Publications by authors named "Alexandra Philipsen"

136 Publications

Disentangling ADHD's Presentation-Related Decision-Making-A Meta-Analytic Approach on Predominant Presentations.

Front Psychiatry 2021 18;12:519840. Epub 2021 Feb 18.

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

Deficient decision-making (DM) in attention deficit/hyperactivity disorder (ADHD) is marked by altered reward sensitivity, higher risk taking, and aberrant reinforcement learning. Previous meta-analysis aggregate findings for the ADHD combined presentation (ADHD-C) mostly, while the ADHD predominantly inattentive presentation (ADHD-I) and the predominantly hyperactive/impulsive presentation (ADHD-H) were not disentangled. The objectives of the current meta-analysis were to aggregate findings from DM for each presentation separately. A comprehensive literature search of the PubMed (Medline) and Web of Science Database took place using the keywords "ADHD," "attention-deficit/hyperactivity disorder," "decision-making," "risk-taking," "reinforcement learning," and "risky." Random-effects models based on correlational effect-sizes were conducted. Heterogeneity analysis and sensitivity/outlier analysis were performed, and publication biases were assessed with funnel-plots and the egger intercept. Of 1,240 candidate articles, seven fulfilled criteria for analysis of ADHD-C ( = 193), seven for ADHD-I ( = 256), and eight for ADHD-H ( = 231). Moderate effect-size were found for ADHD-C ( = 0.34; = 0.0001; 95% CI = [0.19, 0.49]). Small effect-sizes were found for ADHD-I ( = 0.09; = 0.0001; 95% CI = [0.008, 0.25]) and for ADHD-H ( = 0.1; = 0.0001; 95% CI = [-0.012, 0.32]). Heterogeneity was moderate for ADHD-H. Sensitivity analyses show robustness of the analysis, and no outliers were detected. No publication bias was evident. This is the first study that uses a meta-analytic approach to investigate the relationship between the different presentations of ADHD separately. These findings provide first evidence of lesser pronounced impairment in DM for ADHD-I and ADHD-I compared to ADHD-C. While the exact factors remain elusive, the current study can be considered as a starting point to reveal the relationship of ADHD presentations and DM more detailed.
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http://dx.doi.org/10.3389/fpsyt.2021.519840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930744PMC
February 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

EEG Data Quality: Determinants and Impact in a Multicenter Study of Children, Adolescents, and Adults with Attention-Deficit/Hyperactivity Disorder (ADHD).

Brain Sci 2021 Feb 10;11(2). Epub 2021 Feb 10.

Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, 68159 Mannheim, Germany.

Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (n = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
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http://dx.doi.org/10.3390/brainsci11020214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916500PMC
February 2021

Occurence of Post-Traumatic Stress Symptoms, Anxiety and Depression in the Acute Phase of Transient Ischemic Attack and Stroke.

Psychiatr Q 2021 Jan 2. Epub 2021 Jan 2.

Universitätsklinikum Bonn AöR, Klinik und Poliklinik für Psychiatrie, Bonn, Germany.

Rates of post-traumatic stress symptoms, anxiety and depression are increased in patients having experienced a transient ischemic attack (TIA) or stroke several months ago. However, data of psychiatric symptoms in the acute phase within the first days after ictus are lacking. In 20 patients with stroke and 33 patients with TIA we assessed disease severity by means of the NIHSS, levels of depression and anxiety by HADS, PTSD-like symptoms by PC-PTSD, quality of life (HrQoL) by SF-12, and coping style by brief COPE Inventory within the first 5 days after ictus. NIHSS on admission was lower in patients with TIA (0 ± 1) than in patients with stroke (3 ± 2, p < 0.001). HADS depression score was significantly higher in patients with stroke (7.0 ± 4.5) than in patients with TIA (4.9 ± 4.0). HADS anxiety score, HrQoL and coping styles were similar between TIA and stroke patients (p > 0.05). 5 and 3 of 33 TIA patients as well as 4 and 3 of 20 stroke patients had at least 11 points in the HADS anxiety and depression score respectively (p = 0.001). 2 of 33 TIA patients and 2 of 20 stroke patients had more than 2 points in the PC-PTSD (p = 0.646). We did not find consistent correlations between the NIHSS and the psychometric parameters. Within the first five days after patients having experienced a TIA or stroke PTSD-like, anxious and depressive symptoms are more common than in the general population. As the acute psychological status after ictus is predictive for psychiatric comorbidity years later physicians should pay attention and adequately treat psychiatric symptoms already in the acute phase of stroke.Trial Registration: German Clinical Trials Register, DRKS00021730, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021730 , registered 05/19/2020- Retrospectively registered.
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http://dx.doi.org/10.1007/s11126-020-09873-9DOI Listing
January 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

Molecular and neurocircuitry mechanisms of social avoidance.

