Songfa Zhong

A neurochemical approach to valuation sensitivity over gains and losses

Prospect theory proposes the hypothesis that people have diminishing sensitivity in valuing increases in the size of monetary outcomes, for both gains and losses. For decision-making under risk, this implies a tendency to be risk-tolerant over losses while being generally risk averse over gains. We offer a neurochemistry-based model of the diminishing valuation sensitivity hypothesis. Specifically, we propose that dopamine tone modulates the sensitivity towards valuation of gains while serotonin tone modulates the sensitivity towards valuation of losses. Consequently, higher dopamine tone would yield a more concave valuation function over gains while higher serotonin tone would yield a more convex valuation function over losses. Using a neurogenetics strategy to test our neurochemical model, we find that subjects with the 9-repeat allele of DAT1 (lower DA tone) are more risk-tolerant over gains than subjects with the 10-repeat allele, and that subjects with the 10-repeat allele of STin2 (higher 5HT tone) are more risk-tolerant over losses than subjects with the 12-repeat allele. Overall, our results support the implications of our model and provide the first neurogenetics evidence that risk attitudes are partially hard-wired in differentiating between gain- and loss-oriented risks.

All-trans Retinoic Acid Upregulates Reduced CD38 Transcription in Lymphoblastoid Cell Lines from Autism Spectrum Disorder.

Deficits In social behavior In mice lacking the CD38 gene have been attributed to Impaired secretion of oxytocin. In humans, similar deficits in social behavior are associated with autistic spectrum disorder (ASD), for which genetic variants of CD38 have been pinpointed as provisional risk factors. We sought to explore, in an in vitro model, the feasibility of the theory that restoring the level of CD38 in ASD patients could be of potential clinical benefit. CD38 transcription is highly sensitive to several cytokines and vitamins. One of these, all-trans retinoic acid (ATRA), a known inducer of CD38, was added during cell culture and tested on a large sample of N = 120 lymphoblastoid cell (LBC) lines from ASD patients and their parents. Analysis of CD38 mRNA levels shows that ATRA has an upmodulatory potential on LBC derived from ASD patients as well as from their parents. The next crucial issue addressed in our study was the relationship between levels of CD38 expression and psychological parameters. The results obtained indicate a positive correlation between CD38 expression levels and patient scores on the Vineland Adaptive Behavior Scale. In addition, analysis of the role of genetic polymorphisms in the dynamics of the molecule revealed that the genotype of a single-nucleotide polymorphism (rs6449182; C>G variation) in the CpG island of intron 1, harboring the retinoic-acid response element, exerts differential roles in CD38 expression in ASD and in parental LBC. In conclusion, our results provide an empirical basis for the development of a pharmacological ASD treatment strategy based on retinoids.

Dopamine D4 Receptor Gene Associated with Fairness Preference in Ultimatum Game

In experimental economics, the preference for reciprocal fairness has been observed in the controlled and incentivized laboratory setting of the ultimatum game, in which two individuals decide on how to divide a sum of money, with one proposing the share while the second deciding whether to accept. Should the proposal be accepted, the amount is divided accordingly. Otherwise, both would receive no money. A recent twin study has shown that fairness preference inferred from responder behavior is heritable, yet its neurogenetic basis remains unknown. The D4 receptor (DRD4) exon3 is a well-characterized functional polymorphism, which is known to be associated with attention deficit hyperactivity disorder and personality traits including novelty seeking and self-report altruism. Applying a neurogenetic approach, we find that DRD4 is significantly associated with fairness preference. Additionally, the interaction among this gene, season of birth, and gender is highly significant. This is the first result to link preference for reciprocal fairness to a specific gene and suggests that gene × environment interactions contribute to economic decision making.

U-shaped relation between plasma oxytocin levels and behavior in the trust game.

