INTRODUCTION
The increasing prevalence of internet usage has led to a surge in internet gaming worldwide [1]. This trend is especially pronounced in Korea, where internet gaming has emerged as a favored leisure activity in the 21st century. However, this growing popularity has given rise to the concerning issue of excessive internet gaming. This excessive gaming can be associated with detrimental effects on psychological and social well-being, and in some instances, the development of psychiatric disorders [2]. The rise in internet gaming parallels the increasing incidence of Internet gaming disorder (IGD) [3], with adolescents being particularly affected and often exhibiting declining engagement in school activities.
There have been many efforts to reveal the mechanism underlying the pathophysiology of IGD. Similar to other addictive disorders, the reward circuit has been proposed as a key mechanism in IGD. Several neurotransmitters are involved in this circuit, with dopamine and serotonin considered primary contributors [4]. A positron emission tomography study in adult males with IGD demonstrated dysregulation of striatal D2 receptors, which was positively correlated with years of excessive gaming [5]. Furthermore, a potential interaction between dopamine D2 and serotonin 5-HT2A receptors has been suggested [5]. The role of serotonin in IGD is also implied by reports of therapeutic benefits of selective serotonin reuptake inhibitors in some patients [6], although it remains uncertain whether these effects are directly mediated by the reward circuit. Additionally, several studies have examined differences in serum brain-derived neurotrophic factor levels between individuals with IGD and controls, but the findings remain inconclusive [7,8].
Cocaine- and amphetamine-regulated transcript (CART) has been investigated as a potential biomarker for addictive disorders. In animal studies, hypoactivity of the CART system was associated with increased vulnerability to drug addiction in specific rat strains [9]. Another study suggested that CART plays a regulatory role in the mesolimbic dopamine system, which is critically involved in the neurobiological mechanisms of addiction [10].
This peptide has been believed to influence reward, reinforcement, feeding behavior, and substance abuse [11]. Previous researches indicate CART’s presence in brain regions associated with reward, motivation, and appetite. In individuals with substance abuse, alterations in CART mRNA and protein expression have been noted in these brain areas [12], with mutations in the CART gene potentially contributing to alcoholism [13]. Although several studies have explored serum CART levels in relation to drug abuse and alcoholism, research on its impact on IGD remains limited. Recently, our research group have reported a decrease in the expression of the serum CART level in young adults with IGD, suggesting the possibility of the CART as a biomarker of IGD [14].
Previous studies have suggested a link between specific personality traits or temperaments and IGD. For instance, adolescent boys with novelty-seeking and harm avoidance traits have a higher likelihood of problematic internet use, similar to girls with less self-directedness and cooperativeness traits [15]. Previous investigations also revealed a correlation between harm avoidance and smartphone addiction [16]. Considering these findings, it is reasonable to hypothesize a connection between personality/temperament and IGD, although current evidence is limited. Some evidence suggests that personality and temperament traits in IGD patients may differ from those in patients with other addictive disorders. A study comparing IGD and alcohol dependence found that alcohol dependence severity correlated positively with harm avoidance scores, whereas IGD severity correlated positively with novelty-seeking scores [17].
In the present study, we investigated the potential differences in serum CART levels between adolescents with IGD and healthy controls (HCs) to clarify the involvement of CART in the pathophysiology of IGD. Additionally, we investigated differences in personality and temperament traits between these two groups, as well as potential correlations between serum CART levels and personality/temperament within the IGD group. Given prior research, we hypothesized that serum CART levels would be lower in the adolescent IGD group, and that these levels would negatively correlate with novelty-seeking and harm-avoidance traits within the IGD group.
METHODS
Participants
A total of 114 adolescents were enrolled in this study; 43 met the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for IGD (mean age, 15.74 years), and the remaining 71 comprised the HC group (mean age, 15.55 years). The participants were recruited from the Catholic University of Korea Seoul Saint Mary’s Hospital. Exclusion criteria for the patient group included any history of chronic physical illnesses, regular medication usage, and coexisting psychiatric disorders such as alcohol and nicotine dependence.
