Effect of green tea on reward learning in healthy individuals: a randomized, double-blind, placebo-controlled pilot study
© Zhang et al.; licensee BioMed Central Ltd. 2013
Received: 28 January 2013
Accepted: 31 May 2013
Published: 18 June 2013
Both clinical and preclinical studies revealed that regular intake of green tea reduced the prevalence of depressive symptoms, as well as produced antidepressant-like effects in rodents. Evidence proposed that disturbed reward learning has been associated with the development of anhedonia, a core symptom of depression. However, the relationship between green tea and reward learning is poorly investigated. Our goal was to test whether chronic treatment with green tea in healthy subjects affects the process of reward learning and subsequently regulates the depressive symptoms.
Seventy-four healthy subjects participated in a double-blind, randomized placebo-controlled study with oral administration of green tea or placebo for 5weeks. We used the monetary incentive delay task to evaluate the reward learning by measurement of the response to reward trial or no-reward trial. We compared the reaction time of reward responsiveness between green tea and placebo treatment. Furthermore, we selected Montgomery-Asberg depression rating scale (MADRS) and 17-item Hamilton Rating Scale for Depression (HRSD-17) to estimate the depressive symptoms in these two groups.
The results showed chronic treatment of green tea increased reward learning compared with placebo by decreasing the reaction time in monetary incentive delay task. Moreover, participants treated with green tea showed reduced scores measured in MADRS and HRSD-17 compared with participants treated with placebo.
Our findings reveal that chronic green tea increased the reward learning and prevented the depressive symptoms. These results also raised the possibility that supplementary administration of green tea might reverse the development of depression through normalization of the reward function.
KeywordsGreen tea Depression Reward learning Anhedonia
Green tea (Camelia sinensis) is one of the most popular beverages in both eastern and western world. Increasing evidence indicates that green tea extracts as well as their main component, the polyphenol epigallocatechin gallate (EGCG), has multiple health benefits, such as the anti-stress, anticancer and antioxidants effects [1–4]. In particularly, a recent investigation found that higher consumption of green tea led to a lower prevalence of depressive symptoms in elderly Japanese individuals . Additionally, a preclinical study demonstrated that green tea exerted antidepressant-like effects in a mouse behavioral models of depression, and the mechanism may involve inhibition of the hypothalamic-pituitary-adrenal (HPA) axis . These findings suggested that there might be a link between green tea consumption and the depressive symptoms. However, the underlying mechanism mediating in the treatment of green tea for depression in the clinic is poorly investigated.
Anhedonia is a core characteristic usually seen in depressed patients and is widely used to evaluate the treatment outcome of depression [7–9]. Impairment of reward learning is associated with a number of psychiatric disorders in humans including depression . Anhedonia is also linked with reduced pleasure, altered motivation and disturbed reward learning [11, 12]. Additionally, the reduced reward function was associated with the persistence of anhedonia in depressed subjects . We hypothesize that chronic treatment with green tea would improve the reward learning compared with control subjects.
The monetary incentive delay (MID) task is usually used to assess the effort-related aspects of central reward processing for investigations of the relationship between depressive behavior and impairments in reward learning in depression . Therefore, we hypothesized that green tea might play a critical role in modulation of reward learning and contribute to the phenotype of depressive symptom. The major goal of the current study was to evaluate the effects of green tea on reward learning and clinical outcome of depression after 5 weeks of treatment.
Demographic characteristics of participants
Age (mean, sd)
24.55, 4.74 y
26.79, 4.48 y
Education (mean, sd)
16.14, 2.29 y
16.42, 2.67 y
MADRS (mean, sem.)
HRSD-17 (mean sem.)
Major tea polyphenols and the amounts present in the powder used in the current study
Monetary incentive delay (MID) task
The MID task was applied with previous reports [14, 20] with a minor modification and was consisted of 30 potentially reward trials, 30 no-reward trials, and 30 periods of fixation with an overall mean duration equal to trials. In total, trials lasted between 7.5 and 10.5 sec (mean: 9 sec). Thus, the total duration of the task was 13.5 min. Cues signaled potentially reward outcomes (red circle), or no-reward outcomes (green circle). Cue was presented with a variable duration for 4.5 – 9.5 sec (mean 7 sec) of each trial. On incentive trials, participants could win or avoid losing money by pressing the button during target presentation. When the target was pushed in a rewarding trial, participants earned 1 Yuan. Subjects were informed that they would receive one-third of the money they won during the MID in each session after completion of the study. Twelve practice trials were used to determine the shortest reaction time to a target of the subjects. The presentation time of the target was regulated according to the practice data to ascertain an equal feedback response and a similar total monetary reward for all subjects. The reaction time (ms) to reward and no-reward stimuli were recorded by the computer during each trial.
The written informed consent was sent to the participants before the study. The scores of MADRS and HRSD-17 were measured as the baseline level. The next day, the participants were randomly divided into two groups based on their sequence of enrolment in the study and were treated with green tea powder or placebo, respectively. The green tea powder and the placebo (pure microcrystalline cellulose) were packed at the weight of 400 mg of each package. The green tea powder or placebo was dissolved in hot water and was taken 30 min after each meal (three times per day) for consecutive five weeks. Both the participants and the observers of the behavioral assessment were blind on the assignment of the experiment. One day after the last intake of green tea, participants were evaluated by MADRS and HRSD-17. Subsequently, the monetary incentive delay task was introduced into the participants and the reaction time (ms) to reward and no-reward stimuli were recorded by the computer.
