Recent Progress in Psychiatric Genetics—Some Hope but No Hype

The reputation of the field of psychiatric genetics has recently become tarnished in the view of many human geneticists. Too many linked loci were claimed and withdrawn, too many association studies published and not confirmed, and, more recently, too many new and different chromosomal regions have been implicated for the same disorder. Here, we summarize recent trends, focusing on research that moves away from traditional linkage studies. Some promising strategies include psychopharmacogenetics and consideration of endophenotypes such as neurophysiological and behavioral markers in addition to the clinical diagnosis. Utilization of rapid and automated methods for scoring genetic variants in large-scale association studies followed by multivariate analyses, which include environmental as well as genetic data, will likely fare better than traditional linkage analysis in disentangling the complex genetics of psychiatric disorders. Some notable areas of recent progress include quantification of the genetic complexity of autism, identification of genetic variants protecting individuals from alcoholism, and the description of several polymorphisms likely to be relevant to behavior and psychiatry. The most notable example may be a common variant that affects the transcription rate in the promoter for the serotonin transporter gene that may be relevant for individual differences in the response to common antidepressants

Enjoyment of Sexualization is Associated with Alcohol Use, Self-Objectification is Not

The main purpose of this study was to determine how the enjoyment of sexualization impacts the relationship between self-objectification and alcohol use. Alcohol use is prevalent within college communities and may lead to damaging experiences. Participants were 892 undergraduate women who completed an online questionnaire including measurements of self-objectification, enjoyment of sexualization, as well as an alcohol survey. A general linear model was used to analyze these relationships and interactions. Data analysis showed that while enjoyment of sexualization was associated positively with alcohol use, self-objectification was not, and there was no significant interaction between the two variables. This provides evidence that enjoyment of sexualization is a more significant potential risk factor for drinking behavior than self-objectification. This understanding may lead to the reduction of alcohol consumption risk factors in women through therapies aimed at decreasing enjoyment of sexualization

Gender Moderates the Association between 5-HTTLPR and Decision-making under Ambiguity but Not under Risk

Decisions made under ambiguity may involve a different genetic architecture than those made under risk. Because gender moderates the effect of genetic polymorphisms on serotonin function and because there are gender differences in decision-making, the present study examined potential gender moderation of associations between polymorphisms in important serotonin system candidate genes (serotonin transporter [SLC6A4] and tryptophan hydroxylase-2 [TPH2]) and performance on a decision-making task (Iowa Gambling Task, IGT) in healthy, adults (N = 188; 62% women). Subjects were genotyped for the well-studied SLC6A4 promoter variant 5-HTTLPR and a TPH2 single nucleotide polymorphism in intron-8 (rs1386438). Genotype at rs1386438was not associated with performance on the IGT. A significant gender by 5-HTTLPR genotype interaction effect was detected when decision-making was under ambiguity (i.e., the first block of 20 choices) but not under risk (blocks 2–5). Performance on the first block of 20 choices was not correlated with performance on subsequent blocks, supporting the interpretation that early performance on the IGT indexes decision-making under ambiguity, while performance on blocks 2–5 indexes decision-making under risk. These findings suggest that decision-making under ambiguity and risk may have different genetic architectures and that individual differences in decision-making under ambiguity are associated with genetic variation in SLC6A4

Oxytocin Receptor (\u3ci\u3eOXTR\u3c/i\u3e) Single Nucleotide Polymorphisms Indirectly Predict Prosocial Behavior through Perspective Taking and Empathic Concern