Trust underpins much of social and economic exchanges across human societies. In experimental economics, the Trust Game has served as the workhorse for the study of trust in a controlled incentivized setting. Recent evidence using intranasal drug administration, aka ‘sniffing’, suggests that oxytocin (OT) can function as a social hormone facilitating trust and other affiliative behaviors. Here we hypothesized that baseline plasma OT is a biomarker that partially predicts the degree of trust and trustworthiness observed in the trust game. Using a large sample of 1,158 participants, we observed a significant U-shaped relationship between plasma OT with the level of trust, and marginally with the level of trustworthiness, especially among males. Specifically, subjects with more extreme levels of plasma OT were more likely to be trusting as well as trustworthy than those with moderate levels of plasma OT. Our results contribute to a deeper understanding of the biological basis of human trust and underscore the usefulness of peripheral plasma OT measures in characterizing human social behavior.

Dissociable contribution of prefrontal and striatal dopaminergic genes to learning in economic games

Significance Game theory is used throughout the social and biological sciences to study behavior in social interactions. Recent research suggests an important role for the dopamine neurotransmitter system in these types of decisions. This study used a competitive game to study how people varied in their decision-making processes and related these differences in the set of genes that carry out biological functions required for dopaminergic functioning. We found that genes differentially expressed in separate brain regions influenced distinct components of people’s decision-making processes and that a surprising degree of consistency exists with what is known at the brain level about how people make decisions in social interactions. Game theory describes strategic interactions where success of players’ actions depends on those of coplayers. In humans, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating such behavior. Here we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Specifically, using gene-set analysis, we systematically examined contribution of different dopamine genes to variation in a multistrategy competitive game captured by (i) the degree players anticipate and respond to actions of others (belief learning) and (ii) the speed with which such adaptations take place (learning rate). We found that variation in genes that primarily regulate prefrontal dopamine clearance—catechol-O-methyl transferase (COMT) and two isoforms of monoamine oxidase—modulated degree of belief learning across individuals. In contrast, we did not find significant association for other genes in the dopamine pathway. Furthermore, variation in genes that primarily regulate striatal dopamine function—dopamine transporter and D2 receptors—was significantly associated with the learning rate. We found that this was also the case with COMT, but not for other dopaminergic genes. Together, these findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior.

Social Cognitive Role of Schizophrenia Candidate Gene GABRB2

The occurrence of positive selection in schizophrenia-associated GABRB2 suggests a broader impact of the gene product on population fitness. The present study considered the possibility of cognition-related GABRB2 involvement by examining the association of GABRB2 with psychosis and altruism, respectively representing psychiatric and psychological facets of social cognition. Four single nucleotide polymorphisms (SNPs) were genotyped for quantitative trait analyses and population-based association studies. Psychosis was measured by either the Positive and Negative Syndrome Scale (PANSS) or antipsychotics dosage, and altruism was based on a self-report altruism scale. The minor alleles of SNPs rs6556547, rs1816071 and rs187269 in GABRB2 were correlated with high PANSS score for positive symptoms in a Han Chinese schizophrenic cohort, whereas those of rs1816071 and rs1816072 were associated with high antipsychotics dosage in a US Caucasian schizophrenic cohort. Moreover, strongly significant GABRB2-disease associations were found among schizophrenics with severe psychosis based on high PANSS positive score, but no significant association was observed for schizophrenics with only mild psychosis. Interestingly, in addition to association with psychosis in schizophrenics, rs187269 was also associated with altruism in healthy Han Chinese. Furthermore, parallel to correlation with severe psychosis, its minor allele was correlated with high altruism scores. These findings revealed that GABRB2 is associated with psychosis, the core symptom and an endophenotype of schizophrenia. Importantly, the association was found across the breadth of the psychiatric (psychosis) to psychological (altruism) spectrum of social cognition suggesting GABRB2 involvement in human cognition.