Cell Mol Life Sci 2021 Feb 30;78(4):1163-1189. Epub 2020 Sep 30.

Division of Medical Psychology, Department of Psychiatry, University Hospital, Venusberg-Campus 1, 53127, Bonn, Germany.

Humans and animals live in social relationships shaped by actions of approach and avoidance. Both are crucial for normal physical and mental development, survival, and well-being. Active withdrawal from social interaction is often induced by the perception of threat or unpleasant social experience and relies on adaptive mechanisms within neuronal networks associated with social behavior. In case of confrontation with overly strong or persistent stressors and/or dispositions of the affected individual, maladaptive processes in the neuronal circuitries and its associated transmitters and modulators lead to pathological social avoidance. This review focuses on active, fear-driven social avoidance, affected circuits within the mesocorticolimbic system and associated regions and a selection of molecular modulators that promise translational potential. A comprehensive review of human research in this field is followed by a reflection on animal studies that offer a broader and often more detailed range of analytical methodologies. Finally, we take a critical look at challenges that could be addressed in future translational research on fear-driven social avoidance.
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http://dx.doi.org/10.1007/s00018-020-03649-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904739PMC
February 2021

Effects and feasibility of psychological interventions to reduce inattention symptoms in adults with ADHD: a systematic review.

J Ment Health 2020 Sep 21:1-14. Epub 2020 Sep 21.

Institute of General Practice and Family Medicine, University Hospital, LMU Munich, Munich, Germany.

Background: Adult ADHD is common, highly comorbid, and restricts daily functioning. However, only a minority of patients receive appropriate treatment.

Aims: Primary objective: To identify psychological interventions that diminish inattention symptoms in adults with ADHD. Secondary objective: To evaluate feasibility aspects.

Methods: A search in PubMed, Cochrane Library, PsycInfo, PSYNDEX, and Eric was conducted. Interventions were grouped in: ADHD coaching, neuro feedback, cognitive training, psychoeducation, and behavioral therapy. Inattention symptoms were evaluated using standardized mean differences. Study quality was rated with the Cochrane Risk of Bias tool. Feasibility was assessed by number and time of sessions, setting, and qualification of the provider.

Results: A total of N = 2229 results were identified, 19 randomized controlled studies were included in the analysis. Behavioral therapy showed effects on inattention symptoms [SMD: 0.44-1.71] when compared to inactive controls. In terms of feasibility, longer interventions did not outperform shorter ones and individual sessions were not superior to group sessions. No effects were given for neuro feedback, cognitive training, and psychoeducation in comparison to controls.

Conclusion: For adults with ADHD behavioral therapy seems an effective intervention to reduce inattention symptoms. In terms of feasibility, brief interventions may be valuable for a primary care setting.
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http://dx.doi.org/10.1080/09638237.2020.1818189DOI Listing
September 2020

Feasibility trial of the dialectical behavior therapy skills training group as add-on treatment for adults with attention-deficit/hyperactivity disorder.

J Clin Psychol 2021 Mar 2;77(3):516-524. Epub 2020 Sep 2.

ADHD Outpatient Program, Hospital de Clínicas de Porto Alegre, Department of Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Objective: Our aim was to explore the feasibility, and efficacy of a Dialectical Behavior Therapy Skill Training Group (DBT-ST) as an add-on treatment for adult attention-deficit/hyperactivity disorder (ADHD) in Latin America.

Method: Adults with ADHD (n = 31) with stable medication treatment for ADHD and residual symptoms (ASRS > 20) were randomly assigned to DBT-ST (n = 16) or treatment as usual (TaU; n = 15) for 12 weeks. Feasibility was accessed by attendance and completion rates at 12 weeks. Efficacy outcomes were measured with the ASRS, and performed at 0, 6, 12, and 16 weeks.

Results: The DBT-ST protocol had 81.25% completion rate, with a mean attendance of 87.25% of the sessions. No significant interactions between group and time were detected for outcome measures.

