PMDD- What is it?
Premenstrual dysphoric disorder (PMDD), a severe mood disorder, is characterised by cognitive–affective and physical symptoms in the week before menses and affects millions of women worldwide
Recognised in the DSM-5, the criteria for which includes symptoms such as:
- Irritability or anger, often with increased interpersonal conflicts
- Depressed mood, hopelessness, or self-deprecating thoughts
- Anxiety, tension or feeling on edge
- Mood swings, tearfulness, sensitivity to rejection
- Sense of feeling overwhelmed or out of control
- Other symptoms can include loss of interest in usual activity, fatigue, sleep and appetite changes, as well as symptoms often associated with PMS such as breast tenderness, swelling or bloating.
To be diagnosed with PMDD symptoms a minimum number of these symptoms must have been present for the majority of menstrual cycles in the past year, and greatest severity of symptoms must be present from 3-4 days prior to menses onset, and up to three days post-menses onset. Symptoms must be absent in the post-menstrual week. Other psychiatric diagnoses must be excluded.
What causes PMDD?
Potential initiating factors include central nervous system sensitivity to reproductive hormones, genetic factors, stress and a history of trauma. It appears that PMDD occurs not due to differences in hormones between women with PMDD and those without, but more altered sensitivity to normal fluctuations of estrogen and progesterone.
Progesterone and allopregnanolone
Progesterone and allopregnanolone increase in the luteal (post-ovulatory) phase of the cycle and decrease rapidly around menses; exposure followed by rapid withdrawal may be a central factor in PMDD, due to the impact of allopregnanolone on GABA(A) receptor function.
Estradiol overall enhances serotonergic function, and the symptoms of low mood, food cravings, irritability, anger and impaired cognitive functions are all things which are influenced by serotonin. Low oestrogen states are associated with decreased serotonin transporter gene expression, lower monoamine oxidase A and catechol-O-methyltrasnferase expression, and may impact brain-derived neurotrophic factor.
Women with PMDD may be more sensitive to the effects of estrogen’s effects on serotonin, and consequently show serotonin abnormalities in the luteal phase of the cycle as estrogen levels decline.
Lower BDNF levels and the Met allele for the BDNF Val66Met polymorphism have been associated with greater risk for depression and other neuropsychiatric conditions. BDNF levels are upregulated by serotonergic antidepressants, modified by estradiol and shown variance through the menstrual cycle. Women with PMDD have been shown to have significantly higher serum BDNF in the luteal phase than control groups, with significantly higher serum BDNF in the lute phase compared to the follicular phase. However, interestingly the reverse was shown in women with PMS.
History of trauma or stress
History of trauma and significant stress exposure, including emotional and physical abuse has been strongly associated with moderate to severe PMS and PMDD in multiple studies, though not all corroborate this association. PTSD and PMDD have likewise been strongly associated comorbidities. A potential mechanism leading to heightened PMDD in women with history of chronic stress and trauma is due to the blunting of allopregnenaole, which has been shown to occur in animal models after exposure to repeated or chronic stress. Administration of exogenous allopregnenalone has been shown in preclinical research to correct Hypothalamic-Pituitary-Adrenal axis function and reduce chronic stress-induced depressive and anxiety-like behaviour.
Immune Activation and Inflammation
Inflammation may be associated with PMDD’s pathophysiology, with the luteal phase associate with increased production of sIL-6R and TNF-α compared to the early follicular phase, and upregulated IL-6 gene expression in the luteal compared to follicular phase. Serum hs-CRP was positively associated with elevated menstrual symptom scores in health women, independently of differences in sex steroid hormone levels.
Now we’ve looked at some of the possible causes of PMDD, what can we do about it? Coming up next… 💕