Cognitive Impairment, Schizophrenia Spectrum and Other Psychotic Disorders
Conditions
Keywords
cognition, schizophrenia, schizoaffective disorder
Brief summary
The proposed project aims to establish the feasibility and tolerability of delivering repetitive transcranial magnetic stimulant (rTMS) combined with computerized cognitive training in patients with Schizophrenia or Schizoaffective Disorder and cognitive difficulties. The investigators will conduct a 2 week randomized controlled trial study evaluating computerized cognitive training combined with either active or sham rTMS on cognitive and functional outcomes in adults with Schizophrenia or Schizoaffective Disorder.
Detailed description
Schizophrenia affects approximately 1.1% of U.S adults per year and is among the most disabling psychiatric illnesses, due primarily to poor functioning related to cognitive dysfunction. Negative (e.g. flattened affect, limited speech output, lack of motivation) and cognitive symptoms (e.g. poor executive functioning, attention and working memory) are by far the leading cause of social, occupational and educational disability and functional impairment in patients with schizophrenia. Since the advent of antipsychotic medications, Schizophrenia treatment has improved significantly with respect to positive symptom control. However, there are limited resources for improving cognitive symptoms in Schizophrenia, which remain disabling for most with the diagnosis. Cognitive remediation and cognitive training programs have shown promise in improving these symptoms. Specifically, adults with Schizophrenia show significant improvements in cognition after participating in 2 weeks of computer based cognitive training. Functional capacity has also been shown to improve with longer periods of computer-based cognitive training. However, the effects of cognitive training alone may be most effective in the short-term. Longer term effectiveness of cognitive training has yet to be shown. There has been emergent interest in using neuromodulation for treatment of cognitive decline in people with various illnesses including children with ADHD, adults with schizophrenia and older adults with late life depression. Specifically, high frequency (20Hz) rTMS applied to the dorsolateral prefrontal cortex (DLPFC) bilaterally has been shown to improve working memory in patients with schizophrenia. By improving neuroplasticity and working memory, rTMS could significantly improve effects of cognitive training in patients with schizophrenia. Combination cognitive training and rTMS treatment has been used in patients with depression with promising results. Previously, the implementation of cognitive training programs in clinical settings was challenged by the intensity of required patient engagement. However, our group and others have applied computerized training programming that is accessible remotely, improving accessibility and engagement. Thus, computerized training offers a feasible and scalable combination with neuromodulation treatment. Here, we propose to test rTMS, in combination with a computerized cognitive training program, to remediate cognitive dysfunction in Schizophrenia and Schizoaffective Disorder in a pilot randomized clinical trial. Aim: Conduct a randomized pilot and feasibility study of active versus sham rTMS combined with computerized cognitive training program in adults with Schizophrenia or Schizophreniform Disorders, comparing neurocognitive and functional outcomes between groups. 1a) the investigators hypothesize favorable differences between groups in acute improvement on neuropsychological executive functioning, as measured by the Screen for Cognitive Impairment in Psychiatry (SCIP). 1b) The investigators hypothesize favorable differences between groups in daily functioning as measured by the Canadian Objective Assessment of Life Skills (COALS) and the WHO Disability Assessment Schedule (WHODAS) in participants receiving CrTMS compared to controls.
Interventions
DEVICErTMS
Participants will receive either active or sham bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) for 12.5 min per side.
BEHAVIORALComputerized cognitive training
All participants will receive computerized cognitive training for 40 min after each rTMS session.
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
participants will be masked to the TMS versus sham treatment. Sham treatment will be very similar to active TMS without the active magnetic stimulation
Intervention model description
randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 * Diagnosis of schizophrenia or schizoaffective disorder * Psychotic symptoms are stable
Exclusion criteria
* Active substance use * History of seizures or seizure disorder * Active psychosis or recent psychiatric hospitalization * Use of medications that could impair cognitive functioning
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Groups on Neuropsychological Testing | 2 weeks | Evaluate differences in neuropsychological functioning between active and sham rTMS groups using the Screen for Cognitive Impairment in Psychiatry (SCIP). Scores are reported as Z-scores standardized to age-adjusted normative data. A Z-score of 0 represents the population mean, and each unit reflects one standard deviation from that mean. Higher Z-scores indicate better cognitive performance. Scores are interpreted relative to normative expectations rather than a diagnostic threshold. Change scores represent the value at 2 weeks minus the baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in WHODAS Total Score From Baseline to 2 Weeks | 2 weeks | Disability was measured using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), a standardized instrument assessing functional impairment across multiple domains of daily living. Total scores range from 0 to 100, with higher scores indicating greater disability. Change scores were calculated as the value at 2 weeks minus the baseline value. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the St. Louis Metropolitan area.
Pre-assignment details
Twelve participants provided informed consent; six were randomized and six were not assigned to an intervention.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 19.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
| WHODAS Total Score | 31.33 Score STANDARD_DEVIATION 35.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 1 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
None listed