Patient description: The patient is a 47-year-old Asian woman complaining of persistent feelings of sadness. She lost interest in activities she used to enjoy. She states that her mood is mostly depressed for the past 3 weeks. She also lost her appetite , which led to about 5kg weight loss. She complains of loss of energy and feelings of worthlessness nearly every day. She is not using any drugs and she does not smoke. She doesn't drink alcohol. 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 recently diagnosed with colon cancer and he is starting his chemotherapy. There is nothing remarkable in her past medical history and her drug history is only positive for Vit D3 1000 units daily. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 22.0-55.0,  Bipolar Disorder (Healthy Controls) 1. Male or female age 18-55 2. No history of psychiatric disorder, as assessed using the Mini-International Neuropsychiatric Interview (MINI). 3. Non-Clinical Levels of Emotion Dysregulation, as assessed using the Difficulties in Emotion Regulation Scale (DERS) Non-clinical levels of emotion dysregulation will be defined as a score < 80 on the DERS  (Healthy Controls) 1. Current or history of psychiatric disorders 2. Endorsement of clinical levels of emotion dysregulation 3. Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol); schizophrenia; delusional disorder; and psychotic disorders. 4. Current pregnancy. 5. Medical illness or non-psychiatric medical treatment that would likely interfere with study participation 6. Neurologic disorder, prior neurosurgical procedure, prior electroconvulsive therapy (ECT) or TMS, history of seizures or head trauma. 7. Presence of metallic implants that would interfere with safety during fMRI scanning. (Bipolar Disorder Group) 1. Male or female age 18-55 2. Diagnosis of Bipolar I Disorder (BD-I), as assessed through MINI. 3. Current mood state euthymic. a. Hamilton-Depression Rating Scale (HAM-D-17) and Young Mania Rating Scale (YMRS) will be used to assess current depressive and manic symptoms. Euthymia will be defined as a HAM-D-17 score <10 and YMRS score <12. 4. Clinical Levels of Emotion Dysregulation, as assessed using the DERS. Clinical levels of emotion dysregulation will be defined as a score > 80 on the DERS (Bipolar Disorder Group) 1. Current symptoms of mania or depression (YMRS score >12, HAM-D-17 score >10). 2. Medication instability (<3 months). 3. Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol), verified by urine toxicology screen; schizophrenia; delusional disorder; and psychotic disorders. 4. Current pregnancy. 5. Medical illness or non-psychiatric medical treatment that would likely interfere with study participation 6. Neurologic disorder, prior neurosurgical procedure, prior ECT or TMS, history of seizures or head trauma. 7. Presence of metallic implants that would interfere with safety during fMRI scanning