Neurofeedback for Treatment Resistant Depression

Up to two-thirds of patients diagnosed with major depressive disorder (MDD) will not respond
to standard pharmacological and psychological interventions and will be considered treatment
resistant (TR-MDD). Decreased reactivity to positive stimuli, indexed by low amygdala
reactivity to positive autobiographical memory recall, may be a causal mechanism interfering
with recovery from TR-MDD. Previous work in our lab suggests that individuals who do respond
to antidepressant medications show increased amygdala activity that is indistinguishable from
controls relative to baseline, while TR-MDD individuals fail to show this increase in
amygdala activity. Furthermore, the investigators have found that MDD participants (more
generally, not specifically TR- MDD) are indeed able to increase their amygdala response
during positive memory recall via real-time fMRI neurofeedback (rtfMRI-nf) training, and that
this increase is associated with large and rapid reductions in depressive symptoms. Here, the
investigators propose to evaluate whether rtfMRI-nf training to increase the amygdala
response to positive memories may serve as an intervention for TR-MDD. 100 TR-MDD individuals
will be randomly assigned under double-blind conditions to receive 5 amygdala rtfMRI-nf or 5
control rtfMRI-nf sessions where they are trained to regulate a parietal region putatively
not involved in emotional processing or MDD. The investigators will assess changes in
amygdala activity, severity of clinical symptoms, and autobiographical memory deficits.
Success will suggest a new non- pharmacological, non-invasive intervention for a
traditionally treatment-resistant population of MDD individuals.

Inclusion Criteria:

- right-handed adults (ages 18 - 55) with a primary diagnosis of MDD according to
diagnostic criteria DSM-5 for recurrent MDD who are currently depressed will be
recruited to participate

- must be able to give written informed consent prior to participation

- must have fewer than 45% memories categorized as specific on the Autobiographical
Memory Test

- must have a SHAPS score > 4, indicating the presence of anhedonia

- unmedicated or stable on an SSRI antidepressant regime (at least 3 weeks to ensure
symptoms are stable)

- previously failed to respond to two previous SSRI medications according to either a
medical record review or clinical interview during Visit 1

Exclusion Criteria:

- have a clinically significant or unstable cardiovascular, pulmonary, endocrine,
neurological, gastrointestinal illness or unstable medical disorder

- met DSM-IV criteria for alcohol and/or substance dependence (other than nicotine)
within 12 months prior to screening

- have a history of traumatic brain injury

- are unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g.,
shrapnel inside body)

- are currently pregnant or breast feeding

- are unable to complete questionnaires written in English

- current (within 3 weeks of testing) use of any antipsychotics, anticonvulsants,
stimulants, benzodiazepines, beta-blockers, or other medications (except SSRI
antidepressants) likely to influence cerebral blood flow. Effective medications will
not be discontinued for the purposes of the study. Inclusion of patients on stable
antidepressant medications was decided in order to allow generalization towards a real
world population

- have a DSM-5 diagnosis of psychotic or organic mental disorder, bipolar I or II
disorder or any past or current manic or hypomanic symptoms, autism, or a primary
diagnosis of an anxiety disorder (though co-morbid anxiety will not be excluded)

- have any eye problems or difficulties in corrected vision.