The purpose of this study is to better understand mental illness and will test the hypotheses that while viewing affective stimuli, patient groups will show increased blood oxygenation level dependent (BOLD) signal by fMRI after lorazepam.

This study will enroll participants between the ages of 16 and 60, who have a psychotic illness (such as schizophrenia, bipolar disorder, and schizoaffective disorder). The study will also enroll eligible participants without any psychiatric illness, to compare their brains.

The study will require participants to have 3-4 sessions over a few weeks. The first session (may be over two visits) will include a diagnostic interview and several questionnaires (qols) to assess eligibility. Subsequently, there will will be two separate functional magnetic resonance imaging (fMRI) sessions in which lorazepam or placebo will be given prior to the MRI. During the fMRI the participants will also be asked to answer questions. Additionally, the participants will have their blood drawn, women of child bearing potential will have a urine pregnancy test, vital signs taken, and asked to complete more qols.

• Schizophrenia
• Bipolar Disorder
• Healthy
• Psychosis
• Schizophreniform Disorders
• Schizo Affective Disorder

• Other: Placebo and fMRI
  A dose of Placebo will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
  Other Name: inactive medication
• Drug: Lorazepam and fMRI
  A dose of Lorazepam (assigned to one of two dose levels between subjects: 0.01 mg/kg or 0.02 mg/kg) will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. There will be two fMRIs done approximately 1 week apart and after the assessment visit. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
  Other Name: Ativan

• Placebo Comparator: Healthy Controls
  Interventions:

  • Other: Placebo and fMRI
  • Drug: Lorazepam and fMRI
• Experimental: Early Psychosis patients
  Interventions:

  • Other: Placebo and fMRI
  • Drug: Lorazepam and fMRI
• Experimental: Schizophrenia or Schizoaffective disorder patients
  Interventions:

  • Other: Placebo and fMRI
  • Drug: Lorazepam and fMRI
• Experimental: Bipolar disorder patients
  Interventions:

  • Other: Placebo and fMRI
  • Drug: Lorazepam and fMRI

Early psychosis (EP) patients:

Inclusion Criteria:

• Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, bipolar disorder type 1, with history of psychosis, or other specified/unspecified psychotic disorder; or, meets Structured Interview for Psychosis Syndromes (SIPS) criteria for Presence of Psychotic Symptoms or Brief Intermittent Psychotic Syndrome (BIPS)
• Ability and willingness to give informed consent to participate;
• 16-25 years old
• Positive symptom onset ≤ 2 years
• No history of active substance use disorder in the past 2 months
• Not currently on an involuntary treatment order
• Not taking chronic narcotics, barbiturates, benzodiazepines
• Absence of suicidal thoughts with plans or intentions, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
• No changes in psychotropic medication within the prior 4 weeks and for half of EP sample, or not taking antipsychotic medication within the prior 4 weeks. Patients may take as needed doses of benzodiazepines as clinically prescribed, as long as those doses are not required within 5 half-lives of an MRI session
• Ability to tolerate small, enclosed spaces without anxiety
• No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, cerebral spinal fluid (CSF)shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators
• Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 pounds (lbs), men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.

Exclusion:

• If a woman of child bearing age, not pregnant or trying to become pregnant
• History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure
• History of closed head injury, for example (e.g.) loss of consciousness > ~5 min, hospitalization, neurological sequela

Schizophrenia/schizoaffective and bipolar disorder patients

Inclusion Criteria:

• Ability and willingness to give informed consent to participate;
• 16- 60 years old
• Meets DSM- 5 criteria for schizophrenia, or schizoaffective disorder (SCZ), or bipolar disorder type 1, with history of psychosis bipolar affective disorder (BAD)
• Duration of positive symptom onset > 2 years
• No history of active substance use disorder in the past 2 months
• Not currently on an involuntary treatment order
• Not taking chronic narcotics, barbiturates, benzodiazepines
• Absence of suicidal thoughts with plans or intentions, as assessed by C-SSRS
• No changes in psychotropic medication within the prior 4 weeks. Patients may take as needed doses of benzodiazepines as clinically prescribed, as long as those doses are not required within 5 half-lives of an MRI session
• Ability to tolerate small, enclosed spaces without anxiety
• No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, CSF shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators
• Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 lbs, men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.

Exclusion:

• If a woman of child bearing age, not pregnant or trying to become pregnant
• History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure
• History of closed head injury, for example (e.g.) loss of consciousness > ~5 min, hospitalization, neurological sequela

Healthy control subjects:

Inclusion Criteria:

• Ability and willingness to give informed consent to participate
• Age 16 - 60
• No history of (h/o) past or current mental illness (except for simple phobias), but prior h/o substance abuse ok if in remission for greater than 5 years
• Not taking any medication, prescription or non-prescription, with psychotropic effects (birth control medications allowed)
• No first-degree family members with a history of a psychotic disorder (including bipolar disorder)
• Ability to tolerate small, enclosed spaces without anxiety
• No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, CSF shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators
• Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 lbs, men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.

Exclusion:

• If a woman of child bearing age, not pregnant or trying to become pregnant
• History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure
• History of closed head injury, for example (e.g.) loss of consciousness > ~5 min, hospitalization, neurological sequela