Significant outcomes
Reward sensitivity can be parsed into striving towards multiple rewards and fixation to a specific reward.
Openness to Rewards and Insatiability by Reward sensitivity have distinct relationship with personality traits and ADHD symptoms.
The TPH2 promoter polymorphism was associated specifically with Insatiability by Reward.
Limitations
The reward sensitivity instrument was developed post hoc, applied in a Fennic language and requires further development and characterisation together with related instruments.
While the sample was reasonably large, and birth cohort representative, the association of TPH2 genotype and reward sensitivity remains to be independently replicated.
Introduction
Reinforcement sensitivity theory (RST) has been stated to occupy a unique space in literature as a strong basic construct of temperament (Corr, Reference Corr, Corr and Matthews2009; Gray and McNaughton, Reference Gray and McNaughton2000; Walker et al., Reference Walker, Jackson and Frost2017). In describing the principal brain mechanisms behind animal and human behaviour, the Gray’s RST (Gray, Reference Gray, Ekman and Davidson1994) is arguably the most important theoretical approach to explain individual differences, via the reward and punishment sensitivities (e.g. Collins et al., Reference Collins, Jackson, Walker, O’Connor and Gardiner2017). The behavioural predictions of RST have been examined across a broad range of areas, including psychopathy (e.g. Broerman et al., Reference Broerman, Ross and Corr2014; De Pascalis et al., Reference DePascalis, Scacchia, Sommer and Checcucci2019), criminal behaviour (e.g. Arnett and Newman, Reference Arnett and Newman2000; Leue et al., Reference Leue, Brocke and Hoyer2008), forgiveness (e.g. Johnson et al., Reference Johnson, Kim, Giovannelli and Cagle2010), substance abuse (e.g. Derefinko et al., Reference Derefinko, Eisenlohr-Moul, Peters, Roberts, Walsh, Milich and Lynam2016; Papinczak et al., Reference Papinczak, Connor, Harnett and Gullo2018), and there is considerable empirical evidence supporting the main tenets of RST (e.g. Bijttebier et al., Reference Bijttebier, Beck, Claes and Vandereycken2009; Gaher et al., Reference Gaher, Hahn, Shishido, Simons and Gaster2015; Meis et al., Reference Meis, Erbes, Kramer, Arbisi, Kehle-Forbes, DeGarmo, Shallcross and Polusny2017). Three functionally independent motivational subsystems comprise RST: the behavioural approach system (BAS), the fight/flight/freeze system (FFFS), and the behavioural inhibition system (BIS) (Gray and McNaughton, Reference Gray and McNaughton2000; Corr, Reference Corr, Corr and Matthews2009; Collins et al., Reference Collins, Jackson, Walker, O’Connor and Gardiner2017).
In Gray’s theory, a psychobiological trait, called sensitivity to reward or reward sensitivity, reflects the functional outcomes of the activity in the BAS (Gray, Reference Gray, Ekman and Davidson1994). Growing evidence suggests that in particular reward sensitivity is associated with important behavioural choices that have major implications to health, such as excessive consumption of palatable foods and use of addictive substances (Emery and Simons, Reference Emery and Simons2017; Joyner et al., Reference Joyner, Bowyer, Yancey, Venables, Foell, Worthy, Hajcak, Bartholow and Patrick2019; Tatnell et al., Reference Tatnell, Loxton, Modecki and Hamilton2019); it has also been found to predict recurrence of manic episodes in bipolar disorder (Kwan et al., Reference Kwan, Bauer, Hautzinger and Meyer2020). In contrast, low reward sensitivity can predict symptoms of depression (Hausman et al., Reference Hausman, Kotov, Perlman, Hajcak, Kessel and Klein2018). Generally, reward sensitivity as the component of temperament and personality encompasses individual differences in the tendency to detect, pursue, and derive pleasure from positive stimuli (Gray and McNaughton, Reference Gray and McNaughton2000; Corr, Reference Corr, Corr and Matthews2009). The BAS is primarily organised around pathways using the neurotransmitter dopamine and can be defined as the tendency to engage in motivated approach behaviour in the presence of rewarding stimuli (Gray and McNaughton, Reference Gray and McNaughton2000; DeYoung, Reference DeYoung2013).
