Publications by authors named "Esther Sobanski"

48 Publications

Common and distinct neural connectivity in attention-deficit/hyperactivity disorder and alcohol use disorder studied using resting-state functional magnetic resonance imaging.

Alcohol Clin Exp Res 2021 Mar 9. Epub 2021 Mar 9.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Background: A link between attention-deficit/hyperactivity disorder (ADHD) and alcohol use disorder (AUD) has been widely demonstrated. In this study, we used neuroimaging to investigate the connectivity traits that may contribute to the comorbidity of these disorders.

Methods: The study included an AUD group (N = 18), an ADHD group (N = 17), a group with AUD + ADHD comorbidity (N = 12) and a control group (N = 18). We used resting-state functional connectivity in a seed-based approach in the default mode networks, the dorsal attention network, and the salience network.

Results: Within the default mode networks, all affected groups shared greater connectivity toward the temporal gyrus when compared to the control group. Regarding the dorsal attention network, the Brodmann area 6 presented greater connectivity for each affected group in comparison with the control group, displaying the strongest aberrations in the AUD + ADHD group. In the salience network, the prefrontal cortex showed decreased connectivity in each affected group compared to the control group.

Conclusions: Despite the small and unequal sample sizes, our findings show evidence of common neurobiological alterations in AUD and ADHD, supporting the hypothesis that ADHD could be a risk factor for the development of AUD. The results highlight the importance of an early ADHD diagnosis and treatment to reduce the risk of a subsequent AUD.
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http://dx.doi.org/10.1111/acer.14593DOI Listing
March 2021

Herbal High: Substance-Induced Psychosis after Consumption of Seeds of the Hawaiian Baby Woodrose.

Z Kinder Jugendpsychiatr Psychother 2021 Mar 4:1-5. Epub 2021 Mar 4.

Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Mainz, Germany.

Seeds of the Hawaiian Baby Woodrose (HBWR, Argyreia nervosa) are known as "legal or herbal highs" and can be easily purchased online in Germany. They contain various ergot alkaloids, including lysergic acid amide (LSA), which is chemically related to lysergic acid diethylamide (LSD). Pharmacological data are limited but suggest that LSA-concentration in HBWR seeds is highly variable, and that adverse psychiatric and somatic effects are not related to LSA-dosage. Anecdotal, mostly cross-sectional clinical case reports describe spontaneous remission of intoxication-related somatic and psychiatric symptoms as well as intoxication-related death. Treatment recommendations for LSA-induced psychiatric syndromes are not available. We report here on the clinical course and treatment of a drug-induced psychosis after consumption of HBWR seeds. The adolescent had consumed HBWR seeds once before without suffering any negative effects.
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http://dx.doi.org/10.1024/1422-4917/a000792DOI Listing
March 2021

Validation of the German Version of the Mind Excessively Wandering Scale (MEWS-G).

Fortschr Neurol Psychiatr 2021 Feb 26. Epub 2021 Feb 26.

Klinik für Psychiatrie und Psychotherapie, Zentralinstitut für Seelische Gesundheit Klinische Fakultät Mannheim, Universität Heidelberg.

Increasing evidence shows that unintentional mind wandering is linked to Attention Deficit Hyperactivity Disorder (ADHD) and that its frequency contributes to symptom severity and functional impairment in ADHD. However, empirical data on mind wandering in adult ADHD are still scarce, and a validated scale to assess mind wandering in German adult ADHD patients is lacking. The primary aim of this study is to assess the psychometric properties of the German version of the recently published Mind Excessively Wandering Scale (MEWS-G) in terms of factorial structure and factor stability, internal consistency and construct validity. Analyses were performed in 128 adults with ADHD, clinical and healthy controls. As described for the original English 15-item version of the scale, we found lowest item-total-correlations for items 6, 10 and 14 with item-total correlation of all: 0.54/ADHD: 0.32 (item 6), all: 0.55/ADHD: 0.39 (item 10) and all: 0.11/ADHD: -0.04 (item 14). Item-total correlations for the remaining items were 0.65-0.86 and Cronbach Alpha was 0.96 indicating good internal consistency of the 12-item version of scale, on which we based all further analyses. Principal component analysis indicated a one- and two- factorial scale structure respectively explaining 71.7 % and 78.7 % of variance. Both factors showed good stability with lower stability of the factor-2 solution if sample size was reduced. The two-factorial solution also had many cross-loadings and a strong correlation of both factors in confirmatory factorial analysis (rf1f2 = 0.87). It probably describes related and interdependent, but not distinct facets of mind wandering, which strongly argues for the one factorial structure of the scale. Mean MEWS-G score in ADHD was 23.77 ± 7.85 compared to 7.64 ± 7.27 in controls (p < .0001). According to ROC, the optimal cut-off point to discriminate ADHD and controls is at MEWS-G score = 13. On the symptom level, MEWS-G score was correlated with ADHD, depressive and total psychiatric symptom scores, on the personality level with neuroticsm and negatively with conscientiousness and on the functional level with social interaction difficulties and impaired self-efficacy. In summary, our study shows that MEWS-G is a reliable, valid instrument to assess spontaneous mind wandering in adult ADHD and to discriminate between ADHD and controls.
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http://dx.doi.org/10.1055/a-1362-9743DOI Listing
February 2021

Safety Profile of Methylphenidate Under Long-Term Treatment in Adult ADHD Patients - Results of the COMPAS Study.

Pharmacopsychiatry 2020 Nov 5;53(6):263-271. Epub 2020 Oct 5.

Department of Psychiatry and Psychotherapy - University of Bonn, Bonn, Germany.

Introduction: The Comparison of Methylphenidate and Psychotherapy in adult ADHD Study (COMPAS) was a prospective, randomized multicenter clinical trial, comparing methylphenidate (MPH) with placebo (PLAC) in combination with cognitive behavioral group psychotherapy (GPT) or individual clinical management (CM) over the period of 1 year. Here, we report results on treatment safety.

Methods: MPH and PLAC were flexibly dosed. Among 433 randomized patients, adverse events (AEs) were documented and analyzed on an "as received" basis during week 0-52. Electrocardiogram data were recorded at baseline and week 24.

