The purpose of this research study is to examine the effect of social connectedness on the brain. Study procedures include one Magnetic Resonance Imaging (MRI) or functional Magnetic Resonance Imaging (fMRI) scan, one Positron Emission Tomography (PET) scan, one Magnetic Resonance Spectroscopy (MRS) scan, an electroencephalogram (EEG), and in-person and phone call follow-ups.

The purpose of this study is to examine the effect of social connectedness (social isolation and loneliness) on synaptic density in the brain using PET scans. Participants will have a screening appointment to determine eligibility. Participants will participate in the following study procedures:

MRI or fMRI scan: the purpose of the MR scan is to help us identify the different regions of the brain on the PET scans. Participants may be asked to do some cognitive and behavioral tasks during parts of the MR scan.

PET scan: an arterial catheter and one or two IV catheters will be placed (one for radiotracer injection and one to take blood samples). The radiotracer, [18F]SDM-8 will be used. A radiotracer is a minimal amount of a drug that is labeled with a very small amount of a radioactive substance that binds to receptors in the brain and can be detected by a special camera in the PET scanner.

Electroencephalography (EEG): EEG is a procedure that allows measurement of physiological brain responses. Sensors placed on and around the head record small electrical currents produced by the brain.

Follow-up phone calls and appointments: participants will have follow-up phone calls every 3 months for 9 months following scan visits, and an in-person follow-up appointment 1 year after scans to assess mood and cognition, as well as document any changes. Follow-up assessments may continue for up to 5 years after the year one follow-up appointment.

Some subjects may be asked to return after the 1 year follow-up period to repeat study procedures to examine changes over time.

Inclusion Criteria:

• able to give written informed consent
• age 55+
• English speaking

Exclusion Criteria:

• contraindication to MRI scanning including claustrophobia, high girth, moderate to significant white matter atrophy, and presence of ferromagnetic material in the body, including orthodontic braces or other non MR-compatible foreign bodies. All participants will be screened for metal objects by the same methods used for routine clinical MRI scanning
• for women: pregnancy or breastfeeding
• serious medical or neurological illness that in the opinion of the PI would interfere with the scientific goals of the study or participant safety
• pervasive developmental disorders (PDD) or primary psychotic disorders
• meet DSM-5 criteria for current severe substance use disorder (except marijuana or nicotine)
• head injury that led to significant long term decline in cognitive abilities as seen by decline in grades or work performance
• current psychosis, active significant suicidal (score of 6 on MADRS suicide item) or homicidal ideation
• lifetime history of neurologic abnormality including seizure disorder, cerebrovascular, or neoplastic lesion, neurodegenerative disorder, or significant head trauma resulting in post-traumatic amnesia >24 hours
• full scale IQ lower than 70
• contraindications to PET (e.g. poor venous access for placement of venous lines)
• history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year
• history of a bleeding disorder or currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto) *for subjects obtaining arterial line.
• blood donation within 8 weeks of the start of the study
• REM sleep disorder
• brain injury (TBI, seizure/epilepsy, stroke, TIA) in lifetime (self-report and medical chart review)
• electroconvulsive or ketamine therapy, or similar therapies that have rapid effects on brain neurochemistry within the past 6 months
• high risk for stroke (above first quartile on Framingham Stroke Risk Profile)
• current cancer

Transdiagnostic sample of older individuals (age 55+ years) with stress disorders without psychosis including individuals with MDD, bipolar disorder, post-traumatic stress disorder (PTSD), dysthymia, and non-psychiatric individuals.