Engaging in prosocial behavior can provide positive outcomes for self and others. Prosocial tendencies contribute to the propensity to engage in prosocial behavior.The oxytocin receptor gene (OXTR) has also been associated with prosocial tendencies and behaviors. There has been little research, however, investigating whether the relationship between OXTR and prosocial behaviors is mediated by prosocial tendencies.This relationship may also vary among different types of prosocial behavior. The current study examines the relationship between OXTR, gender, prosocial tendencies, and both altruistic and public prosocial behavior endorsement. Students at a midwestern university (N = 398; 89.2% Caucasian; Mage = 20.76; 26.6% male) provided self-report measures of prosocial tendencies and behaviors and buccal cells for genotyping OXTR polymorphisms. Results indicated that OXTR single nucleotide polymorphism (SNP) rs2268498 genotype significantly predicted empathic concern, whereas gender moderated the association between several other OXTR SNPs and prosocial tendencies. Increased prosocial tendencies predicted increased altruistic prosocial behavior endorsement and decreased public prosocial behavior endorsement. Our findings suggest an association between genetic variation in OXTR and endorsement of prosocial behavior indirectly through prosocial tendencies, and that the pathway is dependent on the type of prosocial behavior and gender

Does gender moderate associations among impulsivity and health-risk behaviors?

The present study explores the relations among gender, impulsivity and three health-risk behaviors relevant to young adults (tobacco use, alcohol problems and gambling problems) in a sample of 197 college-age individuals. We sought to determine whether impulsivity is associated with health-risk behaviors in the same ways for men and women. For tobacco use and gambling problems, men were at higher risk than women, and impulsivity was not significantly associated with higher risk. Higher levels of motor impulsivity in men accounted for a significant amount of the gender difference in risk for alcohol problems. That is, impulsivity as measured by the Barratt Impulsiveness Scale (version 11), mediated the association between gender and risk for alcohol problems. For impulsivity as measured by Stop Signal Reaction Time (i.e. response inhibition), gender moderated the association between impulsivity and alcohol problems. Specifically, lower levels of impulsivity were associated with greater risk for alcohol problems in both men and women, but the effect was stronger in men. We speculate that this seemingly paradoxical result might be the result of coping drinking to deal with negative affect associated with behavioral overcontrol. These findings suggest that prevention efforts might well focus on identifying individuals at high risk for alcohol problems, especially males, by assessing response inhibition

Association Between the Serotonin Transporter Triallelic Genotype and Eating Problems is Moderated by the Experience of Childhood Trauma in Women

Objective—This study investigated a potential interaction between the triallelic polymorphism of the serotonin transporter gene (SLC6A4) promoter and the experience of childhood trauma on the number of problem eating behaviors. Methods—The study sample was comprised of 439 (64.7% female) Caucasian college students (mean age = 22.49, SD = 6.12). Participants completed questionnaires that assessed eating problems and experience of trauma in childhood (ages 0-12) and donated cheek cells for 5- HTTLPR and rs25531 genotyping. Results—Women carrying a lower expressing allele (i.e. LG or S) who were exposed to higher levels of childhood trauma reported significantly higher mean numbers of eating problems (gender × genotype × trauma interaction, p = .006). Discussion—These results are consistent with findings that the lower expressing alleles of the SLC6A4 promoter are associated with increased sensitivity to the negative impact of childhood stressors on adult behavioral outcomes

Serotonin System Gene Polymorphisms Are Associated with Impulsivity in a Context Dependent Manner

Impulsivity is a risk factor for adverse outcomes and characterizes several psychiatric disorders and risk for suicide. There is strong evidence that genetic variation influences individual differences in impulsivity, but the details are not yet understood. There is growing interest in better understanding the context dependency of genetic effects that is reflected in studies examining gender specificity, gene × environment interaction and epistasis (gene-gene interaction). In a cross-sectional study we examined whether polymorphisms in six serotonin system candidate genes and the experience of early life trauma (age 0–12) were associated with individual differences in impulsivity in a nonclinical sample of Caucasian university students (N = 424). We specifically tested potential gender specific, gene-gene, and gene × environment (early life trauma) effects. In our main analyses with Barratt Impulsiveness Scale (BIS-11) total score, there were significant (i.e., p \u3c .01 and False Discovery Rate \u3c .10) interactions between (1) gender and TPH2 (rs1386483) genotype; (2) gender and HTR2A (rs6313) genotype; and epistatic interactions among (3) 5-HTTLPR and MAOA uVNTR; (4) 5-HTTLPR and rs6313 and (5) HTR1B (rs6296) and rs6313 genotypes. Our results strongly support the explicit investigation of context-dependent genetic effects on impulsivity and may help to resolve some of the conflicting reports in the literature

Does gender moderate associations among impulsivity and health-risk behaviors?