Typically reward sensitivity has been measured by the Carver & White BIS/BAS Scales (Carver and White, Reference Carver and White1994) and, more recently, also by The Jackson 5 (J5; Jackson, Reference Jackson2009), Reinforcement Sensitivity Theory Personality Questionnaire (RST-PQ; Corr and Cooper, Reference Corr and Cooper2016), or the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ; Torrubia et al., Reference Torrubia, Avila, Molto and Caseras2001). In recent years, careful analysis of the existing questionnaires has suggested that some significant theoretical and operational limitations exist (Corr and Cooper, Reference Corr and Cooper2016). It has been argued that the process of scale construction has not strongly adhered to the theoretical postulates of the RST, and as a result, the construct validity of the available questionnaires may be suboptimal. Either have the instruments defined reward sensitivity as a homogenous construct, while the case can be made that it is multidimensional (e.g. Corr, Reference Corr2016), or introduced components that should not be taken as synonymous to reward sensitivity, such as impulsivity or goal directedness.
Rewards constitute a major incentive in the balance between approach and avoidance, and the sensitivity to rewards should have implications to other fundamental mechanisms guiding behaviour such as basic emotions (e.g. Collins et al., Reference Collins, Jackson, Walker, O’Connor and Gardiner2017; Lahvis, Reference Lahvis2017; Montag et al., Reference Montag, Widenhorn-Müller, Panksepp and Kiefer2017). Nevertheless, no investigation has examined the relationship of reward sensitivity to the traits as measured by the Affective Neuroscience Personality Scale (ANPS; Davis et al., Reference Davis, Panksepp and Normansell2003; Davis and Panksepp, Reference Davis and Panksepp2011) which has been constructed bottom up to study traits predicted by the basic neuroscience research in animals (Panksepp, Reference Panksepp1998; Montag and Panksepp, Reference Montag and Panksepp2017). Nearly all seven proposed basic emotive systems characterised by the ANPS include brain regions that have been suggested to contribute to reward sensitivity (Panksepp, Reference Panksepp2016). Reward sensitivity has also been strongly related to the brain areas highlighted in studies on Attention deficit hyperactivity disorder (ADHD) (e.g. Avila et al., Reference Avila, Parcet and Barro’s-Loscertales2008; Holroyd et al., Reference Holroyd, Baker, Kerns and Müller2008; Hahn et al., Reference Hahn, Notebaert, Dresler, Kowarsh, Reif and Fallgatter2014; Adrián-Ventura et al., Reference Adrián-Ventura, Costumero, Parcet and Ávila2019; Luo et al., Reference Luo, Weibman, Halperin and Li2019). ADHD patients are reported to have higher scores of affective temperaments and difficulties with regulation of behaviour directed towards rewards (e.g. Torrente et al., Reference Torrente, López, Lischinsky, Cetkovic-Bakmas and Manes2017), and reward sensitivity could be considered an endophenotype of ADHD.
While much of reward sensitivity research has paid attention to the role of dopamine neurons, the function of serotonergic neurotransmission is also crucial (Fletcher et al., Reference Fletcher, Tampakeras and Yeomans1995; Bari et al., Reference Bari, Theobald, Caprioli, Mar, Aidoo-Micah, Dalley and Robbins2010). Transient activation of dorsal raphe elicits strong reinforcement signals, but 5-HT neurons of dorsal raphe enhance reward waiting (Luo et al., Reference Luo, Zhou and Liu2015). These neurons also change their tonic firing rates across trials of reward and punishment, suggestive of signalling on multiple timescales (Cohen et al., Reference Cohen, Amoroso and Uchida2015). Of the genetic variants shaping the individual differences in the serotonergic system, the serotonin transporter promoter polymorphism has been associated with reward responses in environmentally sensitive manner (Richards et al., Reference Richards, Arias Vásquez, von Rhein, van der Meer, Franke, Hoekstra, Heslenfeld, Oosterlaan, Faraone, Buitelaar and Hartman2016), and the composite of risk alleles of three serotonin-related genes was associated with BAS scores (Pearson et al., Reference Pearson, McGeary and Beevers2014). Levels of serotonin in the central nervous system (CNS) depend on the activity of tryptophan hydroxylase 2, the rate-limiting enzyme of the synthesis of serotonin. The −703 G/T polymorphism of the TPH2 gene (rs4570625) has been associated with amygdalar responsiveness (Brown et al., Reference Brown, Peet, Manuck, Williamson, Dahl, Ferrell and Hariri2005; Canli et al., Reference Canli, Congdon, Gutknecht, Constable and Lesch2005), risk of affective disorder (Gao et al., Reference Gao, Pan, Jiao, Li, Zhao, Wei, Pan and Evangelou2012), and with behavioural inhibition (Latsko et al., Reference Latsko, Gilman, Matt, Nylocks, Cofman and Jasnow2016). This genotype is associated with functional connectivity (Tao et al., Reference Tao, Chattun, Yan, Geng, Zhu, Shao, Lu and Yao2018) and white matter integrity (Ping et al., Reference Ping, Xu, Zhou, Lu, Lu, Shen, Jiang, Dai, Xu and Cheng2019) in the brain. A recent systematic review and meta-analysis concluded that the TPH2 rs4570625 polymorphism is significantly associated with psychiatric disorders such as unipolar depression, bipolar disorder, schizophrenia, and suicide (Ottenhof et al., Reference Ottenhof, Sild, Lévesque, Ruhe and Booij2018). The risk allele has been the major, G-allele, and the well-powered studies and meta-analysis have pointed at a much larger effect if the risk allele carriers are compared to the T/T-homozygotes. The experimental studies have, however, usually compared G/G homozygotes to T-allele carriers, owing to the low frequency of the minor T allele.
