The neurobiology of retinoic acid in affective disorders

Abstract

Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from Vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain ; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute to the pathophysiology of depression.

Vitamine A et vieillissement cérébral

“…Des etudes recentes rapportent que les retinoïdes jouent egalement un rôle important dans le systeme nerveux central adulte (Lane et Bailey, 2005 ;Bremner et McCaffery, 2007 ;Tafti et Ghyselinck, 2007) en particulier dans des regions ou la plasticite neuronale est tres importante, i.e. l'hippocampe, le cortex prefrontal median ainsi que les regions retrospleniales.…”

Neurotransmitters Level in Hypothyroid Male Albino Rats after Isotretinoin Treatment

“…Retinoid receptors are concentrated in the limbic area that have been associated with depression, including the amygdala, prefrontal cortex and hippocampus. Retinoid also influence neurochemical system that have been implicated in depression, in particular, dopamine but to some extent serotonin and nor epinephrine (Bremner and McCaffery, 2008). According to Bremner and McCaffery (2008), these effects can be translated into behavioral effects, including symptoms of affective disorders.…”

Antioxidant Vitamins and Their Use in Psychiatry

“…Vitamin A' nın biyolojik olarak aktif metaboliti retinoik asittir ve çekirdekteki bir grup reseptör ailesine bağlanarak gen ekspresyonunu düzenler. [15] Metabolizması Vitamin A, hayvansal kaynaklı gıdalarda retinil esterleri olarak bulunur ve barsak lümeninde retinol ve serbest yağ asitlerine parçalanır. Barsak hücresine alınan retinolden tekrar retinil esterleri oluşturulur.…”

“…Hayvan modellerinde de 13-cis-retinoik asit maruziyetinin depresyon benzeri davranışlara, öğrenme ve bellekte bozulmaya neden olduğu belirtilmektedir. [15] Akne tedavisinde kullanılan aktif metabolit 13-cis-RA'in depresyon ve özkıyım düşüncelerine neden olabileceği iddiaları mevcuttur. [34] 13-cis-retinoik asitin erişkindeki nörogenezi azaltarak ve serotonerjik nörotransmiter sisteminin bileşenlerinin ekspresyonunu değiş-tirerek hayvanlarda depresyon benzeri davranışları indüklediği öne sürülmüş-tür.…”