Data are expressed as mean ± SEM. The statistical analyses of the reward learning and depressive behavioral data in green tea and placebo-treated subjects were performed using repeated-measure ANOVA. Values of p<0.05 were considered statistically significant.
Effect of green tea on the reaction time in the monetary incentive delay task
Effect of green tea on the scores of MADRS and HRSD-17
Our results showed that oral administration of green tea increased the reward-learning ability compared with control group in healthy young volunteers. Moreover, participants treated with green tea showed reduced scores measured in MADRS and HRSD-17 compared with placebo. With the evidence that anhedonia influence reward decision-making, we propose that green tea would probably have the potential for normalization of anhedonia through improve reward learning and have implications for the prevention of depression.
A recent study showed that green tea extract treatment can reduce hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in response to stress in mice . Systemic administration of lipopolysaccharide (LPS) could induce depression in the forced swimming-induced despair behaviour model in mice. Pretreatment with green tea extract prevented LPS-induced immobility in a dose-dependent manner via COX-2 inhibition . Clinically effective antidepressant medications exert their therapeutic actions partially by modulating HPA function through the regulation of receptor expression, subsequently ameliorating many of the behavioral disturbances associated with depressive-like states [26, 27]. A further research is needed to determine the regulatory effect of green tea on glucocorticoids receptors expression and the target genes involved in the reward learning process and the improvement of depressive symptoms. Furthermore, a significant antidepressant-like effect was detected in mice that received a single intraperitoneal injection of green tea in the forced swim test when compared with the control . A cross-sectional study revealed that higher green tea and coffee consumption was associated with a lower prevalence of depressive symptoms, suggesting that higher consumption of green tea, coffee and caffeine may confer protection against depression .
Anhedonia has long been presumed as a core feature of major depressive disorder based on the Feighner criteria in 1972 . The American Psychological Association defines anhedonia as “report feeling less interest in hobbies, not caring anymore, or not feeling any enjoyment in activities that were previously considered pleasurable” . Anhedonia and depressed mood are two required symptoms for a diagnosis of major depressive disorder [31, 32]. It has been indicated previously that anhedonia is associated with impaired reward learning in depressed patients . We confirmed that chronic treatment with green tea can improve the reward learning compared with baseline in healthy subjects at time of inclusion. Our results showed that oral administration of green tea increased the reward-learning ability compared with placebo.
It was proposed thirty years ago that dopamine deficiency and the reduction in dopamine (DA) transmission were involved in anhedonia, in individual’s experience of pleasure and in response to rewarding stimuli [33–36]. The mesolimbic and nigrostriatal DA system appears to be related primarily to reward system function and responsiveness to the environment . In clinic, there is no effective intervention for anhedonia Although there are medications that alleviate several depressive symptoms, the current used pharmacotherapies (e.g., SSRIs) do not adequately address motivational and reward-processing deficits in depression [37–39]. It has been reported that the active component of green tea, EGCG, inhibited psychostimulants-induced hyperactivity in part by modulating dopaminergic transmission . Additionally, the findings from epidemiological studies revealed that consumption of green tea was inversely correlated with neurodegenerative diseases including Parkinson's disease. The further investigation showed that EGCG produced a protective effect against dichlorodiphenyl-trichloroethane (DTT)-induced cell death, and that prior exposures to EGCG activate an endogenous protective mechanism in the dopaminergic cells, which is believed to play a causative role in the etiology of Parkinson's disease . Moreover, EGCG also could reduce oxidative stress and neurotoxicity in different model systems of Alzheimer's disease and modulate the expression of cell survival and cell death genes .
In recent years, there has been considerable interest in investigating the neuroprotective effects of green tea polyphenolic constituent with its biological and pharmacological activities relevant to human health . A previous study a mouse behavioral model showed that green tea exerts antidepressant-like effects, and the underlying mechanism may involve inhibition of the HPA axis . Psychological stress activated HPA which resulted in the increasing release of glucocorticoids. It was also found that EGCG also could ameliorate the cognitive impairments induced by psychological stress possibly related with the declining glucocorticoids levels and the increasing contents of catecholamines and 5-HT . Whether the increased reward-learning activity induced by chronic green tea administration is due to the regulation on neuroendocrinology systems, such as HPA function, requires future investigation.
Regular dietary intake of green tea can maintain a stable concentration in the body and may have valuable effects on health. However, drinking a beverage containing green tea extract too much can lead to hepatotoxicity [44–46]. The hepatotoxicity is probably due to EGCG or its metabolites which, under particular conditions related to the patient's metabolism, can induce oxidative stress in the liver [47–49]. Therefore, the toxicity should be taken into consideration in the condition of high oral consumption of green tea polyphenols. Additionally, the baseline amount of tea consumed in participants was screened before enrolment, and the participants whose daily intake of tea was more than three cups were excluded from the study. In the current study, the difference of baseline amount of tea in two groups was not significant. Therefore, the data in this experiment cannot be explained by an under measurement of effect.
In summary, our results indicate that chronic treatment of green tea increased reward learning compared with placebo in monetary incentive delay task and reduced total scores in Montgomery-Asberg depression rating scale and 17-item Hamilton Rating Scale for Depression. Reward-learning deficits contributed to the anhedonic symptoms and the treatment outcome of depression. The current findings suggest that reduced reward learning might associate with the presence of depression. The regulatory role of green tea on the reward learning raised the potential for development of new treatments for depression by selecting complementary options.
Monetary incentive delay
Montgomery-Asberg depression rating scale
17-item Hamilton rating scale for depression.
This work was supported by the National Natural Science Foundation of China (No.81270720).
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