Investigating Gulf War Illness in Veterans

* INCLUSION CRITERIA:

Inclusion criteria for all veterans:

* Ability to provide informed consent
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Age 48-70 at time of enrollment into VA IN-DEPTH Study
* Veterans who were deployed to Gulf Region ODS/S between August 1990 - June 1991.
* Self-reported completion of at least the seventh grade of school.
* Fluency in speaking, reading, and understanding English.
* Underwent screening as part of the VA IN-DEPTH study and were unanimously determined to be eligible by the IN-DEPTH Adjudication Committee.
* Agree not to smoke in the 4 hours prior to CPET procedure

EXCLUSION CRITERIA:

Exclusion criteria for all veterans:

* Current or past psychotic disorder including depression with psychosis, bipolar disorder with psychotic symptoms and schizophrenia
* Current DSM-5-defined major depression disorder, generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or obsessive-compulsive disorder unless managed for more than six months with a stable treatment regimen
* Current or past substance use disorder within last five years as diagnosed on the Structured Clinical Interview for DSM-5 (SCID-5). Prior or prescription marijuana use within the past five years will not be an exclusion.
* Current suicidal ideation
* History of head injury leading to moderate or severe traumatic brain injury, as detailed by loss of consciousness for greater than 30 minutes, a Glasgow Coma Score of 12 or less at the time of injury, post-traumatic amnesia greater than one day, or brain-scan changes related to a head injury. Persons having a history of mild TBI (mTBI) will not be excluded.
* Women who are pregnant, breastfeeding, or are within one-year post-partum.
* Current or previous malignancy. A history of malignancy that has fully resolved with surgical resection only (e.g. no chemotherapy, radiation therapy, or immunotherapy) will be allowed.
* Current systemic immunologic disorders (e.g. Type 1 diabetes, rheumatoid arthritis). Local immunological disorder (e.g. atopic dermatitis, stable autoimmune thyroid disease) and allergic disorders will be allowed.
* Current or previous long-term immune suppressive therapy. Systemic steroid use, even short-term, must not have been used within the month prior to enrollment
* Any medical condition that would make the study procedures risky for the participant (e.g. congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, severe osteoarthritis, exercise-induced angina and poorly controlled asthma).
* Active participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study.
* Inability to perform the bicycling exercise task. (e.g. coronary artery disease, not having a lower limb, disabling stroke)
* Not willing to allow for research data and samples to be shared broadly with other researchers.
* Symptom severity that makes it impossible for the volunteer to travel to NIH for extended inpatient evaluation
* Use of medications with a high-risk for withdrawal-related complications (i.e. long-acting opiates or benzodiazepines).

Additional Exclusion criteria for participants undergoing TMS:

\- Pacemaker, implanted pump, stimulator, cochlear implant or metal objects inside the eye or skull.

Participants with unconfirmed metal may have further evaluation to rule out metal in the eye or skull.

Participants without metal after evaluation may proceed to TMS.

\- A personal history of seizure disorder

Additional Exclusion criteria for participants undergoing MRI:

\- Metal in the body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or having a history of being a welder or metal worker, since small metal fragments may be in the eye. Participants with unconfirmed metal may have further evaluation to rule out metal in the eye

or skull. Participants without metal after evaluation may proceed to MRI.

* Substantial claustrophobia
* Inability to lie on back for up to 2 hours

Additional Exclusion criteria for Healthy Veteran Controls:

\- Meets modified Kansas criteria for GWI.