"New pharmacologic approaches to early psychosis: Taking aim at the hippocampus"
Donald C. Goff, MD
Director, Nathan Kline Institute for Psychiatric Research
Marvin Stern Professor and Vice Chair for Research
Psychiatry Department, NYU Grossman School of Medicine
Objectives
The activity is designed to help the learner
- Describe evidence of hippocampal atrophy, clinical correlates, and associated molecular factors during early psychosis
- Explain the current debate about whether antipsychotics promote or prevent hippocampal atrophy
- Explain the rationale for a trial of citalopram in early psychosis and describe the results
- Explain the rationale for a trial of levetiracetam in early psychosis and describe preliminary results
Summary
An important model for early psychosis suggests that hippocampal activity at rest is increased in early psychosis and associated with hippocampal atrophy. The increased hippocampal activity may drive psychosis and the hippocampal volume loss may be associated with a poor clinical course. In treatment naïve schizophrenia patients we found significant hippocampal atrophy during the first eight weeks of antipsychotic treatment associated with duration of untreated psychosis (DUP) and markers of inflammation, oxidative stress and reduced brain neurotrophic factor (BDNF); no additional atrophy was observed during 12 months of maintenance treatment. To correct a possible deficit of BDNF in early psychosis, we conducted a trial of citalopram in stabilized first episode patients and observed improvement in negative symptoms compared to placebo in patients with long DUP but no effect on hippocampal volume. We are now studying whether levetiracetam might attenuate elevated hippocampal activation in early psychosis as a potential protective treatment to reduce psychosis and protect against hippocampal atrophy. Results of a pilot placebo-controlled dose-finding trial will be presented.
This talk is sponsored by the Luton Lecture Fund, Department of Psychiatry and Behavioral Sciences. This educational activity received no commercial support.