Neurocognitive Dysfunctions and Their Therapeutic Modulation in Patients With Methamphetamine Dependence: A Pilot Study

Abstract

Aim: Methamphetamine (MA) abuse and dependence are increasing worldwide and are commonly associated with cognitive deficits. Some studies indicate that such impairments can improve if users become abstinent, but overall results remain inconclusive. Hence, we have performed a longitudinal case-control study investigating key surrogates for attention and impulsive decision-making before and after treatment. Methods: Thirty patients with MA dependence and 24 non-substance-abusing control participants were recruited. Groups were matched on age, sex and education. All subjects performed a baseline assessment to obtain neurocognitive measures of sustained attention and delay discounting. Patients subsequently participated in an MA-specific relapse prevention program including repeated monitoring of relapse status. After 3 months, participants of both groups were reevaluated for neurocognitive performance. Results: At baseline, MA patients showed a significantly higher number of omissions compared to controls, indicative of lower sustained attention. Interestingly, we observed a steep decrease of omissions in MA patients to control-group level post treatment. On the other hand, MA patients discounted delayed rewards significantly stronger than controls, indicating a more impulsive choice behavior both before and after treatment. Limitation: The results should be interpreted with care because of the small sample and short follow-up period. Conclusion: Our data support earlier findings on partial recovery of cognitive deficits in MA patients. They also strengthen the indication for recently recommended psychotherapeutic interventions and may provide a behavioral monitoring tool to inform treatment progress.

Probabilistic Reversal Learning Deficits in Patients With Methamphetamine Use Disorder—A Longitudinal Pilot Study

“…Since the sample size is small and some values had to be imputed, this interpretation should be treated with caution and requires confirmation in larger studies. On the other hand, the results fit plausibly to the existing data: Bernhardt et al (12) showed that sustained attention deficits in patients with MUD could also normalize over a 3-month therapy period. Along those lines, Volkow et al (17) and Wang et al (44) found an improvement in motor and verbal memory.…”

“…As described previously ( 12 ), inpatients provided weekly urine samples, and additional drug screening was performed in cases of clinical suspicion or after prolonged absences (during inpatient stay). Patients were randomly assigned to drug screening with a probability of 1/6 on working days.…”

“…There is considerable evidence for MA-related neurobiological deficits (1,4), including persistent gliosis and apoptosis in dopaminergic and serotonergic neurons (5) and abnormalities in morphology and function of fronto-striatal and limbic regions (6)(7)(8)(9). Functionally, these changes have been linked to a broad range of cognitive impairments (10,11), including multiple domains such as attention control, working memory and executive functions especially decision making (12)(13)(14)(15)(16)(17).…”

“…Studies consistently show that maladaptive and impulsive decision making is common in MUD, where patients favor smaller immediate rewards over larger later rewards (12,(18)(19)(20)(21)(22). Although impulsive choice is influenced by the dynamic interaction of biases in delay and reward magnitude (23), it is unclear whether temporal discounting in MUD reflects deficits in processing and integrating reward contingencies and consequences.…”

“…Although it is clear that SUD is associated with deficits in learning contingencies, a few studies have used PRL paradigms that can mirror these learning impairments in MUD. In addition, studies have shown that changes in cognitive function such as sustained attention can predict treatment outcomes ( 29 , 30 ) or can improve with treatment ( 12 ); however, it is unclear whether addiction-specific treatment can improve longitudinal changes in cognitive flexibility and improve deficits in learning outcome contingencies in MUD.…”