Cortico‐limbic connectivity in <i>MAOA</i>‐L carriers is vulnerable to acute tryptophan depletion

Eisner, Patrick; Klasen, Martin; Wolf, Dhana; Zerres, Klaus; Eggermann, Thomas; Eisert, Albrecht; Zvyagintsev, Mikhail; Sarkheil, Pegah; Mathiak, Krystyna A.; Zepf, Florian Daniel; Mathiak, Klaus

doi:10.1002/hbm.23475

Cited by 20 publications

(19 citation statements)

References 115 publications

(136 reference statements)

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“…Furthermore, methodological differences may also explain why others have reported ATD effects. For example, seed-based approaches provide more power due to strong a priori hypotheses regarding the functional connectivity of the seed region and, therefore, capture more subtle connectivity changes (Eisner et al, 2017). Similarly, other ATD studies use resting-state data but analyze measures, like fractional amplitude Table 2).…”

Section: Discussionmentioning

confidence: 99%

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

Deza‐Araujo

Neukam

Marxen

et al. 2018

Human Brain Mapping

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It has been shown that the functional architecture of the default mode network (DMN) can be affected by serotonergic challenges and these effects may provide insights on the neurobiological bases of depressive symptomatology. To deepen our understanding of this possible interplay, we used a double‐blind, randomized, cross‐over design, with a control condition and two interventions to decrease (tryptophan depletion) and increase (tryptophan loading) brain serotonin synthesis. Resting‐state fMRI from 85 healthy subjects was acquired for all conditions 3 hr after the ingestion of an amino acid mixture containing different amounts of tryptophan, the dietary precursor of serotonin. The DMN was derived for each participant and session. Permutation testing was performed to detect connectivity changes within the DMN as well as between the DMN and other brain regions elicited by the interventions. We found that tryptophan loading increased tryptophan plasma levels and decreased DMN connectivity with visual cortices and several brain regions involved in emotion and affect regulation (i.e., putamen, subcallosal cortex, thalamus, and frontal cortex). Tryptophan depletion significantly reduced tryptophan levels but did not affect brain connectivity. Subjective ratings of mood, anxiety, sleepiness, and impulsive choice were not strongly affected by any intervention. Our data indicate that connectivity between the DMN and emotion‐related brain regions might be modulated by changes in the serotonergic system. These results suggest that functional changes in the brain associated with different brain serotonin levels may be relevant to understand the neural bases of depressive symptoms.

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Section: Discussionmentioning

confidence: 99%

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

Deza‐Araujo

Neukam

Marxen

et al. 2018

Human Brain Mapping

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“…1). These various 5-HT-related polymorphisms may form an interactive system that determines the aetiology and prognosis of various forms of affective disorder (17,(99)(100)(101)(102) . However, the most evidenced serotonergic genetic influence on behaviour is the 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) polymorphism of the serotonin transporter gene (SLC6A4) (103)(104) .…”

Section: Role Of Genetics In Moderating Effects Of L-tryptophan Supplmentioning

confidence: 99%

Tryptophan supplementation and serotonin function: genetic variations in behavioural effects

Gibson

2018

Proc. Nutr. Soc.

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The neurotransmitter serotonin has a role in affective disorders such as depression and anxiety, as well as sleep, cognitive function and appetite. This review examines the evidence that serotonin-related genotypes may moderate the behavioural effects of supplementation with the serotonin precursor amino acid l-tryptophan (TRP), on which synthesis of serotonin (or 5-hydroxytryptamine; 5-HT) depends. However, 95 % of serotonin is synthesised and used in the periphery, and TRP is also metabolised via non-5-HT routes such as the kynurenine pathway. Moreover, understanding of genotypes involved in regulation of serotonin raises questions over the generalisability of TRP effects on behaviour across individuals with varied serotonergic genotypes. To date, only differences between variants of the 5-HT transporter-linked promoter region (5-HTTLPR) have been investigated in relation to behavioural effects of TRP supplementation. Effects of 5-HTTLPR genotypes are usually compared between the alleles that are either high (L/L') or low (S/S') expressing of mRNA for the 5-HT transporter receptor. Yet, another key genetic variable is sex: in women, the S/S' genotype predicts sensitivity to improved mood and reduced cortisol by TRP supplementation, during stressful challenges, whereas the L/L' genotype protects against stress-induced mood deterioration. In men, the L/L' genotype may confer risk of stress-induced increases in negative affect; there are insufficient data to assess effects on male S/S' genotypes. However, better-powered studies to detect sex by genotype by stress by TRP interactions, as well as consideration of more genotypes, are needed before strong conclusions and recommendations for behavioural effects of TRP treatment can be reached.

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“…In addition, heathy L- MAOA carriers showed prominent structural and functional changes in the corticolimbic network, which plays a crucial role in regulating emotional states during the recall of negative events 17 . Recent work showed that L- MAOA carriers are more susceptible to pharmacological regulation by serotonin, with changes in the corticolimbic network, indicating a possible link between the serotoninergic system and MAOA genotype 38 . The effects of MAOA genotype on the dopaminergic system remain controversial.…”

Section: Introductionmentioning

confidence: 99%

MAOA variants differ in oscillatory EEG & ECG activities in response to aggression-inducing stimuli

Jeong

Jin

et al. 2019

Sci Rep

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Among the genetic variations in the monoamine oxidase A ( MAOA ) gene, upstream variable number tandem repeats (uVNTRs) of the promoter have been associated with individual differences in human physiology and aggressive behaviour. However, the evidence for a molecular or neural link between MAOA uVNTRs and aggression remains ambiguous. Additionally, the use of inconsistent promoter constructs in previous studies has added to the confusion. Therefore, it is necessary to demonstrate the genetic function of MAOA uVNTR and its effects on multiple aspects of aggression. Here, we identified three MAOA alleles in Koreans: the predominant 3.5R and 4.5R alleles, as well as the rare 2.5R allele. There was a minor difference in transcriptional efficiency between the 3.5R and 4.5R alleles, with the greatest value for the 2.5R allele, in contrast to existing research. Psychological indices of aggression did not differ among MAOA genotypes. However, our electroencephalogram and electrocardiogram results obtained under aggression-related stimulation revealed oscillatory changes as novel phenotypes that vary with the MAOA genotype. In particular, we observed prominent changes in frontal γ power and heart rate in 4.5R carriers of men. Our findings provide genetic insights into MAOA function and offer a neurobiological basis for various socio-emotional mechanisms in healthy individuals.

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Cortico‐limbic connectivity in MAOA‐L carriers is vulnerable to acute tryptophan depletion

Cited by 20 publications

References 115 publications

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

Tryptophan supplementation and serotonin function: genetic variations in behavioural effects

MAOA variants differ in oscillatory EEG & ECG activities in response to aggression-inducing stimuli

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