Sodium Butyrate For Improving Cognitive Function In Schizophrenia

Sodium Butyrate As A Treatment For Improving Cognitive Function In Schizophrenia

The purpose of this grant is to evaluate the efficacy of sodium butyrate as a novel treatment for cognitive deficits in schizophrenia (SZ). The aims will be to evaluate its effects on improving symptoms and functioning in SZ, and the relationship of the drug's clinical effects to epigenetic and inflammation related biochemical changes.

The persistent cognitive deficits which can be appreciated across the course of SZ, from prodromal to chronic SZ, may be the most important underlying dysfunction in preventing functional, occupational, and social recovery in SZ compared to other symptom domains. Sodium butyrate is a short chain fatty acid and binds to the zinc site of histone deacetylases (HDAC). The inhibition of HDAC results in histone hyperacetylation. This study aims to evaluate its effects on improving symptoms and functioning in SZ, and the relationship of the drug's clinical effects to epigenetic and inflammation related biochemical changes.

The proposed study will be a double blind study of the effects of sodium butyrate on cognitive function and symptoms in chronic SZ patients showing continued cognitive deficits.The primary specific aims of the proposal will be to test the the MATRICS (MCCB) battery,delayed recall performance, and performance on real world functional tasks as assessed by the USCD Performance- Based Skills Assessment Battery (UPSA). In addition, we will also investigate whether sodium butyrate may improve other aspects of cognition.

We will also explore whether improvement in cognition is related to change in HDAC activity in peripheral blood cells and changes in inflammatory makers in the blood, and assess whether there is any improvement in psychopathology as measured by PANSS scale.

Inclusion Criteria:

1. Subjects who have cognitive deficits as indicated by a score of < 85 on RBANS,
2. meet criteria for DSM-5 diagnosis of chronic SZ, schizoaffective disorder (SA),
3. Subjects who are stably treated with antipsychotic medications and are not in acute exacerbation of illness symptoms.

Exclusion Criteria:

1. History of mental retardation or pervasive developmental disorder,
2. Subjects with a current serious neurological/CNS disorder (such as seizure disorder, stroke or multiple sclerosis) or brain trauma,
3. Current treatment with valproic acid, butyrate drugs, sulforaphane, or other drugs or chemicals known to have high HDAC inhibitory activity,
4. Pregnancy,
5. Severe unstable medical condition,
6. Current suicidal or homicidal thoughts,
7. Current alcohol or substance abuse (other than nicotine or occasional marijuana) in the last month.