Sex-Hormone Genes and Gender Difference in Ultimatum Game: Experimental Evidence from China and Israel

Combining the methodologies of experimental economics and molecular genetics, we report a genetic association between sex-hormone genes and ultimatum game (UG) behavior in a discovery sample from China and a replication sample from Israel. The androgen receptor gene is found to be associated with UG responder behavior for male but not female subjects in the Chinese population, but this finding is not replicated in the Israeli sample. The estrogen receptor β gene is significantly associated with female UG responder behavior but not for male subjects in the Chinese sample. This finding is marginally replicated in the Israeli sample. Overall, our findings provide suggestive evidence on a gender specific relationship between sex-hormone genes and UG responder behavior, and can contribute to a deeper understanding of gender differences in fairness preference at the level of molecular genetics.

Delay discounting, genetic sensitivity, and leukocyte telomere length

Significance This paper makes a singular contribution to understanding the association between biological aging indexed by leukocyte telomeres length (LTL) and delay discounting measured in an incentivized behavioral economic task. In a large group of young, healthy undergraduates, steeper delay discounting is significantly associated with shorter LTL, while controlling for risk attitude and health-related behaviors. Notably, we found that delay discounting and risk attitude—two fundamental determinants of economic preferences—are independently associated with LTL. Moreover, for the first time to our knowledge, the effects of well-studied oxytocin and estrogen receptor polymorphisms are shown to specifically moderate the impact of impatience on LTL. Our work suggests a path to integrate behavioral economic methodology to supposed biological mechanisms associated with health outcomes. In a graying world, there is an increasing interest in correlates of aging, especially those found in early life. Leukocyte telomere length (LTL) is an emerging marker of aging at the cellular level, but little is known regarding its link with poor decision making that often entails being overly impatient. Here we investigate the relationship between LTL and the degree of impatience, which is measured in the laboratory using an incentivized delay discounting task. In a sample of 1,158 Han Chinese undergraduates, we observe that steeper delay discounting, indexing higher degree of impatience, is negatively associated with LTL. The relationship is robust after controlling for health-related variables, as well as risk attitude—another important determinant of decision making. LTL in females is more sensitive to impatience than in males. We then asked if genes possibly modulate the effect of impatient behavior on LTL. The oxytocin receptor gene (OXTR) polymorphism rs53576, which has figured prominently in investigations of social cognition and psychological resources, and the estrogen receptor β gene (ESR2) polymorphism rs2978381, one of two gonadal sex hormone genes, significantly mitigate the negative effect of impatience on cellular aging in females. The current results contribute to understanding the relationship between preferences in decision making, particularly impatience, and cellular aging, for the first time to our knowledge. Notably, oxytocin and estrogen receptor polymorphisms temper accelerated cellular aging in young females who tend to make impatient choices.

Competitiveness and Stress

This study explores the relationship between competitiveness and stress. In Experiment 1, we examine the response of cortisol, the primary stress hormone, during both piece-rate and tournament tasks. We find that the more competitive tournament task induces a higher cortisol response than the less competitive piece-rate task. Moreover, more competitively inclined subjects exhibit higher stress responses induced by the tasks. In Experiment 2, we manipulate stress using the Trier Social Stress Test and find that induced stress does not significantly affect competitiveness. Taken together, our findings suggest a tendency for people who are competitively disposed to have high stress response.

Computational substrates of social norm enforcement by unaffected third parties

Enforcement of social norms by impartial bystanders in the human species reveals a possibly unique capacity to sense and to enforce norms from a third party perspective. Such behavior, however, cannot be accounted by current computational models based on an egocentric notion of norms. Here, using a combination of model-based fMRI and third party punishment games, we show that brain regions previously implicated in egocentric norm enforcement critically extend to the important case of norm enforcement by unaffected third parties. Specifically, we found that responses in the ACC and insula cortex were positively associated with detection of distributional inequity, while those in the anterior DLPFC were associated with assessment of intentionality to the violator. Moreover, during sanction decisions, the subjective value of sanctions modulated activity in both vmPFC and rTPJ. These results shed light on the neurocomputational underpinnings of third party punishment and evolutionary origin of human norm enforcement.