS Even if severity of depression did not affect our results, it may be necessary to compare GDT responses in ADHD patients with and without current depression. CONCLUSIONS Risk as a motor of disadvantageous decision making needs to be taken into account in therapeutic contexts as a maintenance factor of dysfunctional behaviour. The findings of study 2 are in line with postulated alterations of emotional state adjustment in ADHD. The link between decisions making and emotional regulation in ADHD needs further attention in research.

Severity of Childhood Attention-Deficit Hyperactivity Disorder—A Risk Factor for Personality Disorders in Adult Life?

Some evidence points to an increased rate of cluster B and C personality disorders (PDs) in adult ADHD patients. In order to assess axis II disorders comprehensively we used the diagnostic instrument of the WHO. In sixty adult out-patients with ADHD according to DSM-IV criteria PDs were assessed with the International PD Examination (IPDE) and severity of childhood ADHD with the Wender-Utah-Rating Scale (WURS). We found at least one PD in 25% of cases. Cluster C PDs were most common (36.6%) followed by Cluster B (23.3%) and A (8.3%). Avoidant (21.7%) and borderline (18.3%) were the most frequent single PD entities. ADHD patients with PD suffered from significantly more severe childhood ADHD compared to those without co-occurring PD. Applying the IPDE we confirmed a high number of PDs among adult ADHD patients. Our findings point to a higher vulnerability for the development of PDs in patients with severe childhood ADHD.

Small amygdala – high aggression? The role of the amygdala in modulating aggression in healthy subjects

Objective. Several lines of evidence suggest an association between the amygdala and the modulation of aggressive behaviour. Previous morphometric brain imaging studies have focused on the role of the amygdala in the context of pathologic neuropsychiatric conditions like depression, personality disorders, and dysphoric and aggressive behaviour in epilepsy. In order to better understand the physiological role of the amygdala in modulating aggressive behaviour we investigated the relationship between amygdala volumes and lifetime aggression in healthy subjects. Methods. Morphometric brain scans were obtained in 20 healthy volunteers. Amygdala volumes were measured by manually outlining the boundaries of the structure following a well established and validated protocol. Careful psychiatric and psychometric assessment was done to exclude any psychiatric disorder and to assess lifetime aggressiveness with an established and validated psychometric instrument (i.e. Life History of Aggression Assessment (LHA)). Results. All volunteers scored in the normal range of lifetime aggression. Volunteers with higher aggression scores displayed a 16–18% reduction of amygdala volumes. There was a highly significant negative correlation between amygdala volumes and trait aggression. Conclusion. The extent of volumetric differences in this study is remarkable and suggests that amygdala volumes might be a surrogate marker for the personality property of aggressiveness in healthy human beings.

Risky decision-making in borderline personality disorder

Impulsivity is a core feature of borderline personality disorder (BPD). Thereby, individuals with BPD are most often explicitly aware of the deleterious long-term consequences of their impulsive behaviors, but still engage in them. Therefore, the aim of the present study was to test decision-making in BPD. Female individuals with BPD (n=21) and female controls without BPD (CG; n=29) were compared on the Game of Dice Task (GDT) with regard to disadvantageous decision-making and feedback processing. In the GDT rules for reinforcement and punishment are explicitly clear and the outcome is defined by probabilities. By providing feedback about the outcome of previous decisions, the GDT is a valid measure to simulate decision-making in real life situations. Main results revealed that women with BPD make risky decisions significantly more often than the CG. Moreover, they show reduced capacities to advantageously utilize feedback. As deficits in decision-making were correlated with BPD symptom severity and impulsivity, risky decision-making may be a relevant maintenance factor for the disorder.

Common ground in Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD)-review of recent findings.

Considerable overlap in diagnostic criteria and shared psychopathologic symptoms in attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) have stimulated research activities in this field. Longitudinal studies have shown that BPD is frequently diagnosed in adult patients who had been diagnosed with ADHD in childhood. The question of whether ADHD and BPD randomly co-occur as comorbidities, have similar origins or share common pathological mechanisms remains unresolved. Some authors suggest that ADHD contributes to the development of BPD via various mechanisms, and therefore consider it a risk factor for later BPD development.In this article the evidence for the co-occurrence of these disorders will be reviewed as well as studies on their common genetic and environmental influences. Temperamental and developmental issues will be reviewed, and shared features such as impulsivity and emotion dysregulation discussed. From a therapeutic perspective, few studies have investigated psychotherapeutic treatment of the comorbid condition, though the issue is highly important to the management of patients suffering from both disorders. Some thought is given to how therapeutic methods and approaches can be modified to benefit patients, and to their possible succession.

