Molecular imaging of the serotonin system in human behaviour
Author: Borg, Jacqueline
Date: 2007-03-09
Location: Föreläsningssalen, Magnus Huss, Karolinska Universitetssjukhuset Solna
Time: 09.00
Department: Institutionen för klinisk neurovetenskap / Department of Clinical Neuroscience
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thesis.pdf (402.5Kb)
Abstract
The serotonin (5-HT) neurotransmission system has a role in essential
physiological and psychological functions such as sleep, eating
behaviour, sexuality, perception, emotion and cognition. Individual
measures of serotonin biomarkers in the living human brain can be
obtained using positron emission tomography (PET) imaging, direct
measures of. The interindividual variability in these measures can then
be related to human behavioural output. In combination with genotyping,
this strategy provides an approach to complex chain of events linking the
genetic endowment to higher brain functions. The present thesis includes
a series of PET studies aimed to increase understanding of the role of
serotonin in higher brain functions in man.
In study I, fifteen control subjects were examined with PET and [11C]WAY100635,
a radioligand that is selective for the serotonin 5-HT1A receptor.
Personality traits were assessed with the Temperament and Character
Inventory (TCI) self-report questionnaire. Availability of 5-HT1A
receptor was found to correlate inversely with scores for
self-transcendence, a personality trait covering religious behaviour and
attitudes. This finding indicates that the serotonin system may serve as
a biological underpinning for spiritual experiences. Interestingly, the
observed several-fold variability in 5-HT1A receptor density may partly
explain why people vary greatly in spiritual zeal.
In study II, twenty-four control subjects were examined with [11C]WAY100635
PET and a battery of tests covering all major cognitive domains. There
were no significant correlations between regional 5-HT1A binding and
cognitive performance. The results do not provide support for involvement
of the 5-HT1A receptor in cognitive functioning in man, thereby
questioning the predictive validity of some currently used animal models
in translational neuroscience.
In study III, seventeen volunteers were examined with [11C]MADAM PET and
a battery of cognitive tests. Serotonin transporter (5-HTT) availability
in cortical regions correlated significantly with performance in
sustained attention. The results support a role for the serotonin system
in some but not all cognitive functions in man.
In study IV, fifty-four control subjects were examined with [11C]WAY100635
PET and a battery of cognitive tests. Subjects were genotyped for the
5-HTT linked polymorphic region (5-HTTLPR), a functional polymorphism in
the promoter region of the 5-HTT gene. The short (S) allele of the
5-HTTLPR has been associated with depression as well as anxiety-related
personality traits. Carriers of the S allele of the 5-HTTLPR did not
differ from non-carriers with respect to [11C]WAY100635 binding potential
in any of the brain regions studied. S-carriers however performed
significantly better in the Wisconsin Card Sorting Test. These
observations suggest that functional implications of the 5-HTTLPR are not
likely to be mediated by differences in 5-HT1A density and that other
biomarkers must be considered for future investigations at phenotype
level.
The present studies of serotonergic biomarkers in man provide new
evidence for a role of the serotonin system in complex human behaviour
such as cognitive functions and personality traits.
List of papers:
I. Borg J, Andree B, Soderstrom H, Farde L (2003). "The serotonin system and spiritual experiences." Am J Psychiatry 160(11): 1965-9
Pubmed
II. Borg J, Andree B, Lundberg J, Halldin C, Farde L (2006). "Search for correlations between serotonin 5-HT1A receptor expression and cognitive functions--a strategy in translational psychopharmacology." Psychopharmacology (Berl) 185(3): 389-94
Pubmed
III. Borg J, Lundberg J, Kizling I, Halldin C, Farde L. (1970). "The serotonin transporter in the human brain has a putative role in attention a PET study with [11C]MADAM." (Submitted)
IV. Borg J, Henningsson S, Saijo T, Inoue M, Bah J, Lundberg J, Jovanovic H, Andrée B, Halldin C, Eriksson E, Farde F. (1970). "Serotonin transporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in man." (Manuscript)
I. Borg J, Andree B, Soderstrom H, Farde L (2003). "The serotonin system and spiritual experiences." Am J Psychiatry 160(11): 1965-9
Pubmed
II. Borg J, Andree B, Lundberg J, Halldin C, Farde L (2006). "Search for correlations between serotonin 5-HT1A receptor expression and cognitive functions--a strategy in translational psychopharmacology." Psychopharmacology (Berl) 185(3): 389-94
Pubmed
III. Borg J, Lundberg J, Kizling I, Halldin C, Farde L. (1970). "The serotonin transporter in the human brain has a putative role in attention a PET study with [11C]MADAM." (Submitted)
IV. Borg J, Henningsson S, Saijo T, Inoue M, Bah J, Lundberg J, Jovanovic H, Andrée B, Halldin C, Eriksson E, Farde F. (1970). "Serotonin transporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in man." (Manuscript)
Issue date: 2007-02-16
Rights:
Publication year: 2007
ISBN: 978-91-7357-134-0
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