Results: Comparing 205 patients who received ≥1 dose of MPH with 209 patients who received PLAC, AEs occurring significantly more frequently in the MPH group were decreased appetite (22 vs. 3.8%), dry mouth (15 vs. 4.8%), palpitations (13 vs. 3.3%), gastrointestinal infection (11 vs. 4.8%), agitation (11 vs. 3.3%), restlessness (10 vs. 2.9%), hyperhidrosis, tachycardia, weight decrease (all 6.3 vs. 1.9%), depressive symptom, influenza (both 4.9 vs. 1.0%), and acute tonsillitis (4.4 vs. 0.5%). Syncope occurred significantly more often in the PLAC group (2.4 vs. 0%). Clinically relevant ECG changes occurred very rarely in both groups. Serious AEs were rare and without a significant group difference. The comparison of 206 patients treated with GPT versus 209 patients who received CM revealed no major differences. Serious AE classified as psychiatric occurred in 5 cases in the CM group and in 1 case in the GPT group.

Conclusion: In this so far longest-running clinical trial, methylphenidate treatment was safe and well-tolerated.
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http://dx.doi.org/10.1055/a-1207-9851DOI Listing
November 2020

Effects of 12-Week Methylphenidate Treatment on Neurometabolism in Adult Patients with ADHD: The First Double-Blind Placebo-Controlled MR Spectroscopy Study.

J Clin Med 2020 Aug 11;9(8). Epub 2020 Aug 11.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Attention deficit hyperactivity disorder (ADHD) is a frequent neurodevelopmental disorder that often persists into adulthood. Methylphenidate (MPH) is the first-line treatment for ADHD; however, despite its wide usage, little is known about its neurometabolic effects. Until now, no randomized and blinded clinical trials have been conducted addressing the neurometabolic signals of MPH administration in adults with ADHD. In the current study, the authors investigated how MPH intake and group psychotherapy (GPT) influence brain neurometabolism over the course of three months. The authors hypothesized a decrease in the anterior cingulate cortex (ACC) glutamate concentration following MPH administration. This study was part of a double-blind multicenter trial (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS)) investigating the effects of MPH and GPT in patients with adult ADHD. Using single-voxel magnetic resonance spectroscopy (MRS) of the pregenual ACC and the left cerebellar hemisphere (CHL), we investigated the concentration of glutamate plus glutamine (Glx), N-acetyl-aspartate, creatine, total choline containing compounds, and myo-inositol in patients before and after 12 weeks of treatment. Neither MPH nor GPT significantly influenced the Glx concentration or any of the other metabolite concentrations in the ACC and CHL after 12 weeks. Therefore, contrary to the hypothesis, no change in the prefrontal Glx signal was detected after MPH treatment. Given that MRS does not differentiate between glutamate in the synaptic cleft and in neuronal tissue, MPH-induced down-regulation of glutamatergic neurotransmission in the ACC might only affect the concentration of glutamate in the synaptic cleft, while the general availability of glutamate in the respective neuronal tissue might be unaffected by MPH intake. The observed lack of any MPH-induced normalization in metabolite concentrations is less surprising, considering that the baseline sample did not significantly differ from a healthy control group. Future studies of other regions, such as the basal ganglia, and the use of novel methods, such as whole brain MRS and multimodal imaging approaches, are necessary.
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http://dx.doi.org/10.3390/jcm9082601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464267PMC
August 2020

Does helping mothers in multigenerational ADHD also help children in the long run? 2-year follow-up from baseline of the AIMAC randomized controlled multicentre trial.

Eur Child Adolesc Psychiatry 2020 Oct 5;29(10):1425-1439. Epub 2019 Dec 5.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.

ADHD often affects multiple generations in a family. Previous studies suggested that children with ADHD benefit less from therapy if parents are also affected, since ADHD symptoms interfere with treatment implementation. This two-group randomised controlled trial examined whether targeting maternal ADHD boosts the efficacy of parent-child training (PCT) for the child's ADHD. Here, we report follow-up results 2 years from baseline. Mothers of 144 mother-child dyads (ADHD according to DSM-IV) were examined for eligibility (T1) and randomised to 12 weeks of intensive multimodal treatment comprising pharmacotherapy and DBT-based cognitive behavioural group psychotherapy (TG, n = 77) or clinical management comprising non-specific counselling (CG, n = 67) for Step 1 (concluded by T2). Subsequently, all dyads participated in 12 weekly PCT sessions for Step 2 (concluded by T3). In Step 3, participants received maintenance treatments for 6 months (concluded by T4). At 24 months after baseline (T5), we performed follow-up assessments. The primary endpoint was child ADHD/ODD score (observer blind rating). Outcomes at T5 were evaluated using ANCOVA. Assessments from 101 children and 95 mothers were available at T5. Adjusted means (m) of ADHD/ODD symptoms (range 0-26) in children did not differ between TG and CG (mean difference = 1.0; 95% CI 1.2-3.1). The maternal advantage of TG over CG on the CAARS-O:L ADHD index (range 0-36) disappeared at T5 (mean difference = 0.2; 95% CI - 2.3 to 2.6). Sensitivity analyses controlling for medication and significant predictors of follow-up participation showed unchanged outcomes. Within-group outcomes remained improved from baseline. At the 24-month follow-up, TG and CG converged. The superiority of intensive treatment regarding maternal symptoms disappeared. In general, cross-generational treatment seems to be effective in the long term. (BMBF grant 01GV0605; registration ISRCTN73911400).
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http://dx.doi.org/10.1007/s00787-019-01451-0DOI Listing
October 2020

Neurochemical sex differences in adult ADHD patients: an MRS study.

Biol Sex Differ 2019 10 29;10(1):50. Epub 2019 Oct 29.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Relevant sex differences in symptomatology are discussed. This study compared brain neurometabolism in the anterior cingulate cortex (ACC) and left cerebellar hemisphere in age- and IQ-matched adult male (mADHD) and female (fADHD) ADHD patients.

Methods: We studied 48 (ACC) and 42 (cerebellum) male/female pairs of stimulant-free patients with adult ADHD. Single voxel magnetic resonance spectroscopy (MRS) was used to investigate creatine (Cre), total choline (t-Cho), glutamate + glutamine (Glx), N-acetylaspartate, and myo-inositol. The mADHD and fADHD groups were compared using robust linear regression. The level of significance was corrected for multiple tests using the Benjamini-Hochberg approach.

Results: For the ACC, the signals of Cre (p = 0.008) and t-Cho (p = 0.004) showed significant effects of the age covariate as well as an interaction of sex and age (Cre: p = 0.033; t-Cho: p = 0.040). For the Glx signal, an interaction of sex and age could also be observed (p = 0.033). For cerebellar neurometabolites, the signals of t-Cho (p = 0.049) and Glx (p = 0.049) showed significant effects of the factor sex.

