Disappearance of treatment-resistant depression after damage to the orbitofrontal cortex and subgenual cingulate area: a case study

Although post-stroke depression is a well-characterized disorder, there is less understanding of how pre-existence of depression is affected by a stroke.

We describe a patient with treatment-resistant major depression, which had been ongoing for 14 years but disappeared shortly after onset of a subarachnoid hemorrhage. Her cognitive function and functional status were mostly unaffected by the stroke. However, she no longer excessively regretted past events. Lesions were found in the orbitofrontal cortex, which is involved in feeling regret, and in the adjacent subgenual cingulate area, which is metabolically hyperactive in treatment-resistant depression and is the target for deep-brain stimulation for relief of treatment-resistant depression. The lesions from the stroke may have caused the disappearance of the patient’s treatment-resistant depression by alleviating excessive regret and decreasing the elevated activity in these areas.

This patient’s clinical course may shed light on the neuropsychological and neurophysiological mechanisms of major depression of the melancholic subtype.