Abstract
Objective
Creativity drives both individual progress and societal development. With the development of the gene-environment interaction theory, investigating the physiological and psychological mechanisms underlying creativity has become increasingly essential. Grounded in Bronfenbrenner’s ecological systems theory, this study employs the gene-environment (G × E) paradigm to investigate the interaction between serotonin system genes and the parent–child relationship in influencing adolescent creativity.
Methods
In study 1, questionnaire surveys and DNA genotyping techniques were used to select a sample of 707 middle school students (Mage = 13.95, SD = 0.42). The 5-HT MGPS was constructed by including TPH2 rs4570625, SLC6A4 rs1042173, 5-HTR1A rs6295, and MAOA rs6323 genes to examine the interaction between the parent–child relationship and 5-HT MGPS in influencing adolescent creativity. In study 2, a behavioral experiment on creativity was conducted as supplementary data to further validate the robustness of the interaction between the parent–child relationship and 5-HT MGPS in predicting creativity.
Results
(1) Parent–child relationship positively predicts adolescent creativity; (2) Data from both questionnaires and behavioral experiments indicate that the interaction between parent–child relationship and 5-HT MGPS predicts creativity; (3) The results of regions of significance test support the hypothesis that the interaction pattern between parent–child relationship and 5-HT MGPS aligns with the differential susceptibility model.
Conclusions
These findings highlight the critical role of the interaction between genetic and environments on creativity. Furthermore, the interaction pattern between the parent–child relationship and 5-HT MGPS aligns with the differential susceptibility model, suggesting that the environment can moderate the influence of genetic factors to a certain extent.
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Introduction
From Isaac Newton’s formulation of the law of universal gravitation, allegedly inspired by a falling apple, to Steve Jobs’ design of the iPhone, innovation has consistently propelled societal and national progress. As a core manifestation of innovation, creativity plays a crucial role in both individual and collective development1. Creativity refers to a cognitive ability defined by the capacity to generate ideas, solutions, or products that are both novel and practical17. Notably, creativity is influenced not only by environments but also by genetic factors, which play a significant role23. Consequently, it is crucial to comprehensively consider both genetic and psychological factors and investigate their interactive effects on adolescent creativity.
The influence of parent–child relationship on creativity
According to Bronfenbrenner’s Ecological Systems Theory, the family serves as a fundamental component of people’s ecological systems7. As the early and most influential microenvironment, the family—particularly the parent–child relationship—shapes both physical and psychological development from birth. A study conducted in China indicated that primary school students with closer relationships with their parents exhibited higher creativity55. Similarly, Jankowska and Gralewski21 found that positive parenting style promote the development of creativity in children.
Nonetheless, previous studies have not consistently supported the finding. A study in China found a negative association with parent–child relationships and adolescent creativity, suggesting that higher parent–child relationships may predict lower creativity levels48. The contradictory result may be due to the omission of genetic factors, as most previous studies focused on environmental influences (Jankowska & Gralewski et al., 2024). Based on this, the present study will integrate serotonin system genes, which are highly correlation with creativity, to examine how gene-environment interactions influence adolescent creativity. Additionally, this study proposed the parent–child relationship is a significant predictor of creativity in adolescents.
The influence of serotonin system genes on creativity
Serotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter essential for regulating various psychological processes, including emotion, cognition, and reward22. Advancements in molecular genetics have increasingly emphasized the role of 5-HT in influencing individual creativity (See Fig. 1)18,24. A genome-wide study in Finland showed the association between 5-HT, creativity, and musical ability44. Moreover, single nucleotide polymorphisms (SNPs) within serotonin system genes influence the functioning of the prefrontal cortex (PFC), a critical brain region responsible for higher-order cognitive functions, including creative thinking34,38. 5-HT is extensively distributed across the prefrontal cortex, where its endogenous release modulates the expression of serotonin receptor genes, thereby shaping emotional regulation, cognitive processing, and reward33.
The Neurobiological Foundation of Creativity24.
