Anhedonia After a Selective Bilateral Lesion of the Globus Pallidus

Abstract

Case Presentation 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

Association of PTPRB gene polymorphism with drug addiction

“…Long-term changes have been observed in the globus pallidus in narcotic addiction [Pearson et al, 1976]. Recent studies showed that the ventral tegmental area (VTA) project fibers to the globus pallidus as well as the nucleus accumbens (NAc), and NAc cells subsequently project to the ventral globus pallidus [Kalivas et al, 1999;Berridge, 2003;Wise, 2004;Miller et al, 2006]. The present data identified a possible expansion of LD blocks in the PTPRB 5 0 flanking region and near Ser127Gly (Fig.…”

Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue

“…However, a potential side effect of DBS in Parkinson's disease is the onset of apathy which is believed to be secondary to decreased pallidal responsivity, a finding in agreement with our observation of increased symptoms of fatigue in the context of reduced pallidal responses to reward stimuli. Similarly, a consistent body of clinical data on cerebrovascular insults has associated apathy with a disruption of the normal activity of the GPi and its related thalamo-frontal and prefrontal circuits [37], [38], characterized by the inability to initiate thoughts or behaviors [39]. Finally, studies from the animal literature strongly implicate the globus pallidus in reward, motivation, and effort-related choice behavior [40]–[42], all processes that have been found to be critically affected in CFS patients.…”

Disentangling pleasure from incentive salience and learning signals in brain reward circuitry

“…We suggest that these VP neuronal signals for reward components could be related to reports of activity in human posterior VP positively correlated with pleasant food images (17) and mechanisms by which opioid and related stimulation in a VP hotspot can modulate the hedonic impact of sensory rewards (33,36,77). Conversely, one could speculate that impairment of hedonic signals in NAc-VP pathways could contribute to clinical manifestations of anhedonia or incentive motivation impairment in depression and related disorders (78) or to dysphoria after lesions encroaching on the VP hotspot (79)(80)(81).…”