It thus appears that the minor T-allele, especially in homozygotes, is protective against a variety of mental health disorders, but the mediating mechanisms are not known. In our studies on representative birth cohort samples, the G/G homozygotes and G/T heterozygotes have appeared similar in many respects, but a rather large distinction of T/T homozygotes has been apparent with regard to lower neuroticism, higher extraversion, and higher conscientiousness (Lehto et al., Reference Lehto, Vaht, Mäestu, Veidebaum and Harro2015) as well as low aggressiveness, depressiveness, and trait anxiety (Laas et al., Reference Laas, Kiive, Mäestu, Vaht, Veidebaum and Harro2017). The strikingly low aggressiveness in the male TPH2 rs4570625 T/T homozygotes, both during the years at school and later in adult life, however, remained unexplained by anxiety. Owing to the role of serotonin in the control of aggressive urges (Miczek et al., Reference Miczek, Mos and Olivier1989; Harro and Oreland, Reference Harro and Oreland2016) and the relationship between pursuits of aggression as reward (Golden et al., Reference Golden, Heins, Venniro, Caprioli, Zhang, Epstein and Shaham2017), it is, however, plausible that the relationship between TPH2 genetic variation and aggression could involve reward sensitivity.
The first aim of the present study was to identify common items for operational measurement of reward sensitivity and to explore for any emerging factor structure. The second purpose was to analyse the associations of the obtained reward sensitivity construct with the ANPS, presence of symptoms of ADHD, and with the TPH2 genotype.
Material and methods
Sample
This study was carried out on the Estonian sample of the European Youth Heart Study (1998/1999), which was subsequently incorporated into the longitudinal Estonian Children Personality Behaviour and Health Study (ECPBHS). The European Youth Heart Study sample of the ECPBHS consists of two birth cohorts. The rationale and procedure of sample formation, and further data collection waves have been described elsewhere in detail (Harro et al., Reference Harro, Eensoo, Kiive, Merenäkk, Alep, Oreland and Harro2001; Tomson-Johanson et al., Reference Tomson-Johanson, Kaart, Kiivet, Veidebaum and Harro2020). ECPBHS is highly representative of two birth cohorts of a local population, as 79% of subjects of the randomised regional sample participated in the original data collection. All the subjects are of European descent. Data collection has been conducted at ages 9 (only the younger cohort), 15, 18, 25, and 33 (only the older cohort). Data used in the present analyses were collected at age 25 or, if not available for age 25, then from the study wave at age 33. The original size of the total sample is n = 1238, but all data necessary for the analyses presented in this paper were n = 811 to 824. This study was approved by the Ethics Review Committee on Human Research of the University of Tartu, and written informed consent was obtained from all the participants and in case of minors also from their parents.
