Brain reactivity during aggressive response in women with premenstrual dysphoric disorder treated with a selective progesterone receptor modulator

Abstract

Premenstrual dysphoric disorder (PMDD) is a psychiatric condition characterized by late luteal phase affective, cognitive, and physical impairment. The disorder causes significant suffering in about 5% of women in their reproductive age. Altered sensitivity of cognitive-affective brain circuits to progesterone and its downstream metabolite allopregnanolone is suggested to underlie PMDD symptomatology. Core mood symptoms include irritability and anger, with aggression being the behavioral outcome of these symptoms. The present study sought to investigate the neural correlates of reactive aggression during the premenstrual phase in women with PMDD, randomized to a selective progesterone receptor modulator (SPRM) or placebo. Self-reports on the Daily Record of Severity of Problems were used to assess PMDD symptoms and gonadal hormone levels were measured by liquid chromatography tandem mass spectrometry. Functional magnetic resonance imaging was performed in 30 women with PMDD, while performing the point subtraction aggression paradigm. Overall, a high SPRM treatment response rate was attained (93%), in comparison with placebo (53.3%). Women with PMDD randomized to SPRM treatment had enhanced brain reactivity in the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex during the aggressive response condition. The fronto-cingulate reactivity during aggressive responses depended on treatment, with a negative relationship between brain reactivity and task-related aggressiveness found in the placebo but not the SPRM group. The findings contribute to define the role of progesterone in PMDD symptomatology, suggesting a beneficial effect of progesterone receptor antagonism, and consequent anovulation, on top-down emotion regulation, i.e., greater fronto-cingulate activity in response to provocation stimuli.

Towards Phenotyping Suppressed Anger in Perimenopausal Women with Lyfas Biomedical Application: A Comprehensive Diagnostic Reliability Study

“…Spearman's correlation (ρ) study shows that all the parameters are significantly (p<0.05, CI 95%) to CAS to predict SA, except the E2 and Cortisol. In general, studies reveal that E2 and progesterone levels are raised during anger [55] so as with the Cortisol level as an adaptive response to the anger-induced threat mechanism [56]. High positive correlations can be seen between CAS and BMI corroborating the fact that being overweight often leads to higher episodes of mood swings, which is further supported by the study of [27]; CAS and LF/HF (high sympathetic or less parasympathetic drive) each has a ρ score of 0.65; followed by TSH (ρ = 0.62, high mood swing seen in hypothyroidism); HbA1c (mood disorders associated with diabetics), SBP, DBP (mood issues and irritations found with hypertensives), and SD2/SD1 (reflects heightened anxiety episodes with ρ = 0.61), each; while negative correlations are found in SDNN (ρ = -0.23) as high SDNN reflects good mental health state, and no correlation is evident in E2, Age, and Cortisol (ρ close to 0).…”

Síndrome pré-menstrual: possibilidades de cuidados para atenuação dos sintomas

“…Os moduladores seletivos dos receptores da progesterona (MSRP) são substâncias sintéticas derivadas dos esteroides que têm a capacidade de ocupar os receptores da progesterona e passam a ter ação como antagonista, agonista-antagonista ou agonista desse hormônio, dependendo do tecido alvo 26 .…”

“…Existe uma relação entre os sintomas da SPM e as flutuações de progesterona durante a fase lútea, juntamente com evidências de estudos de supressão ovariana. De fato, a inibição da ovulação leva à remissão dos sintomas, ao passo que a adição de hormônio ovariano os restabelece 26 .…”

Gabrb2 knock-out mice exhibit double-directed PMDD-like symptoms: GABAAR subunits, neurotransmitter metabolism disruption, and allopregnanolone binding

“…Recent literature hypothesized that PMDD pathophysiology is caused by an impaired GABAA receptors (GABAARs) response to dynamic ALLO fluctuations across the menstrual cycle [10], which primarily occur in the brain [11]. Moreover, neuroimaging has revealed greater cerebellar grey matter volume and metabolism in patients with PMDD, together with altered serotonergic and GABAergic neurotransmission [12], and other brain areas are also involved [12][13][14]. The role of GABAARs in the brain, particularly the subunit function, has attracted research interest [15,16].…”