Pharmacological Modulation of Hippocampal Activity in Psychosis 2
Condition: Schizophrenia; Psychosis
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders
Intervention: Levetiracetam (LEV) 500 mg; Placebo
Intervention description: The levetiracetam pill will look just like the placebo pill.; The placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.
Intervention MeSH terms: Levetiracetam
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 2-way crossover, double-blind, randomized controlled study
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: During Visit 2, participants will be randomly assigned to an intervention arm in which they will receive two 250mg LEV capsules or two placebo capsules. Both the participant and the research team will be blinded to which arm each participant is in. During Visit 3, the participant will undergo cross-over and receive either two 250mg LEV capsules or two placebo capsules (whichever intervention they did not receive in Visit 2).
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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)