Reward Openness and Insatiability Scale
The Reward Openness and Insatiability Scale (ROIS) that is used in this manuscript to measure reward sensitivity was constructed post hoc making use of previously collected information on personality. Three experienced behavioural scientists independently extracted items thought to reflect reward sensitivity from the Estonian versions of International Personality Item Pool NEO (IPIP) (Goldberg, Reference Goldberg, Mervielde, Deary, De Fruyt and Ostendorf1999; Mõttus et al., Reference Mõttus, Pullmann and Allik2006), Barratt Impulsiveness Scale (BIS-11; Patton et al., Reference Patton, Stanford and Barratt1995; Akkermann et al., Reference Akkermann, Nordquist, Oreland and Harro2010), the brief version of the ANPS (Davis et al., Reference Davis, Panksepp and Normansell2003; Harro et al., Reference Harro, Laas, Eensoo, Kurrikoff, Sakala, Vaht, Parik, Mäestu and Veidebaum2019), Spielberger State-Trait Anxiety Inventory (STAI; Spielberger et al., Reference Spielberger, Gorsuch, Lushene, Vagg and Jacobs1983; Akkermann et al., Reference Akkermann, Nordquist, Oreland and Harro2010), and Adaptive and Maladaptive Impulsivity Scale (AMIS) (Paaver et al., Reference Paaver, Eensoo, Pulver and Harro2006; Tomson-Johanson et al., Reference Tomson-Johanson, Kaart, Kiivet, Veidebaum and Harro2020). The extracted items were discussed, and an initial pool of items was formed with consensus. This item pool consisted of 69 items: 11 items from BIS-11, 13 items from ANPS, 9 items from AMIS, 2 items from STAI, and 34 items from IPIP. The z-value transformation for responses of the items was performed before the statistical analysis.
In order to explore preliminary factor structure of the eventual reward sensitivity instrument, principal component analysis (PCA) with Direct Oblimin rotation (delta = 0) was carried out on all 69 items. The Kaiser–Meyer–Olkin (KMO) measure of sampling adequacy value was 0.84 which indicates that the sample was adequate for factor analysis. Bartlett’s test of sphericity was significant, χ 2(2346) = 7332.14, p < 0.0001, indicating that factor analysis was appropriate for this data. To determine the number of factors to extract, both the scree plot and eigenvalues were considered. The scree plot indicated that the data best fit a two-factor or four-factor solution. The eigenvalues of the first two components were 7.551 (accounted for 10.94% of total variance) and 7.083 (accounted for 10.27% of total variance), respectively. The next two components had eigenvalues 2.758 (accounted for 4.00% of total variance) and 2.532 (accounted for 3.67% of total variance), respectively. The communalities of items were from 0.035 to 0.539.
Affective Neuroscience Personality Scale
We used the adaptation (Harro et al., Reference Harro, Laas, Eensoo, Kurrikoff, Sakala, Vaht, Parik, Mäestu and Veidebaum2019) of the short version of the ANPS (Davis et al., Reference Davis, Panksepp and Normansell2003) that is a self-report instrument constructed bottom up to correspond to the activity in neural circuits underlying basic emotive systems as defined in animal research (Panksepp, Reference Panksepp1998; Davis and Panksepp, Reference Davis and Panksepp2011). It comprises scales termed ANGER, FEAR, SADNESS, SEEKING, CARE, and PLAY, each measured with six items, each on a 5-point scale. Data on ANPS were available for 423 subjects in the ECPBHS younger cohort and 502 subjects in the older cohort.
Measures of ADHD symptoms
Subjects filled in the Estonian version of the World Health Organization Adult ADHD Self-Report Scale (ASRS) symptom checklist (Kessler et al., Reference Kessler, Adler, Ames, Demler, Faraone, Hiripi, Howes, Jin, Secnik, Spencer, Ustun and Walters2005; Kiive and Harro, Reference Kiive and Harro2013; Kiive et al., Reference Kiive, Laas, Akkermann, Comasco, Oreland, Veidebaum and Harro2014), an instrument composed of 18 questions based on Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria of ADHD. The ASRS consists of nine items that represent symptoms related to inattention and nine items assessing symptoms of hyperactivity/impulsivity. Each of the items is scored on a five-point Likert rating scale with 0 = “never,” 1 = “rarely,” 2 = “sometimes,” 3 = “often,” and 4 = “very often” based on the participant’s experiences over the last 6 months. Six of the 18 questions most predictive of symptoms consistent with ADHD (Kessler et al., Reference Kessler, Adler, Ames, Demler, Faraone, Hiripi, Howes, Jin, Secnik, Spencer, Ustun and Walters2005) are the basis for the ASRS Screen (M = 1.37, SD = 0.59, Cronbach α = 0.68). The total score is calculated by summing the values of all items (M = 1.30, SD = 0.50, Cronbach α = 0.86). The higher the score is the more symptoms are pronounced. In addition to the sum score, the two subscales Inattention (M = 1.42, SD = 0.55, Cronbach α = 0.80) and Hyperactivity/Impulsivity (M = 1.18, SD = 0.59, Cronbach α = 0.80) are calculated.
