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Bičı́ková, Marie; Tallová, Jaroslava; Hill, Martin; Krausová, Zuzana; Hampl, Richard

doi:10.1023/a:1026622704704

Cited by 57 publications

(8 citation statements)

References 19 publications

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“…A similar anxiolytic potential has been demonstrated for the peripheral 3α-pregnane steroid 3α,5α-THDOC [41, 42, 44]. Although first studies investigating 3α-reduced neuroactive steroid levels in anxiety disorders found no differences in 3α,5α-THP levels between patients suffering from mixed anxiety-depressive disorder [22], generalized anxiety disorder [20] or generalized social phobia [45] and healthy controls, first studies of our research group in patients with panic disorder suggested that 3α-reduced neuroactive steroids may play a pivotal role in human anxiety.…”

Section: Neuroactive Steroids As Endogenous Modulators Of Depression mentioning

confidence: 65%

“…Decreased PS levels have been found in patients suffering from depression [19], generalized anxiety disorder [20] and generalized social phobia [21]. In contrast, in women suffering from mixed anxiety-depressive disorder [22] or from premenstrual syndrome (PMS) [23], elevated PS plasma concentrations have been observed, suggesting that the pattern of dysregulated pregnenolone/PS levels may vary with different psychiatric disorders.…”

Section: Neuroactive Steroids As Endogenous Modulators Of Depression mentioning

confidence: 99%

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Neuroactive Steroids in Depression and Anxiety Disorders: Clinical Studies

et al. 2006

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Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3α-reduced pregnane steroids are potent positive allosteric modulators of the γ-aminobutyric acid type A (GABA_A) receptor. During major depression, there is a disequilibrium of 3α-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3α-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3α,5α-tetrahydrodeoxycorticosterone. The modulation of GABA_A receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds.

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Section: Neuroactive Steroids As Endogenous Modulators Of Depression mentioning

confidence: 65%

Section: Neuroactive Steroids As Endogenous Modulators Of Depression mentioning

confidence: 99%

Neuroactive Steroids in Depression and Anxiety Disorders: Clinical Studies

et al. 2006

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“…Although the endocrine stress response is decreased also in human pregnancy, longitudinal data suggests that anxiety levels in healthy women are unchanged by pregnancy [22]. In addition, endogenous levels of allopregnanolone do not seem to be altered in anxiety disorders [23,24,25,26], other than panic disorder [27,28]. …”

Section: Introductionmentioning

confidence: 99%

Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

et al. 2014

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Background: Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has an inhibitory function through interaction with the GABA_A receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy covary with concurrent self-rated symptoms of depression and anxiety. Methods: Ninety-six women in pregnancy weeks 37-40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory. Their serum allopregnanolone was analyzed by Celite chromatography and radioimmunoassay. Results: Ten women had elevated depression scores (MADRS-S ≥13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the normal range (39.0 ± 17.9 vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson's correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. Conclusion: High allopregnanolone serum concentrations may protect against depressed mood during pregnancy.

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“…The 5α-reduced metabolite of P 4 , 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP)is thought to play a major role in the regulation of the stress axis and has been implicated in the etiology, expression, and/or treatment of some hormone- and/or stress-sensitive neuropsychiatric disorders (anxiety, depression, schizophrenia; [5–8]). Studies in people have shown lower3α,5α-THP concentrations in plasma and cerebrospinal fluid are associated with anxiety and major depression disorders [7, 9–11]. Furthermore, pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and/or fluvoxamine, can increase 3α,5α-THP in CSF coincident with reductions in depression and anxiety symptoms in both men and women [7, 12–13].…”

Section: Introductionmentioning

confidence: 99%

Progesterone facilitates exploration, affective and social behaviors among wildtype, but not 5α-reductase Type 1 mutant, mice

Koonce

Frye

2013

Behavioural Brain Research

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Progesterone (P4) facilitates exploration, anxiety and social behaviors in estrogen (E2)-primed mice. Some of these effects may be due to actions of its 5α-reduced metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP). In order to address the role of P4 and its metabolite, 3α,5α-THP, a mouse model was utilized. We hypothesized that if P4’s metabolism to 3α,5α-THP is essential to facilitate exploratory, anti-anxiety and social behaviors of mice, then wildtype, but not 5α-reductase knockout (5α-RKO), mice will have greater expression of these behaviors. Experiment 1: Mice were ovariectomized (ovx), E2-primed and administered P4 (0, 125, 250, or 500 μg) subcutaneously and then tested 4 hours later in a battery of tasks: open field, elevated plus maze, and social interaction. Experiment 2: Ovx, E2-primed mice were administered P4 (4 mg/kg), 3α,5α-THP (4 mg/kg), medroxyprogesterone acetate (MPA, which does not convert to 3α,5α-THP; 4 mg/kg), or vehicle subcutaneously and tested 4 hours later. There was a dose-dependent effect of P4 to wildtype, but not 5α-RKO, mice. Neither WT, nor 5α-RKO, mice had increased exploration, anti-anxiety or pro-social behavior with MPA administration. Progesterone only exerted effects on anti-anxiety behavior, and increased 3α,5α-THP in the prefrontal cortex and hippocampus, when administered to wildtype mice. 3α,5α-THP to both WT and 5α-RKO mice increased exploration, anti-anxiety and social interaction and 3α,5α-THP levels in the hippocampus and prefrontal cortex. Thus, metabolism of P4 by the 5α-reductase enzyme may be essential for enhancement of these behaviors.

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Cited by 57 publications

References 19 publications

Neuroactive Steroids in Depression and Anxiety Disorders: Clinical Studies

Neuroactive Steroids in Depression and Anxiety Disorders: Clinical Studies

Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

Progesterone facilitates exploration, affective and social behaviors among wildtype, but not 5α-reductase Type 1 mutant, mice

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