Reconsidering classifi cations of depression syndromes: Lessons from neuroactive steroids and evolutionary sciences

Abstract

Neurosteroids (NS) refers to steroids synthesized by the brain, neuroactive steroids (NAS) refers to steroids that, independent of their origin, are capable of modifying neural activities. NAS bind to and modulate different types of neurotransmitter receptors at the membrane level. The gamma-aminobutyric acid (GABA) and sigma receptor complexes have been the most extensively studied. After intracellular oxidation, tetrahydroprogesterone (THP) to dihydroprogesterone (DHP), and tetrahydrodeoxycorticosterone (THDOC) to dihydrodeoxycorticosterone (DHDOC) bind to the progesterone intracellular receptor (PR), and in this way can also regulate membrane composition through gene expression. Although NAS levels change in depression syndromes, in particular THP decreases while THDOC increases, levels return to normal baseline with recovery; however, normalization is not necessary for successful therapy. Studies attempting to pinpoint the possible use of NAS levels as biological markers were unsuccessful. Data from studies on the evolution of nervous systems, evolutionary developmental biology, as well as anatomical and physiological findings, preclude that the disorders that result when the brain succumbs to psychiatric ailments can be categorically classified. Persistence in maintaining essentialist classifications may help to explain why, until now, the search for biological markers in psychiatry has been an unrewarding effort. It is proposed that it would be more fruitful to focus on relationships between NAS and symptoms of psychiatric disorders, rather than with typologically defined disorders. © 2008 Springer Netherlands.