The dual pathway model of creativity suggests that producing creative outcomes relies on both cognitive flexibility and goal-directed thinking25. The 5-HT-PFC circuit is a crucial neural pathway that regulates both cognitive flexibility and goal-directed behavior. Recent studies in mice have shown that 5-HT release in the PFC significantly enhances cognitive flexibility, a critical component of creativity30. While prior research has identified specific loci within the serotonin system associated with individual creativity, most studies have primarily focused on single genes20,58. Given that 5-HT regulation in the human body involves a complex interplay of synthesis, transport, receptor mediation, and breakdown—each influenced by different 5-HT genes—a more comprehensive multi-gene method is essential. Therefore, this study will examine key genes and loci involved in human creative process.
The expression levels and enzymatic activity of TPH2 play an essential role in determining serotonin production in the brain32. The T allele at rs4570625 has been identified as a sensitivity allele, with carriers demonstrating higher creativity levels in positive environments41,57. Meanwhile, the SLC6A4 gene encodes the serotonin transporter protein, a key regulator of serotonin availability and neurotransmission19. Studies have found a link between the SLC6A4 gene and creative performance, particularly in dance, suggesting that variations in the serotonin pathway may facilitate creative expression in artistic domains2,31. Furthermore, Resnick et al.35 found that the T allele at the rs1042173 locus of the SLC6A4 gene represents a sensitivity allele, with mutations at this locus impacting cognitive functioning.
In addition, the 5-HTR1A gene serves as a key receptor in serotonin’s interaction with its target sites. By regulating neuronal excitability and signal transduction, 5-HTR1A is related to emotion, cognition, and behavior37. Toshchakova et al.43 found that the G allele at the rs6295 locus of the 5-HTR1A gene is associated with increased creativity and cognitive flexibility. Finally, monoamine oxidase A (MAOA) is responsible for the breakdown of serotonin in the human body16. The G allele of the MAOA gene as a sensitivity allele, with carriers of the high-activity MAOA genotype (G allele) exhibiting reduced cognitive flexibility under adverse environmental conditions, which can negatively impact creative thinking42.
The influence of the interaction between serotonin system genes and parent–child relationship on creativity
For decades, with the advancement of gene × environment theory, it has become increasingly important to investigate the effects of gene-environment interactions on psychological development. Creativity, as an ability highly correlated with neural system, is influenced by both environmental and genetic factors45. In previous studies, creativity has been shown to be influenced by a combination of family factors and inherited genes59. A study among Chinese college students found that the interaction between family environment and 5-HT could predict the creativity56. Yu et al.51 found that the interaction between the TPH1 gene rs623580 polymorphism in the serotonin system and the father’s parenting style could predict adolescent creativity. The more negative the father’s parenting style, the lower the creativity level of individuals carrying the risk genotype of rs623580. Thus, we propose that the parent–child relationship and serotonin system genes jointly determine the level of people’s creativity development, and their interaction can predict creativity.
Notably, it is important to investigate the impact of the interaction between genes and the environment on creativity, but it is also necessary to further illustrate the specific interaction patterns between genes and the environment. That is, whether the influence of 5-HT genes on creativity will change with the variation of parent–child relationship. Nowadays, two primary models explain gene-environment interactions: the diathesis-stress model and the differential susceptibility model. The diathesis-stress model suggests that individuals carrying risk genotypes are more susceptible to adverse outcomes when exposed to negative environmental factors9,29. However, the differential susceptibility model suggests that individuals with the same genotype may perform worse in negative environments but better in positive ones5.
In most cases, the environment is a factor that can be changed, which indicates that the influence of genes on individual psychology is not actually fixed. Compared to genetic factors, the parent–child relationship is more controllable. As a result, individuals with the same 5-HT genes genotype may follow different developmental trajectories depending on their environmental experiences54. Therefore, an increasing number of researchers emphasize that the differential susceptibility model provides a better explanation for gene-environment interactions3,53. Additionally, Sun et al.41 found that the interaction between maternal authoritative parenting and the TPH2 gene rs4570625 within the serotonin system predicts creativity, and the interaction pattern conforming to the differential susceptibility model. Based on this, we hypothesize that the gene × environment interaction conform the differential susceptibility model.