Measures
Junior Temperament and Character Inventory
Both the IGD and HC groups completed the Junior Temperament and Character Inventory (JTCI), assessing temperament and character traits [18]. Each question has a maximum score of 5. Temperament encompasses four dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and reflects the influence of genetics on personality. The character part of the JTCI evaluates the impact of the environment on personality and consists of three dimensions (self-directedness, cooperativeness, and self-transcendence). Higher scores indicate a stronger inclination towards specific temperaments or character traits.
Young’s Internet Addiction Test
The severity of internet gaming addiction was assessed using Young’s Internet Addiction Test (Y-IAT). Y-IAT scores were collected from participants in both groups. Comprising 20 items, the Y-IAT employs a 5-point Likert scale, yielding a total score ranging from 20 to 100. Higher scores indicate a greater likelihood of addiction. Scoring ranges are as follows: 20-39, normal; 40-69, potentially addicted; and ≥70, addicted.
Beck Depression Inventory-II and Beck Anxiety Inventory
The severity of depression and anxiety was assessed using the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively. Both inventories comprise 21 items, with scores ranging from 0 to 3 based on the severity of depression and anxiety symptoms.
Serum CART levels
To measure serum CART levels, 10 mL of blood was collected from each participant into a serum separator tube. After clotting for 30 minutes, the samples were centrifuged at approximately 1,000×g for 15 minutes to obtain the supernatant. The serum samples were treated with protease inhibitor cocktail (Roche) to prevent protein degradation and stored at -80°C until use. An enzyme-linked immunosorbent assay (ELISA) kit (Elabscience) was used to determine serum CART concentrations, following the manufacturer’s instructions.
Statistical analyses
The independent t-test was used to compare demographic data and clinical characteristics between the IGD and HC groups. Pearson’s correlation analysis was performed to assess the association of serum CART levels with temperament and personality traits in the IGD group. A p-value<0.05 was considered significant. All statistical analyses were conducted using SPSS software (version 27; IBM Corp.).
RESULTS
Table 1 presents the demographic and clinical data. Mean age and sex distribution did not differ between the two groups (p=0.506). The IGD group had a higher number of weekly gaming hours, along with significantly elevated Y-IAT, BDI-II, and BAI scores, compared to the HC group.
The IGD group exhibited a significantly lower serum CART level compared to the HC group (p=0.031) (Figure 1). We also investigated temperament and personality traits in both groups. In the IGD group, there were markedly higher levels of novelty seeking and harm avoidance, while levels of persistence, self-directedness, and cooperativeness were significantly lower than in the HC group.
Correlation analyses were also undertaken to examine the relationship between CART levels and other clinical characteristics in the IGD group. Notably, no significant correlations emerged between CART levels and clinical parameters, including weekly gaming hours, Y-IAT scores, BDI-II scores, and BAI scores. However, a significant correlation was observed between serum CART levels and cooperativeness (p=0.003) (Figure 2). No significant correlations were identified between CART levels and other temperament or personality traits.
DISCUSSION
Our study aimed to investigate the potential role of CART in the pathophysiology of IGD among adolescents by analyzing relevant clinical characteristics. We first compared CART levels and various clinical parameters between the IGD and HC groups. Additionally, we examined differences in temperament and personality traits between these two groups.
Adolescents diagnosed with IGD exhibited notably lower CART levels compared to the HC group. This suggests that CART levels, previously linked primarily to drug addiction, may also be associated with IGD in adolescents. Recently, decreased serum CART levels were reported in young adults with IGD [14]. Furthermore, there were no relationships between reduced CART level and severity of IGD, indicating that decreased serum CART level could be a trait marker for developing IGD [14]. In this study, the reduction of serum CART level did not show a significant correlation with the severity of addiction in adolescents with IGD as well. Therefore, the results of this study support the possibility that low blood CART levels might reflect a propensity not only for substance addiction but also for other behavioral addictions, such as IGD, suggesting CART as a candidate biomarker which could be used for development of therapeutics in addictive disorders.
