Sleep Quality, Cognitive Performance, and Computerized Cognitive Training

Poor sleep quality is common in neuropsychiatric conditions and some of the problems associated with poor sleep at night may be due to medication side effects or reduced efficacy of certain treatments. Poor sleep quality has been implicated in cognitive impairments, with the sleep quality to cognition association so strong that specialized assessments have been developed to examine the subjective association between poor nighttime sleep and daytime cognitive impairment.

Computerized cognitive training (CCT) is a training procedure designed to build cognitive skills, with a goal of improvement of functional outcomes. CCT is also a learning-based approach and previous studies have shown that successful CCT interventions lead to changes in brain circuitry. It is also known, however, that many cases who are treated with CCT fail to make treatment-related gains. Recent studies have suggested that this may be associated with failures to engage in the training procedures, which could be related to sleep related impairments.

Increased anticholinergic load can also substantially disrupt the process of training related gains directly. Antihistaminergic effects, common to many antidepressant and antipsychotic medications, can lead to daytime sedation and sleepiness, which both interferes with treatment but also interferes with nighttime sleep as well

In previous clinical trials, Lurasidone was associated with reductions in sleepiness and with cognitive gains that exceeded practice effects. One viable hypothesis is that Lurasidone has both direct beneficial effects on cognition and substantial indirect benefits, due to the lack of histamine receptor occupancy, lack of anticholinergic effects, and direct promotion of positive nighttime sleep outcomes.

Thus, a broad-spectrum naturalistic comparison of Lurasidone-treated patients with patients treated with other medications is proposed. This would include examining the level of engagement in CCT treatment, measurement of CCT training gains, and relating engagement and training gains with concurrent sleep quality, measured by actigraphy.

Poor sleep quality is common in neuropsychiatric conditions and some of the problems associated with poor sleep at night may be due to medication side effects or reduced efficacy of certain treatments.

These impairments in daytime cognition seem most significant in areas relevant to daytime learning and nighttime memory consolidation, which has important implications for the success of rehabilitation focused psychiatric treatments. These treatments are learning based and functional and social skills are trained with teaching, which cannot be successful in the presence of significant memory consolidation problems. Reduced levels of slow wave sleep are likely to lead to problems in the consolidation of information presented for learning.

Computerized cognitive training (CCT) is a training procedure designed to build cognitive skills, with a goal of improvement of functional outcomes. CCT is also a learning-based approach and previous studies have shown that successful CCT interventions lead to changes in brain circuitry. It is also known, however, that many cases who are treated with CCT fail to make treatment-related gains. Recent studies have suggested that this may be associated with failures to engage in the training procedures, which could be related to sleep related impairments. These impairments could lead either to failures to concentrate during the daytime or failures to consolidate at night. As a result, the commonly expected benefits on neuroplasticity associated with CCT may be interrupted by poor sleep and this may lead to reduced benefits associated with combined skills training and CCT interventions.

In addition to the adverse effects of impaired sleep on consolidation and daytime alertness, there are multiple ways that these processes can be disrupted pharmacologically through several different factors. Increased anticholinergic load can substantially disrupt the process of training related gains directly. Antihistaminergic effects, common to many antidepressant and antipsychotic medications, can lead to daytime sedation and sleepiness, which both interferes with treatment but also interferes with nighttime sleep as well.

In a previous study, treatment with Quetiapine was previously found to induce substantial sleepiness and was associated with essentially no practice related improvements in cognition across 4 assessment time periods In contrast, Lurasidone was associated with reductions in sleepiness and with cognitive gains that exceeded practice effects. Thus, some of the differences in cognitive performance between quetiapine and Lurasidone could be due to sleep disturbance, in addition to the intrinsic benefits of lurasidone on cognition. One viable hypothesis is that Lurasidone has both direct beneficial effects on cognition and indirect benefits, due to the lack of histamine receptor occupancy, lack of anticholinergic effects, and direct promotion of positive nighttime sleep outcomes.

Thus, a broad-spectrum naturalistic comparison of Lurasidone-treated patients with patients treated with other medications is proposed. This would include baseline cognitive performance, measurement of treatment-related gains, and wearable devices.

The assessments goals would be to measure nighttime sleep, engagement in CCT, and cognitive gains over the study period. The primary outcome is cognitive gains with training over the treatment period.

Eligibility Criteria:
Inclusion Criteria:

Meets Diagnostic Criteria Patients with major depression or bipolar disorder will have baseline Brief Assessment of Cognition (BACS) composite scores of 0.5 Standard deviations (SD) below normative standards Patients with schizophrenia spectrum conditions will have baseline BACS composite scores 1.0 SD below normative standards Able and willing to give informed consent Expected length of stay at least 8 weeks.

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Exclusion Criteria:

* Symptoms Attributed to neurological Causes Seizure disorder Sensory impairments precluding CCT Current treatment with vortioxetine or tricyclic antidepressants Patients with mood disorders will be excluded if they have BACS composite scores more than 2.5 SD below normative standards Patients with schizophrenia spectrum conditions will be excluded if they have BACS composite scores more than 3.0 SD below normative standards