Current study
Most previous studies have focused on the influence of single nucleotide polymorphisms on psychology and behavior, providing valuable insights into the occurrence patterns of psychological and behavioral traits. However, the limitations of single-gene research are becoming increasingly apparent, particularly in terms of low effect sizes, limited result reliability, and the inability to capture additive genetic effects. In contrast, the multilocus genetic profile score (MGPS) method can obtain stronger genetic effects and enhance the interpretability of results. Based on this, the present study examines how the interaction between multiple serotonin system genes and the parent–child relationship influences adolescent creativity, aiming to illustrate the mechanisms of creativity from both physiological and psychological perspectives. The following hypotheses are proposed:
Hypothesis 1
The parent–child relationship can predict adolescent creativity.
Hypothesis 2
The interaction between parent–child relationships and 5-HT MGPS can predict adolescent creativity.
Hypothesis 3
The interaction pattern between parent–child relationships and 5-HT MGPS aligns with the differential susceptibility model.
Study 1: The influence of multiple genes × environment interaction on adolescent creativity
Objective
This study investigates the effects of parent–child relationships, 5-HT MGPS, and their interaction on adolescent creativity using both questionnaire methods and genotyping techniques. Additionally, the study examines whether the gene × environment interaction pattern aligns with the differential susceptibility model.
Participants
Research on the interaction between genes and the environment, Starr et al.39 suggested that when the interaction between genes and the environment reaches a significant level (0.05), the effect size is generally 0.01 to 0.02. Thus, we used G*Power 3.1.9.2 to calculate the sample size before the survey and the results showed that 395 and 787 participants were needed. The participants in this study were recruited from a middle school in Changsha City, Hunan Province, and the survey was conducted in June 2022. The study was approved by the school’s Ethics Committee, and the research procedures underwent thorough review by professionals to ensure the protection of participants’ rights. A total of 731 questionnaires were collected. After eliminating invalid samples, 707 valid samples remained (Mage = 13.95 SD = 0.42). Among the participants, there were 338 females (47.8%) and 369 males (52.2%).
Methods
Parent–child relationship
Parent–child Intimacy Questionnaire (PCIQ) prepared by Buchanan et al.8 was adopted. The scale includes two dimensions of father-child relationship and mother–child relationship, with a total of 18 items (e.g., you feel close to your father/ mother), using Likert 1–5 points score, from 1 to 5 is “strongly disagree” to “strongly agree”, the higher the score is, the closer the father-child relationship/mother–child relationship. In this study, the Cronbach’s α coefficient of the father-child relationship subscale was 0.93. The Cronbach’s α coefficient of the mother–child relationship subscale was 0.92.
Creativity
The Chinese version of the Creativity Self-Report Scale revised by Yu et al.52, which includes 24 items (e.g., I often have some unconventional ideas), is scored using Likert5 points, from 1 “never” to 5 “always”. The scale includes three dimensions, namely fluency, originality and flexibility. The higher the score, the better the individual’s creative tendency and skills in thinking. In this study, the Cronbach’s α coefficient of each subscale was 0.79, 0.85, 0.86, respectively, and the Cronbach’s α coefficient of the total scale was 0.93.
Saliva sample collection, DNA extraction and genotyping
After the saliva samples were collected, the technicians from the biological company will pack the samples in sample boxes and send them back to the Lab. Then, the samples would undergo DNA extraction and purification using the imLDRTM multiplex SNP typing kit. The DNA extraction and genotyping were conducted on rs4570625, rs1042173, rs6295 and rs6323. The specific PCR primer information is presented in Supplementary Table 1. PCR reaction conditions are as follows: 95 °C for 2 min; 94 °C for 20 s, 65 °C for 40 s, and 72 °C for 1.5 min, with total 11 cycles; 94 °C for 20s, 59 °C for 30s, 72 °C for 1.5 min. With total 24 cycles; finally, 72 °C for 2 min. After single base extension reaction, genotyping was conducted using GeneMapper 4.1 software. The detection platform and technology used in this study had high reliability (genotyping efficiency being greater than 98%).
Statistical analyses
First, potential common method bias in the questionnaires was assessed using Harman’s single-factor test. Additionally, The Hardy–Weinberg equilibrium test and Minor Allele Frequencies test were conducted for the 5-HT genes to ensure the genetic sample’s representativeness. Next, the 5-HT multilocus genetic profile score (5-HT MGPS) was calculated by summing the functional impact of individual SNPs, assigning a score of 1 to each sensitivity allele. As the number of sensitivity alleles increased, the MGPS score correspondingly increased40.
