Pharmacological Modulation of Hippocampal Activity in Psychosis 2

The purpose of this study is to test whether administration of levetiracetam (LEV), a commonly used anti-epileptic that alters neurotransmitter release, can reduce hippocampal hyperactivity in people with psychotic disorders. Specifically, the investigators will utilize two functional magnetic resonance imaging (MRI) techniques: 1) blood-oxygen-level-dependent (BOLD) contrast will assess activity with a visual scene processing task that engages the anterior hippocampus and 2) arterial spin labeling (ASL) will assess baseline activity. Previous studies in people with psychotic disorders have shown that the hippocampus is hyperactive and more activity correlates with worsening of clinical symptoms. Therefore, the aim of this study is to use an intervention to further understand the underlying mechanisms of the hippocampus in psychosis.


Eligibility Criteria:
Inclusion Criteria:

Inclusion criteria for psychosis subjects

1. Men and women age 18 - 65.
2. Communicative in English.
3. Provide voluntary, written informed consent.
4. Physically healthy by medical history.
5. BMI \> 17.5 and \< 45.
6. Diagnosis of a psychotic disorder confirmed by Structured Clinical Interview for Diagnostic and Statistical Manual-5 (SCID) or diagnostic interview with a trained clinician.
7. Stable medication regimen over at least the past two weeks, including the use of either an oral or intramuscular administration of an antipsychotic medication.
8. For females, no longer of child-bearing potential, or agreeing to practice effective contraception during the study (e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap \[diaphragm or cervical/vault caps\] with spermicidal foam/gel/film/cream/suppository; male partner sterilization; or true abstinence when this is in line with the preferred and usual lifestyle of the subject); and,
9. For females of child-bearing potential, must have a negative urine pregnancy test before MRI and drug administration.
10. Not breastfeeding/nursing at time of screening or at any time during the study.

Inclusion criteria for healthy controls

1. All of the above except for subjects will be psychiatrically healthy and not taking psychotropic or potentially psychoactive prescription medication.

----

Exclusion Criteria:

Exclusion criteria for psychosis subjects

1. Age less than 18 or greater than 65.
2. Not communicative in English.
3. Unable to provide written informed consent.
4. Current medical or neurological illness.
5. History of severe head trauma.
6. BMI \< 17.5 or \> 45.
7. Meets criteria for diagnosis of substance or alcohol use disorder within the past month.
8. Positive urine pregnancy test during the study.
9. Breastfeeding/nursing at time of screening or at any time during the study.
10. Conditions that preclude MR scanning (as defined in the Screening Form)
11. Conditions that preclude study drug administration (as defined in the Screening Form)

Exclusion criteria for healthy controls

All of the above and in addition:

1. Current use of psychotropic or potentially psychoactive prescription medication.
2. Major psychiatric disorder as determined by Diagnostic and Statistical Manual -5 (major depression, bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, etc)