Conclusion: This is the largest study yet to analyze sex differences in brain neurochemistry in adult patients with ADHD. Different age-dependent t-Cho signals in the ACC might be associated with delayed myelinization in mADHD. Further MRS studies in adult ADHD, accounting for possible sex effects, are warranted to validate the present findings.
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http://dx.doi.org/10.1186/s13293-019-0264-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821019PMC
October 2019

Long-term Effects of Multimodal Treatment on Adult Attention-Deficit/Hyperactivity Disorder Symptoms: Follow-up Analysis of the COMPAS Trial.

JAMA Netw Open 2019 05 3;2(5):e194980. Epub 2019 May 3.

Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.

Importance: Knowledge about the long-term effects of multimodal treatment in adult attention-deficit/hyperactivity disorder (ADHD) is much needed.

Objective: To evaluate the long-term efficacy of multimodal treatment for adult ADHD.

Design, Setting, And Participants: This observer-masked, 1.5-year follow-up of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a prospective, multicenter randomized clinical trial, compared cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) and methylphenidate (MPH) with placebo (2 × 2 factorial design). Recruitment started January 2007 and ended August 2010, and treatments were finalized in August 2011 with follow-up through March 2013. Overall, 433 adults with ADHD participated in the trial, and 256 (59.1%) participated in the follow-up assessment. Analysis began in November 2013 and was completed in February 2018.

Interventions: After 1-year treatment with GPT or CM and MPH or placebo, no further treatment restrictions were imposed.

Main Outcomes And Measures: The primary outcome was change in the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score from baseline to follow-up. Secondary outcomes included further ADHD rating scale scores, observer-masked ratings of the Clinical Global Impression scale, and self-ratings of depression on the Beck Depression Inventory.

Results: At follow-up, 256 of 433 randomized patients (baseline measured in 419 individuals) participated. Of the 256 patients participating in follow-up, the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score was assessed for 251; the mean (SD) baseline age was 36.3 (10.1) years; 125 patients (49.8%) were men; and the sample was well-balanced with respect to prior randomization (GPT and MPH: 64 of 107; GPT and placebo: 67 of 109; CM and MPH: 70 of 110; and CM and placebo: 55 of 107). At baseline, the all-group mean ADHD Index of Conners Adult ADHD Rating Scale score was 20.6, which improved to adjusted means of 14.2 for the GPT arm and 14.7 for the CM arm at follow-up with no significant difference between groups (difference, -0.5; 95% CI, -1.9 to 0.9; P = .48). The adjusted mean decreased to 13.8 for the MPH arm and 15.2 for the placebo arm (difference, -1.4; 95% CI, -2.8 to -0.1; P = .04). As in the core study, MPH was associated with a larger reduction in symptoms than placebo at follow-up. These results remained unchanged when accounting for MPH intake at follow-up. Compared with participants in the CM arm, patients who participated in group psychotherapy were associated with less severe symptoms as measured by the self-reported ADHD Symptoms Total Score according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) of Conners Adult ADHD Rating Scale (AMD, -2.1; 95% CI, -4.2 to -0.1; P = .04) and in the subscale of reducing pure hyperactive symptoms, measured via the Diagnostic Checklist for the diagnosis of ADHD in adults (AMD, -1.3; 95% CI, -2.8 to 0.1; P = .08). Regarding the Clinical Global Impression scale assessment of effectiveness, the difference between GPT and CM remained significant at follow-up (odds ratio, 1.63; 95% CI, 1.03-2.59; P = .04). No differences were found for any comparison concerning depression as measured with the Beck Depression Inventory.

Conclusions And Relevance: Results from COMPAS demonstrate a maintained improvement in ADHD symptoms for adults 1.5 years after the end of a 52-week controlled multimodal treatment period. The results indicate that MPH treatment combined with GPT or CM provides a benefit lasting 1.5 years. Confirming the results of the core study, GPT was not associated with better results regarding the primary outcome compared with CM.

Trial Registration: isrctn.org Identifier: ISRCTN54096201.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.4980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547099PMC
May 2019

Sequential treatment of ADHD in mother and child (AIMAC study): importance of the treatment phases for intervention success in a randomized trial.

BMC Psychiatry 2018 12 13;18(1):388. Epub 2018 Dec 13.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany.

Background: The efficacy of parent-child training (PCT) regarding child symptoms may be reduced if the mother has attention-deficit/hyperactivity disorder (ADHD). The AIMAC study (ADHD in Mothers and Children) aimed to compensate for the deteriorating effect of parental psychopathology by treating the mother (Step 1) before the beginning of PCT (Step 2). This secondary analysis was particularly concerned with the additional effect of the Step 2 PCT on child symptoms after the Step 1 treatment.

Methods: The analysis included 143 mothers and children (aged 6-12 years) both diagnosed with ADHD. The study design was a two-stage, two-arm parallel group trial (Step 1 treatment group [TG]: intensive treatment of the mother including psychotherapy and pharmacotherapy; Step 1 control group [CG]: supportive counseling only for mother; Step 2 TG and CG: PCT). Single- and multi-group analyses with piecewise linear latent growth curve models were applied to test for the effects of group and phase. Child symptoms (e.g., ADHD symptoms, disruptive behavior) were rated by three informants (blinded clinician, mother, teacher).

Results: Children in the TG showed a stronger improvement of their disruptive behavior as rated by mothers than those in the CG during Step 1 (Step 1: TG vs. CG). In the CG, according to reports of the blinded clinician and the mother, the reduction of children's disruptive behavior was stronger during Step 2 than during Step 1 (CG: Step 1 vs. Step 2). In the TG, improvement of child outcome did not differ across treatment steps (TG: Step 1 vs. Step 2).

Conclusions: Intensive treatment of the mother including pharmacotherapy and psychotherapy may have small positive effects on the child's disruptive behavior. PCT may be a valid treatment option for children with ADHD regarding disruptive behavior, even if mothers are not intensively treated beforehand.

Trial Registration: ISRCTN registry ISRCTN73911400 . Registered 29 March 2007.
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http://dx.doi.org/10.1186/s12888-018-1963-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293507PMC
December 2018

Internalized stigma, anticipated discrimination and perceived public stigma in adults with ADHD.

Atten Defic Hyperact Disord 2019 Jun 19;11(2):211-220. Epub 2018 Oct 19.

