A PET study of 5-HT1A receptors at different phases of the menstrual cycle in women with premenstrual dysphoria

Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm, Sweden.
Psychiatry Research (Impact Factor: 2.47). 01/2007; 148(2-3):185-93. DOI: 10.1016/j.pscychresns.2006.05.002
Source: PubMed


The cause of premenstrual dysphoric disorder (PMDD) is largely unknown. It has been hypothesized that normal ovarian function triggers PMDD-related biochemical events within the brain and that serotonin plays an important role. In the present study, positron emission tomography (PET) and [carbonyl-(11)C]WAY-100635 were used to examine serotonin 5-HT(1A) receptors in a control group of women and in a group of women with PMDD. Two PET examinations were performed in each subject, one before (follicular phase) and one after ovulation (luteal phase). Each subject's menstrual cycle was confirmed by ultrasonography of the ovaries as well as with hormone levels in blood and urine. The 5-HT(1A) binding potential was measured in six regions of interest and calculated according to the simplified reference tissue model. In the raphe nuclei, the 5-HT(1A) binding potential changed from the follicular to the luteal phase of the menstrual cycle in asymptomatic controls. In women with PMDD, the observed change between phases was significantly smaller. The results are in concordance with previously reported challenge studies of 5-HT(1A) receptor-mediated effects indicating different serotonergic responses between women with PMDD and controls. The study principally provides new support, in vivo, for a serotonergic dysregulation in women with PMDD.

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    • "Neuroimaging findings in PMDD suggest menstrual cycle phase-by-diagnosis interaction effects, indeed highlighting the relevance of hormone fluctuations in this disorder [Epperson, 2013]. Moreover, a proton magnetic resonance spectroscopy ( 1 H-MRS) study implicated a gamma-aminobutyric acid (GABA) interaction with ovarian hormones and neurosteroids in the pathophysiology of PMDD [Epperson et al., 2002], and a PET study suggested a role for serotonin in PMDD [Jovanovic et al., 2006]. "
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    ABSTRACT: Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2014; 35(9). DOI:10.1002/hbm.22486 · 5.97 Impact Factor
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    • "Cortical gammaaminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. 1H-MRS 8 PMDD, 12 control* GABA in midline occipital cortex From follicular to luteal phase, occipital GABA decreased in controls but increased in PMDD women to higher levels than controls Reference region Jovanovic et al. 2006. A PET study of 5- HT1A receptors at different phases of the menstrual cycle in women with premenstrual dysphoria. "

    01/2014; 1(2):120-141. DOI:10.3934/Neuroscience.2014.2.120
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    • "It is tenable that an affection of these structures could lead to poor attention, and working memory deficits, symptoms which individuals with chronic occupational stress have described experiencing [5], [6], [65]. The preset data is in line with results from a fMRI study by Sandström et al., showing a decreased activation of the dlPFC among 10 patients suffering from occupational stress [6], and with a fMRI study by Qin et al., which detected a reduced activation of the dlPFC in healthy subjects who performed a working memory task under acute stress [51]. "
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    ABSTRACT: There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM) and white matter (WM) volumes, and the volumes of hippocampus, caudate, and putamen - structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment.
    PLoS ONE 06/2013; 8(6):e64065. DOI:10.1371/journal.pone.0064065 · 3.23 Impact Factor
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