Exploring the Relationship between Adherence to Therapy, Treatment Acceptability, and Clinical Outcomes in Adults with Attention-Deficit/Hyperactivity Disorder: Results from the COMPAS Multicenter Randomized Controlled Trial.

INTRODUCTION: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied. OBJECTIVE: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo. METHOD: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted. RESULTS: Participants rated psychotherapy as moderately effective, attended 78.40-94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment. DISCUSSION: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument.

Exploring the efficacy of dialectical behaviour therapy and methylphenidate on emotional comorbid symptoms in adults with attention Deficit/Hyperactivity disorder: Results of the COMPAS multicentre randomised controlled trial.

This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on emotional symptoms in adults with ADHD. This longitudinal multicentre RCT compared four groups (GPT+MPH, GPT+PLB, CM+MPH, and CM+PLB) over five assessment periods, from baseline to week 130. Emotional symptomatology was assessed using SCL-90-R subscales. Of the 433 randomised participants, 371 remained for final analysis. At week 13, the GPT+MPH group showed smaller reductions in anxiety symptoms than the CM groups, but the differences disappeared at subsequent assessments. Improvements in emotional symptom were significantly predicted by reductions in core ADHD symptoms in all groups except the GPT+MPH group. The unexpected lack of between-group differences may be explained by a "floor effect", different intervention settings (group vs. individual), and psychotherapy type. Multiple regression analyses suggest a more specific effect of combined interventions (GPT+MPH). Implications for clinical practice are discussed. Clinical trial registration: ISRCTN54096201 (Current Controlled Trials).

Developing Advanced AI Ecosystems to Enhance Diagnosis and Care for Patients with Depression.

Major Depressive Disorder (MDD) has a significant impact on the daily lives of those affected. This concept paper presents a project that aims at addressing MDD challenges through innovative therapy systems. The project consists of two use cases: a multimodal neurofeedback (NFB) therapy and an AI-based virtual therapy assistant (VTA). The multimodal NFB integrates EEG and fNIRS to comprehensively assess brain function. The goal is to develop an open-source NFB toolbox for EEG-fNIRS integration, augmented by the VTA for optimized efficacy. The VTA will be able to collect behavioral data, provide personalized feedback and support MDD patients in their daily lives. This project aims to improve depression treatment by bringing together digital therapy, AI and mobile apps to potentially improve outcomes and accessibility for people living with depression.

Chatbot-supported psychoeducation in adult attention-deficit hyperactivity disorder: randomised controlled trial.

BACKGROUND: Although psychoeducation is generally recommended for the treatment of adult attention-deficit hyperactivity disorder (ADHD), participation in clinical psychoeducation groups is impeded by waiting times and the constrained number of patients who can simultaneously attend a group. Digital psychoeducation attempts are promising, but the rapidly expanding number of apps lack evidence and are mostly limited to only a few implemented interactive elements. AIMS: To determine the potential of digital, self-guided psychoeducation for adult ADHD, a newly developed interactive chatbot was compared with a previously validated, conventional psychoeducation app. METHOD: Forty adults with ADHD were randomised, of whom 17 participants in each group completed self-guided psychoeducation based on either a chatbot or conventional psychoeducation app between October 2020 and July 2021. ADHD core symptoms were assessed before and after the 3-week interventions, using both the blinded observer-rated Integrated Diagnosis of ADHD in Adulthood interview and the self-rated ADHD Self-Assessment Scale (ADHS-SB). RESULTS: Observer- and patient-rated ADHD symptoms were significantly reduced from pre- to post-intervention (observer-rated: mean difference -6.18, 95% CI -8.06 to -4.29; patient-rated: mean difference -2.82, 95% CI -4.98 to -0.67). However, there were no group × intervention interaction effects that would indicate a stronger therapeutic benefit of one of the interventions. Likewise, administered psychoeducational knowledge quizzes did not show differences between the groups. No adverse events were reported. CONCLUSIONS: Self-guided psychoeducation based on a chatbot or a conventional app appears similarly effective and safe for improving ADHD core symptoms. Future research should compare additional control interventions and examine patient-related outcomes and usability preferences in detail.

Multimodal assessment of adult attention-deficit hyperactivity disorder: A controlled virtual seminar room study.

