The goal of this clinical trial is to investigate the effect of a four-weeks, intensive virtual reality (VR)-based cognitive remediation (training) programme involving simulated daily-life challenges on cognition and functional capacity in symptomatically stable patients with mood disorders (depression or bipolar disorder) or psychosis spectrum disorders (F20-F29; e.g. schizophrenia or schizotypal disorder).

The investigators hypothesize that VR-based cognitive remediation vs. a VR control treatment has a beneficial effect on cognition after four-weeks treatment completion (primary outcome assessement time) measured with a novel ecologically valid VR test of daily-life cognitive functions (The CAVIR test; primary outcome measure), a verbal learning and memory composite score based on a traditional neuropsychological test and a performance-based measure of daily functioning (secondary outcome measures). Finally, for exploratory purposes, the study will examine neuronal underpinnings of treatment effects, and effects on additional measures of cognition, functioning and self-ratings scales (tertiary outcomes).

The current study will include outpatients with a mood disorders (unipolar - or bipolar disorder) in full or partial remission at the time of inclusion (score ≤ 14 on the Hamilton Depression or a psychosis spectrum disorders (F20-F29) that have been assessed to be relatively symptom stable by their treating clinician upon referral to the study. To accommodate for an approximately 20% drop-out rate from baseline to treatment completion (the primary outcome assessement time point), the investigators will recruit up to 66 participants (33 participants per intervention arm) to obtain complete data for minimum 54 participants (27 participants per arm).

Recruitment will be carried out through the outpatient Copenhagen Affective Disorder Clinic, the outpatient, early intervention clinics for psychotic disorders (OPUS), other mental health centres in the Capital Region of Denmark, and through advertisements on relevant websites.

After inclusion, the baseline assessements are scheduled and completed over two days, one to five days apart. On day 1, the participant is assessed with the virtual cognition test (the CAVIR test) and a comprehensive neuropsychological test battery. Participants also complete questionnaires concerning subjective cognitive complaints, quality of life and general acceptance of virtual reality technology. Functional capacity is assessed using a clinician-rated interview and a performance-based assessment. For participants with mood disorders, mood symptoms are rated with the Hamilton Depression Rating Scale (HDRS-17) and Young Mania Rating Scale (YMRS). For participants with psychosis spectrum disorders, positive and negative symptoms are rated with the Scale for the Assessement of Positive symptoms (SAPS) and Brief Negative Symptom Scale (BNSS), respectively. Finally, sleep quantity and quality in the past 3 days is recorded. Later the same day an fMRI scan is carried out encompassing a spatial working memory N-back task, a word encoding paradigm in which participants must encode and subsequently recognize words of typical household items, a resting state, and a structural scan. On day 2, participants' daily life functional capacity is assessed with The Assessement of Motor and Process Skills (AMPS) by an AMPS-certified occupational therapist in a standardized test kitchen.

The virtual reality cognition test, neuropsychological assessments, questionnaires, clinical symptom ratings, assessements of functional capacity (including AMPS) and fMRI scan are repeated within 2 weeks of treatment completion (primary outcome assessement time). All assessments except for the fMRI scan are repeated again 3 months after treatment completion to assess durability.

Participants are randomized upon full completion of the baseline assessement with allocation being carried out using the automated randomization module in the online Research Electronic Data Capture (REDcap) system based on an uploaded blocked randomization list stratified by age (< or ≥ 35 years) and diagnosis (mood disorders v. psychosis spectrum disorder)

Inclusion Criteria:

• Fluent Danish skills
• Meet the International Classification of Diseases 10th edition (ICD-10) diagnosis of unipolar disorder, bipolar disorder (types I and II) or a psychosis spectrum disorder (i.e. F20-F29) confirmed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview
• Patients must have objective and subjective cognitive impairment at the time of inclusion. Objective cognitive impairment is defined a total score on the Screen for Cognitive Impairment in Psychiatry - Danish version (SCIP-D) ≥ 0.5 standard deviations (SD) below the expected total score based on age, education, and gender or as a score ≥ 0.5 SD below the expected score on a minimum of two out of the five subtests (verbal learning test - immediate, working memory test, verbal fluency test, verbal learning, test - delayed, and processing speed test). Subjective cognitive impairment is defined as a score ≥ 14 on the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA).

Exclusion Criteria:

• Current drug or substance abuse
• A daily use of benzodiazepines >22.5 mg oxazepam or >7.5 mg diazepam (cutoffs for doses with limited cognitive side effects)
• Comorbid neurological disorder
• Previous serious head trauma
• Dyslexia
• Pregnancy
• Claustrophobia (fMRI scan)
• Having a pacemaker or other metal implants inside the body (fMRI scan)
• Having had electroconvulsive therapy in the 3 months prior to inclusion

The study has a double-blinded design. Neither the participant nor the outcome-assessors will know whether the participant is receiving VR-based cognitive remediation or VR control treatment