COVID-19

Depression is very common and poses a huge disease burden. About 20% of the US population suffers from depression at least once in their lifetime. Inflammations that are hidden inside our body as a result of aging, obesity, chronic diseases, or certain treatments (e.g., interferon for hepatitis C) appear to cause depressive symptoms and even clinical depression. Individuals with such inflammations are more likely to suffer from depression and are less likely to respond to currently available antidepressant medications. This study will test theophylline, a medication currently used for asthma treatment, as a new way to mitigate depressive symptoms in response to such inflammations. This study begins with a 90-minute screening session to determine whether participants are eligible to join the main study. Those who meet the eligibility criteria will then join the main study, which will consist of taking theophylline or methylcellulose (i.e., oral placebo) for 2 weeks at home and an 8-hour session at the UCLA Medical Center. Approximately 20 healthy adults will be recruited for participation in the study. During the course of the study, participants will take theophylline or methylcellulose for 2 weeks at home and then will be injected either lipopolysaccharide (LPS) or saline (i.e., intravenous placebo) at the UCLA Medical Center. LPS is a bacterial substance that can initiate chemical reactions that are similar to those seen in individuals with mild sickness symptoms, such as a slight increase in body temperature, muscle aches, or tiredness. It is a safe way of investigating the body's response to inflammation and how these changes may alter cognitive, emotional, or neural function. It has been given thousands of times to healthy volunteers - both younger and older adults - without any serious side effects.

Inclusion Criteria:

• in good general health (as evaluated during the phone and in-person screening sessions)
• aged 18-65 years
• if female, using adequate birth control

Exclusion Criteria:

• history of hypersensitivity to xanthine derivatives (a contraindication to theophylline treatment)
• pregnant or planning to become pregnant in the next 6 months
• current breastfeeding
• chronic diseases such as cardiovascular disease, hepatic impairment, peptic ulcer disease, and seizure disorders
• current use of prescription medications such as steroids, non-steroid anti-inflammatory drugs, immune modifying drugs, opioid analgesics, and psychotropics
• Axis I psychiatric disorders including current major depressive disorder
• current depressive symptoms assessed by the Patient Health Questionnaire (PHQ-9 ≥ 5)
• heavy smoking (1 pack or more per day)
• excessive caffeine use (>600 mg/day)
• Body-mass index > 35 due to the effects of obesity on cytokine activity
• evidence of recreational drug use from urine test
• evidence of pregnancy from urine test
• evidence of clinically significant rhythm abnormality on a resting electrocardiogram (ECG)
• clinically significant abnormalities on screening laboratory tests