Serotonin Transporter (5-HTTLPR) Genotype and Childhood Trauma are Associated with Individual Differences in Decision Making

Stoltenberg, Scott F.; Lehmann, Melissa K.; Anderson, C.; Nag, P.V. Sunil; Anagnopoulos, Cheryl

doi:10.3389/fgene.2011.00033

Cited by 27 publications

(28 citation statements)

References 39 publications

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“…However, little is known on how childhood traumatic events may affect this developmental process. In humans, there is only one study suggesting that childhood trauma may be associated with lower decision-making abilities (Stoltenberg et al, 2011). This study did not find any interactions between some polymorphisms in the serotonin transporter gene and childhood abuse on decision-making performance.…”

Section: Introductioncontrasting

confidence: 58%

HPA axis genes may modulate the effect of childhood adversities on decision-making in suicide attempters

Guillaume

Perroud

Jollant

et al. 2013

Journal of Psychiatric Research

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Decision-making impairment is found in several neuropsychiatric disorders, including suicidal behavior, and has been shown to be modulated by genes. On the other hand, early trauma has been associated with poor mental health outcome in adulthood, in interaction with genetic factors, possibly through sustained alterations in the hypothalamo-pituitary-adrenal axis (HPA axis). Here, we aimed to investigate the effect of childhood trauma and its interaction with HPA-axis related genes on decision-making abilities in adulthood among a sample of suicide attempters. The Iowa Gambling Task (IGT) was used to assess decisionmaking in 218 patients with a history of suicide attempt. Participant fulfilled the Childhood Trauma Questionnaire to report traumatic childhood experiences. Patients were genotyped for single-nucleotide polymorphisms within CRHR1 and CRHR2 genes. Patients with a history of sexual abuse had significantly lower IGT scores than non-sexually abused individuals.Polymorphisms within CRHR1 and CRHR2 genes interacted with both childhood sexual abuse and emotional neglect to influence IGT performance. In conclusion, childhood sexual abuse and emotional neglect may have long-term effects on decision-making through an interaction with key HPA axis genes. Even if these results need to be replicated in other samples, impaired decision-making may thus be the dimension through which child maltreatment, in interaction with HPA axis related genes, may have a sustained negative impact on adult mental health.

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Section: Introductioncontrasting

confidence: 58%

HPA axis genes may modulate the effect of childhood adversities on decision-making in suicide attempters

Guillaume

Perroud

Jollant

et al. 2013

Journal of Psychiatric Research

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“…The COMT (catechol- O -methyltransferase) gene polymorphism leading to an increased level of endogenous dopamine, and serotonin transporter (5-HTTLPR) polymorphisms have been associated to decision-making impairments (Heitland et al 2012; Homberg et al 2008; Malloy-Diniz et al 2013). However, the results concerning 5-HT are somewhat contradictory (Gendle and Golding 2010; Heitland et al 2012; Homberg et al 2008; Koot et al 2012; Lage et al 2011; Macoveanu et al 2013; Pittaras et al 2013; Stoltenberg et al 2011; Zeeb et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Individual behavioral and neurochemical markers of unadapted decision-making processes in healthy inbred mice

et al. 2016

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One of the hallmarks of decision-making processes is the inter-individual variability between healthy subjects. These behavioral patterns could constitute risk factors for the development of psychiatric disorders. Therefore, finding predictive markers of safe or risky decision-making is an important challenge for psychiatry research. We set up a mouse gambling task (MGT)—adapted from the human Iowa gambling task with uncertain contingencies between response and outcome that furthermore enables the emergence of inter-individual differences. Mice (n = 54) were further individually characterized for locomotive, emotional and cognitive behavior. Individual basal rates of monoamines and brain activation after the MGT were assessed in brain regions related to reward, emotion or cognition. In a large healthy mice population, 44 % showed a balanced strategy with limited risk-taking and flexible choices, 29 % showed a safe but rigid strategy, while 27 % adopted risky behavior. Risky mice took also more risks in other apparatus behavioral devices and were less sensitive to reward. No difference existed between groups regarding anxiety, working memory, locomotion and impulsivity. Safe/rigid mice exhibited a hypoactivation of prefrontal subareas, a high level of serotonin in the orbitofrontal cortex combined with a low level of dopamine in the putamen that predicted the emergence of rigid behavior. By contrast, high levels of dopamine, serotonin and noradrenalin in the hippocampus predicted the emergence of more exploratory and risky behaviors. The coping of C57bl/6J mice in MGT enables the determination of extreme patterns of choices either safe/rigid or risky/flexible, related to specific neurochemical and behavioral markers.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-016-1192-2) contains supplementary material, which is available to authorized users.

