PTSD Sex-specific Enzyme Issues

LeeLemonoil

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Relationships between cerebrospinal fluid GABAergic neurosteroid levels and symptom severity in men with PTSD. - PubMed - NCBI

Relationships between cerebrospinal fluid GABAergic neurosteroid levels and symptom severity in men with PTSD.
Rasmusson AM1, King MW2, Valovski I3, Gregor K4, Scioli-Salter E2, Pineles SL2, Hamouda M3, Nillni
Abstract
Allopregnanolone and pregnanolone (together termed allo + pregnan) are neurosteroid metabolites of progesterone that equipotently facilitate the action of gamma-amino-butyric acid (GABA) at GABAA receptors. The adrenal steroid dehydroepiandrosterone (DHEA) allosterically antagonizes GABAA receptors and facilitates N-methyl-D-aspartate (NMDA) receptor function. In prior research, premenopausal women with posttraumatic stress disorder (PTSD) displayed low cerebrospinal fluid (CSF) levels of allo + pregnan [undifferentiated by the gas chromatography-mass spectrometry (GC-MS) method used] that correlated strongly and negatively with PTSD reexperiencing and negative mood symptoms. A PTSD-related decrease in the ratio of allo + pregnan to 5α-dihydroprogesterone (5α-DHP: immediate precursor for allopregnanolone) suggested a block in synthesis of these neurosteroids at 3α-hydroxysteroid dehydrogenase (3α-HSD). In the current study, CSF was collected from unmedicated, tobacco-free men with PTSD (n = 13) and trauma-exposed healthy controls (n = 17) after an overnight fast. Individual CSF steroids were quantified separately by GC-MS. In the men with PTSD, allo + pregnan correlated negatively with Clinician-Administered PTSD Scale (CAPS-IV) total (ρ=-0.74, p = 0.006) and CAPS-IV derived Simms dysphoria cluster (ρ=-0.71, p = 0.01) scores. The allo+pregnan to DHEA ratio also was negatively correlated with total CAPS (ρ=-0.74, p = 0.006) and dysphoria cluster (ρ=-0.79, p = 0.002) scores. A PTSD-related decrease in the 5α-DHP to progesterone ratio indicated a block in allopregnanolone synthesis at 5α-reductase. This study suggests that CSF allo + pregnan levels correlate negatively with PTSD and negative mood symptoms in both men and women, but that the enzyme blocks in synthesis of these neurosteroids may be sex-specific. Consideration of sex, PTSD severity, and function of 5α-reductase and 3α-HSD thus may enable better targeting of neurosteroid-based PTSD treatments.
 
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LeeLemonoil

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Neurosteroid Levels in the Orbital Frontal Cortex of Subjects with PTSD and Controls: A Preliminary Report. - PubMed - NCBI

Neurosteroid Levels in the Orbital Frontal Cortex of Subjects with PTSD and Controls: A Preliminary Report.


Abstract
Background:
Neurosteroids mediate stress signaling and have been implicated in the pathogenesis of post-traumatic stress disorder (PTSD) in both preclinical and clinical studies. Compared to controls, subjects with PTSD exhibit altered neurosteroid levels in peripheral blood and cerebrospinal fluid as well as hypoactivity in the medial orbital frontal cortex (mOFC). Therefore, the aim of this study was to compare neurosteroid levels in the mOFC of subjects with PTSD (n = 18) and controls (n = 35).

Methods:
Gray matter was dissected from fresh-frozen mOFC, and levels of the neurosteroids pregnenolone, allopregnanolone, pregnanolone, epiallopregnanolone, epipregnanolone, tetrahydrodeoxycorticosterone, and androsterone were determined by gas chromatography - tandem mass spectrometry (GC/MS/MS).

Results:
Analyses of unadjusted levels revealed that males with PTSD had significantly decreased levels of allopregnanolone (p = 0.03) compared to control males and females with PTSD had significantly increased levels of pregnenolone (p = 0.03) relative to control females. After controlling for age, postmortem interval, and smoking status, results showed that males with PTSD had significantly decreased levels of androsterone (t 46 = 2.37, p = 0.02) compared to control males and females with PTSD had significantly increased levels of pregnanolone (t 46 = -2.25, p = 0.03) relative to control females.

Conclusions:
To our knowledge, this is the first report of neurosteroid levels in postmortem brain tissue of subjects with PTSD. Although replication is required in other brain regions and in a larger cohort of subjects, the results suggest a dysregulation of allopregnanolone and androsterone in males with PTSD and pregnanolone in females with PTSD in the mOFC.
 
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LeeLemonoil

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It‘s no wonder that not everyone with mood-issues gets positive effects from supplementing the big 3 - Dhea, Preg, Prog.

Some can’t facilitate the actual needed and protective steroids from those and other metabolites result.

The same is true for androsterone - Sulfate and Dheas. Supplementing the unsulfated substances doesn’t necessarily result in sulfated specimen.
In actual fact, two different pathways are involved
 

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