Pharmacologic Modulation of Hippocampal Activity in Psychosis
Condition: Schizophrenia; Psychosis
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders
Intervention: Levetiracetam 500 mg
Intervention description: Levetiracetam (LEV) regulates neuronal synaptic exocytosis and calcium-induced neurotransmitter release and has a therapeutic effect on the excitation-inhibition balance of the hippocampus.
Intervention MeSH terms: Levetiracetam
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hippocampus

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. 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.
    

Eligibility 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 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)