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, J 5, 68159, Mannheim, Germany.

The objective of this study is to assess internalized stigma, perceived public stigma, anticipated discrimination and their associations with demographic, psychiatric and psychosocial characteristics in adult ADHD. Stigmatization was assessed with the Internalized Stigma of Mental Illness Scale, the Questionnaire on Anticipated Discrimination and the Questionnaire on Public Stereotypes Perceived by Adults with ADHD. The sample comprised n = 104 adults with ADHD, of whom n = 24 (23.3%) reported high internalized stigma, n = 92 (88.5%) anticipated discrimination in daily life and n = 70 (69.3%) perceived public stigma. Internalized stigma and/or anticipated discrimination correlated with ADHD symptoms, psychological distress, self-esteem, functional impairment and quality of life and was associated with ADHD family history and employment status. Most frequently perceived stereotypes were doubts about the validity of ADHD as a mental disorder. Internalized stigma and anticipated discrimination are highly prevalent in adult ADHD and correlate with the burden of disease. ADHD is associated with characteristic public stereotypes, which are distinct from stereotypes related to other mental disorders. Stigmatization should be considered in the clinical management of adult ADHD and evaluated further in future studies.
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http://dx.doi.org/10.1007/s12402-018-0274-9DOI Listing
June 2019

A multicentre randomized controlled trial on trans-generational attention deficit/hyperactivity disorder (ADHD) in mothers and children (AIMAC): an exploratory analysis of predictors and moderators of treatment outcome.

Z Kinder Jugendpsychiatr Psychother 2019 Jan 7;47(1):49-65. Epub 2018 Aug 7.

2b bb) Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy.

Objective: We examined predictors and moderators of treatment outcome in mothers and children diagnosed with ADHD in a large multicentre RCT.

Method: In total, 144 mother-child dyads with ADHD were randomly assigned to either a maternal ADHD treatment (group psychotherapy and open methylphenidate medication, TG) or to a control treatment (individual counselling without psycho- or pharmacotherapy, CG). After maternal ADHD treatment, parent-child training (PCT) for all mother-child dyads was added. The final analysis set was based on 123 dyads with completed primary outcome assessments (TG: n = 67, CG: n = 56). The primary outcome was the change in each child's externalizing symptoms. Multiple linear regression analyses were performed.

Results: The severity of the child's externalizing problem behaviour in the family at baseline predicted more externalizing symptoms in the child after PCT, independent of maternal treatment. When mothers had a comorbid depression, TG children showed more externalizing symptoms after PCT than CG children of depressive mothers. No differences between the treatment arms were seen in the mothers without comorbid depression.

Conclusions: Severely impaired mothers with ADHD and depressive disorder are likely to need additional disorder-specific treatment for their comorbid psychiatric disorders to effectively transfer the contents of the PCT to the home situation (CCTISRCTN73911400).
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http://dx.doi.org/10.1024/1422-4917/a000602DOI Listing
January 2019

ESCAlate - Adaptive treatment approach for adolescents and adults with ADHD: study protocol for a randomized controlled trial.

Trials 2018 May 18;19(1):280. Epub 2018 May 18.

Institute for Forensic Psychology and Psychiatry, Saarland University, Kirrberger Straße, 66421, Homburg, Saarland, Germany.

Background: Over the last decade, a wide range of attention-deficit/hyperactivity disorder (ADHD) treatment approaches for adults, including both pharmacological interventions and psychosocial treatments, have been proposed and observed to be efficient. In practice, individual treatment concepts are based on results of clinical studies as well as international guidelines (NICE Guidelines) that recommend a step-by-step treatment approach. Since the evidence supporting this approach is limited, the aim of the present study is to determine an optimal intervention regarding severity levels of ADHD symptomatology conducting a randomized controlled trial.

Method: We aim to include 279 ADHD subjects aged between 16 and 45 years. First, participants are randomized to either a face-to-face psychoeducation, telephone assisted self-help (TASH), or a waiting control group (Step 1). All participants assigned to the control group are treated using TASH after a 3-month waiting period. Participants are then allocated to one of three groups, based on their remaining severity level of ADHD symptoms, as (1) full responder, (2) partial responder, or (3) non-responder (Step 2). Full responders receive counseling, partial responders receive either counseling only or counseling and neurofeedback (NF), and non-responders receive either pharmacological treatment only or pharmacological treatment and NF, followed by a 3 month period without intervention.

Discussion: The naturalistic sample is one of the study's advantages, avoiding highly selective inclusion or exclusion criteria. The efficacy of an evidence-based stepped care intervention is explored by primary (reduction of severity of ADHD symptoms) and secondary outcomes (functional outcomes, e.g., quality of life, anger management, enhancement of psychosocial well-being). Predictors of therapeutic response and non-response are being investigated at each step of intervention. Further, sex differences are also being explored.

Trial Registration: This study is registered by the German Trial Register (reference number: DRKS00008975 ), 23 October 2015.
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http://dx.doi.org/10.1186/s13063-018-2665-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960079PMC
May 2018

Does the efficacy of parent-child training depend on maternal symptom improvement? Results from a randomized controlled trial on children and mothers both affected by attention-deficit/hyperactivity disorder (ADHD).

Eur Child Adolesc Psychiatry 2018 Aug 23;27(8):1011-1021. Epub 2018 Jan 23.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.

Multimodal treatment of children with ADHD often includes parent-child training (PCT). However, due to the high heritability, parents of children with ADHD are frequently also affected by the disorder, which is likely to constitute a significant barrier to successful treatment of the child. This secondary analysis of our randomized controlled multicentre AIMAC trial (ADHD in mothers and children) investigates whether children's outcomes following parent-child training in combination with maternal ADHD treatment depend on maternal symptom improvement. In a first step focusing on treatment of maternal ADHD, 144 mothers of mother-child dyads were randomized to multimodal ADHD treatment (group psychotherapy plus methylphenidate) or clinical management (mainly supportive counselling). After 12 weeks (T2), a 12-week PCT program (T2-T3) for all mother-child dyads was added to treat children's ADHD. Maternal symptomatology (CAARS-O:L; SCL-90-R) and children's externalizing symptoms (ADHD-ODD Scale, SDQ) were repeatedly assessed (T1 = baseline, T2, T3). Effects of changes in maternal symptomatology (T1-T2) on the change in children's symptom scores (T1-T3) were analysed using a general linear model, controlling for baseline scores, study centre, and maternal treatment group. 125 mother-child dyads were analysed. Mothers showed significant improvements in ADHD symptoms and overall psychopathology [CAARS-O:L ADHD index: mean - 3.54, SE 0.74 p < 0.0001; SCL-90-R Global Severity (GS): mean - 11.03, SE 3.90, p = 0.0056]. Although children's externalizing symptoms improved significantly (ADHD-ODD Scale: mean - 4.46, SE 0.58, p < 0.0001), maternal improvement had no effect on children's outcomes after Bonferroni-Holm correction for multiple testing. The findings do not support our hypothesis that children's outcomes following PCT for ADHD depend on maternal symptom improvements.Trial register CCT-ISRCTN73911400.
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http://dx.doi.org/10.1007/s00787-018-1109-0DOI Listing
August 2018

Effectiveness of Psychotherapy in Adult ADHD: What Do Patients Think? Results of the COMPAS Study.

