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Neuropsychopharmacological properties of neuroactive steroids in depression and anxiety disorders

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Abstract

Neuroactive steroids modulate neurotransmission through modulation of specific neurotransmitter receptors such as γ-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 3α-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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Abbreviations

3α-ADIOL:

5α-androstane3α, 17β-diol

5α-THP:

3α, 5α-tetrahydroprogesterone, allopregnanolone

3α, 5β-THP:

3α, 5β-tetrahydroprogesterone

3α, 5α-THDOC:

3α, 5α-tetrahydrodeoxycorticosterone, allotetrahydrodeoxycorticosterone

3α-HSD:

3α-hydroxysteroid dehydrogenase

3β, 5α-THP:

3β, 5α-tetrahydroprogesterone, isopregnanolone

5α-DHP:

5α-dihydroprogesterone, 5α-pregnane-3,20 dione

5α-DHDOC:

5α-dihydrodeoxycorticosterone

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

CCK-4:

cholecystokinin–tetrapeptide

CSF:

cerebrospinal fluid

DHEA:

dehydroepiandosterone

DHEAS:

dehydroepiandosterone sulfate

DOC:

deoxycortisosterone

ECT:

electroconvulsive therapy

GABA:

γ-aminobutyric acid

HPA-axis:

hypothalamic-pituitary-adrenal axis

NMDA:

N-methyl-D-Aspartate

OVX:

ovarectomized

PBT:

pentobarbital

PPD:

post-partum depression

PMDD:

premenstrual dysphoric disorder

PMS:

premenstrual syndrome

PS:

pregnenolone sulfate

PSD:

partial sleep deprivation

PTSD:

post-traumatic stress disorder

rTMS:

repetitive transcranial magnetic stimulation

SSRI:

selective serotonin re-uptake inhibitor

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Acknowledgement

The authors thank Mrs. A. Johnson and Mr. K. Neuner for valuable technical assistance in our studies. These studies were supported by the Deutsche Forschungsgemeinschaft and a Tandem project of the Max Planck Society.

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Authors and Affiliations

  1. Department of Psychiatry, Ludwig Maximilian University, Nussbaumstr. 7, 80336, Munich, Germany

    Daniela Eser, Cornelius Schüle, Thomas C. Baghai, Peter Zwanzger, Frank Padberg & Rainer Rupprecht

  2. Department of Neuroscience, Tor Vergata University of Rome, 00133, Rome, Italy

    Elena Romeo, Flavia di Michele & Augusto Pasini

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  1. Daniela Eser
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  2. Cornelius Schüle
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Correspondence to Rainer Rupprecht.

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Eser, D., Schüle, C., Romeo, E. et al. Neuropsychopharmacological properties of neuroactive steroids in depression and anxiety disorders. Psychopharmacology 186, 373–387 (2006). https://doi.org/10.1007/s00213-005-0188-z

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