Allopregnanolone Is Associated with a Stress-Induced Reduction of Heart Rate Variability in Premenstrual Dysphoric Disorder

Abstract

Human survival and wellbeing require appropriate responses to stress, including a highly coordinated and efficient nervous system control of the heart rhythm. During stress, a greater disinhibition of the vagal nerve is reflective of poor stress adaptability, which may be relevant in premenstrual dysphoric disorder (PMDD)—a debilitating affective condition thought to be marked by dysregulated stress processing and sensitivity to allopregnanolone. In the present study, women with PMDD (n = 17) and healthy controls (n = 18), who did not take medication, smoke, or consume illicit drugs, and who were free of other psychiatric conditions, participated in the Trier Social Stress Test, during which we measured the high frequency of the heart rate (HF-HRV) and allopregnanolone using ultra-performance liquid chromatography tandem mass spectrometry. Relative to their baseline, women who have PMDD, but not the healthy controls, experienced a reduction in HF-HRV during stress anticipation (p ≤ 0.05) and stress (p ≤ 0.01). Their recovery from stress was significantly delayed (p ≤ 0.05). Absolute peak HF-HRV change from baseline was significantly predicted by baseline allopregnanolone only in the PMDD group (p ≤ 0.01). The present study shows how an interaction between stress and allopregnanolone—which have both been separately implicated in PMDD—underlies PMDD expression.

Long read sequencing characterises a novel structural variant, revealing underactive AKR1C1 with overactive AKR1C2 as a possible cause of severe chronic fatigue

“…This would be particularly the case for multi-system chronic fatigue disorders like ME/CFS, fibromyalgia and long covid. Gastrointestinal dysfunction and hypocortisolism are common in these conditions, as is dysregulation of the autonomic nervous system [42][43][44] which may similarly be modulated by neurosteroids [45,46]. These conditions are also more common in women [47,48], as might be expected if higher P is a factor.…”

Periovulatory Subphase of the Menstrual Cycle Is Marked by a Significant Decrease in Heart Rate Variability

“…Although the present study was not powered to detect a subphase–diagnosis interaction, we assigned the diagnosis to repeat the analysis in healthy participants only, ensuring that the hypothesized periovulatory decrease in HRV is observed when restricted to the healthy participants. In accordance with DSM-5 criteria, PMDD diagnosis in the proposed study was assessed prospectively and was defined as a 30% or greater increase in symptoms [ 39 ].…”

“…The analysis segment was defined as a 4 min period from the middle of the recording and 120 s out each way. Preprocessing of HF-HRV is described in detail in Hamidovic et al [ 39 ].…”

Visuospatial Function in Women with Premenstrual Dysphoric Disorder

“…Women with a lifetime psychiatric disorder, except anxiety and depression (based on the Structured Clinical Interview for DSM Disorders (SCID)), and current (i.e., within the past 12 months) DSM-5 Major Depressive Disorder or an anxiety disorder (based on SCID) were excluded from the study. Once enrolled, the participants filled out the Daily Record of Severity of Problems (DRSP) survey [19] over 2-3 menstrual cycles, which was used for assigning PMDD diagnosis in the present study [20]. Women were assigned to the PMDD group if they had a 30% or greater increase in 5 or more symptoms (one had to be affective in nature) on days −7 to −1 relative to days +6 to +12 of the menstrual cycle [21].…”