Neuroimaging Evidence of Cerebellar Involvement in Premenstrual Dysphoric Disorder

Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California 90095-1740, USA.
Biological psychiatry (Impact Factor: 10.26). 02/2011; 69(4):374-80. DOI: 10.1016/j.biopsych.2010.09.029
Source: PubMed


Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic disorder that is characterized by affective symptoms, including irritability, depression, and anxiety, which arise in the luteal phase of the menstrual cycle and resolve soon after the onset of menses. Despite a prevalence of up to 8% in women of reproductive age, few studies have investigated the brain mechanisms that underlie this disorder.
We used positron emission tomography with [(18)F] fluorodeoxyglucose and self-report questionnaires to assess cerebral glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison subjects in the follicular and late luteal phases of the menstrual cycle. The primary biological end point was incorporated regional cerebral radioactivity (scaled to the global mean) as an index of glucose metabolism. Relationships between regional brain activity and mood ratings were assessed. Blood samples were taken before each session for assay of plasma estradiol and progesterone concentrations.
There were no group differences in hormone levels in either the follicular or late luteal phase, but the groups differed in the effect of menstrual phase on cerebellar activity. Women with PMDD but not comparison subjects showed an increase in cerebellar activity (particularly in the right cerebellar vermis) from the follicular phase to the late luteal phase (p = .003). In the PMDD group, this increase in cerebellar activity was correlated with worsening of mood (p = .018).
These findings suggest that the midline cerebellar nuclei, which have been implicated in other mood disorders, also contribute to negative mood in PMDD.

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    • "Toward a functional neuroanatomy of PMDD fMRI 8 PMDD, 12 controls BOLD activation during an emotional word Go/NoGo task in whole-brain (corrected) and frontal cortex, amygdala and nucleus accumbens ROIs Symptomatic women with PMDD had higher amygdala activation by negative words and lower nucleus accumbens activation by positive words than controls No Rapkin et al. 2011. Neuroimaging evidence of cerebellar involvement in PMDD FDG PET 12 PMDD, 12 controls "

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    • "Although the temporal relationship between peak luteal progesterone and occurrence of mood changes is obvious (Bäckström et al., 2003), results of clinical case–control studies are inconsistent. Many studies reported no significant differences in levels of estradiol and progesterone between women who are affected by premenstrual syndrome and those who are not (review in Bäckström et al., 2003; Andreen et al., 2009; Rapkin et al., 2011). In other studies , PMS patients had either decreased (Dennerstein et al., 1984; Munday et al., 1981) or increased (Eriksson et al., 1992; Redei and Freeman, 1995) levels of progesterone. "
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    ABSTRACT: Contradictory findings show both positive and negative effect of progesterone on the premenstrual mood changes in women. Here we present the study investigating this relationship on the large sample of premenstrual women. 122 healthy, reproductive age women collected daily morning saliva samples and recorded intensity scores for the mood symptoms: irritability, anger, sadness, tearfulness, insomnia, and fatigue. Saliva samples were assayed for progesterone concentrations and mood intensity scores were used to calculate behavioral indices. Women with low Aggression/Irritability and Fatigue had consistently higher progesterone levels during the luteal phase than women with high Aggression/Irritability and Fatigue. Additionally, Aggression/Irritability and Fatigue correlated negatively with maximal progesterone value during the luteal phase. Our results demonstrated a negative effect of low progesterone level on the premenstrual mood symptoms such as aggressive behavior and fatigue in healthy reproductive age women. This supports a previously proposed model of biphasic action of progesterone metabolites on mood.
    Full-text · Article · Aug 2012 · Biological psychology
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    ABSTRACT: Cyclic stretching and growth factors like TGF-β have been used to enhance extracellular matrix (ECM) production by cells in engineered tissue to achieve requisite mechanical properties. In this study, the effects of TGF-β1 were evaluated during long-term cyclic stretching of fibrin-based tubular constructs seeded with neonatal human dermal fibroblasts. Samples were evaluated at 2, 5, and 7 weeks for tensile mechanical properties and ECM deposition. At 2 weeks, +TGF-β1 samples had 101% higher collagen concentration but no difference in ultimate tensile strength (UTS) or modulus compared to -TGF-β1 samples. However, at weeks 5 and 7, -TGF-β1 samples had higher UTS/modulus and collagen concentration, but lower elastin concentration compared to +TGF-β1 samples. The collagen was better organized in -TGF-β1 samples based on picrosirius red staining. Western blot analysis at weeks 5 and 7 showed increased phosphorylation of ERK in -TGF-β1 samples, which correlated with higher collagen deposition. The TGF-β1 effects were further evaluated by western blot for αSMA and SMAD2/3 expression, which were 16-fold and 10-fold higher in +TGF-β1 samples, respectively. The role of TGF-β1 activated p38 in inhibiting phosphorylation of ERK was evaluated by treating samples with SB203580, an inhibitor of p38 activation. SB203580-treated cells showed increased phosphorylation of ERK after 1 hour of stretching and increased collagen production after 1 week of stretching, demonstrating an inhibitory role of activated p38 via TGF-β1 signaling during cyclic stretching. One advantage of TGF-β1 treatment was the 4-fold higher elastin deposition in samples at 7 weeks. Further cyclic stretching experiments were thus conducted with constructs cultured for 5 weeks without TGF-β1 to obtain improved tensile properties followed by TGF-β1 supplementation for 2 weeks to obtain increased elastin content, which correlated with a reduction in loss of pre-stress during preconditioning for tensile testing, indicating functional elastin. This study shows that a sequential stimulus approach - cyclic stretching with delayed TGF-β1 supplementation - can be used to engineer tissue with desirable tensile and elastic properties.
    Preview · Article · Mar 2011 · Journal of Biomechanics
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