Anhedonia after a selective bilateral lesion of the globus pallidus.

Mr. A, a 34-year-old man, came to our outpatient clinic for treatment of a major depressive episode. His history was also notable for polysubstance abuse and dependence in sustained remission, with prior abuse of alcohol, LSD, and other hallucinogens and prior dependence on marijuana, cocaine, opiates, and Ecstasy (MDMA [3,4-methylenedioxymethamphetamine]). He began using alcohol at age 9, marijuana at age 12, cocaine at age 13, opiates at age 20, and Ecstasy at age 21. He had a history of depressive symptoms 6 years earlier in the context of active substance dependence and chronic back pain but had no other prior psychiatric diagnosis or treatment. One year before presentation to our clinic, he had been smoking cocaine daily, using Ecstasy several days a week, and consuming two to 10 alcoholic drinks daily but reported no depressive symptoms. After consuming cocaine, Ecstasy, oxycodone, and methadone at a party, he became aggressive and was brought to an emergency room. There, he ingested all of his remaining methadone to prevent it from being discovered. He reported no suicidal intentions surrounding this ingestion. He became unresponsive, hypoxic, and hypotensive. Mr. A was resuscitated and then stabilized in an intensive care unit over 4 days. After this overdose, Mr. A became acutely depressed. He endorsed a depressed mood, anhedonia, low energy, difficulties concentrating and remembering, feelings of hopelessness and guilt, poor self-esteem, social isolation, increased sleep, and a 20-lb weight gain over the ensuing year. He reported the disappearance of drug cravings and remained abstinent from all recreational drugs other than an occasional glass of wine with dinner. He reported that he no longer experienced pleasure from drinking alcohol. Four serial urine toxicology screens were negative over 6 months. Mr. A developed a resting tremor of his left hand, slight rigidity of his right arm and left leg, and slowing of rapid alternating movements of his left hand, all of which were still present 16 months after the overdose, as assessed by a movement disorders specialist. He had no prior history of neurological problems. A magnetic resonance imaging (MRI) scan of his brain revealed a selective bilateral lesion of the globus pallidus (Figure 1), with clear involvement of the internal globus pallidus on the right and both internal and external globus pallidus on the left. The bilateral lesion was small, selective, and restricted to the globus pallidus. There were no other lesions or findings on the MRI. Comprehensive neuropsychological tests revealed intact cognitive functions, including attention, working memory, and executive function, and an indicated absence of a frontal-subcortical syndrome (Table 1). Basic blood tests, including a CBC, a basic metabolic panel, liver function tests, and thyroid function tests, were all within normal limits at the time Mr. A came to our clinic. There was no known family history of affective disorders or substance abuse.