Treatment to Enhance Cognition in Bipolar Disorder

Cognitive dysfunction is increasingly recognized as a major feature of bipolar disorder (BD), present by illness onset, persistent into euthymia, and associated with functional outcome. Deficits are qualitatively similar to those seen in schizophrenia (SZ), and may be quantitatively similar in some patient groups, e.g. in patients with a history of psychosis. Despite strong associations between cognitive impairment and functional outcomes in BD, treatment for these symptoms at present is inadequate. Pharmacotherapies do little to address cognitive symptoms, and may even worsen them. Psychosocial cognitive remediation (CR) treatments have been developed to target these symptoms and their functional correlates, and have shown early promise in patients with SZ in improving both neurocognition and community functioning. However, despite the overlap of neurocognitive deficits between patients with SZ and BD, no studies to date have extended neuroscience-based CR to patients with BD. The present study aims to assess the efficacy of CR treatment in patients with BD with a history of psychosis using a 70-hour CR paradigm compared to a dose-matched computer-based control. It is hypothesized that patients in the CR group will exhibit improvements in cognitive and community functioning compared to controls, which will persist during a 6-month durability phase. Additionally, putative mechanisms of functional change will be examined, including mediator effects of cognitive and clinical change on community functioning. 130 patients with BD with a history of psychosis recruited from the Psychotic Disorders Programs at McLean Hospital will be randomized into either the CR or computer control group. CR will be administered using the BrainWorks program, neuroscience-based training programs that have shown early promise in patients with SZ. Participants will be assessed on measures of clinical, cognitive, and community functioning at baseline, following the 70-hour treatment or control phase, and again 6 months later. Participants may opt to participate in an functional magnetic resonance imaging (fMRI) study at pre- and post-treatment; resting state, task-based and functional connectivity, and diffusion tensor imaging data will be collected to evaluate preliminary evidence of neurobiological changes after training versus control. Additionally, participants may opt in to participation in two tasks of reward sensitivity including the Probabilistic Reward task and Richard's Delay Discounting. These tasks are administered pre- and post-treatment to evaluate the role of reward in treatment response as well as the potential for CR to modulate reward processing. This project is in keeping with the NIH's stated strategic priorities for improving mental health outcomes in patients and strengthening the impact of National Institute of Mental Health (NIMH)-supported research on public health, with specific recommendations for broad implementation of effective psychosocial interventions.

Inclusion criteria

• Clinical diagnosis of BD with psychosis
• Positive and Negative syndrome Scale (PANSS) < 75; PANSS Psychosis item scores = 3 or under; Young Mania Rating Scale (YMRS) = 6 or under
• Age between 18 and 50
• Within 10 years of illness onset
• Legal and mental competency of the participant

Exclusion criteria

• Age under 18 or over 50
• PANSS >75; PANSS Psychosis item scores >3; YMRS > 6
• Legal or mental incompetence (legal incompetence defined by any guardianship (including of person or treatment guardianship); mental incompetence defined by failure of the informed consent survey)
• Psychiatric inpatient status at time of enrollment
• Delirium secondary to medical illness
• Psychotic or mood disorder due to general medical or neurological illness
• History of head trauma
• History of seizure disorder or photo-sensitive seizures
• Use of anticholinergic medication, clozapine or olanzapine at baseline
• Rapid-cycling bipolar disorder
• Diagnosis of current substance abuse (past month) or substance dependence within the past year.