TPH2 rs4570625 genotyping
Genomic DNA was extracted from whole blood samples using Qiagen QIAamp® DNA Blood Midi Kit. Genotyping for TPH2 G-703 T (rs4570625) was performed as previously described (Lehto et al., Reference Lehto, Vaht, Mäestu, Veidebaum and Harro2015) with the Applied Biosystems ViiA™ 7 Real-Time PCR System using the TaqMan® Pre-Designed SNP Genotyping Assay with Solis BioDyne 5 × HOT FIREPol® Probe qPCR Mix Plus (ROX). All DNA samples of the ECPBHS (n = 1234) were successfully genotyped. In total, the sample included 749 G/G homozygotes (60.7%), 432 G/T heterozygotes (35.0%), and 53 T/T homozygotes (4.3%). Minor allele frequency was 0.22. The genotype frequencies were in Hardy–Weinberg equilibrium (chi-squared 0.887; expected frequencies 61.2, 34.1, and 4.7%, respectively).
Statistical analysis
Statistical analysis was carried out using SPSS v. 18 software. Correlations between test scores were assessed by Pearson correlation, and assessment of factor structure of the new reward sensitivity scale was carried out by PCA with oblique rotation. In order to analyse the association of scales of ROIS and the modules of ANPS or ADHD, multiple linear regression analysis was the carried out. Hierarchical cluster analysis (cluster method: between-groups linkage, measure: Peason correlation) was used for analysis of structure of correlation pattern between modules of ANPS and subscales of ROIS. Hierarchical cluster analysis is typically applied with an eye to determining how n entities – objects, scales, sentences, subjects, etc. – can be grouped into m < n clusters that exhibit high within-group similarity and low similarity to other groups (e.g. King, Reference King2015) and better reveal the general pattern of associations between the psychological constructs. While the relationship of ROIS and ANPS was examined, the ANPS-derived items were omitted from ROIS data. Owing to dissimilar groups sizes, ROIS test scores in TPH2 genotype groups were assessed by both non-parametric Kruskal-Wallis test and one-way analysis of variance (ANOVA); since the results were similar the latter with post hoc comparisons by Tamhane’s T2 tests is described in Results. Before statistical analysis for all the scales, the mean item score was computed (i.e. sum of the items is divided by number of items in scale). In the statistical analysis, the conventional 5% level was used to assess the significance.
Results
Structure of the ROIS
Out of the initial item pool, 28 items were selected on the basis of factor loadings, communalities, and internal homogeneity and included in a new factor analysis (PCA, Direct Oblimin rotation, delta = 0). The KMO measure of sampling adequacy value was 0.86 which indicated that the dateset was appropriate for factor analysis. Bartlett’s test of sphericity was significant, χ 2(378) = 7095.7, p < 0.0001, also indicating that factor analysis was appropriate for these data. The scree plot revealed a clear factor structure with the four factors accounting for 46.4% of the total variance. The communalities of items were from 0.200 to 0.620. The four factors explained 18.2%, 15.5%, 6.5%, and 6.2% of the variance, respectively, and factor loadings were, respectively, between 0.504 and 0.775, 0.514 and 0.720, 0.360 and 0.805, and 0.503 and 0.695.
The component correlation matrix demonstrated two factors (Factor 1 and Factor 4) in a positive correlation r = 0.40, as well as the two other factors (Factor 2 and Factor 3; r = 0.31). Such a pattern of correlations indicates the hierarchical structure of the test, so there are two second-order factors and four first-order factors. Fig. 1 provides illustration of all 28 items located in two-dimensional factor space. Content of included items translated into English, their factor loadings, and the sources where analogous items have been used are available in Supplementary Table 1.
Fig. 1. Items of the Reward Opennesss and Insatiability Scale loading on the higher-order factors Insatiablity by Reward and Openness to Rewards. Principal component analysis with oblique rotation (Direct Oblimin).
