Functional Brain Imaging Alterations in Acne Patients Treated With Isotretinoin

Bremner, J. Douglas; Fani, Negar; Ashraf, Ali; Votaw, John R.; Cummins, Thomas K.; Vaccarino, Loredana; Goodman, Mark M.; Reed, Lai; Siddiq, Sajid; Nemeroff, Charles B.

doi:10.1176/appi.ajp.162.5.983

Cited by 106 publications

(85 citation statements)

References 75 publications

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“…All subjects suffered from acne. Administration of isotretinoin (but not antibiotic) was associated with a 16% decrease in brain metabolism in the orbitofrontal cortex after four months of treatment (Bremner et al 2005).…”

Section: Ra and The Frontal Cortexmentioning

confidence: 92%

The neurobiology of retinoic acid in affective disorders

Bremner

McCaffery

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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144

154

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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.

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Section: Ra and The Frontal Cortexmentioning

confidence: 92%

The neurobiology of retinoic acid in affective disorders

Bremner

McCaffery

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Self Cite

144

154

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“…However, there are also studies suggesting that there is no evidence of such a link (Jick et al, 2000;Jacobs et al, 2001;Ferahbas et al, 2004;Chai et al, 2005). One recent study used positron emission tomography to examine brain function in patients with treatment-resistant acne (Bremner et al, 2005). In patients treated with 13-cis-RA, but not antibiotic, there was a significant decrease in orbitofrontal cortical metabolism.…”

Section: Introductionmentioning

confidence: 99%

Chronic Administration of 13-Cis-Retinoic Acid Increases Depression-Related Behavior in Mice

O’Reilly

Shumake

González-Lima

et al. 2006

Neuropsychopharmacol

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Retinoid signaling plays a well-established role in neuronal differentiation, neurite outgrowth, and the patterning of the anteroposterior axis of the developing neural tube. However, there is increasing evidence that nutritional vitamin A status and retinoid signaling play an important role in the function of the adult brain. 13-Cis-retinoic acid (13-cis-RA) (isotretinoin or Accutane), a synthetic retinoid that is an effective oral treatment for severe nodular acne, has been linked with depression and suicide in patients. The purpose of this study was to test the hypothesis that chronic administration of 13-cis-RA would lead to depression-related behaviors in mice. Young, adult male mice received 13-cis-RA (1 mg/kg) by daily intraperitoneal injection for 6 weeks. This treatment paradigm produced plasma levels of 13-cis-RA that are comparable to those reported in human patients taking Accutane. In both the forced swim test and the tail suspension test, we found that 13-cis-RA-treated mice spent significantly more time immobile compared to vehicle-treated controls. In the open field test, there was no change in anxiety-related behavior in 13-cis-RA-treated mice. Furthermore, chronic administration of 13-cis-RA did not impair locomotion in either the open field or the rotarod test. Taken together, these results suggest that administration of 13-cis-RA increases depression-related behaviors in mice.

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“…Так, в ходе исследований метаболизма в тканях мозга методом позитронной эмиссионной томографии, J. Bremner и соавт. [49] установили уменьшение объема коры орбитофрон-тальной зоны через 4 мес лечения у 21% пациентов по сравнению с 2% пациентов, получающих анти-биотики, и доказали наличие прямой связи между головными болями и приемом препарата. Хотя именно связь этих зон, ответственных за развитие депрессии, с приемом препарата не была доказана.…”

Section: клиническая дерматология и венерология 6 2015unclassified