Multimodal Virtual Reality Assessment of Medication Effects in Attention-Deficit/Hyperactivity Disorder and Its Distinction From Depression: Cross-Sectional Study.

BACKGROUND: Over the past 2 decades, virtual reality-based neuropsychological tasks have gained traction as tools for objectively assessing symptoms of attention-deficit/hyperactivity disorder (ADHD), offering enhanced ecological validity by simulating naturalistic environments. To complement realistic settings with an ecologically valid task, we recently developed the virtual email sorting task (VEST), which immerses participants into an office environment where they sort emails while being exposed to distractors.

OBJECTIVE: This study examined for the first time the VEST's sensitivity to medication effects and its specificity in differentiating ADHD from other psychiatric disorders that share overlapping cognitive symptoms, such as major depressive disorder (MDD).

METHODS: A total of 23 unmedicated individuals with ADHD, 23 medicated individuals with ADHD, and 16 unmedicated individuals with MDD completed the VEST. During alternating distractor phases (DP) and nondistractor phases (NDP), we recorded the participants' task performance; head, torso, and leg actigraphy; eye movements; and brain activity using functional near-infrared spectroscopy (fNIRS), and subjective symptom ratings. Correlational analyses of main objective and subjective task-related parameters were computed. Data were analyzed using mixed-design ANOVAs.

RESULTS: Processing time variability increased over time in participants with MDD and unmedicated ADHD as indicated by a group × block interaction (P=.04; η2p=0.10), while a group × phase interaction (P=.009; η2p=0.15) revealed that medicated participants with ADHD showed an increase during DP compared to NDP. Moreover, both ADHD groups exhibited increased head movements during DP compared to NDP (trend group × phase interaction: P=.09; η2p=0.08), an effect not observed in the MDD group, and higher rotation during DP in unmedicated individuals with ADHD (P<.001; η2p=0.23). Also, scores in 3 out of 4 subjective symptom intensity ratings of inattention, impulsivity, and emotional dysregulation were higher in at least 1 of the ADHD groups compared to the MDD group. No significant group differences were found in actigraphy measures of the arm and torso, fNIRS brain activity, or eye-tracking data. Regarding correlational analyses, inattention was correlated to off-task gaze (r=0.28; P=.03), hyperactivity with mean processing time (r=0.33; P=.01) and head movement (r=0.35; P=.006), and impulsivity with error rate (r=0.35; P=.006), and various significant correlations between objective parameters were found.

CONCLUSIONS: Our findings highlight the potential of the VEST to differentiate between ADHD and MDD, as well as to detect medication-related effects within ADHD. The results underscore the value of multimodal and ecological assessment approaches with distractors in the evaluation of attentional and behavioral symptoms. The VEST may offer a standardized way to investigate complex behavior in mental disorders in research settings and, potentially, in clinical practice. However, further studies with greater statistical power are needed to confirm these findings.

TRIAL REGISTRATION: German Clinical Trials Register DRKS00031259; https://www.drks.de/search/de/trial/DRKS00031259/details.