This study aims to examine the scientific mechanisms of whole-body hyperthermia (WBH), a novel, rapidly acting, single session antidepressant and anxiolytic therapy. It also aims to determine its feasibility and acceptability in women with postpartum depression (PPD). The study will enroll four cohorts of participants: healthy postpartum controls; postpartum women with PPD; healthy adult controls; and adults with major depressive disorder or anxiety disorders in a longitudinal protocol.

Whole-body hyperthermia has already been shown to be feasible, acceptable, and effective in major depressive disorder (MDD) populations, with an open-label study and a subsequent randomized, double-blind, sham-controlled study both demonstrating efficacy. Some evidence indicates that the antidepressant effect may be due to immune mechanisms, though it may also be mediated through direct neural effects of hyperthermia

This project aims to establish a protocol to deliver WBH therapy to patients with mood and anxiety disorders to collect information about scientific mechanisms. It also seeks to extend treatment to a specific population: a single session WBH treatment could be of tremendous interest to depressed postpartum women who wish to avoid medications and time away from their infants.

The mechanistic work will be completed with the four cohorts. By examining mechanisms in all four groups, investigators will be able to determine mechanisms unique to ill individuals as well as any mechanistic differences between MDD and PPD. In addition, the investigators aim to establish feasibility and acceptability of this protocol in postpartum women. Why? Over 80% of women deliver a child, and 15-20% of all women develop significant postpartum mental illness, usually depression and anxiety.

Participants will be divided into two groups: those undergoing a simplified protocol to test feasibility and acceptability in the postpartum (Group 1) and those undergoing a more time-intensive protocol to evaluate mechanisms (Group 2). In addition, participants in Group 2 will be eligible to enroll in a sub-study (Group 2: Sub-Study) including up to 10 fMRI session.

Inclusion Criteria

• Group 2

  • Arm 1: Healthy women or transgender men 18-50 years of age, ≤ 6 months postpartum
  • Arm 2: Women and transgender men 18-50 years of age, ≤ 6 months postpartum, meeting criteria for a major depressive episode in the postpartum period on the MINI.
  • Arm 3: Healthy adults of both sexes 18-50 years of age.
  • Arm 4: Adults of both sexes 18-50 years of age meeting criteria for an episode of major depression or generalized anxiety disorder on the Mini International Neuropsychiatric Interview (MINI)

• Group 2: Sub-study

  • Subjects enrolled in Group 2 are eligible for an optional additional sub-study (Group 2: Sub-study); inclusion criteria are the same as for Group 2.

Exclusion criteria for all:

• For logistics, we will exclude individuals with BMI >30 and waist size > 35, who may not fit comfortably in the sauna dome for all cohorts described above.
• For contraindications to hyperthermia, we will exclude from all cohorts listed above, individuals with severe cardiovascular disease, including congestive heart failure, coronary artery disease, uncontrolled hypertension, and hypotension; pregnancy; active substance use disorders; recent major injuries or surgeries (<1 week prior); impaired sweating (those with multiple sclerosis, diabetes mellitus with neuropathy, central nervous system disease, heat insensitivity); a history or family history of malignant hyperthermia, fever or active signs of infection; taking medications that may have interactions with hyperthermia (for example, barbiturates, diuretics, and beta blockers) and the use of an antipyretic or anihistamine medication in the 12 hours prior to the WBH intervention. Individuals with above mentioned conditions will be excluded since either WBH might deteriorate their conditions or it is unknown how their condition will be affected by WBH.
• For contraindications to immune analyses, we will exclude individuals with conditions that might affect immune analyses, including individuals with known active autoimmune or endocrine disease and individuals with active infection at baseline.

Additional exclusion criteria by cohort or applicable study group:

• Group 2

  • Arm 1: For psychiatric contraindications, we will exclude individuals with a history of psychiatric disorders as assessed by MINI since the cohort will consist of mentally healthy individuals as a control group.
  • Arm 2: For psychiatric contraindications, we will exclude individuals with bipolar disorder or other Axis I psychiatric disorders except depressive and anxiety disorders and individuals taking antidepressants who are unwilling to hold antidepressant dose steady from recruitment through study termination. In this cohort we exclude individuals with other psychiatric disorders except depressive and anxiety disorders to rule out the effect of other psychiatric diseases on the outcome.
  • Arm 3: For psychiatric contraindications, we will exclude individuals with a history of psychiatric disorders as assessed by MINI since the cohort will consist of mentally healthy individuals as a control group.
  • Arm 4: For psychiatric contraindications, we will exclude individuals with bipolar disorder or other Axis I psychiatric disorders except depressive and anxiety disorders and individuals taking antidepressants who are unwilling to hold antidepressant dose steady from recruitment through study termination. In this cohort we exclude individuals with other psychiatric disorders except depressive and anxiety disorders to rule out the effect of other psychiatric diseases on the outcome.

• Group 2 and Group 2: Sub-study - All participants

  • For contraindications to use of the e-Celsius capsule that will be used to measure core temperature, we will exclude individuals with pacemakers or any other electric medical implant, individuals with a current intestinal disorder that could lead to obstruction of the digestive tract including gastroparesis, individuals with history of diverticula, individuals with history of past surgical procedures in the gastrointestinal tract, individuals with a swallowing disorder and individuals with Crohn's disease.

• Study Group 3 - All participants

  • For contraindications to MRI, individuals with metal in the body will be excluded from participating in the MRI portion of the research since magnetic fields in MRI scanners can cause dangerous interactions in patients with metallic foreign bodies: projectile effect, twisting, burning, artifacts, and device malfunction (interference with a pacemaker).