German Validation of the Conners Adult ADHD Rating Scale–Self-Report: Confirmation of Factor Structure in a Large Sample of Participants with ADHD

Objective: The Conners Adult ADHD Rating Scales (CAARS) assess symptoms specific to adults that are frequently used and have been translated into German. The current study tests the factor structure of the CAARS in a large sample of German adults with ADHD and compares the means of the CAARS subscales with those of healthy German controls. Method: CAARS were completed by 466 participants with ADHD and 851 healthy control participants. Confirmatory factor analysis was used to establish model fit with the American original. Comparisons between participants with ADHD and healthy controls and influences of gender, age, and degree of education were analyzed. Results: Confirmatory factor analysis showed a very good fit with the model for the American original. Differences between ADHD participants and healthy controls on all Conners Adult ADHD Rating Scales–Self-Report (CAARS-S) subscales were substantial and significant. Conclusion: The factor structure of the original American model was successfully replicated in this sample of adult German ADHD participants.

Effects of suppression and acceptance of sadness on the urge for non-suicidal self-injury and self-punishment

The present study wanted to test the course of the urge for non-suicidal self-injury (UNSSI) and the urge for self-punishment (USP) when suppressing or accepting upcoming emotions in response to a sadness-inducing film clip in female participants with borderline personality disorder (BPD). Thirty-six women with BPD were allocated either to a condition in which they were asked to engage in expressive suppression or acceptance while watching a sadness-inducing film clip. Ratings of UNSSI, USP, and positive and negative emotions were assessed prior to the clip (baseline), immediately after it (t1) and after a 5min waiting period (t2), during which participants viewed landscape pictures. Additionally, physiological measures were obtained. Main results revealed a significant increase in UNSSI from baseline to t2 in the acceptance, but not in the suppression group. Furthermore, USP scores significantly increased from baseline to t2 in the acceptance, but not in the suppression condition. However, there was no differential impact on the sympathetic and parasympathetic branch depending on strategy. The results are in line with recent literature showing that expressive suppression in BPD may also have an adaptive function.

Discrete Global but No Focal Gray Matter Volume Reductions in Unmedicated Adult Patients With Attention-Deficit/Hyperactivity Disorder

BACKGROUND Gray matter reduction mainly in the anterior cingulate cortex, the basal ganglia, and the cerebellum has been reported in attention-deficit/hyperactivity disorder (ADHD). Yet, respective data remain contradictory and inconclusive. To clarify if structural alteration in these brain areas can be verified in a large cohort of adult patients and if a history of stimulant medication has an effect on brain structure, magnetic resonance imaging was performed in the context of a clinical trial on the efficacy of group psychotherapy, clinical management, methylphenidate, and placebo (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study Trial). METHODS Between January 2007 and August 2010, 1480 patients from seven study centers across Germany, aged 18 to 58, were prescreened; 518 were assessed for eligibility; 433 were randomized; and 187 were eligible for neuroimaging. The control group included 121 healthy volunteers. Structural magnetic resonance imaging data sets were acquired. Following strict quality control, 131 patient and 95 control data sets could be analyzed. All patients were unmedicated for at least 6 months. The established method of voxel-based morphometry (VBM8 segmentation and diffeomorphic anatomical registration through exponentiated lie normalization) was used to assess global and regional brain volumes. RESULTS Patients displayed subtle global cerebral volume reductions. There was no evidence of regional gray matter volume abnormalities. The inattentive ADHD subtype was linked to smaller volumes in the left dorsolateral prefrontal cortex. A history of previous medication did not modulate brain volumes. CONCLUSIONS ADHD in adulthood is associated with global rather than regional volumetric abnormalities. Previous use of stimulant medication does not seem to modify subsequent brain volumes in a significant way.