1. Understanding Cognitive Disability in Schizophrenia Cameron S. Carter MD University of California at Davis

2. Schizophrenia is common and can lead to lifelong disability 1% of population world wide Males and females equally affected but females have later onset and better functional outcome Onset in late adolescence, early adulthood Loss of function, inability to achieve expected function

3. Schizophrenia Chronic psychiatric disorder characterized by disruption in affective,cognitive, behavioral, and social domains that results in poor ability to maintain adaptive functioning in the community. Usually manifest itself between the ages of 18-25

4. Etiology:Genetics Highly heritable Risk increases with relationship e.g. 10% for first degree relative or fraternal twin, 50% concordance for monozygotic twin Environmental factors certain but poorly characterized (intrauterine malnutrition, viral illnesses, perinatal insults, drug exposure) Gene environment interactions affect brain development and function

5. Schizophrenia as a Developmental Disorder Most strongly associated risk genes (e.g. NRG, DISC1, RGS4) affect early brain development People who go on to develop schizophrenia show lower school achievement and more behavioral problems during childhood Onset during early adolescence during massive brain development Environmental risks factors have their impact during critical developmental windows (e.g. maternal influenza, early, heavy cannabis use, late) Some environmental risk factors may be mediated through activation of maternal immune system that may in turn impact brain development and synaptic function

6. Cognition In Schizophrenia Present at onset and throughout the life span Impaired cognition is a strong predictor of disability in schizophrenia (e.g. Green 1997). (Note signs of impaired cognition in Nash’s adolescence) Currently available treatments have little impact on cognitive disability in schizophrenia, however, there are ways to increase functional outcome. Perhaps the most amenable to investigation using modern, non invasive neuroscientific tools

7. Symptoms At least 4 weeks of 2 of the following Hallucinations Delusions Negative symptoms (poor motivation, social withdrawal) Disorganization (Look for ex. of these symptoms while viewing the movie) Minimum duration of 6 months of continuous signs of illness

8. Improved Management to Improve Functional Outcomes in Schizophrenia Early intervention important for improving functional outcome Rehabilitative therapies e.g. supportive employment and education improve outcomes Develop novel medication treatments targeting cognition Validate neurorehabilitation approaches (Decide which treatment is best for Nash and why)