Retinoic Acid and Affective Disorders

Abstract

Objective Isotretinoin (13-cis-retinoic acid, or 13-cis-RA) (Accutane), approved by the FDA for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psychosis. Retinoic acid (RA), the active form of vitamin A, regulates gene expression in the brain, and isotretinoin is its 13-cis isomer. Retinoids represent a group of compounds derived from vitamin A that perform a large variety of functions in many systems, in particular the CNS, and abnormal retinoid levels can have neurological effects. Although infrequent, proper recognition and treatment of psychiatric side effects in acne patients is critical given the risk of death and disability. This paper reviews the evidence for a relationship between isotretinoin, depression and suicidality. Data Sources Evidence examined includes: 1) case reports; 2) temporal association between onset of depression and exposure to the drug; 3) challenge-rechallenge cases; 4) class effect (other compounds in the same class, like vitamin A, having similar neuropsychiatric effects); 5) dose response; and 6) biologically plausible mechanisms. Study Selection All papers in the literature related to isotretinoin, depression and suicide were reviewed, as well as papers related to class effect, dose response, and biological plausibility. Data Extraction Information from individual articles in the literature was extracted. Data Synthesis The literature reviewed is consistent with an association between isotretinoin administration, depression and suicide in some individuals. Conclusions The relationship between isotretinoin and depression may have implications for a greater understanding of the neurobiology of affective disorders.

The effect of abscisic acid chronic treatment on neuroinflammatory markers and memory in a rat model of high-fat diet induced neuroinflammation

“…RA has beneficial cognitive effects, rectifying memory deficits in rodent models of Alzheimer disease. However, the clinical and animal model data show an association between RA administration and the symptoms of depression [15]. Chronic treatment with ABA has beneficial antidepressant effects demonstrated by increased sucrose intake, increased swimming in the forced swim test, and reduced expression of CRH and RARα mRNA in the rat hypothalamus in control rats, with no reported side effects [16].…”

Psychiatric Comorbidity in Patients with Acne

“…Isotretinoin ( er doses of isotretinoin were found to be associated with a greater risk of depression [28].…”

Hypothalamic Inflammation and Glioses as Aetiopathogenetic Factor in High Fat Diet Induced Obesity and Various Therapeutic Options to Resolve it

“…144 ABA given chronically has been shown to be a useful antidepressant as shown by increased sucrose intake, increased swimming in the forced swim test and decreased expression of CRH and RARα mRNA in the rat hypothalamus in control rats with no reported side effects. 145 Thus Sanchez-Sarua et al tried to show if dietary ABA could improve cognitive defects resulting from a HFD induced neuroinflammation. HFD increases the levels of neuroinflammation markers in the brain 146 and may be a link between obesity and degenerative disorders via IR.…”