Discussion: The DBT-ST was feasible as add-on treatment for adult patients with ADHD in Latin America. Replicating previous findings, DBT-ST has shown no significantly higher improvement in ADHD symptoms in comparison with TaU. Registered at the Clinical Trials database (NCT03326427).
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http://dx.doi.org/10.1002/jclp.23049DOI Listing
March 2021

Aggravation of symptom severity in adult attention-deficit/hyperactivity disorder by latent Toxoplasma gondii infection: a case-control study.

Sci Rep 2020 09 1;10(1):14382. Epub 2020 Sep 1.

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

Toxoplasma gondii (T. gondii) has a high worldwide prevalence and an underestimated impact on neuropsychiatric disorders. Previous studies related T. gondii to disorders associated with the dysfunctional dopaminergic system. However, an association between T. gondii infection and adult attention-deficit/hyperactivity disorder (ADHD) has not yet been studied. In a sex- and age-matched case-control study, we investigated the seropositivity, serointensity, and avidity of latent T. gondii infection in adult ADHD patients and examined the influence of those variables on the symptomatology of ADHD. Of 140 participants, 20.0% were seropositive for anti-T. gondii IgG and 0% for anti-T. gondii IgM. T. gondii seropositivity was associated with 2.8-fold increase in the odds of ADHD in a confounder-adjusted multivariable analysis. Age and consumption of raw/undercooked meat were confirmed as significant predictors of T. gondii seropositivity. Multiple linear regression analysis of self-rated ADHD-related symptom severity in all participants revealed a significant association with T. gondii seropositivity, elevated IgG titers (serointensity), and stronger anti-T. gondii IgG avidity. Overall symptom severity was increased in seropositive ADHD patients compared to seronegative subjects with ADHD. In particular, hyperactivity was significantly associated with serointensity. We conclude that there is a high rate of T. gondii seropositivity in adults with ADHD. Additionally, our results suggest a clinical impact of latent T. gondii infection on ADHD-related symptoms in a serointensity- and avidity-dependent manner.
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http://dx.doi.org/10.1038/s41598-020-71084-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463265PMC
September 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

The Role of Cathepsins in Memory Functions and the Pathophysiology of Psychiatric Disorders.

Front Psychiatry 2020 24;11:718. Epub 2020 Jul 24.

Neurohomeostasis Research Group, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.

Cathepsins are proteases with functions in cellular homeostasis, lysosomal degradation and autophagy. Their role in the development of neurodegenerative diseases has been extensively studied. It is well established that impairment of proper cathepsin function plays a crucial role in the pathophysiology of neurodegenerative diseases, and in recent years a role for cathepsins in mental disorders has emerged given the involvement of cathepsins in memory function, hyperactivity, and in depression- and anxiety-like behavior. Here we review putative cathepsin functions with a special focus on their role in the pathophysiology of psychiatric diseases. Specifically, cathepsins are crucial for maintaining cellular homeostasis, particularly as part of the autophagy machinery of neural strategies underlying acute stress response. Disruption of cathepsin functions can lead to psychiatric diseases such as major depressive disease (MDD), bipolar disorder, and schizophrenia. Specifically, cathepsins can be excreted a process called secretory autophagy. Thereby, they are able to regulate extracellular factors such as brain-derived neurotrophic factor and perlecan c-terminal fragment LG3 providing maintenance of neuronal homeostasis and mediating neuronal plasticity in response to acute stress or trauma. In addition, impairment of proper cathepsin function can result in impaired synaptic transmission by compromised recycling and biogenesis of synaptic vesicles. Taken together, further investigations on cathepsin functions and stress response, neuroplasticity, and synaptic transmission will be of great interest in understanding the pathophysiology of psychiatric disorders.
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http://dx.doi.org/10.3389/fpsyt.2020.00718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393989PMC
July 2020

[ADHD in the transition to adulthood: prevalence, symptoms, risks, and care].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Jul;63(7):910-915

Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Medizinische Fakultät und Uniklinik Köln, Universität zu Köln, Köln, Deutschland.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In contrast to earlier assumptions, ADHD at least partially persists into adulthood in 50-80% of the patients.This narrative review article highlights the risks, treatment options, and care requirements associated with the transition to adulthood. Available epidemiological and routine care data and guidelines are reviewed and screened for indications and recommendations to improve the health-care of adolescents with ADHD.Epidemiological and routine care data point to a care gap for adolescents with ADHD in the sensitive phase of transition from adolescence to adulthood. Specific transition concepts should be expanded and their effectiveness scientifically investigated.
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http://dx.doi.org/10.1007/s00103-020-03175-yDOI Listing
July 2020

The Senses of Agency and Ownership in Patients With Borderline Personality Disorder.

