Anxiety & Depression Association of America

Multi-modal Assessment of Gamma-aminobutyric Acid (GABA) Function in Psychosis

Purpose

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 psychosis which includes conditions like schizophrenia, schizoaffective disorder, and mood disorders). 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 initial assessments (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.

Conditions

Schizophrenia
Bipolar Disorder
Healthy
Psychosis
Schizophreniform Disorders
Schizo Affective Disorder
Major Depression With Psychotic Features

Eligibility

Eligible Ages: Between 16 Years and 60 Years
Eligible Genders: All
Accepts Healthy Volunteers: Yes

Criteria

Early psychosis (EP) patients:

Inclusion Criteria:

- Meets DSM5 criteria for schizophrenia, schizophreniform disorder, schizoaffective
disorder, bipolar disorder type 1, with history of psychosis, major depressive
disorder, with history of psychosis, brief psychotic disorder, or other
specified/unspecified psychotic disorder; or, meets SIPS criteria for Presence of
Psychotic Symptoms or Brief Intermittent Psychotic Syndrome (BIPS).

- Ability and willingness to give informed consent to participate;

- 16-35 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 increases in psychotropic medication within the prior 4 weeks reflecting clinical
instability 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 (SCZ) and bipolar affective disorder (BAD) 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, or bipolar
disorder type 1, with history of psychosis bipolar affective disorder

- 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 increases in psychotropic medication within the prior 4 weeks reflecting clinical
instability. 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

Study Design

Phase: Phase 4
Study Type: Interventional
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: The two MRI sessions will will be scheduled about 1 week apart. If you are a woman, we may need to schedule the scanning session to coincide with a certain phase of your menstrual cycle.
Primary Purpose: Basic Science
Masking: Double (Participant, Care Provider)
Masking Description: Study coordinator and participant are blinded to medication administration.

Arm Groups

Arm	Description	Assigned Intervention
Placebo Comparator Healthy Controls		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 (vitals, qols) and optional blood draw 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 names: 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 (vitals, qols) and optional blood draw 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 names: Ativan
Experimental Early Psychosis patients		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 (vitals, qols) and optional blood draw 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 names: 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 (vitals, qols) and optional blood draw 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 names: Ativan
Experimental Schizophrenia or Schizoaffective disorder patients		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 (vitals, qols) and optional blood draw 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 names: 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 (vitals, qols) and optional blood draw 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 names: Ativan
Experimental Bipolar disorder patients		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 (vitals, qols) and optional blood draw 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 names: 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 (vitals, qols) and optional blood draw 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 names: Ativan

Recruiting Locations

More Details

Status: Recruiting
Sponsor: University of Michigan

Study Contact

Gabi Skinner, BS
734-615-3645
GABAStudy@med.umich.edu

Detailed Description

- Please note the collaborator (NIMH) is requesting that an NCT number be obtained prior to receiving the award number. - Initial assessment(s) may be done via videoconference due to Covid.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.