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

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.

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)

Healthy control subjects:

Inclusion Criteria:

• Ability and willingness to give informed consent to participate
• 18- 60 years old
• No history of (h/o) past or current mental illness (except for simple phobias), but prior h/o substance abuse okay 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
• 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)