J Atten Disord 2019 Jul 26;23(9):1047-1058. Epub 2017 Jul 26.

1 Medical Campus University of Oldenburg, School of Medicine and Health Sciences, Psychiatry and Psychotherapy - University Hospital, Karl-Jaspers-Klinik, Bad Zwischenahn, Germany.

Objective: In the multicenter study Comparison of Methylphenidate and Psychotherapy in Adult ADHD (COMPAS), the efficacy of treatments has been primarily evaluated by observer-rated symptom change. Here, we additionally analyzed the patients' subjective evaluation of therapy effects.

Method: COMPAS compared ADHD-specific group therapy with unspecific clinical management with/without concomitant pharmacotherapy in a four-armed design. Evaluation through the patients' retrospective perspective was performed after 1 year (post-treatment) and after another 1.5 years (follow-up).

Results: In respect to patients' subjective ratings, ADHD-specific group psychotherapy outperformed unspecific management post-treatment ( z = 4.88, p < .0001) and at follow-up ( z = 2.90, p = .004). Rank correlations with rater-based symptom change were small to moderate (post-treatment: r = 0.28, follow-up: r = 0.16).

Conclusion: Therapy evaluation based on the patients' perspective supports the concept of ADHD-specific group psychotherapy as a potentially useful therapy option in ADHD.
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http://dx.doi.org/10.1177/1087054717720718DOI Listing
July 2019

Anger and aggression in borderline personality disorder and attention deficit hyperactivity disorder - does stress matter?

Borderline Personal Disord Emot Dysregul 2017 17;4. Epub 2017 Mar 17.

Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.

Background: The impact of stress on anger and aggression in Borderline Personality Disorder (BPD) and Attention Deficit Hyperactivity Disorder (ADHD) has not been thoroughly investigated. The goal of this study was to investigate different aspects of anger and aggression in patients with these disorders.

Methods: Twenty-nine unmedicated female BPD patients, 28 ADHD patients and 30 healthy controls (HC) completed self-reports measuring trait anger, aggression and emotion regulation capacities. A modified version of the Point Subtraction Aggression Paradigm and a state anger measurement were applied under resting and stress conditions. Stress was induced by the Mannheim Multicomponent Stress Test (MMST).

Results: Both patient groups scored significantly higher on all self-report measures compared to HCs. Compared to ADHD patients, BPD patients reported higher trait aggression and hostility, a stronger tendency to express anger when provoked and to direct anger inwardly. Furthermore, BPD patients exhibited higher state anger than HCs and ADHD patients under both conditions and showed a stress-dependent anger increase. At the behavioral level, no significant effects were found. In BPD patients, aggression and anger were positively correlated with emotion regulation deficits.

Conclusions: Our findings suggest a significant impact of stress on self-perceived state anger in BPD patients but not on aggressive behavior towards others in females with BPD or ADHD. However, it appears to be pronounced inwardly directed anger which is of clinical importance in BPD patients.
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http://dx.doi.org/10.1186/s40479-017-0057-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356413PMC
March 2017

Daytime Sleepiness in Adults With ADHD: A Pilot Trial With a Multiple Sleep Latency Test.

J Atten Disord 2016 Dec 17;20(12):1023-1029. Epub 2014 Apr 17.

Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Objective: To evaluate sleep latency (SL) during the multiple sleep latency test (MSLT) and subjective daytime sleepiness in adult ADHD and controls.

Method: Subjective daytime sleepiness was assessed by Epworth Sleepiness Scale (ESS) in 27 unmedicated adults with ADHD and in 182 controls. Thirteen ADHD patients and 26 controls underwent MSLT after one night of polysomnography (PSG).

Results: Mean MSLT-SL was 10.6 ± 4.8 min in ADHD and 12.2 ± 4.2 min in controls (n.s.). Mean ESS score was 9.3 ± 4.9 points in ADHD and 6.9 ± 3.4 points in controls (p < .005). MSLT-SL and ESS scores correlated inversely by trend (r = -.45, p < .1) but not with ADHD symptoms or ADHD subtype.

Conclusion: Adults with ADHD do not differ from controls in mean MSLT-SL but experience increased subjective daytime sleepiness. Patients with subjective higher daytime tiredness fell asleep faster during MSLT.
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http://dx.doi.org/10.1177/1087054714529456DOI Listing
December 2016

Delay discounting and response disinhibition under acute experimental stress in women with borderline personality disorder and adult attention deficit hyperactivity disorder.

Psychol Med 2016 11 30;46(15):3137-3149. Epub 2016 Aug 30.

Department of Psychosomatic Medicine and Psychotherapy,Central Institute of Mental Health,Mannheim,Germany.

Background: Impulsivity is a core feature of borderline personality disorder (BPD) and attention deficit hyperactivity disorder (ADHD). In BPD, impulsive behavior primarily occurs under acute stress; impulse control deficits under non-stress conditions may be partly related to co-morbid ADHD. We aimed to investigate whether acute experimental stress has an impact on self-reported impulsivity, response inhibition (action withholding, action cancelation) and delay discounting in BPD compared to ADHD.

Method: Thirty female BPD patients, 28 female ADHD patients (excluding patients with co-morbid BPD and ADHD), and 30 female healthy controls (HC) completed self-reports and behavioral measures of impulsivity (IMT, assessing action withholding; GoStop, measuring action cancelation, Delay Discounting Task) under baseline conditions and after an experimental stress induction (Mannheim Multicomponent Stress Test).