Front Psychiatry 2020 9;11:474. Epub 2020 Jun 9.

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

Patients with borderline personality disorder (BPD) not only experience a strong instability in their affect and interpersonal relations but also disturbances in their self-experience, including dissociation and body-alienation symptoms. It is not yet understood whether an altered sense of ownership (SoO) or sense of agency (SoA) may contribute to these disturbances. One recent hypothesis is that patients with BPD have a reduced sense of self and are therefore more likely to misattribute external objects or actions to their own self than healthy individuals. The present study followed up this hypothesis by investigating whether BPD patients have a more flexible body representation than healthy participants. More specifically, the active rubber hand illusion (aRHI) was applied to 21 patients with BPD and the same number of healthy participants. Using established subjective, electrodermal, and behavioral measures, the participants' SoO and SoA were assessed during the aRHI. The findings show self-reported evidence for higher SoO under anatomical hand congruency as compared to anatomical incongruency, but no evidence for group differences between BPD patients and healthy participants. This finding is inconsistent with previous findings of an enhanced SoO-related body plasticity in BPD patients. Regarding SoA, the findings show self-report evidence of higher SoA in BPD patients versus healthy participants, although this group difference was not evident in the implicit SoA measure (intentional binding). In summary, the present study only reveals partial evidence for a higher body plasticity in BPD patients. Instead, the observed variability in results appears better explainable by some generally elevated perceptual suggestibility of BPD individuals.
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http://dx.doi.org/10.3389/fpsyt.2020.00474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296131PMC
June 2020

[Nonpharmacological treatment options for attention deficit hyperactivity disorder in adulthood: an update].

Nervenarzt 2020 Jul;91(7):591-598

Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Bonn AöR, Venusberg-Campus 1, Gebäude 80/82, 53127, Bonn, Deutschland.

Attention deficit hyperactivity disorder (ADHD) in adulthood is a frequent disorder with a prevalence of 2.5%, which can successfully be treated by pharmacotherapy in 50-70% of cases, depending on the response criteria. Therefore, besides medication nonpharmacological interventions are an important component of the treatment. The essential nonpharmacological interventions are presented and described with respect to the evidence for treatment. According to the S3 guidelines an extensive psychoeducation (PE) functions as the basis of the treatment. If there is still a need for treatment after PE and the clarification of associated disorders, pharmacotherapy is applied. Further psychosocial interventions can then be used as accompaniment or supplement, e.g. when the effectiveness of medication treatment is insufficient. In particular, cognitive behavioral concepts and their variations (dialectic behavioral therapy, metacognitive training, reasoning and rehabilitation therapy) and coaching should be mentioned here, which show increasing evidence for treatment. Neurofeedback can be used if no other psychosocial treatment options are delayed or omitted due to the treatment. Mindfulness training and sport interventions seem to be meaningful as supplementation but similarly to the individualized cognitive training, further research studies are necessary to enable clear statements regarding treatment evidence in adulthood. Further controlled investigations regarding the effectiveness of nonpharmacological interventions on ADHD and associated symptoms and disorders are therefore desirable.
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http://dx.doi.org/10.1007/s00115-020-00916-xDOI Listing
July 2020

Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear.

Proc Natl Acad Sci U S A 2020 05 8;117(21):11781-11787. Epub 2020 May 8.

Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University Hospital Bonn, 53105 Bonn, Germany;

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance.
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http://dx.doi.org/10.1073/pnas.1920147117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261088PMC
May 2020

Exploring Self-Paced Embodiable Neurofeedback for Post-stroke Motor Rehabilitation.

Front Hum Neurosci 2019 20;13:461. Epub 2020 Jan 20.

Neuropsychology Lab, Department of Psychology, University of Oldenburg, Oldenburg, Germany.

