Decreased 5‐HT 1A receptor binding has been associated with Alzheimer's disease (AD) and interpreted as a consequence of neuron loss. The purpose of the present study was to compare [ 11 C]WAY100635 binding to the 5‐HT 1A receptor in the hippocampus, entorhinal cortex, amygdala and pericalcarine cortex in mild AD patients and elderly controls. AD patients ( n = 7) and elderly control subjects ( n = 8) were examined with positron emission tomography (PET) and [ 11 C]WAY100635. PET data acquisition was performed with an ECAT EXACT HR system. Wavelet‐aided parametric images of nondisplaceable binding potential ( BP ND ) were generated using Logan's graphical analysis with cerebellum as the reference region. Correction for partial volume effects was performed with the Müller–Gärtner method. Regions of interest (ROIs) were applied to the individual parametric images, and the regional BP ND was calculated as the average parametric voxel value within each ROI. In addition to comparisons between subject groups, correlations between BP ND values and scores on the Mini‐Mental State Examination, Disability Assessment for Dementia (DAD), and Neuropsychiatric Inventory were expressed by Pearson correlation coefficients. Mean regional BP ND was lower in AD patients than in control subjects, and the difference was statistically significant for the hippocampus, entorhinal cortex, and amygdala. A statistically significant correlation was obtained between hippocampal BP ND values and DAD scores. The results of the present study corroborate and extend previous findings of decreased 5‐HT 1A binding in AD and strengthen the support for 5‐HT 1A receptor PET as a tool for the assessment of neurodegenerative changes in mild AD.

(S,S)-[11C]MeNER ((S,S)-2-(α-(2-[11C]methoxyphenoxy)benzyl)morpholine) is a positron emission tomography (PET) radioligand recently applied in clinical studies of norepinephrine transporters (NETs) in the human brain in vivo. In view of further assessment of the suitability of (S,S)-[11C]MeNER as a NET radioligand, its metabolism and the identity of the in vivo radiometabolites of (S,S)-[11C]MeNER are of great interest.

The human serotonin transporter (5-HTT) gene is one of the most extensively studied in psychiatry. A functional polymorphism in the promoter region of the 5-HTT gene (5-HTTLPR) has been associated with several psychiatric disorders as well as anxiety-related personality traits. In search of a mechanistic understanding of the functional implications of 5-HTTLPR, the influence of this polymorphism on regional 5-HT1A receptor density has previously been examined in two positron emission tomography (PET) studies in humans, yielding, however, contradictory results. In the present study, 54 control subjects were examined with [11C]WAY 100635 PET and a battery of cognitive tests. Regional binding potential (BP) of [11C]WAY 100635 to 5-HT1A receptor was calculated for the dorsal raphe nuclei, the hippocampus, the anterior cingulate, the insula, the temporal cortex and the frontal cortex. The influence of 5-HTTLPR genotype on regional 5-HT1A BP and cognitive performance was investigated. No differences in 5-HT1A receptor density between carriers and non-carriers of the S allele were found. Thus, we could not replicate any of the previously reported associations between 5-HTTLPR and 5-HT1A density. There was, however, a highly significant association between 5-HTTLPR genotype and performance in Wisconsin Card Sorting Test; carriers of the S allele had a superior performance compared to the LL carriers. These observations suggest that functional implications of the 5-HTTLPR polymorphism are not likely to be mediated by differences in 5-HT1A expression levels and that other biomarkers must be considered for future investigations at phenotype level.

Animal studies and studies of human aging have suggested that the serotonin 5-HT1A receptor may serve as a biomarker for cognitive functioning and a target for pharmacological treatment of cognitive deficits.