Our exploration of temperament and personality traits sought to identify tendencies more common in adolescents with IGD. Notably, the IGD group displayed higher novelty seeking and harm avoidance scores. This suggests that adolescents with a disposition for seeking novel stimuli may be more susceptible to developing IGD. Moreover, adolescents with a stronger inclination toward harm avoidance might struggle to suppress the urge to engage in internet gaming when confronted with unpleasant situations, such as heavy academic workloads. This interpretation aligns with the comparatively lower persistence and self-directedness scores of the IGD group.
In this study, the correlation between novelty seeking or harm avoidance and CART levels did not reach statistical significance, which contrasts with our initial hypothesis. One possible explanation is the relatively small sample size, raising the likelihood of a type II error; with a larger cohort, the association might have emerged more clearly. However, caution is warranted in interpreting this null finding solely as a sample size limitation. An alternative explanation is that the neurobiological pathways underlying elevated novelty seeking or harm avoidance traits may be independent from the mechanisms associated with CART level reduction in adolescents with IGD. This possibility highlights the need for further research to disentangle the complex relationships between personality traits and neurobiological markers in IGD.
However, the notable finding of our study was the correlation between cooperativeness and CART levels. Previous studies have indicated that adolescents with IGD often lack effective social skills, potentially due to inadequate familial support that hampers understanding of family dynamics, which closely relates to the development of cooperativeness [19]. While the relationship between cooperativeness and dopaminergic activity requires further exploration in human studies, recent animal studies have found some evidence for this link. A mouse study revealed that higher dopamine neuron activity in the ventral tegmental area corresponded with increased social interaction [20]. While the correlation between cooperativeness and the dopamine pathway requires further investigation, our findings suggest that dopaminergic activity might have diverse effects on temperament and personality traits.
Another possible explanation for the observed correlation between cooperativeness and CART levels is that it may be mediated through the serotonergic rather than the dopaminergic system. Although direct evidence linking CART and serotonin in IGD is limited, animal studies have reported associations between CART and 5-HT4 receptor regulation in appetite control [21], as well as a potential relationship between CART and 5-HT2A receptors [22]. Taken together, these findings suggest that CART may influence cooperativeness via the serotonergic system rather than the dopaminergic system in individuals with IGD. This, in turn, may imply that CART contributes to reward circuit functioning through serotonergic pathways in IGD. Nonetheless, given the lack of human studies to date, these interpretations remain speculative and require further empirical validation.
Numerous studies have explored the link between CART levels and the likelihood of developing drug addiction, yet research on the correlation between CART levels and IGD remains limited. Moreover, investigations into this relationship specifically among adolescents with IGD are lacking. Given that a significant proportion of IGD cases emerge during adolescence, identifying predictive factors for IGD is important. Our study suggests that the blood CART level has potential in this regard. Additionally, considering the distinct differences in temperament and personality traits between our IGD and HC groups, it is plausible that CART levels are linked to the development of specific types of temperament or personality traits. However, this association requires further exploration.
There were several limitations to our study. While the sex ratio did not show a significant group difference, the relatively small number of female should be taken into account and addressed in future investigations. Additionally, the study only enrolled adolescents, potentially limiting the generalizability of the results to the broader Korean and worldwide populations.
In conclusion, our study revealed lower serum CART levels among IGD adolescents. These adolescents also exhibited a greater tendency toward novelty seeking and harm avoidance, while exhibiting diminished cooperativeness; this could impact interpersonal relationships. Although no significant correlation emerged between CART levels and other personality or temperament scale scores, a noteworthy finding was the significant association between CART levels and cooperativeness in IGD adolescents as it could relate to interpersonal relationships. These findings suggest that serum CART levels may serve as a neurobiological marker for the potential risk of IGD in relation to cooperativeness in adolescents.
PDF Links
PubReader
ePub Link
XML Download
Full text via DOI
Download Citation
Print