Correlation analyses and gene × environment interaction tests were then conducted to examine the relationships between genetic and environmental variables and their effects on adolescent creativity. The Regions of Significance (RoS) method was applied to evaluate whether the gene × environment interaction pattern aligns with the differential susceptibility model. Finally, sensitivity analyses were performed in three stages: (1) Testing gene × environment interaction effects at each independent locus, (2) Constructing (n−1) MGPS models to evaluate interaction effects, and (3) Conducting internal consistency checks to ensure the reliability of the results.
Results
Data availability analysis
Common method bias test
Given that the data were self-reported, Harman’s single-factor test was used to assess potential common method bias. Exploratory factor analysis identified seven factors with eigenvalues greater than 1, with the first factor explaining 29.44% of the variance—well below the critical 40% threshold—indicating no severe common method bias.
Genotype distribution, Hardy–Weinberg equilibrium test and minor allele frequency
The genotype distributions for the serotonin system gene loci were as follows: rs4570625: T/T = 230 (32.5%), T/G = 331 (46.8%), G/G = 146 (20.7%); rs1042173: C/C = 443 (62.7%), C/A = 234 (33.1%), A/A = 30 (4.2%); rs6295: C/C = 411 (58.1%), C/G = 259 (36.6%), G/G = 37 (5.2%); rs6323: G/G = 336 (47.5%), T/G = 164 (23.2%), T/T = 207 (29.3%). Since the MAOA gene is located on the X chromosome, Hardy–Weinberg equilibrium (HWE) tests were conducted only for the three autosomal loci. The results indicated that the observed genotype frequencies did not significantly deviate from the expected distributions: rs4570625: χ2 = 1.78, p = 0.18; rs1042173: χ2 = 0.02, p = 0.90; rs6295: χ2 = 0.21, p = 0.64.
The Minor Allele Frequencies (MAF) for the loci were: THP2 rs4570625: 0.44; SCL6A4 rs1042173: 0.21; 5-HTR1A rs6295: 0.24; MAOA rs6323: 0.59. These MAFs closely match the 1000 Genomes (Chinese Han) and 1000 Genomes (East Asia): THP2 rs4570625: 0.47 (0.44); SCL6A4 rs1042173: 0.21 (0.18); 5-HTR1A rs6295: 0.24 (0.20); MAOA rs6323: 0.38 (0.42). These results confirm the appropriateness of the genetic sampling in this study.
The calculation of multilocus genetic profile score
The serotonin genetic profile score (MGPS) is an approach inspired by previous research40, whereby it is computed by encoding the presence (1) or absence (0) of sensitive genotypes for SNPs. The individual SNP codes are summed, and higher MGPS values reflect higher environmental sensitivity. The computational formula is: MGPS = \(\sum_{i=0}^{N}({G}_{i} \times {\beta }_{i})\). N represents the number of SNPs used for calculation. \({G}_{i}\) is the allele count of an individual at the \(i\)—th SNP. \({\beta }_{i}\) is the weight assigned to this SNP based on the study’s findings.
Descriptive statistics and correlation analysis
Table 1 showed the descriptive statistics and correlation analysis results of each variable. Single gene locus of 5-HT system was not correlated with environmental variables. This reflects the gene, and environmental factors are independent of each other, which conforms to the research paradigm of genetic and environmental interaction13. In addition, the parent–child relationship has a significant positive association with adolescent creativity.
The influence of gene × environment interaction on adolescent creativity
The continuous variables were standardized before analysis. A hierarchical regression was performed with creativity as the dependent variable, while the independent variables included the parent–child relationship, the multilocus genetic profile score (MGPS) of the serotonin system, and their interaction term. To control for Type I errors, p-values were adjusted using the Holm-Bonferroni correction6. The results indicated that the parent–child relationship was a significant positive predictor of adolescent creativity (β = 0.26, p < 0.001, 95% CI = [0.19, 0.33]). Additionally, the interaction between the parent–child relationship and the 5-HT MGPS significantly predicted creativity in adolescents (β = 0.16, p < 0.001, 95% CI = [0.09, 0.23]), with this effect remaining significant after Holm-Bonferroni correction. When the 5-HT MGPS and gene-environment interaction were not included, the R2 of the benchmark model was 0.059. After including the gene-environment interaction, the ΔR2 was 0.024.