Neurofeedback-guided motor-imagery training (NF-MIT) has been proposed as a promising intervention following upper limb motor impairment. In this intervention, paretic stroke patients receive online feedback about their brain activity while conducting a motor-imagery (MI) task with the paretic limb. Typically, the feedback provided in NF-MIT protocols is an abstract visual signal based on a fixed trial. Here we developed a self-paced NF-MIT paradigm with an embodiable feedback signal (EFS), which was designed to resemble the content of the mental act as closely as possible. To this end, the feedback was delivered an embodiable, anthropomorphic robotic hand (RH), which was integrated into a closed-looped EEG-based brain-computer interface (BCI). Whenever the BCI identified a new instance of a hand-flexion or hand-extension imagination by the participant, the RH carried out the corresponding movement with minimum delay. Nine stroke patients and nine healthy participants were instructed to control RH movements as accurately as possible, using mental activity alone. We evaluated the general feasibility of our paradigm on electrophysiological, subjective and performance levels. Regarding electrophysiological measures, individuals showed the predicted event-related desynchronization (ERD) patterns over sensorimotor brain areas. On the subjective level, we found that most individuals integrated the RH into their body scheme. With respect to RH control, none of our participants achieved a high level of control, but most managed to control the RH actions to some degree. Importantly, patients and controls achieved similar performance levels. The results support the view that self-paced embodiable NF-MIT is feasible for stroke patients and can complement classical NF-MIT.
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http://dx.doi.org/10.3389/fnhum.2019.00461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984194PMC
January 2020

Transcranial Alternating Current Stimulation (tACS) as a Tool to Modulate P300 Amplitude in Attention Deficit Hyperactivity Disorder (ADHD): Preliminary Findings.

Brain Topogr 2020 03 23;33(2):191-207. Epub 2020 Jan 23.

Experimental Psychology Lab, Department of Psychology, European Medical School, Cluster for Excellence "Hearing for All", Carl Von Ossietzky University Oldenburg, Ammerländer Heerstr. 114-118, 26129, Oldenburg, Germany.

Studies examining event-related potentials (ERP) in patients affected by attention deficit/hyperactivity disorder (ADHD) have found considerable evidence of reduced target P300 amplitude across different perceptual modalities. P300 amplitude has been related to attention-driven context comparison and resource allocation processes. Altered P300 amplitude in ADHD can be reasonably assumed to be related to ADHD typical cognitive performance deficits. Transcranial alternating current stimulation (tACS) can increase the amplitude of endogenous brain oscillations. Because ERP components can be viewed as event-related oscillations (EROs), with P300 translating into the delta (0-4 Hz) and theta (4-8 Hz) frequency range, an increase of delta and theta ERO amplitudes by tACS should result in an increase of P300 amplitudes in ADHD patients. In this pilot study, 18 adult ADHD patients (7 female) performed three consecutive blocks of a visual oddball task while the electroencephalogram (EEG) was recorded. Patients received either 20 min of tACS or sham stimulation at a stimulation intensity of 1 mA. Individual stimulation frequency was determined using a time-frequency decomposition of the P300. Our preliminary results demonstrate a significant increase in P300 amplitude in the stimulation group which was accompanied by a decrease in omission errors pre-to-post tACS. However, studies including larger sample sizes are advised.
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http://dx.doi.org/10.1007/s10548-020-00752-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066286PMC
March 2020

Physical exercise in attention deficit hyperactivity disorder - evidence and implications for the treatment of borderline personality disorder.

Borderline Personal Disord Emot Dysregul 2020 6;7. Epub 2020 Jan 6.

5Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.

A growing body of literature indicates a potential role for physical exercise in the treatment of attention deficit hyperactivity disorder (ADHD). Suggested effects include the reduction of ADHD core symptoms as well as improvements in executive functions. In the current review, we provide a short overview on the neurophysiological mechanisms assumed to underlie the beneficial effects of exercise. Further, we review the current evidence from experimental studies regarding both acute exercise and long-term interventions in ADHD. While the positive effects observed after acute aerobic exercise are promising, very few well-designed long-term intervention studies have been conducted yet. Moreover, although exercise effects have not yet been studied in borderline personality disorder (BPD), in the end of this paper we derive hypotheses why exercise could also be beneficial for this patient population.
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http://dx.doi.org/10.1186/s40479-019-0115-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945516PMC
January 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

Effects of intranasal oxytocin administration on empathy and approach motivation in women with borderline personality disorder: a randomized controlled trial.

Transl Psychiatry 2019 12 4;9(1):328. Epub 2019 Dec 4.

