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: 2.68). 01/2007; 148(2-3):185-93. DOI: 10.1016/j.pscychresns.2006.05.002
Source: PubMed

ABSTRACT 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
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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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    • "Given the observation that symptoms disappear during spontaneously anovulatory cycles and during gonadotropinreleasing hormone agonist-induced anovulation (Segebladh et al. 2009), it has been suggested that progesterone produced by the corpus luteum is the major symptomprovoking factor. However, the exact mechanism by which progesterone precipitates the symptoms of PMDD is unknown , although interactions with the serotonin system (Jovanovic et al. 2006; Brown et al. 2009) and the GABAergic systems (Epperson et al. 2002; Sundstrom Poromaa et al. 2003) are plausible. Many women with PMDD state that their symptoms worsen during time periods of intense work load and stress (Perkonigg et al. 2004; Sadler et al. 2010). "
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    ABSTRACT: Most prior studies in patients with premenstrual dysphoric disorder (PMDD) indicate a blunted hypothalamus-pituitary-adrenal axis function. However, the relationship between neuroactive progesterone metabolites, such as allopregnanolone, and hypothalamus-pituitary-adrenal (HPA) axis function in PMDD patients is relatively sparsely studied. The primary aims of this study were to assess diurnal variation in circulating cortisol and low-dose dexamethasone suppression in PMDD patients and healthy controls, and the relationship between these two HPA axis indices and allopregnanolone serum concentrations. Twenty-six women with prospectively defined PMDD and 30 healthy controls were recruited. Participants underwent diurnal sampling for cortisol serum concentrations and a low-dose dexamethasone suppression test. In addition, morning allopregnanolone serum concentrations were determined. There was no difference in diurnal secretion of cortisol and degree of dexamethasone suppression of cortisol between PMDD patients and healthy controls. However, PMDD patients with high allopregnanolone levels displayed blunted nocturnal cortisol levels in comparison with healthy controls who had low allopregnanolone serum concentrations. In women with PMDD, diurnal secretion of cortisol may be influenced by allopregnanolone levels of the luteal phase. This finding may be attributed to timing of blood sampling in the late luteal phase as well as the individual level of allopregnanolone but could potentially explain the discrepancies in results between studies examining HPA axis function in women with PMDD.
    Archives of Women s Mental Health 01/2013; 16(2). DOI:10.1007/s00737-013-0327-1
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