In the assessment of adult attention-deficit hyperactivity disorder (ADHD) symptoms, the diagnostic value of neuropsychological testing is limited. Partly, this is due to the rather low ecological validity of traditional neuropsychological tests, which usually present abstract stimuli on a computer screen. A potential remedy for this shortcoming might be the use of virtual reality (VR), which enables a more realistic and complex, yet still standardized test environment. The present study investigates a new VR-based multimodal assessment tool for adult ADHD, the virtual seminar room (VSR). Twenty-five unmedicated ADHD patients, 25 medicated ADHD patients, and 25 healthy controls underwent a virtual continuous performance task (CPT) in the VSR with concurrent visual, auditive, and audiovisual distractions. Simultaneously, head movements (actigraphy), gaze behaviour (eye tracking), subjective experience, electroencephalography (EEG), and functional near-infrared spectroscopy (fNIRS) were recorded. Significant differences between unmedicated patients with ADHD and healthy controls were found in CPT performance, head actigraphy, distractor gaze behaviour, and subjective experience. Moreover, CPT performance parameters demonstrated potential utility for assessing medication effects within the ADHD population. No group differences were found in the Theta-Beta-Ratio (EEG) or dorsolateral-prefrontal oxy-haemoglobin (fNIRS). Overall, the results are very promising regarding the potential of the VSR as an assessment tool for adult ADHD. In particular, the combined assessment of CPT, actigraphy, and eye tracking parameters appears to be a valid approach to more accurately capture the heterogeneous symptom presentation of the disorder.

Gaze-based attention refocusing training in virtual reality for adult attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is characterized by substantial interindividual heterogeneity that challenges the systematic assessment and treatment. Considering mixed evidence from previous neurofeedback research, we present a novel feedback system that relies on gaze behavior to detect signs of inattention while performing a neuropsychological attention task in a virtual seminar room. More specifically, an audiovisual feedback was given whenever participants averted their gaze from the given task. METHODS: Eighteen adults with ADHD and 18 healthy controls performed a continuous performance task (CPT) in virtual reality under three counterbalanced conditions in which either gaze-based feedback, sham feedback, or no feedback was provided. In all conditions, phases of high and low virtual distraction alternated. CPT errors and reaction times, proportions of gaze dwell times (e.g., task focus or distraction focus), saccade characteristics, EEG theta/beta ratios, head movements, and an experience sampling of ADHD symptoms were analyzed. RESULTS: While patients can be discriminated well from healthy controls in that they showed more omission errors, higher reaction times, higher distraction-related dwell times, and more head movements, the feedback did not immediately improve task performance. It was also indicated that sham feedback was rather associated with an aggravation of symptoms in patients. CONCLUSIONS: Our findings demonstrate sufficient suitability and specificity for this holistic ADHD symptom assessment. Regarding the feedback, a single-session training was insufficient to achieve learning effects based on the proposed metacognitive strategies. Future longitudinal, multi-session trials should conclusively examine the therapeutic efficacy of gaze-based virtual reality attention training in ADHD. TRIAL REGISTRATION: drks.de (identifier: DRKS00022370).

Multimodal Virtual Reality-Based Assessment of Adult ADHD: A Feasibility Study in Healthy Subjects.

Neuropsychological assessments are often surprisingly inaccurate in mapping clinically-reported attention-deficit hyperactivity disorder (ADHD) symptoms, presumably due to their low ecological validity. Virtual reality (VR) might offer a potential solution for this problem, given its capability to generate standardized and yet highly realistic virtual environments. As the first adaptation of existing virtual classroom scenarios to an adult population, we developed a Virtual Seminar Room (VSR) for multimodal characterization of ADHD symptoms. To test its feasibility, N = 35 healthy participants were immersed into the VSR via a head-mounted display and carried out a VR-embedded continuous performance task (CPT) under varying levels of distractions in two experimental blocks (24 min each). CPT performance, electroencephalography (EEG) measures, and head movements (actigraphy) were simultaneously recorded and analyzed offline. Although CPT performance remained constant throughout the task, head movements increased significantly from Block 1 to Block 2. In addition, EEG theta (4-7 Hz) and beta (13-30 Hz) power was higher during Block 1 than Block 2, and during distractor-present than distractor-absent phases. Moreover, P300 amplitudes were higher during Block 1 than Block 2, and P300 latencies were prolonged in distractor-absent compared with distractor-present phases. Although the paradigm awaits further improvements, this study confirms the general feasibility of the VSR and provides a first step toward a multimodal, ecologically valid, and reliable VR-based adult ADHD assessment.

Alpha modulation via transcranial alternating current stimulation in adults with attention-deficit hyperactivity disorder.