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“…However, samples of healthy adults and schizophrenics carrying the long allele have been found to have impaired performance on the fi rst block of the IGT (Gu et al, 2013;Stoltenberg and Vandever, 2010;Stoltenberg et al, 2011). Thus, additional research is needed to investigate possible mediators and moderators of the relation between this polymorphism and decision making.…”

Section: Discussionmentioning

confidence: 99%

“…In combination with rs25531, 5-HTTLPR is functionally triallelic and infl uences serotonin transporter gene expression and serotonin concentration in the synaptic cleft (Heils et al, 1996); the short (S) and long-G (LG) alleles are associated with lower serotonin transporter activity than the long-A (LA) allele. 5-HTTLPR low-activity allele carriers have been shown to have impaired performance on the IGT (Homberg et al, 2008;van den Bos et al, 2009;Verdejo-García et al, 2013), although some studies have noted that long-allele carriers show impairment on early trial blocks (Gu et al, 2013;Stoltenberg and Vandever, 2010;Stoltenberg et al, 2011).…”

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confidence: 99%

Maladaptive Decision Making and Substance Use Outcomes in High-Risk Individuals: Preliminary Evidence for the Role of 5-HTTLPR Variation

O’Brien

Lichenstein

Hill

2014

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Individuals with multiple alcohol-dependent (AD) relatives are at increased risk for substance use disorders (SUDs). Prospective, longitudinal studies of high-risk (HR) individuals afford the opportunity to determine potential risk markers of SUDs. The current study assessed the effect of familial risk and genetic variation on Iowa Gambling Task (IGT) performance and tested for an association between IGT performance and SUD outcomes. Method: Individuals from multiplex AD families (n = 63) and low-risk (LR; n = 45) control families, ages 16-34 years, were tested using a computerized version of the IGT. SUD outcomes were assessed at approximately yearly intervals. 5-HTTLPR and COMT genotypes were available for the majority of participants (n = 86). Results: HR offspring showed poorer performance overall on the IGT and especially poor performance on the fi nal trial block (Block 5), indicating a failure to improve decision making with previous experience. The 5-HTTLPR short-allele homozygote participants performed worse than long-allele carriers, with HR S/S carriers exhibiting particularly poor performance. There was no main effect of COMT on IGT performance and no signifi cant COMT by Risk interaction. Signifi cantly more individuals in the HR than LR group met criteria for SUD. Importantly, disadvantageous performance on IGT Block 5 was signifi cantly associated with an earlier age at SUD onset. Conclusions: This is the fi rst study to show that both familial risk of SUD and 5-HTTLPR variation impact performance on the IGT. Poorer IGT performance was associated with earlier onset of SUD, suggesting that HR individuals who fail to appropriately attend to long-term costs and benefi ts during a decision-making task are especially at risk for developing SUD in adolescence and young adulthood. (J. Stud. Alcohol Drugs, 75, 643-652, 2014)

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Serotonin Transporter (5-HTTLPR) Genotype and Childhood Trauma are Associated with Individual Differences in Decision Making

Cited by 27 publications

References 39 publications

HPA axis genes may modulate the effect of childhood adversities on decision-making in suicide attempters

HPA axis genes may modulate the effect of childhood adversities on decision-making in suicide attempters

Individual behavioral and neurochemical markers of unadapted decision-making processes in healthy inbred mice

Maladaptive Decision Making and Substance Use Outcomes in High-Risk Individuals: Preliminary Evidence for the Role of 5-HTTLPR Variation

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