Close inspection of items of Factor 1 reveals this factor as related to impulsive buying and excessive spending (sample Cronbach α = 0.85), so it was named Excessive spending subscale. The items of Factor 4 are related to low self-control and troubles in resisting to temptations (sample Cronbach α = 0.77). This subscale was named Giving in to cravings. These two subscales together characterise the excessive fixation to a particular reward, the higher-order factor thus representing Insatiability by Reward (sample Cronbach α = 0.86). Factor 2 has been labelled Excitement and Novelty subscale owing to its reflection of seeking of new experiences and excitement (sample Cronbach α = 0 0.79). The items of Factor 3 are largely associated with sociability and social exchange (sample Cronbach α = 0.75), so named Social experiences subscale. These two subscales characterise the striving towards multiplicity of rewards, so the higher-order factor has been labelled Openness to Rewards (sample Cronbach α = 0.82). Correlation between scores of Openness to Rewards and Insatiability by Reward was statistically insignificant r = −0.008 (p = 0.82, N = 818). Thus, these two reward sensitivity factors are orthogonal, as reflected in item loadings in Fig. 1.
Relationship between subscales of the ROIS and factors of the ANPS
Cluster analysis (between-groups linkage method, Peason correlation measure) of the scales of ROIS and personality factors of ANPS reveals two clearly separate groupings (Fig. 2). This pattern of associations is also observed in zero-order correlations (Table 1). Openness to Rewards was strongly associated with SEEKING and PLAY, and rather weakly with CARE; weak negative correlations were found with FEAR and SADNESS; and no relationship to ANGER. Insatiability by Reward was, instead, in moderate positive correlation with SADNESS, FEAR, and ANGER, had no relationship with SEEKING or CARE, and very weak but negative correlation with PLAY.
Fig. 2. Dendrogram of cluster analysis of the subscales of Reward Openness and Insatiability Scale (ROIS) and dimensions of the Affective Neuroscience Personality Scale (ANPS). Hierarchical cluster analysis with between-groups linkage method and Peason correlation measure.
Table 1. Pearson correlations between the subscales of the Reward Openness and Insatiability Scale (ROIS) and Affective Neuroscience Personality Scale (ANPS). Mean item scores ± standard deviations are presented in brackets (n = 815)
OR – Openness to Rewards, IR – Insatiability by Reward. Means ± standard deviations are presented in brackets. ROIS scores exclude the items from ANPS in this analysis. * p < 0.05; ** p < 0.001.
Relationship of ADHD symptoms with the ROIS and ANPS
Zero-order pair-wise correlations between scales and subscales of ROIS and ADHD measures show a clear pattern of Insatiability by Reward positively correlated with the ADHD symptoms as measured with the ASRS scales (Table 2), whereas Openness to Rewards correlated very weakly with either inattention or hyperactivity, these weak correlations also being in opposite to each other direction. Multiple regression was performed to clarify the impact of aspects of reward sensitivity and the personality factors of ANPS on ADHD symptoms. The two components of Insatiability by Reward were the major and universal predictors of ADHD symptoms, but the Excitement and Novelty aspect of Openness to Rewards not at all (Table 3). Social experience contributed to Inattention but not to Hyperactivity/Impulsivity. As to the Affective Neuroscience Personality Model, ANGER was related to ADHD Hyperactivity/Impulsivity, but not to Inattention. SADNESS and FEAR had some positive association with either component of ASRS, whereas which association was stronger, did not coincide. CARE had some association with Inattention which was negative. SEEKING was in strong positive association with both aspects of ADHD symptoms, while PLAY had relationship with neither.
Table 2. Pearson correlations between the Reward Openness and Insatiability Scale (ROIS) and Adult ADHD Self-Report Scale (ASRS)
OR - Openness to Rewards, IR – Insatiability by Reward scale (n = 811).
* p < 0.05; ** p < 0.01.
Table 3. Multiple regression models for Adult ADHD Self-Report Scale (ASRS) subscores (n = 811)
THP2 -703 G/T genotype and ROIS
There was no statistically significant difference in Openness to Rewards between the TPH2 genotype groups [F(2, 821) = 0.96; p = 0.384, F(2, 821) = 0.41; p = 0.667, and F(2, 821) = 1.01; p = 0.364 for the total score, Excitement and Novelty subscale, and Social experiences subscale, respectively; Table 4]. However, siginificant differences were found in Insatiability by Reward [F(2, 814) = 6.08; p = 0.002] as well as the Excessive spending [F(2, 814) = 6.06; p = 0.002] and Giving in to cravings [F(2, 814) = 3.18; p = 0.042] subscale. While the scores of G/G and G/T genotypes were similar, the T/T homozygotes had much lower scores.
Table 4. TPH2 effects on reward sensitivity (ROIS subscales) group mean item scores and standard errors and multiple comparisons p-value (Tamhane’s)
OR – Openness to Rewards, IR – Insatiability by Reward.
