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- Henningsson, Susanne, 1977, et al.
(author)
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Genetic Variation in Brain-Derived Neurotrophic Factor Is Associated with Serotonin Transporter but Not Serotonin-1A Receptor Availability in Men
- 2009
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 66:5, s. 477-485
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Journal article (peer-reviewed)abstract
- Background: The serotonergic system, including the serotonin transporter (5-HTT), which is the target of many antidepressants, seems to be influenced by brain-derived neurotrophic factor (BDNF). Methods: Positron emission tomography (PET) was used to address, in 25 and 53 healthy volunteers, respectively, the possible association between six polymorphisms in the gene encoding BDNF and the availability of two proteins expressed by serotonergic neurons: the 5-HTT, measured with the radioligand [C-11]MADAM, and the serotonin-1A (5-HT1A) receptor, measured with [C-11]WAY-100635. Results: Several single nucleotide polymorphisms were associated with [C-11]MADAM binding potential (BP) in most brain regions, male carriers of the valine/valine genotype of the Val66Met polymorphism displaying higher availability. Effect sizes ranged from a 50% to a threefold increase. In contrast, there was no association for [C-11]WAY-100635 BP. The observation that BDNF polymorphisms were associated with 5-HTT availability could be partly replicated in an independent population comprising nine male suicide attempters and nine matched control subjects, in which transporter availability had been measured with single photon emission computed tomography with I-123-beta-CIT as ligand. Conclusions: Our results suggest that genetic variation in BDNF influences 5-HTT but not 5-HT1A receptor density in the human brain.
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| 2. |
- Hillert, Lena, et al.
(author)
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Women with multiple chemical sensitivity have increased harm avoidance and reduced 5-HT(1A) receptor binding potential in the anterior cingulate and amygdala
- 2013
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In: PLOS ONE. - : Public Library Science. - 1932-6203. ; 8:1
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Journal article (peer-reviewed)abstract
- Multiple chemical sensitivity (MCS) is a common condition, characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the underlying mechanisms are unknown. Contrary to the expectations it was recently found that persons with MCS activate the odor-processing brain regions less than controls, while their activation of the anterior cingulate cortex (ACC) is increased. The present follow-up study was designed to test the hypotheses that MCS subjects have increased harm avoidance and deviations in the serotonin system, which could render them intolerant to environmental odors. Twelve MCS and 11 control subjects, age 22-44, all working or studying females, were included in a PET study where 5-HT(1A) receptor binding potential (BP) was assessed after bolus injection of [(11)C]WAY100635. Psychological profiles were assessed by the Temperament and Character Inventory and the Swedish universities Scales of Personality. All MCS and 12 control subjects were also tested for emotional startle modulation in an acoustic startle test. MCS subjects exhibited significantly increased harm avoidance, and anxiety compared to controls. They also had a reduced 5-HT(1A) receptor BP in amygdala (p = 0.029), ACC (p = 0.005) (planned comparisons, significance level 0.05), and insular cortex (p = 0.003; significance level p<0.005 with Bonferroni correction), and showed an inverse correlation between degree of anxiety and the BP in the amygdala (planned comparison). No group by emotional category difference was found in the startle test. Increased harm avoidance and the observed changes in the 5-HT(1A) receptor BP in the regions processing harm avoidance provides a plausible pathophysiological ground for the symptoms described in MCS, and yields valuable information for our general understanding of idiopathic environmental intolerances.
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| 3. |
- Jovanovic, Hristina
(author)
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PET evaluation of central serotonergic neurotransmission in women
- 2008
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Doctoral thesis (other academic/artistic)abstract
- The serotonin (5-HT) system is of central interest in the patophysiology and treatment of several psychiatric disorders including depression, anxiety and suicide. In women, functioning of the 5-HT system is of particular importance since they have been found to suffer more often from 5-HT-associated disorders compared to men. The aim of the present thesis was to further explore the central serotonergic system in women by examining 5- HT1A receptors and 5-HTT binding in two psychiatric disorders, borderline personality disorder (BPD) and premenstrual dysphoric disorder (PMDD), during different phases of the menstrual cycle and in relation to gender. In the first study positron emission tomography (PET) and [11C]WAY100635 were used to examine 5-HT1A receptors in control group of women and in women with PMDD. Two PET examinations were performed in each subject, one before (follicular phase) and one after ovulation (luteal phase). The 5-HT1A binding potential (BP) was measured in six regions of interest and calculated according to the simplified reference tissue model (SRTM). For the region of dorsal raphe nuclei, there was a significant difference between the groups in the change of 5-HT1A receptor binding. The study provides principally new support in vivo, for a serotonergic dysregulation in women with PMDD. In the second study, PET and selective radioligands [11C]WAY100635 and [11C]MADAM were used to study differences in 5-HT1A receptors and 5-HTT BPs between healthy women and men. The BPs were estimated both on the level of anatomical regions and voxel wise, derived by the SRTM and wavelet/Logan plot parametric image techniques respectively. The volume of interest (VOI)-based analysis revealed higher mean 5-HT1A BP and lower mean 5-HTT BP values in women compared to men. The parametric analysis of [11C]WAY100635 and [11C]MADAM images showed similar results to those obtained with VOI analysis. In women, a positive correlation between 5-HT1A receptor and 5-HTT BPs for the region of hippocampus was found. Sex differences in 5-HT1A receptor and 5-HTT binding may reflect biological distinctions in the 5-HT system contributing to sex differences in the prevalence of psychiatric disorders such as depression and anxiety. The result may help understanding sex differences in drug treatment responses to drugs affecting the 5-HT system. In the third study, healthy women were investigated in the follicular and luteal phase of the menstrual cycle with radioligands [11C]WAY100635 and [11C]MADAM to study 5-HT1A and 5-HTT BPs. The BPs values were quantified using the SRTM. The phases of the menstrual cycle were characterized by transvaginal ultrasound (TVS) and plasma levels of hormones estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH) and luteinising hormone (LH). The 5-HT1A receptor and 5-HTT BPs did not significantly differ between follicular and luteal phases in any of the investigated regions. There were no significant correlations between hormones E2 or P4 and 5-HT1A receptors BP or 5-HTT BP in any of the regions, neither did the change in plasma E2 or P4 correlate with the change in 5-HT1A BP or 5-HTT BP values in brain regions. The results provide principally new in vivo evidence on human female biology, suggesting no difference in 5-HT1A receptors and 5-HTT binding between the phases of the menstrual cycle in healthy women that can be revealed with the present methodology. In the fourth study, 5-HT1A receptor BP in female patients with BPD and controls were examined. Out of two hundred female patients with BPD, seven met inclusion criteria (i.e. drug naïve including, no previous or present alcohol or drug abuse/dependency). Eight age and sex matched controls were recruited. PET and selective radioligand [11C]WAY100635 were used to study brain 5-HT1A receptor BP in dorsolateral prefrontal cortex, anterior cingulate, orbitofrontal cortex, amygdala, hippocampus, insula, temporal cortex and dorsal raphe nuclei. BP was estimated using the SRTM. Compared to controls, women with BPD had a significantly lower 5-HT1A receptor BP in the brain regions examined. The results suggest a lower 5-HT1A receptor BP in drug naïve patients with BPD. The finding corroborates previous studies suggesting the impairment of the 5-HT system in patients with BPD. In conclusion, the present thesis provides new evidence for the implication of the serotonin system in psychiatric disorders in women, effects of gonadal hormones and sex differences in serotonergic neurotransmission.
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