Results: Both patient groups reported higher impulsivity than HC, ADHD reported higher trait impulsivity than BPD. On the IMT, ADHD showed significant action-withholding deficits under both conditions, while BPD performed significantly worse than HC under stress. In BPD but not ADHD and HC, action-withholding deficits (IMT) were significantly increased under stress compared to baseline, while no group/stress effects were found for action cancelation (GoStop). Delay discounting was significantly more pronounced in BPD than in HC (no stress effect was found).

Conclusions: In BPD, behavioral deficits in action withholding (but not in action cancelation) appear to be influenced by acute experimental stress. Delay discounting seems to be a general feature of BPD, independent of co-morbid ADHD and acute stress, possibly underlying typical expressions of behavioral impulsivity in the disorder.
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http://dx.doi.org/10.1017/S0033291716001677DOI Listing
November 2016

The effect of methylphenidate intake on brain structure in adults with ADHD in a placebo-controlled randomized trial.

J Psychiatry Neurosci 2016 10;41(6):422-430

From the Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, University Freiburg Medical Center, Hauptstr, Freiburg, Germany (Tebartz van Elst, Maier, Klöppel, Killius, Rump, Perlov); Freiburg Brain Imaging, University Freiburg Medical Center, Freiburg, Germany (Tebartz van Elst, Maier, Klöppel, Killius, Rump, Ebert, Berger); the Department of Neurology, University Freiburg Medical Center, Freiburg, Germany (Klöppel); the Clinical Trials Unit, University Freiburg Medical Center, Freiburg, Germany (Graf); the Central Institute for Mental Health, Mannheim, Germany (Sobanski); the Clinic of Psychiatry and Psychotherapy, University Freiburg Medical Center, Freiburg, Germany (Ebert, Berger, Matthies, Philipsen); the Department for Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany (Warnke); and the Department of Psychiatry and Psychotherapy, Karl Jaspers Clinic, Faculty of Medicine and Health Sciences, European Medical School, Carl von Ossietzky University Oldenburg, Oldenburg, Germany (Philipsen).

Background: Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease.

Methods: We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra.

Results: We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase.

Limitations: Detecting possible neurotoxic effects of methylphenidate might require a longer observation period.

Conclusion: There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082513PMC
http://dx.doi.org/10.1503/jpn.150320DOI Listing
October 2016

Burden of illness and health care resource utilization in adult psychiatric outpatients with attention-deficit/hyperactivity disorder in Europe.

Curr Med Res Opin 2016 09 16;32(9):1547-56. Epub 2016 Jun 16.

h Eli Lilly Benelux , Brussels , Belgium.

Objective: To assess the burden of illness and health care resource utilization of adult nonpsychotic psychiatric outpatients with attention-deficit/hyperactivity disorder (ADHD) in Europe.

Methods: This was a multicountry, cross-sectional, observational study where unselected routine patients from clinical psychiatric outpatient settings were screened and assessed for ADHD. Patients were evaluated using the Clinical Global Impressions of Severity (CGI-S) scale, the Sheehan Disability Scale (SDS), and the EuroQol-5 Dimensions questionnaire. Data on comorbidities, functional impairment, and health care resource utilization were captured.

Results: The study enrolled 2284 patients, of whom 1986 completed the study. The prevalence of ADHD was 17.4%, of whom 46.0% had a previous ADHD diagnosis. Patients with ADHD had a high clinical burden with psychiatric comorbidities, especially depression (43.0%) and anxiety disorders (36.4%). Substance abuse (9.2% vs. 3.4%) and alcohol abuse (10.3% vs. 5.2%) were more common in the ADHD cohort vs. the non-ADHD cohort. Only 11.5% of the patients with ADHD had no other psychiatric disorder. Various measures indicated a significantly poorer level of functioning for patients with ADHD than without ADHD, as indicated by higher scores for CGI-S (3.8 vs. 3.3) and SDS (18.9 vs. 11.6) and higher percentages of debt (35.5% vs. 24.3%) and criminality (13.8% vs. 6.1%). Lastly, the health care resource utilization was considerable and similar between adult psychiatric outpatients diagnosed and not diagnosed with ADHD.

Conclusions: Although care was taken when choosing the sites for this study, to make it representative of the general outpatient adult psychiatric population, caution should be advised in generalizing the findings of our study to the general ADHD or psychiatric outpatient population. This was an observational study, thus no inference on causality can be drawn. Having ADHD imposes a considerable health and social burden on patient and health care resource utilization comparable to other chronic psychiatric disorders.
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http://dx.doi.org/10.1080/03007995.2016.1189892DOI Listing
September 2016

Associations of pineal volume, chronotype and symptom severity in adults with attention deficit hyperactivity disorder and healthy controls.

Eur Neuropsychopharmacol 2016 07 14;26(7):1119-26. Epub 2016 Apr 14.

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Psychosomatic Medicine, Bad Dürkheim, Germany.

The pineal gland, as part of the human epithalamus, is the main production site of peripheral melatonin, which promotes the modulation of sleep patterns, circadian rhythms and circadian preferences (morningness vs. eveningness). The present study analyses the pineal gland volume (PGV) and its association with circadian preferences and symptom severity in adult ADHD patients compared to healthy controls. PGV was determined manually using high-resolution 3T MRI (T1-magnetization prepared rapid gradient echo) in medication free adult ADHD patients (N=74) compared to healthy controls (N=86). Moreover, the Morningness-Eveningness Questionnaire (MEQ), the ADHD Diagnostic Checklist and the Wender-Utah Rating Scale were conducted. PGV differed between both groups (patients: 59.9±33.8mm(3); healthy controls: 71.4±27.2mm(3), P=0.04). In ADHD patients, more eveningness types were revealed (patients: 29%; healthy controls: 17%; P=0.05) and sum scores of the MEQ were lower (patients: 45.8±11.5; healthy controls 67.2±10.1; P<0.001). Multiple regression analyses indicated a positive correlation of PGV and MEQ scores in ADHD (β=0.856, P=0.003) but not in healthy controls (β=0.054, P=0.688). Patients' MEQ scores (β=-0.473, P=0.003) were negatively correlated to ADHD symptoms. The present results suggest a linkage between the PGV and circadian preference in adults with ADHD and an association of the circadian preference to symptom severity. This may facilitate the development of new chronobiological treatment approaches for the add-on treatment in ADHD.
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http://dx.doi.org/10.1016/j.euroneuro.2016.03.016DOI Listing
July 2016

Post Hoc Analysis of Potential Predictors of Response to Atomoxetine for the Treatment of Adults with Attention-Deficit/Hyperactivity Disorder using an Integrated Database.