* p < 0.05; ** p < 0.0001 significant difference of the TPH2 T/T homozygotes from G/G homozygotes as well as G/T heterozygotes.
Discussion
In this study, we have found evidence to suggest that reward sensitivity is comprising of two rather independent components that, respectively, characterise striving to and preference of multiple rewards versus strong fixation on a particular reward. This has not been described previously, possibly owing to the limitations of the existing questionnaires that may have somewhat deviated from the theoretical postulates of the RST or attempted to establish reward sensitivity as a homogenous construct (Corr and Cooper, Reference Corr and Cooper2016; Corr, Reference Corr2016). Being in possession of the large item pool collected from a large, birth cohort representative sample to whom any recognised reward sensitivity instrument had not been administered, we have made an exploratory attempt to examine the internal structure of reward sensitivity. ECPBHS offers the advantage of a database comprising a variety of behavioural items, thus we compiled post hoc an instrument for the measurement of reward sensitivity. This approach has yielded an instrument with two orthogonal dimensions that make intuitive sense, but will require further formal development and rigorous studies to ascertain its applicability.
We selected as the next goal to reveal the relationship of reward sensitivity, as measured with the ROIS, with personality in the affective neuroscience model (Panksepp, Reference Panksepp2016). Empirical studies addressing the position of reward sensitivity in the framework of the Five Factor Model of personality mostly have shown that reward sensitivity is positively associated with Extraversion and negatively with Neuroticism (e.g. Keiser and Ross, Reference Keiser and Ross2011; Segarra et al., Reference Segarra, Poy, Lopez and Molto2014; Smillie and Wacker , Reference Smillie and Wacker2014; Corr and Cooper, Reference Corr and Cooper2016; Smillie et al., Reference Smillie, Jach, Hughes, Wacker, Cooper and Pickering2019). The ANPS has, in contrast to lexical approaches to the structure of personality, been constructed bottom-up to measure personality as revealed in expression on primary emotion systems, defined by neurobiological studies across mammalian species (Panksepp, Reference Panksepp1998). ANPS facets distinctly correlate with measures of white matter integrity in polydrug abusers (Unterrainer et al., Reference Unterrainer, Hiebler-Ragger, Koschutnig, Fuchshuber, Tscheschner, Url, Wagner-Skacel, Reininghaus, Papousek, Weiss and Fink2017), a subject group with likely deviations in reward sensitivity. Recently, problematic use of internet and smartphone addiction were associated with high expression of FEAR and SADNESS, and to a lesser extent ANGER, and to low levels of CARE, PLAY, and SEEKING (Montag et al., Reference Montag, Sindermann, Becker and Panksepp2016). Interestingly, the two reward sensitivity component ROIS clearly differentiated these personality facets so that Insatiability by Reward was associated with ANGER, FEAR, and SADNESS, while Openness to Rewards was, instead, related to SEEKING, PLAY, and CARE. (In relevant analyses, the ANPS-derived items were omitted from ROIS data.) Hierarchical cluster analysis revealed that both facets of Insatiability by Reward were related to the three neuroticism-related ANPS traits with high similarity. The two facets of Openness to Rewards had, however, specific relationship with ANPS traits, so that Excitement and Novelty were more close related to SEEKING than to Social Experience, and the latter was more closely related to PLAY. Of note is the complete absence of association between SEEKING and Insatiability by Reward. This was unexpected because the bottom-up construct of SEEKING was made bearing in mind what is known of dopaminergic control of reward-related behaviour (Panksepp, Reference Panksepp1998; Montag and Panksepp, Reference Montag and Panksepp2017). Direct evidence for a relationship of SEEKING with dopaminergic system and reward-related behaviour in humans is, however, not available, therefore any neurobiological interpretation of this dissociation at present remains speculative. It is nevertheless conceivable that while the mesotelencephalic dopaminergic neurotransmission is vital for search of multiple rewards, it does not contribute to the insatiability aspect of reward sensitivity. It was recently demonstrated that reward-related firing of the ventral tegmental (VTA) dopamine neurons and dopamine release in the nucleus accumbens can be dissociated so that in conditions of orientation towards rewards there is a coupling while the immediate motivated behaviour is associated with dopamine release but not VTA activity (Mohebi et al., Reference Mohebi, Pettibone, Hamid, Wong, Vinson, Patriarchi, Tian, Kennedy and Berke2019). The former must hence be regulated locally, possibly via inhibition of the tonic action of serotonin on the 5-HT2C receptors (Dremencov et al., Reference Dremencov, Newman, Kinor, Blatman-Jan, Schindler, Overstreet and Yadid2005).