Department of Psychology, Laboratory for Biological and Personality Psychology, University of Freiburg, Freiburg, Germany.

Borderline personality disorder (BPD) is characterized by severe interpersonal dysfunction with problems in social cognition, empathy and social approach. Although the neuropeptide oxytocin is known to regulate complex social cognition and behavior in healthy individuals and clinical populations, there is still a lack of evidence for a potential beneficial effect of oxytocin administration on social cognition and social approach in BPD. Fifty-one women with BPD and 51 matched healthy controls were randomized to a double-blind, placebo-controlled, between-subject experimental trial. We administered a single dose of 24 IU oxytocin or placebo intranasally prior to a standardized task measuring affective and cognitive empathy and approach motivation. All participants were free of hormonal contraception and tested in the mid-luteal phase of their menstrual cycle. In the placebo condition, patients with BPD showed reduced cognitive and affective empathy, and less approach behavior motivation than healthy controls. Intranasal oxytocin significantly increased affective empathy and approach motivation in both BPD patients and healthy controls compared to placebo. More importantly, oxytocin administration led to similar scores between BPD and healthy controls. These findings provide the first evidence for a beneficial effect of oxytocin on deficits in affective empathy and approach motivation of BPD. Our results indicate a beneficial effect of a single dose of oxytocin on affective empathy and approach motivation in women with BPD adapting their level of social functioning to healthy controls. Future clinical trials will need to investigate the long-term effects and effectiveness of oxytocin as an add-on treatment for social impairments in BPD.
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http://dx.doi.org/10.1038/s41398-019-0658-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892895PMC
December 2019

Treatment-Resistant Depression and Ketamine Response in a Patient With Bilateral Amygdala Damage.

Am J Psychiatry 2019 12;176(12):982-986

Division of Medical Psychology (Scheele, Zimbal, Mielacher, Hurlemann), Department of Anesthesiology (Delis, Neumann), and Department of Psychiatry (Philipsen, Hurlemann), University Hospital, Bonn, Germany; Laureate Institute for Brain Research, Tulsa, Okla. (Feinstein); and Department of Psychiatry, University of Oldenburg Medical Campus, Bad Zwischenahn, Germany (Hurlemann).

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http://dx.doi.org/10.1176/appi.ajp.2019.18101219DOI Listing
December 2019

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

Patients with cervical intraepithelial neoplasms show different states of health-related quality of life and different coping styles depending on the choice of therapy: findings from the CIN study.

Int J Womens Health 2019 12;11:511-517. Epub 2019 Sep 12.

Department of Psychiatry and Psychotherapy, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.

Purpose: To examine the effects of type of therapy (conservative therapy vs conization) on the psychosocial well-being of patients with cervical intraepithelial neoplasia grade II (CIN II) in a prospective cross-sectional study designed to simplify future choice of therapy.

Patients And Methods: In a cross-sectional study comparing 24 CIN II patients who were treated via conservative therapy with 17 CIN II patients who were treated via conization (not randomized), we examined the association between therapy type and psychosocial well-being after the treatment. Scores on the Hospital Anxiety and Depression Scale (HADS) (prevalence of depression/anxiety), SF-12 (health-related quality of life (HRQoL)) and Brief COPE (coping mechanisms) questionnaires were compared between the two subgroups via nonparametric Mann-Whitney U-tests.

Results: The prevalence of depression/anxiety and mental HRQoL did not differ between patients undergoing conservative therapy and those undergoing conization but differed significantly from those of the healthy population. Regarding physical HRQoL and coping strategies, the conservative therapy subgroup achieved higher scores and better performance.

Conclusion: Patients with CIN II are at risk of developing depressive or anxiety symptoms. The choice of therapy seems to have an influence on physical HRQoL and coping strategies but not on depression/anxiety and mental HRQoL.
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http://dx.doi.org/10.2147/IJWH.S208257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750162PMC
September 2019

Herbal detox - Benzodiazepine withdrawal treatment with the help of St. John's Wort?

Asian J Psychiatr 2019 Oct 23;45:26-27. Epub 2019 Aug 23.

Ark Biodiversity GmbH, Boothstrasse 16, 12207 Berlin, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.ajp.2019.08.006DOI Listing
October 2019

Rapid titration protocol - Experiences with a dynamic novel titration regime for vagus nerve stimulation in a group of depressive patients.