CNS Drugs 2016 04;30(4):317-34

Finnish Institute of Occupational Health, Helsinki, Finland.

Background: Responses to atomoxetine vary for individual patients with attention-deficit/hyperactivity disorder (ADHD). However, we do not know whether any factors can be used to reliably predict how individuals with ADHD will respond to treatment.

Objective: Our objective was to evaluate background variables that facilitate early identification of those adults with ADHD who are likely to respond to treatment with atomoxetine.

Methods: We pooled data for atomoxetine-treated adults with ADHD from 12 clinical trials for a short-term (10-week) analysis, and from 11 clinical trials for a long-term (24-week) analysis. Patients not meeting a response definition [≥30 % reduction in Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version (CAARS-Inv:SV) total score and Clinical Global Impressions of ADHD Severity Scale (CGI-S) score ≤3 at endpoint], or who discontinued, were defined as non-responders. Another definition of response (≥30 % reduction in CAARS-Inv:SV total score at endpoint) was also used in these analyses; only the results with the former definition are shown in this abstract, as the same conclusions were gained with both definitions. A treatment-specified subgroup detection tool (a resampling-based ensemble tree method) was used to identify predictors of response.

Results: Of 1945 adults in the long-term analysis, 548 (28.2 %) were responders to atomoxetine at week 24; 65.2 % of 1397 non-responders had discontinued. Of 4524 adults in the short-term analysis, 1490 (32.9 %) were responders at week 10; 33.2 % of 1006 non-responders had discontinued. No analyzed baseline parameters (age, sex, prior stimulant use, ADHD subtype, CAARS-Inv:SV, CGI-S) were statistically significant predictors of response. Reductions in CAARS-Inv:SV total, CAARS-Inv:SV subscores, and CGI-S at week 4 in the short-term analysis, and at weeks 4 or 10 in the long-term analysis, were statistically significant predictors of response, i.e., patients with versus without these reductions early in treatment were more likely to be clinical responders at later time points. Sensitivity ranged from 28.6 to 85.9 %, and specificity ranged from 23.8 to 86.7 %. Predictors with higher sensitivity had lower specificity, and vice versa.

Conclusions: Reductions in CAARS-Inv:SV and CGI-S scores at weeks 4 and 10 are statistically significant predictors of response to atomoxetine at later time points in adults with ADHD. However, the predictors identified by these analyses are not reliable enough for use in clinical practice. The only currently available method to judge whether individuals with ADHD will respond to atomoxetine is to start treatment and assess the response over an extended period, sometimes longer than 10 weeks.
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http://dx.doi.org/10.1007/s40263-016-0323-xDOI Listing
April 2016

Nightmare frequency in adults with attention-deficit hyperactivity disorder.

Eur Arch Psychiatry Clin Neurosci 2017 Feb 14;267(1):89-92. Epub 2016 Mar 14.

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Schlaflabor, Zentralinstitut für Seelische Gesundheit, Postfach 12 21 20, 68072, Mannheim, Germany.

Nightmare frequency in adult ADHD patients has not yet been studied systematically. In a sample of 65 patients, it could be shown that nightmare frequency was elevated in ADHD patients compared to a sample representative for Germany. Frequent nightmares (once a week or more often) were reported by 4.62 % of the patients and 1.77 % of the controls. This increase was neither explained by the increased dream recall in general nor by the presence of a comorbid mental disorder. Questions about nightmares should be included in the diagnostic procedures for ADHD patients, and it should be tested whether well-established nightmare treatment strategies like imagery rehearsal treatment might be beneficial to those patients with nightmares.
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http://dx.doi.org/10.1007/s00406-016-0686-5DOI Listing
February 2017

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

JAMA Psychiatry 2015 Dec;72(12):1199-210

Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany.

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.
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http://dx.doi.org/10.1001/jamapsychiatry.2015.2146DOI Listing
December 2015

Normal Neurochemistry in the Prefrontal and Cerebellar Brain of Adults with Attention-Deficit Hyperactivity Disorder.

Front Behav Neurosci 2015 28;9:242. Epub 2015 Sep 28.

Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, University Medical Center Freiburg , Freiburg , Germany.

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In an attempt to extend earlier neurochemical findings, we organized a magnetic resonance spectroscopy (MRS) study as part of a large, government-funded, prospective, randomized, multicenter clinical trial comparing the effectiveness of specific psychotherapy with counseling and stimulant treatment with placebo treatment (Comparison of Methylphenidate and Psychotherapy Study). We report the baseline neurochemical data for the anterior cingulate cortex (ACC) and the cerebellum in a case-control setting. For the trial, 1,480 adult patients were contacted for participation, 518 were assessed for eligibility, 433 were randomized, and 187 were potentially eligible for neuroimaging. The control group included 119 healthy volunteers. Single-voxel proton MRS was performed. In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group. We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks' lambda test: p = 0.97) or in the cerebellum (p = 0.62). Thus, we were unable to replicate earlier findings in this methodologically sophisticated study. We discuss our findings in the context of a comprehensive review of other MRS studies on ADHD and a somewhat skeptical neuropsychiatric research perspective. As in other neuropsychiatric disorders, the unclear nosological status of ADHD might be an explanation for false-negative findings.
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http://dx.doi.org/10.3389/fnbeh.2015.00242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585345PMC
October 2015

Does intensive multimodal treatment for maternal ADHD improve the efficacy of parent training for children with ADHD? A randomized controlled multicenter trial.

J Child Psychol Psychiatry 2015 Dec 30;56(12):1298-313. Epub 2015 Jun 30.

Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.

Background: This is the first randomized controlled multicenter trial to evaluate the effect of two treatments of maternal attention-deficit hyperactivity disorder (ADHD) on response to parent-child training targeting children's external psychopathology.

Methods: Mother-child dyads (n = 144; ADHD according to DSM-IV; children: 73.5% males, mean age 9.4 years) from five specialized university outpatient units in Germany were centrally randomized to multimodal maternal ADHD treatment [group psychotherapy plus open methylphenidate medication; treatment group (TG): n = 77] or to clinical management [supportive counseling without psychotherapy or psychopharmacotherapy; control group (CG): n = 67]. After 12 weeks, the maternal ADHD treatment was supplemented by individual parent-child training for all dyads. The primary outcome was a change in the children's externalizing symptom scores (investigator blinded to the treatment assignment) from baseline to the end of the parent-child training 6 months later. Maintenance therapy continued for another 6 months. An intention-to-treat analysis was performed within a linear regression model, controlling for baseline and center after multiple imputations of missing values.

