Predicting adult Attention Deficit Hyperactivity Disorder (ADHD) using vocal acoustic features

Background: It is a key concern in psychiatric research to investigate objective measures to support and ultimately improve diagnostic processes. Current gold standard diagnostic procedures for attention deficit hyperactivity disorder (ADHD) are mainly subjective and prone to bias. Objective measures such as neuropsychological measures and EEG markers show limited specificity. Recent studies point to alterations of voice and speech production to reflect psychiatric symptoms also related to ADHD. However, studies investigating voice in large clinical samples allowing for individual-level prediction of ADHD are lacking. The aim of this study was to explore a role of prosodic voice measures as objective marker of ADHD. Methods: 1005 recordings were analyzed from 387 ADHD patients, 204 healthy controls, and 100 clinical (psychiatric) controls. All participants (age range 18-59 years, mean age 34.4) underwent an extensive diagnostic examination according to gold standard methods and provided speech samples (3 min in total) including free and given speech. Paralinguistic features were calculated, and random forest based classifications were performed using a 10-fold cross-validation with 100 repetitions controlling for age, sex, and education. Association of voice features and ADHD-symptom severity assessed in the clinical interview were analyzed using random forest regressions. Results and Conclusion ADHD was predicted with AUC = 0.76. The analysis of a non-comorbid sample of ADHD resulted in similar classification performance. Paralinguistic features were associated with ADHD-symptom severity as indicated by random forest regression. In female participants, particularly with age < 32 years, paralinguistic features showed the highest classification performance (AUC = 0.86). Paralinguistic features based on derivatives of loudness and fundamental frequency seem to be promising candidates for further research into vocal acoustic biomarkers of ADHD. Given the relatively good performance in female participants independent of comorbidity, vocal measures may evolve as a clinically supportive option in the complex diagnostic process in this patient group. Competing Interest Statement: EA participated and received payments in the national advisory board ADHD of Shire/Takeda. JL is co-founder and CTO of PeakProfiling GmbH. He created audio-features used in this study, that are intellectual property of PeakProfiling GmbH. FH received payments by PeakProfiling GmbH. Clinical Trial: NCT0110462

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

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 x 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: ISRCTN5409620