To further illustrate the gene-environment interaction, a simple slope analysis was conducted. In the low 5-HT MGPS group, parent–child relationship positively predicted creativity (β = 0.10, p = 0.03, 95% CI = [0.01, 0.20]), and in the high 5-HT MGPS group, this positive prediction effect was stronger (β = 0.41, p < 0.001, 95% CI = [0.31, 0.52]) (see Fig. 2a). Notably, individuals with high 5-HT MGPS showed low levels of creativity in a negative parent–child relationship environment, but they could show high levels of creativity in a positive parent–child relationship environment. These findings provide partial support for the differential susceptibility model. Additionally, the Johnson-Neyman technique was applied to further investigate the moderating role of 5-HT MGPS. The Johnson-Neyman plot (see Fig. 2b) indicated that when the MGPS standard deviation exceeded − 1.04, the positive predictive effect of the parent–child relationship on adolescent creativity became increasingly pronounced as MGPS scores increased.
G × E Simple Slope of Adolescent Creativity. (a) is a simple slope plot of G × E; (b) is the Johnson-Neyman slope plot of G × E; PCR is parent–child relationship, the same below.
Sensitivity test
The effect of single gene-environment interactions on adolescent creativity
First, regression analyses were conducted to examine the interaction effects of single gene loci with the environment on creativity. The results revealed that only the interactions between the TPH2 gene rs4570625 and the MAOA gene rs6323 with the environment significantly influenced adolescent creativity (β = 0.15, p < 0.05; β = 0.16, p < 0.01), while the interactions involving other gene loci were not significant. This finding suggests that the cumulative genetic score approach offers a more robust genetic explanation for creativity compared to single-gene studies.
The effect of 5-HT (n−1) MGPS and environment interaction on adolescent creativity
One gene locus was removed at a time, calculating 4 independent 3-locus MGPSs, to examine their interaction with the environment on creativity. The results showed that removing any single gene locus did not alter the significance of the (n−1) MGPS and environment interactions, all of which remained significant. This result indicates that the MGPS method provides more robust and reliable genetic explanations compared to single-gene studies.
Internal consistency analysis
Internal consistency analysis aims to verify whether the results are consistent across different subsamples53. The participants were randomly divided into two subsamples, Subsample 1 (N = 356) and Subsample 2 (N = 351). There were no significant differences between the two subsamples in terms of gender (χ2 = 0.03, p > 0.05), parent–child relationship (t = 0.24, p > 0.05), 5-HT MGPS (t = − 0.05, p > 0.05), and creativity (t = 1.37, p > 0.05). Additionally, each sample was subjected to 1000 bootstrap resamples for regression analysis. The results showed that in both samples, the interaction between the parent–child relationship and the 5-HT MGPS predicted creativity (Sample 1: β = 0.11, t = 2.05, p < 0.05; Sample 2: β = 0.18, t = 3.72, p < 0.001). These findings suggested that the results of the subsamples were largely consistent with those of the overall sample, demonstrating the stability of the findings.
Regions of significance test
To further examine the interaction pattern between the parent–child relationship and the 5-HT MGPS, the Regions of Significance (ROS) method was conducted36 (See Table 2 and Fig. 3). Firstly, the Proportion of Interaction (POI) index was calculated as 0.72. A POI index near 0.5 suggests that the interaction pattern conforms to the differential susceptibility model, whereas a POI index closer to 0 indicates alignment with the diathesis-stress model. Secondly, the judgment criterion for Proportion Affect (PA) follows that of the POI. Next, to ensure that the interaction is not attributable to a nonlinear relationship, we further examined whether X2 or ZX2 predicted creativity. In this study, regression analysis indicated that neither X2 nor ZX2 predicted individual creativity, thus excluding the possibility of a nonlinear relationship. Finally, we used the Holm-Bonferroni correction to adjust the p-values. In conclusion, the interaction pattern between the parent–child relationship and the 5-HT MGPS conforms to the differential susceptibility model.
ROS Test of The Interaction Between Parent–Child Relationship and 5-HT MGPS.
Study 2: Supplementary study—supporting evidence from creative behavior experiment
Objective
Given the limitations of self-reported questionnaire data, this study incorporated behavioral experiments to assess individual creativity levels. These data served as supplementary evidence to further validate the stability and reliability of the interaction between parent–child relationship and 5-HT MGPS on creativity.
