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): 18.0-70.0,  Major Depressive Disorder Ability to provide written informed consent Current Major Depressive Episode (MDE), secondary to either Major Depressive Disorder or Bipolar Disorder (I, II or NOS), diagnosed by structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders-IV-text revision (DSM-IV-TR) Current MDE at least two years duration OR a history of more than 4 lifetime depressive episodes Minimum score at study entry of 20 on the 17-item Hamilton Depression Rating Scale (HDRS-17) Average pre-operative HDRS-17 score of 20 or greater (averaged over four weekly pre-surgical evaluations during the four weeks prior to surgery) and an average pre-operative HDRS-17 score no more than 30% lower than the baseline screening HDRS-17 score A maximum Global Assessment of Functioning of 50 Treatment-resistant depression defined as Failure to respond to a minimum of four different antidepressant treatments, including at least three medications from at least three different classes, evidence-based psychotherapy or electroconvulsive therapy (ECT) administered at adequate doses and duration during the current episode Failure or intolerance of an adequate course of electroconvulsive therapy (ECT) during any episode (confirmed by medical records), or refusal of ECT due to a reason considered to be valid by the study psychiatrist A patient may remain on psychotropic medications during this study. However, doses must remain stable during the 4 weeks prior to surgery, the four weeks post-operatively, and the 24 weeks open stimulation phase. Medications will be changed only if intolerable side effects clearly attributable to the medications develop  Inability to tolerate general anesthesia Significant cerebrovascular risk factors or a previous stroke, documented major head trauma or neurodegenerative disorder Other currently active clinically significant Axis I psychiatric diagnosis including schizophrenia, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder or post-traumatic stress disorder. Patients with severe Axis II personality disorders will also be excluded if the personality disorder is likely to interfere with cooperation and adherence to the study protocol Current psychotic symptoms Evidence of global cognitive impairment Substance abuse or dependence not in full sustained remission (i.e., not active for at least one year) Active suicidal ideation with intent; suicide attempt within the last six months; more than three suicide attempts within the last two years Pregnancy or plan to become pregnant during the study period General contraindications for DBS surgery (cardiac pacemaker/defibrillator or other implanted devices) Inability or unwillingness to comply with long-term follow-up