Higher scores of SEEKING and SADNESS predicted both components of ADHD symptomatology, higher Inattention, and Hyperactivity/Impulsivity. A higher score of ANGER was associated with higher Hyperactivity/Impulsivity, while FEAR contributed to Inattention. Also, the score of Inattention was negatively associated with CARE dimension. Similarly, a recent study of Wernicke et al. (Reference Wernicke, Li, Sha, Zhou, Sindermann, Becker, Kendrick and Montag2019) has found a higher negative emotionality, namely, ANGER, FEAR, and SADNESS, significantly associated with more inattentive, hyperactive/impulsive tendencies of young adults (Wernicke et al., Reference Wernicke, Li, Sha, Zhou, Sindermann, Becker, Kendrick and Montag2019).
Higher scores of the Insatiability by Reward, SEEKING, ANGER SADNESS, and FEAR predicted more severe symptoms of ADHD, while the scores of Social experience and CARE were negatively associated with ADHD symptoms. ADHD individuals are well known by their increased preference for small immediate rewards rather than large delayed ones (Marx et al., Reference Marx, Hacker, Yu, Cortese and Sonuga-Barke2018) and preference of risky decisions (Luman et al., Reference Luman, Oosterlaan, Knol and Sergeant2008). Excessive spending and giving in to cravings are also associated with poor impulse control. On the other hand, in our study, the score of Social experience subscale was negatively associated with ADHD symptoms, which supports the notion that sensation/experience seeking and impulsivity are dissociable constructs and based on partially distinct neurobiological substrates.
The TPH2-703 G/T polymorphism also distinguished Openness to Rewards and Insatiability by Reward in terms of being associated only with the latter. While the functional significance of this polymorphism at the cellular level requires further investigation, the T-allele may relate to hyperfunction of tryptophan hydroxylase (Lin et al., Reference Lin, Chao, Chen, Lai, Chen and Sun2007; Chen et al., Reference Chen, Vallender and Miller2008), and if this were the case, serotonin levels should be particularly high in the T/T homozygotes. This would be well compatible with low aggressiveness, anxiety, and depressiveness. We could observe hardly any effect of the single T-allele, and this is compatible with recent studies on psychiatric patients (see Introduction for references) and with our previous findings on personality, aggressiveness, and anxiety in the ECPBHS sample (Lehto et al., Reference Lehto, Vaht, Mäestu, Veidebaum and Harro2015; Laas et al., Reference Laas, Kiive, Mäestu, Vaht, Veidebaum and Harro2017). Somewhat speculatively, the minor effect of a single T-allele may be caused by the efficient compensatory mechanisms in the synthesis of 5-HT as demonstrated in animal experiments (Kriegebaum et al., Reference Kriegebaum, Song, Gutknecht, Huang, Schmitt, Reif, Ding and Lesch2010).
An obvious limitation of this study lies in the current infeasibility of validation by other reward sensitivity instruments because of the database approach. On the other hand, the latter has the advantage of diverse, population-representative sample tested in uniform, laboratory conditions. Further studies should establish a novel instrument corresponding to the inner structure of reward sensitivity as revealed in the present investigation and compare the ROIS with other instruments and behavioural tests to validate the concept of the separable components of reward sensitivity. Owing to the often poor replicability of findings with candidate gene variants, the association of the TPH2 gene with reward sensitivity requires testing in other populations.
Conclusively, striving towards multiple rewards and strong fixation on a particular reward were distinguished with a novel instrument and demonstrated to have distinct association with affective neuroscience personality and ADHD-like traits, as well as with the genotype of tryptophan hydroxylase 2, the rate-limiting enzyme for serotonin synthesis in the brain.
Supplementary material
To view supplementary material for this article, please visit https://doi.org/10.1017/neu.2020.18
Acknowledgements
We are grateful to the ECPBHS study participants, their parents, and the whole ECPBHS team.
Author contributions
The authors JH, EK, and AP contributed to the design of the study and data collection, literature searches, statistical analysis, and writing of the manuscript. All authors have approved the final manuscript.
Financial support
This work was supported by Estonian Research Council Project IUT20-40, the EC Horizon 2020 project CoCA (H2020-PHC-2015-667302), and the Tallinn University ASTRA project TU TEE financed by the European Union European Regional Development Fund (2014-2020.4.01.16-0033).
Conflict of Interest
None.
Ethical standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
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