Study was redesigned and submitted as a new protocol (NCT04559529).

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. Specifically, we will utilize two functional magnetic resonance imaging (MRI) techniques: 1) blood oxygen level dependence (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. This study will also assess whether patients have improvement in their symptoms after receiving LEV. 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.

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 DSM-V (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; and,
9. For females of child-bearing potential, must have negative urine pregnancy test at time of screening visit and before each testing day.
10. Not breastfeeding/nursing at time of screening or at any time during the study.

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

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 at time of screening, before each testing day, or any potential concern for pregnancy at any time during the study.
9. Breastfeeding/nursing at time of screening or at any time during the study.
10. Conditions that preclude MR scanning
11. Conditions that preclude study drug administration

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 DSM-V (major depression, bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, etc)

Data were collected for a single subject, but study design was changed and study was discontinued. No data were analyzed.

2 weeks The protocol is: a) single dose of 500mg LEV, b) neuroimaging session #1, c) 500mg LEV for 2-weeks and d) imaging session #2. This participant only took a single 500mg dose and never advanced to the protocol components c) and d), i.e. did not complete the study protocol. 93% of LEV is cleared in 48 hours, so monitoring is not necessary beyond 1 week.

no adverse events