Brain's Reward Processing Disrupted in Addiction

Pauline Anderson

February 17, 2017

Neural reward processing may be disrupted in patients with addictive behaviors, a new meta-analysis of imaging studies suggests.

Compared with healthy control persons, patients with a gambling disorder (GD) or substance abuse disorder (SUD) showed decreased activation of the striatum, a core region of the brain reward circuit, during "reward anticipation."

But during "reward outcome," when participants received a reward, those with SUD showed increased striatal activation, whereas individuals with GD showed decreased activation, the study found.

The findings are in line with the learning-deficit theory of addiction and contribute enormously to the understanding of this condition, said the lead author of the study, neuropsychologist Maartje Luijten, PhD, who is an assistant professor at the Behavioural Science Institute, Radboud University, the Netherlands.

"All kinds of mechanisms contribute to the continuation of abuse, and one of the factors is that addicted individuals respond differently than normal individuals to the anticipation and outcome of nondrug rewards," Dr Luijten told Medscape Medical News.

The study was published online February 1 in JAMA Psychiatry.

Reward System "Highjacked"

Despite a growing number of evidence-based treatments for SUD, relapse rates remain at about 50% to 60% within a year. For GD, only a few evidence-based treatments are available, and their efficacy has been largely disappointing.

For the study, investigators searched PubMed for studies that included patients with addictive behaviors and a healthy control group who performed a task involving monetary reward anticipation and/or outcome while undergoing functional MRI (fMRI).

The meta-analysis included 25 studies representing more than 1200 individuals. Across studies, patients with addictive behaviors – the GD group and the SUD group, which included those addicted to nicotine, cocaine, alcohol, or cannabis ― and healthy control persons did not differ with respect to age and sex.

One of the most "innovative" aspects of the research was that it involved an image-based meta-analysis, said Dr Luijten. The investigators asked authors of the original articles to provide whole-brain fMRI data so that they could compare in greater detail brain activation in addicted patients and control participants.

The investigators used seed-based d mapping (SDM), which recreates voxel-level maps of effect sizes and their variance, based on input T maps. SDM allows having both positive and negative values in the same map, which provides richer information and allows the computation of standard meta-analytic measures, such as assessments of between-study heterogeneity.

For the reward anticipation phase, the most striking difference between groups was in the bilateral striatum. Those with addictive behaviors – both the SUD group and GD group – showed decreased activation compared to control persons.

Reduced striatal activation during reward anticipation is in line with the reward deficiency syndrome (RDS) theory, the authors note. According to this theory, people with addictions have a deficit in recruiting brain reward pathways, resulting in chronic hypoactivation of these circuits and supposedly reduced pleasurable experience from nondrug rewards.

This reduced activation is also in line with the incentive sensitization theory, according to which addictive behaviors "highjack" the brain's reward system, resulting in reduced striatal responses to nondrug-related cues but increased responses to drug-related cues.

The authors note that activation in the amygdala was increased rather than decreased in individuals with addiction during reward anticipation. The amygdala plays a role in reward prediction and has a reciprocal influence on striatal activity.

Defective Learning

During the reward outcome phase, those with SUD had enhanced responses in the striatum compared to control persons, whereas for those in the gambling group, reduced activation persisted.

The combination of decreased striatal activation during reward-anticipation and increased striatal activation during reward-outcome in SUD patients may be explained best as resulting from defective neural reward learning for nondrug rewards, said Dr Luijten.

"That may explain why SUD patients are not that motivated to seek out nondrug rewards, and they keep on using drugs," she said.

The reduced striatal activation in the GD group during the reward outcome phase might be because all of the studies in the meta-analysis used a monetary reward. Gamblers, whose addiction is related to money, may not be that responsive to a reward of a small amount of money. The authors also note that it is unclear to what extent socioeconomic status might affect striatal responses to monetary rewards in people with GD.

"We suggest that if you want to better compare gamblers with substance abusers, you should use another reward, for example, sweetened juice or erotic scenes," said Dr Luijten.

She recommended that patients with addictions continue to learn appropriate responses to receiving rewards that are not related to drugs. For example, if they remain abstinent, they might receive movie vouchers.

The researchers did not find any evidence that psychiatric comorbidities, such as attention-deficit/hyperactivity disorder or depression, influenced the findings.

"That means that this may be a phenomenon in all types of addicted individuals, with or without psychiatric comorbidities," said Dr Luijten.

In addition, distinguishing those with an active addiction from abstinent individuals did not seem to influence the results substantially. This, the authors note, highlights "the stability of our findings regardless of the addiction phase."

Funnel plots in the striatum showed no evidence of publication bias for reward anticipation. There was only a weak indication of publication bias for reward outcome.

Treatment Implications?

Commenting on the findings for Medscape Medical News, Muhammad Parvaz, PhD, assistant professor of psychiatry, Icahn School of Medicine at Mount Sinai, New York City, noted that although reward processing deficiencies in addictive disorders have been studied using fMRI for more than a decade, those studies have always used small samples.

"This new study is an important step towards harmonizing these results, not only across different addictive substances of abuse but also comparing them with gambling addiction."

The results, added Dr Parvaz, could have consequences for guiding treatment strategies "to alleviate reward processing deficits that may actually be effective across these addictive disorders."

The study was supported by grants from the Netherlands Organization for Scientific Research. The authors have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online February 1, 2017. Abstract

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