Risk-seeking for losses is associated with 5-HTTLPR, but not with transient changes in 5-HT levels

Neukam, Philipp T.; Kroemer, Nils B.; Deza-Araujo, Yacila I; Hellrung, Lydia; Pooseh, Shakoor; Rietschel, Marcella; Witt, Stephanie H.; Schwarzenbolz, Uwe; Henle, Thomas; Smolka, Michael N.

doi:10.1007/s00213-018-4913-9

Cited by 15 publications

(33 citation statements)

References 90 publications

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“…These participants form part of the sample already reported by Neukam et al (2018). Of these, we discarded five participants who received accidentally the same mixture in all sessions, four participants with excessive movement during the resting-state scan (see section on "Image preprocessing"), four participants with structural brain anomalies (e.g., cysts, enlarged ventricles) detected by a neuroradiologist, two participants who did not complete one resting state scan and 12 participants with limited brain coverage or scanner artifacts in one or all resting-state sessions.…”

Section: Participantsmentioning

confidence: 99%

“…Other behavioral and cognitive measures as well as demographic information were acquired (see Neukam et al (2018) and Supporting Information The resulting main discounting parameters from these tasks (k) were log-transformed in order to approximate them to a normal distribution.…”

Section: Biochemical Measuresmentioning

confidence: 99%

“…M age = 32.68 years, SD age AE 5.81, range = 21-42) were analyzed in this study. These participants form part of the sample already reported by Neukam et al (2018). The detailed recruitment process is described in the Supporting Information Material S1.…”

Section: Participantsmentioning

confidence: 99%

“…Due to missing data the number of complete behavioral datasets ranged from 82 to 85. Other behavioral and cognitive measures as well as demographic information were acquired (see Neukam et al (2018) and Supporting Information…”

Section: Behavioral Assessmentmentioning

confidence: 99%

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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: Participantsmentioning

confidence: 99%

Section: Biochemical Measuresmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Behavioral Assessmentmentioning

confidence: 99%

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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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“…Given that our PET measure has only been shown to provide reliable information about DA functioning within the striatum [35], we were unable to explore the role of baseline DA in extra-striatal regions. Lastly, due to our recruitment strategy [50], our sample was biased in terms of gender ratio and 5-HTTLPR genotype. As such, generalisability of our results is limited.…”

Section: Discussionmentioning

confidence: 99%

Individual differences in dopamine function underlying the balance between model-based and model-free control

Lee

Deserno

Kroemer

et al. 2019

Preprint

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Reinforcement learning involves a balance between model-free (MF) and model-based (MB) systems. Recent studies suggest that individuals with either pharmacologically enhanced levels of dopamine (DA) or higher baseline levels of DA exhibit more MB control. However, it remains unknown whether such pharmacological effects depend on baseline DA.Here, we investigated whether effects of L-DOPA on the balance of MB/MF control depend on ventral striatal baseline DA. Sixty participants had two functional magnetic resonance imaging (fMRI) scans while performing a two-stage sequential decision-making task under 150 mg L-DOPA or placebo (counterbalanced), followed by a 4-hour 18 F-DOPA positron emission tomography (PET) scan (on a separate occasion).We found an interaction between baseline DA levels and L-DOPA induced changes in MB control. Individuals with higher baseline DA levels showed a greater L-DOPA induced enhancement in MB control. Surprisingly, we found a corresponding drug-by-baseline DA interaction on MF, but not MB learning signals in the ventromedial prefrontal cortex. We did not find a significant interaction between baseline DA levels and L-DOPA effects on MF control or MB/MF balance.In sum, our findings point to a baseline dependency of L-DOPA effects on differential aspects of MB and MF control. Individual differences in DA washout may be an important moderator of L-DOPA effects. Overall, our findings complement the general notion where higher DA levels is related to a greater reliance on MB control. Although the relationship between phasic DA firing and MF learning is conventionally assumed in the animal literature, the relationship between DA and MF control is not as straightforward and requires further clarification.

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Beyond substance use disorders

Yates¹

2023

Determinants of Addiction

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Risk-seeking for losses is associated with 5-HTTLPR, but not with transient changes in 5-HT levels

Cited by 15 publications

References 90 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

Individual differences in dopamine function underlying the balance between model-based and model-free control

Beyond substance use disorders

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