Imaging Phosphodiesterase 4B (PDE4B) in People With Psychiatric Disorders With Positron Emission Tomography (PET) and the Radiotracer [18F]PF974

Inclusion criteria

• Willing and able to give voluntary written informed consent.
• Is able to read and write, able to communicate effectively with the investigator, and comply with all study requirements, restrictions, and directions of the research staff.
• Men or women, aged 18 to 70, at screening.
• In good general health as evidenced by medical history, physical examination, electrocardiogram, serum/urine biochemistry, hematology, and serology tests.
• Participants with AUD will have a current diagnosis of AUD according to DSM-5 criteria (i.e., Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) (SCID-5) ascertained diagnosis, confirmed by the Principal Investigators).
• Participants with AUD will meet the following drinking criteria: males will drink > 14 drinks per week and exceed 4 drinks per day at least twice per week; females will drink > 7 drinks per week and exceed 3 drinks per day at least twice per week. They must meet drinking criteria during a consecutive 30-day period within the 90 days prior to intake.
• Participants with PTSD will have a current diagnosis of PTSD according to DSM-5 criteria (CAPS-5 ascertained diagnosis, confirmed by the Principal Investigators. TC subjects must have a DSM-5 criteria traumatic event with no PTSD diagnosis.
• Healthy control subjects will have no current or past diagnosis of AUD or other significant substance use disorder. They will drink less than 5 alcoholic drinks per week with no heavy drinking days (i.e., >4 drinks/day for men; >3 drinks/day for women) in the last 30 days. Subjects who have have a DSM-5 criteria traumatic event with no PTSD diagnosis may also be considered healthy controls for Aim 1.
• Renal function and hepatic function will be within normal limits (for age and sex) on the laboratory tests. Elevated liver enzymes for individuals with alcohol use disorder are permitted at the discretion of the study physician.

Exclusion criteria

• Current significant medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology that would impact the integrity of the data (note that elevated liver enzymes for individuals with AUD will not be exclusionary).
• Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder.
• Current significant psychiatric disorder including severe substance use disorder (other than alcohol or tobacco use disorders*) and past or current psychotic symptoms.
• Regular use in the past 6 months of any prescription, psychoactive or herbal medications (e.g., antidepressants, antipsychotics, anxiolytics) that would impact the integrity of the data; No subject will be asked to stop taking medication to participate in the study. Participants who are regularly taking P-gp and BCRP inhibitors will be excluded.
• Pregnancy or lactation.
• Blood donation within eight weeks of the start of the study.
• History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).
• Unable to safely discontinue or hold aspirin and other NSAID use.
• MRI incompatible implants (i.e., such as pacemaker, artificial joints, non-removable body piercings) and other contraindications for MRI, such as claustrophobia, having implanted or embedded metal objects/fragments or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist).
• Participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits for healthy volunteers.
• Subject who has current, past, or anticipated exposure to radiation in the work place within one year of the proposed research scans that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits.
• Has any condition that, in the opinion of the investigator, would prevent compliance with the study protocol.
• History of complicated alcohol withdrawal including history of delirium tremens; seizure, hospitalization for withdrawal.
• A CIWA score ≥8 at intake or on scan day.
• Subjects who are, in the opinion of the study physician, unable to safely abstain from alcohol overnight prior to their study visits.
• Subjects with a significant history of repeated alcohol withdrawal, defined as 4 or more medicated detoxifications in the previous 5 years