The present study explores the relations among gender, impulsivity and three health-risk behaviors relevant to young adults (tobacco use, alcohol problems and gambling problems) in a sample of 197 college-age individuals. We sought to determine whether impulsivity is associated with health-risk behaviors in the same ways for men and women. For tobacco use and gambling problems, men were at higher risk than women, and impulsivity was not significantly associated with higher risk. Higher levels of motor impulsivity in men accounted for a significant amount of the gender difference in risk for alcohol problems. That is, impulsivity as measured by the Barratt Impulsiveness Scale (version 11), mediated the association between gender and risk for alcohol problems. For impulsivity as measured by Stop Signal Reaction Time (i.e. response inhibition), gender moderated the association between impulsivity and alcohol problems. Specifically, lower levels of impulsivity were associated with greater risk for alcohol problems in both men and women, but the effect was stronger in men. We speculate that this seemingly paradoxical result might be the result of coping drinking to deal with negative affect associated with behavioral overcontrol. These findings suggest that prevention efforts might well focus on identifying individuals at high risk for alcohol problems, especially males, by assessing response inhibition

Association Between the Serotonin Transporter Triallelic Genotype and Eating Problems is Moderated by the Experience of Childhood Trauma in Women

Objective—This study investigated a potential interaction between the triallelic polymorphism of the serotonin transporter gene (SLC6A4) promoter and the experience of childhood trauma on the number of problem eating behaviors. Methods—The study sample was comprised of 439 (64.7% female) Caucasian college students (mean age = 22.49, SD = 6.12). Participants completed questionnaires that assessed eating problems and experience of trauma in childhood (ages 0-12) and donated cheek cells for 5- HTTLPR and rs25531 genotyping. Results—Women carrying a lower expressing allele (i.e. LG or S) who were exposed to higher levels of childhood trauma reported significantly higher mean numbers of eating problems (gender × genotype × trauma interaction, p = .006). Discussion—These results are consistent with findings that the lower expressing alleles of the SLC6A4 promoter are associated with increased sensitivity to the negative impact of childhood stressors on adult behavioral outcomes

Emotion moderates the association between \u3ci\u3eHTR2A\u3c/i\u3e (rs6313) genotype and antisaccade latency

The serotonin system is heavily involved in cognitive and emotional control processes. Previous work has typically investigated this system’s role in control processes separately for cognitive and emotional domains, yet it has become clear the two are linked. The present study, therefore, examined whether variation in a serotonin receptor gene (HTR2A, rs6313) moderated effects of emotion on inhibitory control. An emotional antisaccade task was used in which participants looked toward (prosaccade) or away (antisaccade) from a target presented to the left or right of a happy, angry, or neutral face. Overall, antisaccade latencies were slower for rs6313 C allele homozygotes than T allele carriers, with no effect of genotype on prosaccade latencies. Thus, C allele homozygotes showed relatively weak inhibitory control but intact reflexive control. Importantly, the emotional stimulus was either present during target presentation (overlap trials) or absent (gap trials). The gap effect (slowed latency in overlap versus gap trials) in antisaccade trials was larger with angry versus neutral faces in C allele homozygotes. This impairing effect of negative valence on inhibitory control was larger in C allele homozygotes than T allele carriers, suggesting that angry faces disrupted/ competed with the control processes needed to generate an antisaccade to a greater degree in these individuals. The genotype difference in the negative valence effect on antisaccade latency was attenuated when trial N-1 was an antisaccade, indicating top-down regulation of emotional influence. This effect was reduced in C/C versus T/_ individuals, suggesting a weaker capacity to downregulate emotional processing of task-irrelevant stimuli