Literature DB >> 11772707

GABA(A) receptor-modulating neuroactive steroid composition in patients with panic disorder before and during paroxetine treatment.

Andreas Ströhle1, Elena Romeo, Flavia di Michele, Augusto Pasini, Alexander Yassouridis, Florian Holsboer, Rainer Rupprecht.   

Abstract

OBJECTIVE: Previous studies have shown that neuroactive steroids modulate anxiety and stress reactivity. However, no data on the possible role of these gamma-aminobutyric acid(A) (GABA(A)) receptor-modulating neuroactive steroids in patients with anxiety disorders are available.
METHOD: The concentrations of 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), 3alpha,5beta-THP, 3beta,5alpha-THP, and their precursors were studied in the plasma of 10 patients with panic disorder and 10 matched healthy comparison subjects. In addition, the effects of paroxetine treatment on neuroactive steroid concentrations were studied in the panic disorder patients over a 24-week period.
RESULTS: Unexpectedly, patients with panic disorder had significantly greater concentrations of the positive allosteric modulators 3alpha,5alpha-THP and 3alpha,5beta-THP and significantly lower concentrations of 3beta,5alpha-THP (a functional antagonist for GABA(A) agonistic steroids), which might result in greater GABA(A) receptor-mediated neuronal activity. Paroxetine treatment did not affect neuroactive steroid concentrations, which were highly stable over 24 weeks.
CONCLUSIONS: Differences in neuroactive steroid composition in patients with panic disorder were the opposite of those seen in patients with major depression and may reflect counterregulative mechanisms against the occurrence of spontaneous panic attacks.

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Year:  2002        PMID: 11772707     DOI: 10.1176/appi.ajp.159.1.145

Source DB:  PubMed          Journal:  Am J Psychiatry        ISSN: 0002-953X            Impact factor:   18.112


  28 in total

Review 1.  Neuroactive steroids and anxiety disorders.

Authors:  Jean-Michel Le Mellédo; Glen B Baker
Journal:  J Psychiatry Neurosci       Date:  2002-05       Impact factor: 6.186

2.  S-norfluoxetine microinfused into the basolateral amygdala increases allopregnanolone levels and reduces aggression in socially isolated mice.

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Review 4.  Neurosteroids and GABAergic signaling in health and disease.

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Journal:  Biomol Concepts       Date:  2013-02

Review 5.  Up-regulation of neurosteroid biosynthesis as a pharmacological strategy to improve behavioural deficits in a putative mouse model of post-traumatic stress disorder.

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Review 8.  [Significance of GABAA receptors for the pathophysiology and therapy of panic disorders].

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Journal:  Nervenarzt       Date:  2003-06-24       Impact factor: 1.214

Review 9.  Pregnenolone sulfate as a modulator of synaptic plasticity.

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Journal:  Psychopharmacology (Berl)       Date:  2014-07-06       Impact factor: 4.530

10.  Role of microsomal retinol/sterol dehydrogenase-like short-chain dehydrogenases/reductases in the oxidation and epimerization of 3alpha-hydroxysteroids in human tissues.

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