J Clin Neurosci 2020 Apr 22;74:262-264. Epub 2019 Aug 22.

Universitätsklinikum Bonn AöR, Klinik und Poliklinik für Psychiatrie, Bonn, Germany. Electronic address:

Vagus nerve stimulation (VNS) is an established tool in the psychiatric armamentarium for patients with therapy-resistant depression (TRD) with response rates of approximately 60%. So far, VNS is titrated slowly during ambulatory in-office visits. Thus, antidepressive effects can be expected after approximately six months. We report our experiences with a rapid dosing regime (RDR) with titration start shortly after VNS-implantation. We retrospectively analysed data of six patients with TRD who received VNS. Stimulation parameters were evaluated with regard to clinical side effects, heart rates (HR) and blood pressures (BP). Depressive symptoms were measured by Montgomery-Asberg Depression Rating Scale (MADRS) one week before and three months after implantation of the VNS. All patients received first stimulation between one and four days after surgery. We elevated output current using 0.25 mA titration steps. We increased output current between one and four days after the last titration. All patients received 1.0 mA output current after eight to 14 days post-surgery. HR and BP remained stable in all patients. All side effects were mild and temporary. MADRS scores were significantly lower three months after VNS-implantation (24 ± 8) than one week before VNS-implantation (42 ± 4; p = 0.028). The therapeutic range of VNS-parameters for antidepressive effect was reached quicker without finding increased numbers of side effects. Consequently, by using RDR the antidepressive effect of VNS-therapy for patients with TRD could be reached earlier than using slow titration. Our presented RDR might be able to significantly shorten the "clinical effect gap" due to the neurobiological and titration-related latency.
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http://dx.doi.org/10.1016/j.jocn.2019.08.071DOI Listing
April 2020

[Coercive Measures in Psychiatry - Even if Carried out lege artis Pose a Risk for Complications or Harm].

Psychiatr Prax 2019 Oct 8;46(7):406-408. Epub 2019 Jul 8.

Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Bonn.

Coercive measures in psychiatry are used as a last resort if other means to avert imminent danger failed. Our case shows, that even if all precautions were taken complications may arise: We report about a young man, who had been restrained. After the belts had been partly loosened, he again became extremely aggressive. When the restraints had to be tightened he could grab and swallow the Segufix®-Metal Pin.
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http://dx.doi.org/10.1055/a-0943-4552DOI Listing
October 2019

Intensity-Dependent Effects of Acute Exercise on Executive Function.

Neural Plast 2019 4;2019:8608317. Epub 2019 Jun 4.

Biological Psychology Lab, Department of Psychology, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.

Numerous studies suggest beneficial effects of aerobic exercise at moderate intensity on cognition, while the effects of high-intensity exercise are less clear. This study investigated the acute effects of exercise at moderate and high intensities on executive functions in healthy adults, including functional MRI to examine the underlying neural mechanisms. Furthermore, the association between exercise effects and cardiorespiratory fitness was examined. 64 participants performed in two executive function tasks (flanker and Go/No-go tasks), while functional MR images were collected, following two conditions: in the exercise condition, they cycled on an ergometer at either moderate or high intensity (each = 32); in the control condition, they watched a movie. Differences in behavioral performance and brain activation between the two conditions were compared between groups. Further, correlations between cardiorespiratory fitness and exercise effects on neural and behavioral correlates of executive performance were calculated. Moderate exercise compared to high-intensity exercise was associated with a tendency towards improved behavioral performance (sensitivity index ') in the Go/No-go task and increased brain activation during hit trials in areas related to executive function, attention, and motor processes (insula, superior frontal gyrus, precentral gyrus, and supplementary motor area). Exercise at high intensity was associated with decreased brain activation in those areas and no changes in behavioral performance. Exercise had no effect on brain activation in the flanker task, but an explorative analysis revealed that reaction times improved after high-intensity exercise. Higher cardiorespiratory fitness was correlated with increased brain activation after moderate exercise and decreased brain activation after high-intensity exercise. These data show that exercise at moderate vs. high intensity has different effects on executive task performance and related brain activation changes as measured by fMRI and that cardiorespiratory fitness might be a moderating factor of acute exercise effects. Thus, our results may contribute to further clarify the neurophysiological mechanisms underlying the beneficial effects of exercise on cognition.
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http://dx.doi.org/10.1155/2019/8608317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589258PMC
July 2020

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

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