Participants
Based on the effect size in previous studies, we used G*power 3.1.9.2 to determine the appropriate sample size in the experiment47. Using a medium effect size, α = 0.05, and statistical power = 0.95 to calculate the sample size for 2 × 2 × 2 mixed experimental design, the results show that at least 76 subjects are needed. Participants for this study were selected from the original cohort in Study 1. The behavioral experiment was conducted two months after the initial questionnaire survey. A total of 116 participants from Study 1 were recruited through experiment flyers and were rewarded with stationery upon completion. All participants had normal or corrected-to-normal vision, and none had color blindness or color weakness. Before the experiment, participants were given a ten-minute rest period, during which the experimenter explained the procedure, outlined any precautions, and informed them of their right to withdraw from the experiment at any time. Following the experiment, the questionnaire data, genetic information, and behavioral experiment results were matched, yielding a final sample of 116 valid participants with complete datasets.
Methods
Participants were divided into high and low groups based on their parent–child relationship scores and 5-HT MGPS scores, using the 50th percentile as the cutoff point. Subsequently, a 2 (parent–child relationship: Low vs. High) × 2 (5-HT MGPS: Low vs. High) × 2 (CRAT task: Simple vs. Difficult) mixed experimental design was conducted to investigate the gene-environment (G × E) interaction effect on adolescent creativity. Parent–child relationship and 5-HT MGPS were between-subjects variables, while the difficulty of the CRAT task was a within-subjects variable.
Instrument
The Chinese Remote Associate Test (CRAT) was used as the experimental task to assess creativity. The CRAT materials were provided by a research group at Southwest University, who have successfully applied them in studies on creative thinking27,50. Each CRAT item presented participants with 3 unrelated words, requiring them to identify a word that could be associated with all 3. For instance, given “red,” “nose,” and “sour,” the correct answer would be “strawberry.” The experiment included 30 questions, split evenly between difficult and simple materials. An independent samples t-test comparing performance on difficult and simple materials showed a significant difference in participants’ accuracy rate between the two levels of difficulty (t = 6.20, p < 0.001).
Procedure
The experiment was conducted using E-Prime 3.0 software, with participants seated approximately 60 cm from the computer screen. The display was a 15-inch HP color screen with a refresh rate of 60 Hz. The stimuli were presented in white against a black background. The vertical visual angle for the word images ranged from 6.06 to 6.418 degrees, while the horizontal visual angle ranged from 5.06 to 7.238 degrees, with a resolution of 221 × 255 pixels. Before the formal experiment, participants were introduced to the procedure through a set of instructions and a practice phase. The formal experiment commenced once participants demonstrated a clear understanding of the task and became proficient with the key responses required. All participants had the same educational background, and the number of male and female was balanced. Additionally, all participants were right-handed.
The specific experimental procedure is as follows (see Fig. 4): First, a fixation point is presented at the center of the screen for 600 ms, followed by the question for 7000 ms. Participants need to carefully observe three Chinese characters and think within 7000 ms. After the time is up, they need to report their answers within 2000s. It is important to note that the CRAT task typically evaluates creativity based on accuracy; therefore, the presentation time for words and the report time for answers are fixed. Finally, the answer is displayed on the screen, and the participant matches the word they thought of with the correct answer. Participants judged the correctness by pressing keys (for example, 1 = the thought was consistent with the correct answer, 2 = the thought was inconsistent with the correct answer). If the participants do not come up with an answer, they should not press any key at this step. After completing the above steps, the experiment then automatically proceeds to the next trial.
The Procedure of Chinese Remote Associate Test.
Results
The results showed that the main effect of the parent–child relationship was significant predicted all tasks (see Table 3) (Fs > 6.78, ps < 0.01, η2p > 0.057). Specifically, participants with lower parent–child relationship scores showed significantly lower accuracy on CRAT compared to those with higher scores.
Additionally, the G × E interaction was significant for both average accuracy and accuracy on difficult tasks (F = 5.34, p = 0.02, ηs2p = 0.046; F = 5.24, p = 0.02, ηs2p = 0.045). This result suggested that when solving simple tasks, individuals do not require substantial cognitive resources, and thus the G × E interaction did not show significant differences in accuracy for simple tasks. Furthermore, in the high 5-HT MGPS group, the differences in creativity levels among individuals in different environments are more significant compared to those with low 5-HT MGPS (see Fig. 5). This result further indicates that individuals with sensitive genotypes are more influenced by the environment, conforming to the differential susceptibility model.