Background: One potential therapy treating attention-deficit/hyperactivity disorder (ADHD) is to modulate dysfunctional brain activations using brain stimulation techniques. While the number of studies investigating the effect of transcranial direct current stimulation on ADHD symptoms continues to increase, transcranial alternating current stimulation (tACS) is poorly examined. Previous studies reported impaired alpha brain oscillation (8-12 Hz) that may be associated with increased attention deficits in ADHD. Our aim was to enhance alpha power in adult ADHD patients via tACS, using different methods to explore potential therapeutic effects. Methods: Undergoing a crossover design, adults with ADHD received active and sham stimulation on distinct days. Before and after each intervention, mean alpha power, attention performance, subjective symptom ratings, as well as head and gaze movement were examined. Results: Frequency analyses revealed a significant power increase in the alpha band after both interventions. Despite a trend toward an interaction effect, this alpha power increase was, however, not significantly higher after active stimulation compared to sham stimulation. For the other measures, some additional pre-post effects were found, which were not intervention-related. Conclusion: Our study cannot provide clear evidence for a tACS-induced increase in alpha power in adult ADHD patients, and thus no stimulation related improvement of attention parameters. We provide further recommendations for the future investigation of tACS as a potential ADHD treatment.

Body transfer illusions in the schizophrenia spectrum: a systematic review.

Schizophrenia has been viewed as a disorder of the self. Accordingly, the question arises if and how senses of ownership and agency are impaired in schizophrenia. To address this question, several body transfer illusions (BTIs) have been investigated in schizophrenia patients and other schizophrenia spectrum (SCZ-S) populations. The objective of the study was to systematically review the current evidence from BTIs in the SCZ-S. A systematic literature search in PubMed and CENTRAL (search date: February 12, 2022) was conducted on BTI studies carried out in SCZ-S populations. Studies were included if they were published in English after peer review, reported original research data, related to the SCZ-S, and used a BTI as its study method. Conference papers, study protocols, and reviews were excluded. For each included BTI study, various study characteristics and outcomes were retrieved, and a risk-of-bias score was calculated based on six study quality criteria. K = 40 studies were identified, of which k = 20 studies met the eligibility criteria. For BTI paradigms using visuotactile stimulation, most studies found elevated sense of ownership ratings in SCZ-S populations compared to healthy controls (HC). Implicit illusion measures (e.g., proprioceptive drift), in turn, did not generally indicate elevated embodiment levels in SCZ-S populations. Likewise, no consistent group differences emerged between SCZ-S populations and HC with respect to BTI paradigms using visuomotor stimulation. Furthermore, BTI vividness was found to correlate significantly with core symptoms of schizophrenia and various subclinical characteristics related to the SCZ-S. In line with the self-disturbance hypothesis, SCZ-S populations appear to be affected by aberrations in bodily self-awareness. Review registration: PROSPERO (identifier: CRD42022287960).

Virtual reality in the diagnostic and therapy for mental disorders: A systematic review.

BACKGROUND: Virtual reality (VR) technologies are playing an increasingly important role in the diagnostics and treatment of mental disorders. OBJECTIVE: To systematically review the current evidence regarding the use of VR in the diagnostics and treatment of mental disorders. DATA SOURCE: Systematic literature searches via PubMed (last literature update: 9th of May 2022) were conducted for the following areas of psychopathology: Specific phobias, panic disorder and agoraphobia, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder, eating disorders, dementia disorders, attention-deficit/hyperactivity disorder, depression, autism spectrum disorder, schizophrenia spectrum disorders, and addiction disorders. ELIGIBILITY CRITERIA: To be eligible, studies had to be published in English, to be peer-reviewed, to report original research data, to be VR-related, and to deal with one of the above-mentioned areas of psychopathology. STUDY EVALUATION: For each study included, various study characteristics (including interventions and conditions, comparators, major outcomes and study designs) were retrieved and a risk of bias score was calculated based on predefined study quality criteria. RESULTS: Across all areas of psychopathology, k = 9315 studies were inspected, of which k = 721 studies met the eligibility criteria. From these studies, 43.97% were considered assessment-related, 55.48% therapy-related, and 0.55% were mixed. The highest research activity was found for VR exposure therapy in anxiety disorders, PTSD and addiction disorders, where the most convincing evidence was found, as well as for cognitive trainings in dementia and social skill trainings in autism spectrum disorder. CONCLUSION: While VR exposure therapy will likely find its way successively into regular patient care, there are also many other promising approaches, but most are not yet mature enough for clinical application. REVIEW REGISTRATION: PROSPERO register CRD42020188436. FUNDING: The review was funded by budgets from the University of Bonn. No third party funding was involved.