Back to table of contents Previous article Next article Letter to the EditorFull AccessDr. Borg and Colleagues ReplyJACQUELINE BORG, Psychol., M.Sc., BENGT ANDRÉE, M.D., Ph.D., HENRIK SÖDERSTRÖM, M.D., Ph.D., and LARS FARDE, M.D., Ph.D., JACQUELINE BORGSearch for more papers by this author, Psychol., M.Sc., BENGT ANDRÉESearch for more papers by this author, M.D., Ph.D., HENRIK SÖDERSTRÖMSearch for more papers by this author, M.D., Ph.D., and LARS FARDESearch for more papers by this author, M.D., Ph.D., Stockholm, SwedenPublished Online:1 Sep 2004https://doi.org/10.1176/appi.ajp.161.9.1721AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We appreciate that Dr. Hall and colleagues draw attention to the problem of defining the concepts of “spirituality” and “religion.” Several multidimensional or pluralistic definition systems of religion have indeed been proposed over the years. However, none of them offers a perfect solution to the need of operational tools in research on a possible biological underpinning of religious and spiritual behavior.The authors criticize our article for using the terms “religion” and “spirituality” interchangeably. However, we did not use the concept “religion” in the article. Rather, the concept “religious behavior,” which is operationally defined in the literature (1), denotes cognitive and emotional behavior associated with (the individual’s relationship to their) religious beliefs. The term “spirituality” has been used in a wider context, including internal, subjective experiences, and has not been consistently defined by operational criteria. It is worth noting that the concept of spirituality is not necessarily linked to organized religion.“Religious behavior” and “spirituality” are both covered by the personality subscale of the Spiritual Acceptance Scale, which was used in our study. The Spiritual Acceptance Scale consists of 13 items that include cognitive affirmation and values as well as subjective experiences of mystical quality. Thus, the definition of religion at a sociocultural level, as suggested by Dr. Hall and colleagues, is not covered by the scale used in our study and belongs to a different discussion.Another part of Dr. Hall and colleagues’ criticism is their interpretation that aspects of mystical experiences can be mediated by the central serotonin system. We do not suggest that the serotonin system per se mediates mystical experiences but instead may act as a sensory filter (2). Low serotonin 5-HT1A receptor binding potential may be associated with a low filter function, thus paving the way for sensory stimuli otherwise not experienced. The more narrow focus on mystical experiences in this part of the discussion in our article (pp. 1967–1968) was given by comparisons made with pharmacological mechanisms causing similar experiences in man.Finally, we agree with Dr. Hall and colleagues that it would be interesting to repeat this study in different populations. Epidemiological studies provide support for the view that religious behavior (in a more narrow sense) and spirituality (in a wider sense) are influenced by both genetic and environmental factors (3, 4). Given the previously demonstrated genetic contribution to religious behavior and spirituality, it is a promising strategy to use interindividual variability in neuroreceptor binding as a tool to approach the multifaceted question of why people vary in spiritual zeal and also within the same religious belief system.References1. Hood RW, Spilka B, Hunsberger B, Gorsuch R: The Psychology of Religion: An Empirical Approach, 2nd ed. New York, Guilford, 1996, pp 4–40Google Scholar2. Albert DJ, Walsh ML: Neural systems and the inhibitory modulation of agonistic behavior: a comparison of mammalian species. Neurosci Biobehav Rev 1984; 8:5–24Crossref, Medline, Google Scholar3. Bouchard TJ Jr, Lykken DT, McGue M, Segal NL, Tellegen A: Sources of human psychological differences: the Minnesota Study of Twins Reared Apart. Science 1990; 250:223–228Crossref, Medline, Google Scholar4. Kirk KM, Eaves LJ, Martin NG: Self-transcendence as a measure of spirituality in a sample of older Australian twins. Twin Res 1999; 2:81–87Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 161Issue 9 September 2004Pages 1721-1721 Metrics PDF download History Published online 1 September 2004 Published in print 1 September 2004

The serotonin 5-HT1A receptor has been ascribed a putative role in the pathophysiology and drug treatment of depression. NAD-299 (generic name robalzotan) is a new potential antidepressant with high affinity and selectivity for the 5-HT1A receptor.

The serotonin 5-hydroxytryptamine-1A (5-HT 1A ) receptor subtype is of central interest in research, particularly in the area of pathophysiology and pharmacological treatment of psychiatric disorders. Robalzotan (generic name for NAD-299) is a new putative drug that binds with high selectivity and affinity to 5-HT 1A -receptors in the rodent brain in vitro and in vivo. The aim of this positron emission tomography study was to determine 5-HT 1A receptor occupancy in the cynomolgus monkey brain in vivo after IV injection of robalzotan. Two healthy monkeys were examined with Positron Emission Tomography (PET) and the radioligand [carbonyl- 11 C]WAY-100635, the first after IV administration of 2 μg/kg and 20 μg/kg, and the second after 10 μg/kg and 100 μg/kg IV. 5-HT 1A receptor occupancy was calculated using an equilibrium-ratio analysis. Robalzotan occupied 5-HT 1A receptors in a dose-dependent and saturable manner. The highest 5-HT 1A receptor occupancy (70–80%) was attained after 100 μg/kg. The relationship between robalzotan drug concentration and 5-HT 1A receptor occupancy could be described by a hyperbolic function, which can be used to guide the selection of appropriate doses for the initial studies in man. The study further corroborates that quantitative neuroimaging of receptor binding has potentials for the evaluation and dose finding of new CNS drugs.