Metabolites of progesterone in pregnancy: Associations with perinatal anxiety.

BACKGROUND: Anxiety disorders are the most common psychiatric disorder during the perinatal period and one of the major risk factors for postpartum depression, yet we know little about biological factors in the etiology of perinatal anxiety. A growing literature points to neuroactive steroid (NAS) dysregulation in perinatal mental illness, but directionality has not been clearly demonstrated, results are not consistent, and no studies have investigated NAS in a population with pure anxiety without comorbid depression. We aimed to add to the limited literature by examining the association between anxiety without comorbid depression and metabolic pathways of NAS longitudinally across the peripartum. METHODS: We measured anxiety symptoms by psychological scales and NAS levels using Gas Chromatography-Mass Spectrometry (GC-MS) at the second and third trimester (T2 and T3) and week 6 postpartum (W6) in n = 36 women with anxiety and n = 38 healthy controls. The anxiety group was determined by a data-driven approach, and cross-sectional and longitudinal statistical methods were used to examine the relationship between the study population and NAS. RESULTS: We found that anxiety had a significant moderating effect on the relationship between progesterone and allopregnanolone, with no such effect for the relationships between progesterone and the intermediate (5α-DHP) or isomeric (isoallopregnanolone) compounds in this pathway, and no effects on the corresponding pathway converting progesterone to pregnanolone and epipregnanolone. We also found a less precipitous decline in the ratio of allopregnanolone to progesterone between T3 and W6 in the anxiety group compared to the non-anxiety group. A genotype analysis of a single-nucleotide polymorphism in the AKR1C2 gene demonstrated that the relationship of allopregnanolone to the intermediate metabolite, 5α-DHP, differed by genotype. CONCLUSION: Our exploratory findings indicate that, for pregnant people with anxiety, metabolism is shunted more aggressively toward the endpoint of the progesterone to allopregnanolone metabolic pathway than it is for those without anxiety.

Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology.

Ample evidence suggests that acute stress can worsen symptom severity in Tourette syndrome (TS); however, the neurobiological underpinnings of this phenomenon remain poorly understood. We previously showed that acute stress exacerbates tic-like and other TS-associated responses via the neurosteroid allopregnanolone (AP) in an animal model of repetitive behavioral pathology. To verify the relevance of this mechanism to tic pathophysiology, here we tested the effects of AP in a mouse model recapitulating the partial depletion of dorsolateral cholinergic interneurons (CINs) seen in post-mortem studies of TS. Mice underwent targeted depletion of striatal CINs during adolescence and were tested in young adulthood. Compared with controls, partially CIN-depleted male mice exhibited several TS-relevant abnormalities, including deficient prepulse inhibition (PPI) and increased grooming stereotypies after a 30-min session of spatial confinement - a mild acute stressor that increases AP levels in the prefrontal cortex (PFC). These effects were not seen in females. Systemic and intra-PFC AP administration dose-dependently worsened grooming stereotypies and PPI deficits in partially CIN-depleted males. Conversely, both AP synthesis inhibition and pharmacological antagonism reduced the effects of stress. These results further suggest that AP in the PFC mediates the adverse effects of stress on the severity of tics and other TS-related manifestations. Future studies will be necessary to confirm these mechanisms in patients and define the circuitry responsible for the effects of AP on tics.

A case of reactivation of varicella-zoster virus after BNT162b2 vaccine second dose?

We report a case of itchy papulovesicular rash consistent with varicella-zoster virus reactivation after Pfizer-BioNTech vaccine second dose administration. While there have been cases of varicella-zoster virus reactivation due to COVID-19 or COVID-19 vaccine inoculation in older individuals with pre-existing conditions, this case report describes the first case of varicella-zoster virus reactivation on a healthy, young male in the absence of pre-existing conditions. The mechanisms underlying varicella-zoster virus reactivation in patients with COVID-19 are unknown and should be further characterized.

Acute reduction of visual acuity and visual field after Pfizer-BioNTech COVID-19 vaccine 2nd dose: a case report.

Long-term and rare adverse effects of COVID-19 vaccines are unknown. Hence, it is important to report them to improve the safety profile of the vaccines and enhance their use worldwide. Here, we describe a case of acute visual impairment after Pfizer-BioNTech vaccine second dose.