P300 Modulation via Transcranial Alternating Current Stimulation in Adult Attention-Deficit/Hyperactivity Disorder: A Crossover Study.

Objective: A repeated finding regarding event-related potentials (ERPs) is that patients with ADHD show a reduced P300 amplitude. This raises the question of whether the attention of ADHD patients can be increased by stabilizing the P300. Assuming that the P300 is generated by event-related oscillations (EROs) in the low frequency range (0-8 Hz), one approach to increase the P300 could be to stimulate the patient's P300 underlying ERO by means of transcranial alternating current stimulation (tACS). The aim of this follow-up study was to investigate this hypothesized mechanism of action in adult ADHD patients. Materials and Methods: Undergoing a crossover design, 20 adult ADHD patients (10 female) received an actual stimulation via tACS on one day and a sham stimulation on another day. Before and after each intervention, EEG characteristics (P300 amplitudes, low frequency power) and attention performances (d2 attention test, visual oddball task (VOT)) were recorded. Results: Electrophysiological analyses revealed no evidence for an enhanced P300 amplitude or low frequency power increase after actual stimulation compared to sham stimulation. Instead, a significant effect was found for a stronger N700 amplitude increase after actual stimulation compared to sham stimulation. Consistent with the P300 null results, none of the examined neuropsychological performance measures indicated a tACS-induced improvement in attentional ability. Conclusion: Contrary to a previous study using tACS to modulate the P300 in adult ADHD patients, the current study yields no evidence that tACS can increase the P300 amplitude in adult ADHD patients and that such P300 enhancement can directly improve neuropsychological parameters of attention.

Smartphone-assisted psychoeducation in adult attention-deficit/hyperactivity disorder: A randomized controlled trial.

Psychoeducation is generally recommended in the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), but only few studies have systematically assessed the effects of structured clinical psychoeducation. Moreover, although a considerable number of psychoeducational mobile applications exist, none have provided scientific evidence for their effectiveness or safety. Therefore, the present randomized controlled trial investigated a newly developed, free-to-use psychoeducation app for adults with ADHD as a support to a clinical psychoeducation group. 236 adults with ADHD were contacted for study participation, of whom 60 were finally randomized to a psychoeducation group supported either by our developed smartphone app (n = 30) or by traditional pen-and-paper brochures (n = 30). Psychoeducation treatments were conducted in groups of 10, with 8 weekly one-hour sessions between March 2019 and November 2020. Observer-rated ADHD symptom severity (IDA-R interview) was examined as the primary outcome parameter before and after treatment. Across both interventions, ADHD core symptoms were significantly reduced. Notably, the smartphone-assisted psychoeducation was significantly more effective in improving inattention and impulsivity and led to higher homework compliance than the brochure-assisted psychoeducation. No adverse events were reported.

Multimodal treatment efficacy differs in dependence of core symptom profiles in adult Attention-Deficit/Hyperactivity Disorder: An analysis of the randomized controlled COMPAS trial.

There is broad consensus that to improve the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), the various therapy options need to be tailored more precisely to the individual patient's needs and specific symptoms. This post-hoc analysis evaluates the multimodal effects of first-line medication (methylphenidate [MPH] vs placebo [PLB]) and psychotherapeutic (group psychotherapy [GPT] vs clinical management [CM]) treatments on the ADHD core symptoms inattention, hyperactivity and impulsivity. For the two-by-two factorial, observer-blinded, multicenter, randomized controlled Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS; ISRCTN54096201), 419 outpatients with ADHD were considered for analysis. ADHD symptoms were assessed by blind observer-rated and patient-rated Conners Adult ADHD Rating Scales before treatment (T1), 13 weeks (T2) and 26 weeks (T3) after T1, at treatment completion after 52 weeks (T4), and at follow-up (130 weeks, T5). MPH was superior to PLB in improving symptoms of inattention at almost all endpoints (observer-rated T2, T3, T4, T5; patient-rated T2, T3, T4), while a significant decrease in hyperactivity and impulsivity was at first found after 6 months of treatment. CM compared to GPT decreased inattention and impulsivity in the early treatment phase only (observer-rated T2, patient-rated T2, T3). In conclusion, while MPH seems to have a direct and sustained effect on inattention, premature medication discontinuation should particularly be avoided in patients with hyperactive-impulsive symptoms. Also, especially in high inattention and/or impulsivity presentations, initial individual patient management might be beneficial. Consequently, considering individual core symptom profiles may enhance the efficacy of treatments in adult ADHD.