Effect of Single Dose Intranasal Insulin On Cognitive Function

The purpose of the study is to find out how a small dose of insulin might affect memory, the ability to concentrate, and improve your daily functioning in patients with schizophrenia and schizoaffective disorders. Insulin is not being used to treat diabetes in this study. The investigators propose a single dose, double-blinded, placebo-controlled trial of intranasal insulin in 40 subjects with schizophrenia or schizoaffective disorder to examine insulin's effect on cognition. The specific aims include: Examine the effects of single doses of 40 IU intranasal insulin compared to placebo on cognitive functioning, including attention and memory. Examine whether single dose of intranasal insulin administration will raise serum insulin level and decrease plasma glucose level Insulin will be delivered through an air spray pump into your nose. The investigators will be comparing one dose of insulin (40 International Units) with placebo, an inactive liquid.

Insulin signaling in the brain is associated with improved cognitive function in both animal and human studies. Intranasal administration of insulin, which is non-invasive and minimizes the risk of hypoglycemia, may represent a new intervention approach with the potential to improve cognition and real life functioning in this patient with schizophrenia.

Subjects performed the HVLT Immediate Recall Task. For this task, participants were read aloud a list of 12 words from three taxonomic categories. Participants were read the list three separate times, and after each reading were immediately asked to recall as many words from the list as they could. The number of words recalled successfully was measured before and after intranasal treatment. Values below represent posttreatment performance minus pretreatment performance.

pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration

Subjects performed the HVLT word recall task after a 20-minute delay before and after intranasal treatment. In the HVLT delayed recall task, participants were asked to recall the same list of 12 words dictated in the immediate recall task 20 minutes after the completion of the immediate recall task. Words successfully recalled after the 20-minute delay were measured. Values below represent posttreatment performance minus pretreatment performance.

pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration

Subjects performed a computer-based test designed to measure sustained attention (attention to a specific stimuli over a period of several minutes) before and after intranasal treatment. During this test, participants respond as quickly as possible to any consecutive presentation of identical stimuli on the computer screen. The stimuli (2, 3, and 4-digit targets) were presented with increasing cognitive load in successive blocks. Correct responses, responses made to the second of 2 identical stimuli presented in a row, were scored as hits. False alarms were also recorded. The "d prime score" is a score given to each participant on a scale of 0.0- 1.0 in which discrimination sensitivity is measured. A score of zero equates to no sensitivity, whereas a score of 1.0 equates to perfect sensitivity. Values below represent postreatment performance minus pretreatment performance.

pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration

Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in the previous outcome measure ("CPT d score"). Hits rate refers to each participant's ability to correctly respond to two consecutive target presentations (i.e. correct responses). Hits rate was measured as a proportion of overall attempts (0= no hits, 1.0= 100% accuracy on hits). Values below represent posttreatment performance minus pretreatment performance.

pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration

Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in detail in a previous outcome measure ("CPT d score"). Reaction time of hits refers to the average time each participant took to correctly respond to a stimuli in milliseconds. Values below represent posttreatment performance minus pretreatment performance.

pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration

Subjects performed a computer-based test designed to measure sustained attention before and after intranasal treatment. The task is described in detail in a previous outcome measure ("CPT d score"). False alarm rate refers to the proportion of overall attempts that were characterized as incorrect responses (responses to two non-identical targets). Values below represent posttreatment performance minus pretreatment performance.

pretreatment= in the morning; postreatment= in the afternoon, 30 minutes after intranasal spray administration

Inclusion Criteria: Age 18-65 years Diagnosis of schizophrenia, any subtype or schizoaffective disorder, any subtype Male or female Stable dose of the current antipsychotic drug for at least one month Well established compliance with out-patient treatment per treating clinician's judgement. Able to complete the cognitive assessment battery (must be English speaking) Exclusion Criteria: Inability to provide informed consent Current substance abuse On clozapine or olanzapine Psychiatrically unstable per treating clinician's judgement. Significant medical illnesses including uncontrolled hypertension, diabetes, seizure disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases etc. Incapable to complete the cognitive battery assessment.