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Cognitive function is related to fronto-striatal serotonin transporter levels – a brain PET study in young healthy subjects

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Abstract

Rationale

Pharmacological manipulation of serotonergic neurotransmission in healthy volunteers impacts on cognitive test performance. Specifically, markers of serotonin function are associated with attention and executive functioning, long-term memory, and general cognitive ability. The serotonin transporter (SERT) protein is a key regulator in the serotonin system. We hypothesized that higher performance on tests sensitive to serotonin would be associated with higher SERT levels in specific fronto-striatal brain regions.

Methods

Thirty-two healthy subjects (25 males, mean age 26.0 years, range 19–37) underwent positron emission tomography using the SERT ligand [11C]DASB. Subjects underwent the following tests: Stroop Color Word Test, Trail Making Test B, Rey’s Auditory Verbal Learning Test and Complex Figure Test, logical reasoning subtest from Intelligenz-Struktur-Test 2000 R, and a Danish version of National Adult Reading Test.

Results

We found positive associations between performance on the Stroop Color Word Test and right-sided dorsolateral prefrontal SERT binding (R 2 = 0.12, p = 0.048). Furthermore, scores of logical reasoning (correlating with IQ) and educational level associated positively with SERT binding in the caudate, most prominent on the left side (logical reasoning: R 2 = 0.34, p = 0.0026 (left), R 2 = 0.2, p = 0.022 (right), educational level: R 2 = 0.19, p = 0.012 (left), R 2 = 0.15, p = 0.027 (right)). Scores of logical reasoning also associated with left-sided ventrolateral prefrontal cortex (R 2 = 0.24, p = 0.014). There were no significant associations between SERT binding and tests of long-term episodic memory.

Conclusions

The results imply that in healthy subjects, high SERT binding in fronto-striatal regions is associated with better performance on tasks involving executive function and logical reasoning.

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Acknowledgments

Supported by The Lundbeck Foundation, Rigshospitalet, and the Danish Medical Research Council. The John and Birthe Meyer Foundation is gratefully acknowledged for the donation of the Cyclotron and PET scanner.

Disclosure/conflicts of interest

The authors declare that, except for income received from their primary employers, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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Authors and Affiliations

  1. Neurobiology Research Unit, The Neuroscience Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Karine Madsen, David Erritzoe, Gitte M. Knudsen & Steen G. Hasselbalch

  2. Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Karine Madsen, David Erritzoe, Erik Lykke Mortensen, Anders Gade, William Baaré, Gitte M. Knudsen & Steen G. Hasselbalch

  3. PET and Cyclotron Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Jacob Madsen

  4. The Memory Clinic, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark

    Steen G. Hasselbalch

  5. Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

    Erik Lykke Mortensen

  6. Institute of Psychology, University of Copenhagen, Copenhagen, Denmark

    Anders Gade

  7. Danish Research Center for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark

    William Baaré

  8. Neurobiology Research Unit N9201, University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Steen G. Hasselbalch

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  1. Karine Madsen
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  2. David Erritzoe
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  3. Erik Lykke Mortensen
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  8. Steen G. Hasselbalch
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Correspondence to Steen G. Hasselbalch.

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Madsen, K., Erritzoe, D., Mortensen, E.L. et al. Cognitive function is related to fronto-striatal serotonin transporter levels – a brain PET study in young healthy subjects. Psychopharmacology 213, 573–581 (2011). https://doi.org/10.1007/s00213-010-1926-4

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  • DOI: https://doi.org/10.1007/s00213-010-1926-4

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