Serotonergic modulation in executive functioning: Linking genetic variations to working memory performance

Enge, Sören; Fleischhauer, Monika; Lesch, Klaus‐Peter; Reif, Andreas; Strobel, Alexander

doi:10.1016/j.neuropsychologia.2011.09.038

Cited by 66 publications

(62 citation statements)

References 66 publications

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“…In this context, our finding of enhanced activity in the DLPFC in MAOA-L carriers might also be interpreted in an alternative manner: Cerasa et al [17] and Passamonti et al [19] suggested the high-expressing genetic variant ( MAOA-H carriers) to be accompanied by increased prefrontal activation to compensate for reduced cortical efficiency due to reduced 5-HT function. In the n-back study of Enge et al [18], the amplitude of the N2 ERP as indicator of withholding inadequate prepotent reactions was generally -enhanced in MAOA-L compared to MAOA-H carriers. With regard to the present study, we took the possibility of superior inhibitory control in MAOA-L carriers into account by additionally comparing RTs in incompatible and compatible conditions (irrespective of valence) between MAOA-L and MAOA-H carriers.…”

Section: Discussionmentioning

confidence: 99%

“…), but a trend for faster reactions of MAOA-L carriers in incompatible conditions (t(27) = -1.99, p = 0.06). However, this alternative interpretation needs clarification in future studies, since it is not supported by the behavioral results of the other studies on executive functions and MAOA [17,18,19], and the low-expressing genetic variant has repeatedly been linked to impulsive behavior, which, in turn, is often accompanied by diminished inhibitory control (cf. [65,66]).…”

Section: Discussionmentioning

confidence: 99%

“…Thereby, further investigations on possible epistatic effects of the MAOA polymorphism and a polymorphism in the promoter region of the NE transporter gene ( NET-3081 ; cf. [18]) might also be of interest for the AAT as depicting different aspects of executive functions.…”

Section: Discussionmentioning

confidence: 99%

“…In an n-back task, Cerasa et al [17] showed MAOA-L compared to MAOA-H carriers to display longer RTs and lower activation in the right ventrolateral PFC. Also in an n-back task, Enge et al [18] found inferior performance of MAOA-L compared to MAOA-H carriers in terms of enhanced RTs and slower processing speed as indicated by longer latencies of the P3b event-related potential (ERP). Passamonti et al [19] found MAOA-L carriers to display - by trend - slower RTs than MAOA-H carriers in a go/no-go task.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Variation in MAOA Modulates Prefrontal Cortical Regulation of Approach-Avoidance Reactions

Ernst

Lutz²,

Ehlis

et al. 2013

Neuropsychobiology

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Background: Regulation of automatic approach and avoidance behavior requires affective and cognitive control, which are both influenced by a genetic variation in the gene encoding Monoamine Oxidase A (termed MAOA-uVNTR). Methods: The current study investigated MAOA genotype as a moderator of prefrontal cortical activation measured with functional near-infrared spectroscopy (fNIRS) in 37 healthy young adults during performance of the approach-avoidance task with positive and negative pictures. Results: Carriers of the low- compared to the high-expressing genetic variant (MAOA-L vs. MAOA-H) showed increasing regulatory activity in the right dorsolateral prefrontal cortex (DLPFC) during incompatible conditions (approach negative, avoid positive). This might have been a compensatory mechanism for stronger emotional reactions as shown in previous studies and might have prevented any influence of incompatibility on behavior. In contrast, fewer errors but also lower activity in the right DLPFC during processing of negative compared to positive stimuli indicated MAOA-H carriers to have used other regulatory areas. This resulted in slower reaction times in incompatible conditions, but - in line with the known better cognitive regulation efficiency - allowed them to perform incompatible reactions without activating the DLPFC as the highest control instance. Carriers of one low- and one high-expressing allele lay as an intermediate group between the reactions of the low- and high-expressing groups. Conclusions: The relatively small sample size and restriction to fNIRS for assessment of cortical activity limit our findings. Nevertheless, these first results suggest monoam-inergic mechanisms to contribute to interindividual differences in the two basic behavioral principles of approach and avoidance and their neuronal correlates.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic Variation in MAOA Modulates Prefrontal Cortical Regulation of Approach-Avoidance Reactions

Ernst

Lutz²,

Ehlis

et al. 2013

Neuropsychobiology

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“…However, results of the genetic studies are inconsistent. Some authors found the long allele of 5-HTTLPR to be associated with superior WM performance (Bosia et al, 2010;Zilles et al, 2012), whereas others claimed the short allele to be associated with improved performance (Enge et al, 2011;Anderson et al, 2012). It was argued that these conflicting results may either be due to a task specificity of the 5-HTTLPR (Anderson et al, 2012;Zilles et al, 2012) or due to undetected and moderating environmental factors (Zilles et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users

Havranek

Vonmoos

Müller

et al. 2015

Neuropsychopharmacol

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Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence.

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Investigation of association of serotonin transporter and monoamine oxidase‐A genes with Alzheimer's disease and depression in the VITA study cohort: A 90‐month longitudinal study

Scholz

Jungwirth

Danielczyk

et al. 2014

American J of Med Genetics Pt B

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Alzheimer's disease (AD) and depression (DE) are common psychiatric disorders strongly intertwined with one another. Nevertheless, etiology and early diagnosis of the disorders are still elusive. Several genetic variations have been suggested to associate with AD and DE, particularly in genes involved in the serotonergic system such as the serotonin transporter (SERT/SLC6A4), responsible for the removal from the synaptic cleft, and the monoamine-oxidase-A (MAOA), responsible for the presynaptic degradation of serotonin. Here, we attempt to characterize this pleiotropic effect for the triallelic SERT gene-linked polymorphic region (5HTTLPR) and for the MAOA-uVNTR, in participants in the Vienna-Transdanube-Aging (VITA)-study. The VITA-study is a community-based longitudinal study following a birth cohort (75 years old at baseline examination, n = 606) from Vienna for a period of 90 months with a regular follow-up interval of 30 months. Our main finding, confirming previous reports, is that the 5HTTLPR S-allele is a risk allele for DE (OR = 1.55 CI 95% 1.03-2.32) and its carriers had a steeper increase in SGDS sum score. No association to AD was found. MAOA-uVNTR did not associate with either AD or DE. However, in AD MAOA-uVNTR S-allele carriers a steeper increase of HAMD and STAI1 sum scores (P < 0.05) was observed. Although the VITA-study cohort is rather small with low power to detect gene alterations, the uniqueness of this very thoroughly investigated and homogenous cohort strengthens the results through exceptional data collection. Still, reinvestigation in a larger cohort similar to this, as well as a meta-analysis, is important to confirm these results.

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Serotonergic modulation in executive functioning: Linking genetic variations to working memory performance

Cited by 66 publications

References 66 publications

Genetic Variation in <b><i>MAOA</i></b> Modulates Prefrontal Cortical Regulation of Approach-Avoidance Reactions

Genetic Variation in <b><i>MAOA</i></b> Modulates Prefrontal Cortical Regulation of Approach-Avoidance Reactions

Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users

Investigation of association of serotonin transporter and monoamine oxidase‐A genes with Alzheimer's disease and depression in the VITA study cohort: A 90‐month longitudinal study

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