Analysis of Variance of 5-HT MGPS and Parent–Child Relationship in 3 Levels of Difficulty Tasks. a represents the average accuracy, 5b represents the accuracy of simple tasks, and 5c represents the accuracy of difficult tasks.
Discussion
The longstanding debate over “Nature versus nurture” remains a topic of significant interest. Adolescents’ creativity is influenced not only by environmental factors but also by genetic factors. Based on previous single-gene studies, this research incorporated multiple gene loci of the 5-HT system to construct the 5-HT MGPS and examined the interaction between multiple genes and the environment on the creativity of adolescents. These findings provided additional evidence for theoretical frameworks on adolescent creativity.
The influence of parent–child relationship on creativity
This study found that the parent–child relationship positively predicted adolescent creativity. On the hand, according to ecological systems theory, individual development is influenced by both internal and external ecological factors7. Within the family environment, the parent–child relationship serves as a crucial ecological subsystem that adolescents engage with daily, exerting a profound influence on their psychological and cognitive development. A positive parent–child relationship provides emotional support and security, thereby fostering creative thinking (Liang & Zhang, 2020).
On the other hand, from the sociocultural theory, creativity is not solely a product of innate talent or intelligence but rather develops within specific social and cultural contexts. The development of creativity often occurs through interactions with more experienced people, such as parents, who impart new knowledge, skills, and models of creative thinking15. The parent–child relationship is not only a significant external influence in adolescents’ daily lives but also a fundamental interpersonal necessity. A supportive external environment can effectively promote creativity, while a negative environment may impede its development. Positive parent–child relationships contribute significantly to healthy development and the cultivation of creativity49. Consequently, conducting regular assessments and interventions in the family environment fosters adolescent creativity.
The influence of serotonin system multiple genes on creativity
This study calculated the 5-HT MGPS by including the TPH2, SLC6A4, 5-HTR1A, and MAOA genes and we found that the interaction between the 5-HT MGPS and the parent–child relationship predicted adolescent creativity. From the neurophysiological perspective, the 5-HT system is associated with reward processing, sensitivity to punishment, cognitive flexibility, and goal persistence—factors that are crucial for fostering individual creativity28. 5-HT, as a crucial monoamine neurotransmitter, influences a variety of physiological functions in the human body, including cognition and emotion14,33. Therefore, genes involved in the synthesis, transport, modulation, and breakdown of 5-HT play a crucial role in regulating creativity. Creative thinking engages multiple brain regions, EEG and fMRIS studies have shown that this process involves the dorsolateral prefrontal cortex, precuneus, anterior cingulate cortex, fusiform gyrus, and middle temporal gyrus, which consistently exhibit activation during creative tasks12. Notably, the TPH2, SLC6A4, 5-HTR1A, and MAOA genes are extensively expressed in the prefrontal cortex and anterior cingulate cortex. Based on this, genetic variations in these serotonin-related genes can influence creativity by modulating neural activity within these brain regions.
The gene-environment interaction on adolescent creativity
Compared to the influence of genes alone, the interaction between genes and the environment has a greater influence on creativity and deserves more attention. We used the Regions of Significance (RoS) method and further found that the interaction between the parent–child relationship and 5-HT MGPS predicted creativity, with the interaction pattern aligning with the differential susceptibility model. Meanwhile, the results of behavioral experiments also demonstrated that the interaction between 5-HT MGPS and parent–child relationship significantly predicted the average accuracy rate and the accuracy rate of difficult tasks in the CRAT. Moreover, adolescents with high-sensitivity genotypes show significant differences in creativity levels in negative and positive environments. Adolescents with high 5-HT MGPS can showed better creativity in a positive parent–child relationship environment. This finding suggests that the development of creativity is shaped by environmental plasticity rather than being fixed and indicates that 5-HT MGPS reflects the influence of sensitivity (plasticity) genotypes on creativity development across different environments.
