The Serotonin Connection: Study Sheds Light on PMDD Pathophysiology and Treatment
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A recent study published in Biological Psychiatry, aimed to investigate the interaction between the serotonin system and estradiol in the brain of patients with premenstrual dysphoric disorder (PMDD). [Sacher et al., 2023]
PMDD is a severe form of premenstrual syndrome (PMS) that affects around 3-9% of women of reproductive age and is characterised by a cluster of physical, emotional, and behavioural symptoms that occur in the late luteal phase of the menstrual cycle. While the exact cause of PMDD is not yet fully understood, it is thought to be related to hormonal changes that occur during the menstrual cycle.
The researchers used positron emission tomography (PET) imaging to measure serotonin transporter (SERT) density in the brain of patients with PMDD and healthy controls.
SERT is a protein that regulates the level of serotonin in the brain by taking up excess serotonin from the synapse and is the target of selective serotonin reuptake inhibitors (SSRIs), a class of drugs commonly used to treat PMDD and other mood disorders.
Psychopharmacology of Selective Serotonin Re-uptake Inhibitors (SSRIs) – Mechanism of Action
The study found that SERT density was significantly increased in the midbrain dorsal raphe nucleus (DRN), a key brain region involved in the regulation of mood and emotion, in patients with PMDD compared to controls.
Importantly, the increase in SERT density was only observed in the late luteal phase of the menstrual cycle, when both estradiol and progesterone are decreasing, and not in the periovulatory phase, when estradiol levels are high. An increase in midbrain SERT density with increased central serotonergic uptake followed by extracellular serotonin loss was correlated with depressive symptom severity across the menstrual cycle.
This suggests that dysregulated hormones in the periphery are not the underlying cause of the disorder. Still, rather the brain’s response to normal endogenous hormonal changes differs in patients with PMDD.
The study suggests that targeting the dysregulated serotonin system in the brain is an effective treatment strategy for PMDD.
Overall, the study provides important insights into the neurobiological basis of PMDD and has the potential to advance the clinical treatment of this debilitating disorder. In particular, the findings suggest that patients might benefit from taking SSRIs at specific times during the menstrual cycle to target these changes in the brain. We cover 4 dosing strategies with SSRIs in PMDD.
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