Results: Exactly, 206 dyads were assessed for eligibility, 144 were randomized, and 143 were analyzed (TG: n = 77; CG: n = 66). After 6 months, no significant between-group differences were found in change scores for children's externalizing symptoms (adjusted mean TG-mean CG=1.1, 95% confidence interval -0.5-2.7; p = .1854), although maternal psychopathology improved more in the TG. Children's externalizing symptom scores improved from a mean of 14.8 at baseline to 11.4 (TG) and 10.3 (CG) after 6 months and to 10.8 (TG) and 10.1 (CG) after 1 year. No severe harms related to study treatments were found, but adverse events were more frequent in TG mothers than in CG mothers.

Conclusions: The response in children's externalizing psychopathology did not differ between maternal treatment groups. However, multimodal treatment was associated with more improvement in maternal ADHD. Child and maternal treatment gains were stable (CCT-ISRCTN73911400).
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http://dx.doi.org/10.1111/jcpp.12443DOI Listing
December 2015

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

Biol Psychiatry 2016 12 27;80(12):905-915. Epub 2015 May 27.

Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, Freiburg, Germany.; Freiburg Brain Imaging, Freiburg, Germany.. Electronic address:

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.
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http://dx.doi.org/10.1016/j.biopsych.2015.05.012DOI Listing
December 2016

Impulsivity and Aggression in Female BPD and ADHD Patients: Association with ACC Glutamate and GABA Concentrations.

Neuropsychopharmacology 2016 Jan 4;41(2):410-8. Epub 2015 Jun 4.

Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.

Borderline personality disorder (BPD) and attention-deficit-hyperactivity disorder (ADHD) are both characterized by high impulsivity and difficulties in controlling anger and aggression. In BPD, comorbid ADHD may further increase impulsivity. For both disorders, altered MR spectroscopy levels of the neurotransmitters glutamate and GABA as well as some correlations with impulsivity were previously reported. The objective of this study was to investigate the neurotransmitters glutamate and GABA in relation to impulsivity and aggression as expressed in the anterior cingulate cortex (ACC) in groups of female patients with BPD and ADHD, respectively. Associations of glutamate and GABA levels with further BPD (symptom severity) and ADHD aspects (hyperactivity and inattention) were exploratively evaluated. 1H MR spectra were acquired at 3T to determine glutamate to total creatine ratios (Glu/tCr) and GABA levels from the ACC in a BPD group (n=26), an ADHD group (n=22), and a healthy control (HC) group (n=30); all participants were females. Both patient groups showed higher scores on self-reported impulsivity, anger, and aggression compared with HCs. ACC GABA levels were significantly lower in ADHD than HC. Although measures of impulsivity were positively related to glutamate and negatively to GABA, for aggression only a negative correlation with GABA could be demonstrated. These data provide human in vivo evidence for the role of ACC Glu/tCr and GABA in impulsivity and aggression. If distinct associations of Glu/tCr and GABA for BPD and ADHD can be confirmed in future studies, this might yield implications for more specific pharmacological treatments.
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http://dx.doi.org/10.1038/npp.2015.153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130117PMC
January 2016

Child impact on family functioning: a multivariate analysis in multiplex families with children and mothers both affected by attention-deficit/hyperactivity disorder (ADHD).

Atten Defic Hyperact Disord 2015 Sep 15;7(3):211-23. Epub 2015 Jan 15.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Füchsleinstr. 15, 97080, Würzburg, Germany,

ADHD seriously impacts family functioning, even the more in families with simultaneous parental and child ADHD. The aim of the study was to examine associations between family impact of child ADHD and child, mother and family characteristics in multiplex families with children and mothers both affected by ADHD. One hundred and forty-four mother-child pairs were assessed (children: mean age 9.4 ± 1.7 years, 73.6 % male). Family impact of child ADHD was rated by mothers using the Family Impact Questionnaire (FIQ). Multiple linear regression analyses were performed with child and maternal psychopathology and basic family characteristics such as employment, partnership status and number of children as predictors and FIQ subscores as criteria. Rates of variance explained by family variables were 49 % for negative feelings towards the child, 37 % for impact on partnership, 31 % for impact on social life and 27 % for impact on finances (p < .001, respectively). Pearson correlations with family impact were especially strong for child externalizing symptoms, maternal ADHD and co-morbid symptoms of the mother. The strongest independent predictor was oppositional defiant child behaviour. In ADHD multiplex families, mothers' perception of the impact of an ADHD child on its family can be explained to a substantial degree by child psychopathology, maternal psychopathology and basic family characteristics. Although a cross-sectional design does not allow for causal interpretations, the findings of this study offer important targets for the treatment of ADHD in a family context pointing to the need for assessing and treating parental mental health and co-morbid symptoms besides ADHD core symptoms.
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http://dx.doi.org/10.1007/s12402-014-0164-8DOI Listing
September 2015

Fixing the mirrors: a feasibility study of the effects of dance movement therapy on young adults with autism spectrum disorder.

Autism 2015 Apr 24;19(3):338-50. Epub 2014 Feb 24.

University of Heidelberg, Germany.

From the 1970s on, case studies reported the effectiveness of therapeutic mirroring in movement with children with autism spectrum disorder. In this feasibility study, we tested a dance movement therapy intervention based on mirroring in movement in a population of 31 young adults with autism spectrum disorder (mainly high-functioning and Asperger's syndrome) with the aim to increase body awareness, social skills, self-other distinction, empathy, and well-being. We employed a manualized dance movement therapy intervention implemented in hourly sessions once a week for 7 weeks. The treatment group (n = 16) and the no-intervention control group (n = 15) were matched by sex, age, and symptom severity. Participants did not participate in any other therapies for the duration of the study. After the treatment, participants in the intervention group reported improved well-being, improved body awareness, improved self-other distinction, and increased social skills. The dance movement therapy-based mirroring approach seemed to address more primary developmental aspects of autism than the presently prevailing theory-of-mind approach. Results suggest that dance movement therapy can be an effective and feasible therapy approach for autism spectrum disorder, while future randomized control trials with bigger samples are needed.
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http://dx.doi.org/10.1177/1362361314522353DOI Listing
April 2015