From the perspective of neurotransmitter mechanisms, this study calculated the 5-HT MGPS by selecting alleles with higher promoter activity, which are associated with increased 5-HT levels. According to the dual-process model of creativity, the generation of creativity requires both the cognitive flexibility and the persistence of goal orientation25. A higher 5-HT MGPS enhances cognitive flexibility but reduces goal-directed motivation. In the context of a negative parent–child relationship, adolescents with a higher 5-HT MGPS may exhibit lower executive control abilities, which could hinder the development of creativity. Conversely, the positive parent–child relationship reflects parental care and support. Alleles associated with higher promoter activity are more sensitive to rewards, and positive parent–child relationships align with the principle of reward to some extent. Therefore, adolescents with higher 5-HT MGPS are more likely to cultivate creativity in supportive parent–child environments. This once again result highlights the crucial role of environmental factors in adolescent development. Creating a supportive family, school, and community environment may enable individuals with sensitive genotypes to achieve greater success.
In addition, the results at the genetic level can also provide guidance for practical work. For example, based on students’ MGPS, they can be classified into two groups: environmentally sensitive adolescents and non-environmentally sensitive adolescents. While genetic factors are immutable, fostering positive school and family environments can benefit environmentally sensitive adolescents. Teachers should provide these students with additional attention and support. Regular home visits and mental health screenings should be conducted, and students’ psychological archives ought to be created to minimize the risk of psychological issues among high genetic risk students.
Limitations and future directions
Although this study systematically examined the impact of parent–child relationship × serotonin system multilocus profile scores on adolescent creativity, several limitations should be noted:
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(1)
This study is cross-sectional, limiting the ability to establish causal relationships between variables, and the sample was drawn from a single middle school. Future research should employ longitudinal designs and include more diverse sample sources to enhance generalizability.
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(2)
Although the behavioral experiments on gene-environment interaction have found that the interaction between 5-MGPS and parent–child relationship predicts the accuracy of the CRAT task, it is still necessary to recruit more subjects for experiments in genetic research to obtain more interpretable and robust results. Therefore, we plan to recruit more subjects to conduct gene-environment behavioral experiments when funds permit in the future.
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(3)
Compared to single-gene studies, multilocus genetic study obtains higher effect sizes and enhances the explanatory power of gene-environment interactions by focusing on candidate genes associated with psychological and behavioral traits. However, the multilocus candidate gene approach still does not capture whole-genome variations and may overlook significant genetic factors. Therefore, with sufficient funding in the future, we plan to adopt genome-wide association studies (GWAS) to more comprehensively examine gene-environment interactions.
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(4)
Beyond the 5-HT system examined in this study, other genes are also linked to creativity. For example, research has shown that dopamine and oxytocin receptors are associated with creativity, and the interaction between genetic loci of these receptors and the environment can predict creativity levels10. Therefore, future studies investigating the interplay between multiple gene systems and environmental factors will contribute to a more comprehensive understanding of the genetic mechanisms underlying creativity.
Conclusion
Based on the Ecological Systems Theory, this study adopted the gene-environment research method and included multiple gene loci of the 5-HT system to calculate the 5-HT MGPS, examining the interaction between multiple genes and the environment on the creativity of adolescents. We found that the parent–child relationship positively predicts adolescent creativity, suggesting that a supportive parent–child relationship fosters creative development. Furthermore, the interaction between 5-HT MGPS and the parent–child relationship predicts adolescent creativity, highlighting the combined influence of genetic and environmental factors on creativity development. Finally, the interaction pattern between 5-HT MGPS and the parent–child relationship aligns with the differential susceptibility model. This result emphasizes the importance of environmental factors, as adolescents with sensitive genotypes tend to thrive in positive environments while being more vulnerable in negative environments.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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This work was supported by the Hunan Education Science Key Funding Project (grant numbers XJK23AJD023).
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He Z. and Hu.Y.Q. were responsible for the writing and revision of the manuscript. Zeng Z.H., Zhan L.and Meng L. contributed to the creation of the figures in this article. Liu S.J. was responsible for data collection for the study.
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He, Z., Zhan, L., Zeng, Z. et al. The influence of serotonergic multilocus genetic variants and parent–child relationship on adolescent creativity. Sci Rep 15, 21013 (2025). https://doi.org/10.1038/s41598-025-03038-z
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DOI: https://doi.org/10.1038/s41598-025-03038-z
