Patient description: A 46-year-old Asian woman with MDD complains of persistent feelings of sadness and loss of interest in daily activities. She states that her mood is still depressed most of the days. She complains of loss of energy and feelings of worthlessness nearly every day. She is on anti-depressants for the past 6 months, but the symptoms are still present. She does not drink alcohol or smoke. She used to exercise every day for at least 30 min., but she doesn't have enough energy to do so for the past 3 weeks. She also has some digestive issues recently. She is married and has 4 children. She is menopausal. Her husband was diagnosed with colon cancer a year ago and is undergoing chemotherapy. Her past medical history is unremarkable. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 18.0-65.0,  Depressive Disorder, Major for MDD patients: 1. Male or female outpatients aged 18-65. 2. Able to understand the nature of the study and able to provide written informed consent prior to conduct of any study procedures. 3. In the investigator's opinion, has met DSM-IV-TR for Major Depressive Disorder for at least 4 weeks prior to signing consent, single or recurrent episode, without psychotic features, as the subject's primary psychiatric disorder. 4. Able to communicate in English with study personnel. 5. Has a Hamilton Depression Rating Scale (HDRS) score ≥18 at screening and ≥14 on intervention day. 6. For women of child-bearing potential (i.e., one who is biologically capable of becoming pregnant), must be willing to use a medically acceptable form of birth control or practice abstinence for the duration of her participation in the trial  for MDD patients: 1. Symptoms of depression which, in the investigator's opinion, are better accounted for by a diagnosis other than Major Depressive Disorder. 2. Any of the following diagnoses, as identified by the psychiatric evaluation or study assessments A current DSM-IV-TR Axis I diagnosis of Dementia; or Any current DSM-IV-TR Axis II diagnosis (i.e. personality disorder) that would suggest potential noncompliance with the protocol; or A lifetime history of Schizophrenia, Schizoaffective Disorder, or a Bipolar Disorder Type 1; or A diagnosis claustrophobia severe enough that it would impair ability to be in the Heckel HT3000 hyperthermia device A current (or within 12 months prior to the Screening visit) diagnosis of Anorexia Nervosa or Bulimia Nervosa 3. Subject has met DSM-IV for Substance Abuse in the 3 months prior to screening visit, or non-remitted Substance Dependence in the 6 months prior to screening visit. 4. A diagnosis of an anxiety disorder that is considered by the investigator to be of greater source of distress or functional impairment than the patient's depressive symptoms. Subjects with comorbid anxiety disorders not excluded above and considered to be of secondary importance will be permitted in the study. 5. Participation in concurrent formal psychotherapy during the trial, or in the 2 weeks prior to the screening visit. 6. Individuals with a history of having difficulty swallowing food or large capsules will be excluded from participating in the assessment of core body temperature (because swallowing a large sensor pill is required). The ingestible temperature capsules will not be used in subjects with any known or suspected obstructive disease of the gastrointestinal tract including, but not limited to esophageal stricture, diverticulosis and inflammatory bowel disease (IBD), peptic ulcer disease, Crohn's disease, ulcerative colitis; previous gastrointestinal surgery. 7. Subject has a medical condition or disorder that Is unstable and clinically significant, or Could interfere with the accurate assessment of safety or efficacy of treatment, including: 1. individuals who are using prescription drugs that may impair thermoregulatory cooling, including diuretics, barbiturates, and beta-blockers, or antihistamines, 2. individuals with cardiovascular conditions or problems (uncontrolled hypertension, congestive heart failure, or documented evidence of coronary artery disease) 3. individuals with chronic conditions/diseases associated with a reduced ability initiate thermoregulatory cooling, including Parkinson's, multiple sclerosis, central nervous system tumors, and diabetes with neuropathy, 4. hemophiliacs/individuals prone to bleeding, 5. individuals with a fever the day of study intervention, 6. individuals with hypersensitivity to heat, 7. individuals with recent acute joint injury, 8. individuals with enclosed infections, be they dental, in joints, or in any other tissues. 8. Clinically significant, in the investigator's opinion, abnormal findings on screening laboratory tests or physical exam. 9. Presence of clinically significant suicide risk, based on the investigator's opinion, or a Columbia Suicide Severity Risk Scale (C-SSRS) suicidal ideation score of 4 or 5. Any suicide attempt within 3 months of the Screening visit is exclusionary. 10. Use of any psychotropic medications for 2 weeks (8 weeks for fluoxetine) prior to initiation of the study, with the exception of hypnotic medications (zolpidem, zaleplon, eszopiclone). 11. Need for any non-protocol psychotropic medication during the trial, with the exception of hypnotics used up to four nights per week. 12. Use of any psychoactive dietary or herbal products in the 2 weeks prior to screening visit 2, or at any time during the trial. 13. Women who are pregnant (HCG pregnancy test at screening, or lactating, or who plan to become pregnant during the study. 14. Current participation in any clinical trial that might impact results of this one, which includes participation in another clinical trial for depression, as well as drug trials with agents that might affect mood or regulation of body temperature. 15. Reasonable likelihood for non-compliance with the protocol for any other reason, in the opinion of the Investigator, prohibits enrollment of subject into the study. 16. Obesity and overall size of subject. It will be up to the PI's discretion will consider BMI, waist circumference, and body fat composition when determining and safety of the individual. 17. History of peripheral circulatory disease, for example peripheral vascular disease, deep vein thrombosis (DVT), or lymphedema. 18. History of a cerebral vascular accident 19. History of stroke, epilepsy or cerebral aneurisms 20. Cancer in the last five years. 21. Diabetes mellitus types I or II 22. Any clinically significant autoimmune disease (compensated hypothyroidism allowed) 23. Active alcohol or drug abuse/dependence in the 3 months prior to screening