Neuroactive steroid changes in response to challenge with the panicogenic agent pentagastrin

Tait, Gordon; McManus, Karen; Bellavance, François; Lara, Nathalie; Chrapko, Wendy; Mellédo, Jean-Michel Le

doi:10.1016/s0306-4530(01)00051-8

Cited by 33 publications

(18 citation statements)

References 39 publications

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“…Individuals with panic disorder exhibited a significant decrease in the positive GABA A receptor modulators ALLO and 3α,5β-THP in response to panicogenic sodium lactate/CCK-4 administration and an increase in the negative GABA A receptor modulator 3β,5α-THP, whereas these levels were not altered in healthy volunteers (Strohle et al, 2003). Similarly, induction of panic with pentagastrin in males with panic disorder resulted in an increase in plasma DHEA and a trend for increased ALLO, while no alterations in steroid levels were observed following panic induction in healthy volunteers (Tait et al, 2002). Interestingly, panic induction with CCK-4 was shown to elevate plasma THDOC levels in healthy volunteers, accompanied by an increase in plasma ACTH and cortisol .…”

Section: Neuroactive Steroids and Anxiety Disordersmentioning

confidence: 92%

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

et al. 2007

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1. Neuroactive steroids are steroid hormones that exert rapid, nongenomic effects at ligand-gated ion channels. There is increasing awareness of the possible role of these steroids in the pathology and manifestation of symptoms of psychiatric disorders. The aim of this paper is to review the current knowledge of neuroactive steroid functioning in the central nervous system, and to assess the role of neuroactive steroids in the pathophysiology and treatment of symptoms of schizophrenia, depression, and anxiety disorders. Particular emphasis will be placed on GABAA receptor modulation, given the extensive knowledge of the interactions between this receptor complex, neuroactive steroids, and psychiatric illness. 2. A brief description of neuroactive steroid metabolism is followed by a discussion of the interactions of neuroactive steroids with acute and chronic stress and the HPA axis. Preclinical and clinical studies related to psychiatric disorders that have been conducted on neuroactive steroids are also described. 3. Plasma concentrations of some neuroactive steroids are altered in individuals suffering from schizophrenia, depression, or anxiety disorders compared to values in healthy controls. Some drugs used to treat these disorders have been reported to alter plasma and brain concentrations in clinical and preclinical studies, respectively. 4. Further research is warranted into the role of neuroactive steroids in the pathophysiology of psychiatric illnesses and the possible role of these steroids in the successful treatment of these disorders.

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Section: Neuroactive Steroids and Anxiety Disordersmentioning

confidence: 92%

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

et al. 2007

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“…No alterations of DHEA levels could be determined in panic disorder in the absence of panic attacks (Brambilla et al 2003). However, panic attacks induced experimentally by pentagastrin in panic disorder patients and healthy controls were followed by a significant rise in DHEA plasma levels (Tait et al 2002).…”

Section: Dhea and Dheas In Anxiety Disordersmentioning

confidence: 95%

Neuropsychopharmacological properties of neuroactive steroids in depression and anxiety disorders

et al. 2005

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Neuroactive steroids modulate neurotransmission through modulation of specific neurotransmitter receptors such as gamma-aminobutyric acid type A (GABAA) receptors. Preclinical studies suggested that neuroactive steroids may modulate anxiety- and depression-related behaviour and may contribute to the therapeutical effects of antidepressant drugs. Attenuations of 3alpha-reduced neuroactive steroids have been observed during major depression. This disequilibrium can be corrected by successful treatment with antidepressant drugs. However, non-pharmacological antidepressant treatment strategies did not affect neuroactive steroid composition independently from the clinical response. Further research is needed to clarify whether enhancement of neuroactive steroid levels might represent a new therapeutical approach in the treatment of affective disorders. Nevertheless, the first studies investigating the therapeutical effects of exogenously administered dehydroepiandosterone revealed promising results in the treatment of major depression. In addition, in various anxiety disorders alterations of neuroactive steroid levels have been observed. In panic disorder, in the absence of panic attacks, neuroactive steroid composition is opposite to that seen in depression, which may represent counter-regulatory mechanisms against the occurrence of spontaneous panic attacks. However, during experimentally induced panic attacks, there was a pronounced decline in GABAergic neuroactive steroids, which might contribute to the pathophysiology of panic attacks. In conclusion, neuroactive steroids contribute to the pathophysiology of affective disorders and the mechanisms of action of antidepressants. They are important endogenous modulators of depression and anxiety and may provide a basis for the development of novel therapeutic agents in the treatment of affective disorders.

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“…Studies in humans, however, did not reveal much difference between normal baseline plasma levels of THP in patients with generalized anxiety disorder [Le Melledo and Baker, 2002;Semeniuk et al, 2001], generalized social phobia, panic disorders [Le Melledo and Baker, 2002], as well as those challenged with the panicogenic agent pentagastrin [Tait et al, 2002]. But pentagastrin challenge did produce an increase of DHEA in plasma levels [Tait et al, 2002]. Surprisingly, Strohle et al [2003] found that levels of the anxiolytic NAS THP are higher than normal in patients with panic disorder.…”

Section: Ns and Nas In Anxiety Disordersmentioning

confidence: 99%

Potential use of neurosteroids and neuroactive steroids as modulators of symptoms of depression, anxiety, and psychotic disorders

Dubrovsky

2005

Drug Development Research

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The term ''neurosteroid'' (NS) was introduced by Baulieu in 1981 to name a steroid hormone, dehydroepiandrosterone sulfate (DHEAS), that was found at high levels in the brain long after gonadectomy and adrenalectomy, and shown later to be synthesized by the brain. The term ''neuroactive steroid'' (NAS) refers to steroids that, independent of their origin, are capable of modifying neural activities. NASs bind and modulate different types of membrane receptors. The g-amino butyric acid (GABA) and Sigma receptor complexes have been the most extensively studied, while glycine chloride channels, nicotinic acetylcholine receptors, and voltage-activated calcium channels, although less explored, are also modulated by NASs. Within the glutamate receptor family, N-methyl-D-aspartate (NMDA) receptors, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and kainate receptors have been shown to be targets for NA and NAS modulation. Inside the neuron, Oxidized ring A reduced pregnanes, tetrahydroprogesterone (THP), and tetrahydrodeoxycorticosterone (THDOC) bind to the progesterone intracellular receptor (PR) and in this way can also regulate gene expression. Animal experimentation showed that cardinal symptoms of depression, anxiety, sleep disturbances, and memory dysfunctions are partly regulated by NAS. In turn, NAS and NS levels are modulated by psychotropic medications. NS levels, as well as NAS plasma concentrations, change in patients with depression syndromes, the levels return to normal baseline with recovery, but normalization is not necessary for successful therapy. Rather than with nosological syndromes and psychiatric disorders, NAS and NS steroid DDR Published online in Wiley InterScience (www.interscience.wiley.com).

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Neuroactive steroid changes in response to challenge with the panicogenic agent pentagastrin

Cited by 33 publications

References 39 publications

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

Neuropsychopharmacological properties of neuroactive steroids in depression and anxiety disorders

Potential use of neurosteroids and neuroactive steroids as modulators of symptoms of depression, anxiety, and psychotic disorders

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