Nicotinic Enhancement of Cognitive Remediation Training in Schizophrenia

Nicotinic Enhancement of Cognitive Remediation Training in Schizophrenia

Schizophrenia is marked by problems in attention, memory and problem solving. These deficits predict long-term functional outcome such as the ability to live independently and maintain employment, but they are not ameliorated by currently available medications. Cognitive training improves these functions to some degree, but this approach is time- and resource-intensive. The current project aims at enhancing and accelerating the benefits that people with schizophrenia derive from cognitive training by administering nicotine during some of the training sessions. This would provide the proof of principle for a type of treatment intervention to improve cognitive symptoms of schizophrenia.

The current project aims at determining whether the intermittent presence of nicotine during cognitive training exercises in people with schizophrenia will shorten the training period necessary to induce significant and clinically relevant improvement and enhance the improvement seen after a training period of specified length.

Hypothesis 1a: Nicotine administration during training will increase the size of all measured effects of the training intervention, and will accelerate the time course of performance enhancement on the MCCB and training exercise progression parameters.

Hypothesis 1b: The larger training effects in the Nicotine Group will persist beyond the end of the intervention.

Hypothesis 2a: Within-session progress on the training exercises will be larger in the presence of nicotine than in the presence of placebo.

Hypothesis 2b: These acute nicotine-induced performance elevations will persist beyond the presence of nicotine through subsequent non-drug training sessions, giving evidence of an acute facilitation of learning processes.

Inclusion Criteria:

• Aged 18-60 years.
• DSM diagnosis of schizophrenia or schizoaffective disorder.
• Ability to give written informed consent.
• Either currently smoking and not attempting to quit, or having smoked no more than 80 cigarettes, cigarillos or cigars in lifetime and not at all within the last year.
• Normal or corrected to normal vision (at least 20/50).
• Four weeks of stable pharmacological treatment (same psychiatric medication at same dose) and no foreseeable changes at enrollment.

Exclusion Criteria:

• Alcohol or substance abuse or dependence other than nicotine within the last 12 months.
• Uncontrolled hypertension (resting systolic blood pressure above 150 or diastolic above 90 mm Hg).
• History of myocardial infarction, heart failure, angina, stroke or severe arrhythmias.
• ECG abnormalities.
• History of neurological conditions such as stroke, seizures, dementia or organic brain syndrome.
• Mental retardation.
• Pregnant, verified by urine pregnancy test for females.
• Breast-feeding.
• Treated with benztropine currently or within the last four weeks.