Bipolar Disorder, Healthy, Major Depression With Psychotic Features, Psychosis, Schizo Affective Disorder, Schizophrenia, Schizophreniform Disorders
Conditions
Brief summary
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 like bipolar disorder). The study will also enroll eligible participants between the ages of 18 and 60 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 be two separate functional magnetic resonance imaging (fMRI) sessions in which lorazepam or placebo will be given prior to the fMRI. During the fMRI, the participants will also be asked to answer questions. Additionally, the participants will have their blood drawn, vital signs will be taken, they will be asked to complete more qols, and women of childbearing potential will have a urine pregnancy test.
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.
Interventions
OTHERPlacebo and fMRI
There will be two fMRIs done after the initial assessment and approximately 28 days apart. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. A dose of Placebo will be given approximately 80-90 minutes prior to entering the fMRI scanner. Participants will complete assessments (vitals, questionnaires) and an optional blood draw prior to having each fMRI. Participants will be asked to rate pleasant/unpleasant pictures during their initial assessment visit and to view them during the fMRI.
DRUGLorazepam and fMRI
There will be two fMRIs done after the initial assessment and approximately 28 days apart. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. 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 approximately 80-90 minutes prior to entering the fMRI scanner. Participants will complete assessments (vitals, questionnaires) and optional blood draw prior to having each fMRI. Participants will be asked to rate pleasant/unpleasant pictures during their initial assessment visit and to view them during the fMRI.
Sponsors
University of Michigan
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Caregiver)
Masking description
Study coordinator and participant are blinded to medication administration.
Intervention model description
The two MRI sessions will be scheduled approximately 28 days apart. If you are a woman, we may need to schedule the scanning session to coincide with a certain phase of your menstrual cycle.
Eligibility
Sex/Gender
ALL
Age
16 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Early psychosis (EP) patients: Inclusion Criteria: * Ability and willingness to give informed consent to participate; * 16-35 years old * 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). * 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 the EP sample, 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 fMRI session * Ability to tolerate small, enclosed spaces without anxiety * Vision equal to or better than 20/40 on a Snellen chart, with correction if necessary * 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 difficulty fitting into the fMRI scanner properly.
Exclusion criteria
* If a woman of childbearing 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 * Hypersensitivity to benzodiazepines or to components of the formulation, per judgment of the principal investigator (PI) * Disorders affected by benzodiazepines, such as compromised respiratory function, e.g., chronic obstructive pulmonary disease, or acute, narrow angle glaucoma, per judgment of the principal investigator (PI) 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 DSM5 criteria for schizophrenia, schizoaffective disorder, other specified/unspecified psychotic 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 Columbia-Suicide Severity Rating Scale (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 fMRI session * Ability to tolerate small, enclosed spaces without anxiety * Vision equal to or better than 20/40 on a Snellen chart, with correction if necessary * 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 difficulty fitting into the fMRI scanner properly.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Oxygen Level Dependent (BOLD) Change in Medial Frontal Cortex While Viewing Affective Pictures | Approximately 28 days | Change in brain activity in the medial frontal cortex after being given lorazepam, a medication that changes the activity of GABAergic neurons. Results reflect the difference/change in brain signal between the lorazepam scan and the placebo scan. BOLD change in the dorsomedial prefrontal cortex (dmPFC) was summarized using MATLAB (MatrixLaboratory)'s SPM (Statistical Parametric Mapping) package for eigenvariate extraction, which extracts the first principal component of the voxel time series within an region of interest (ROI). The resulting values are in arbitrary units (AU) reflecting variance-normalized signal after temporal filtering and serial correlation correction, which removes absolute signal scaling. While AU values are not directly interpretable as percent signal change, they preserve relative differences in BOLD change across conditions and are appropriate for statistical comparison. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORStephan Taylor, MD
University of Michigan
Participant flow
Recruitment details
Participants were targeted for recruitment from clinical sites (ex, Program for Risk Evaluation and Prevention (PREP) clinic) using medical record review and/or clinician referral. They were also recruited through research registries (ex, UMHealthResearch.org, departmental psychiatric research registry), via community advertisements (ex, flyers), internet sources such as social media (ex, Facebook/Instagram/Google AdWords paid campaigns), and email blasts.
Pre-assignment details
Of the 240 participants consented, 97 were determined to be ineligible for the trial, leaving 143 total enrolled (17 Early Psychosis patients, 35 Schizophrenia or Schizoaffective disorder patients, 30 Bipolar disorder patients, 61 Healthy controls). Of those 143 enrolled, 24 participants were never randomized to a treatment order. 8 withdrew; 9 were lost to follow-up, and 7 were removed due to physician decision (ex, a change in participant eligibility).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 23.08 years STANDARD_DEVIATION 3.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 112 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 84 Participants |
| Region of Enrollment United States | 5 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 56 | 0 / 114 |
| other Total, other adverse events | 1 / 57 | 6 / 56 | 5 / 114 |
| serious Total, serious adverse events | 1 / 57 | 1 / 56 | 0 / 114 |
Outcome results
None listed