Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.
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PMID:Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats. 1603 93

Isotretinoin (13-cis retinoic acid) is an effective treatment for severe cystic or recalcitrant acne vulgaris; however, concerns have been raised regarding its potential association with depression and suicidal behavior. We sought to explore the proposed relationship between isotretinoin use and the risk of depression and attempted and completed suicide in patients with acne vulgaris by performing a systematic literature search for studies reporting primary data on depression and suicidal behavior in patients treated with isotretinoin for acne vulgaris. Nine studies met the qualifying criteria for our analysis. Rates of depression among isotretinoin users ranged from 1% to 11% across studies, with similar rates in oral antibiotic control groups. Overall, studies comparing depression before and after treatment did not show a statistically significant increase in depression diagnoses or depressive symptoms. Some, in fact, demonstrated a trend toward fewer or less severe depressive symptoms after isotretinoin therapy. This decrease was particularly evident in patients with pretreatment scores in the moderate or clinical depression range. No correlation between isotretinoin use and suicidal behavior was reported, although only one retrospective study presented data on this topic. Although the current literature does not support a causative association between isotretinoin use and depression, there are important limitations to many of the studies. The available data on suicidal behavior during isotretinoin treatment are insufficient to establish a meaningful causative association.
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PMID:Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. 1609 97

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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PMID:Chronic administration of 13-cis-retinoic acid increases depression-related behavior in mice. 1639 5

Isotretinoin is a very effective drug for the treatment of severe recalcitrant acne. However, it's use is associated with many side effects, sometimes is associated with the emergence of psychiatric symptoms. During of a prospective study to evaluate the efficacy and safety of isotretinoin in acne, six male patients, refer difficulties in maintaining adequate penile erection in association with clinical symptoms of depression. To our knowledge this is the first time that this side effect is reported, so the results suggest that further studies of it's use in similar patients are warranted.
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PMID:[Erectile dysfunction during isotretinoin therapy]. 1644 96

Isotretinoin is a synthetic oral retinoid that has great efficacy against severe, recalcitrant, nodulocystic acne. Since its introduction to the market, it has been associated with a variety of adverse psychiatric effects, including depression, psychosis, mood swings, violent behavior, suicide, and suicide attempts. A MEDLINE review was performed to compile all case reports, case series, adverse drug event reportings, and prospective and retrospective studies relating psychiatric adverse events to isotretinoin. In addition, literature linking a biological mechanism for psychiatric adverse events to retinoid signaling pathways was also reviewed. Although a variety of anecdotal and epidemiologic studies are available, the overall lack of concrete scientific data limits any conclusion that can be drawn about a causal relationship between istotretinoin and psychiatric adverse events. Several lines of evidence link retinoid signaling to theorized psychiatric pathogenesis, but are limited in their applicability to adult neurophysiology.
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PMID:Isotretinoin and the controversy of psychiatric adverse effects. 1686 13

Descriptions of psychiatric effects with Accutane (13-cis-retinoic acid (13-cis-RA)) use prompted a series of studies in a rodent model to ascertain its cognitive effects. Previously, we reported no effects on measures of anhedonia and depression in rats treated with 7.5, 22.5, or 30 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459 [16]; S.A. Ferguson, F.J., Cisneros, J.P. Hanig, K.J. Berry, Chronic oral treatment with Accutane (13-cis-retinoic acid) does not increase measures of anhedonia or depression in male and female Sprague-Dawley rats, (in preparation) [19]]. Here, we assessed spatial learning and memory in male and female Sprague-Dawley rats gavaged daily beginning on postnatal day (PND) 59 with vehicle control (soybean oil), 7.5 or 30 mg/kg of 13-cis-RA. We have reported that 7.5 mg/kg produces serum levels of 13-cis-RA comparable to those of humans prescribed Accutane [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all- trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol. 98 (2006) 582-587 [18]]. Three behavioral tasks assessed spatial learning and memory after chronic 13-cis-RA treatment: the escape-reinforced Morris water maze (PNDs 111-115), the food-reinforced 8-arm radial maze (PNDs 132-136), and the water-reinforced NCTR complex maze (PNDs 153-157). Behaviors were measured after a minimum of 52 and maximum of 94 days of 13-cis-RA treatment. 13-cis-RA treatment had no effects on performance of the 8-arm radial maze or the NCTR complex maze. Treatment effects on Morris water maze performance were negligible and neither dose-related nor consistent. Performances of the control group were quite similar to those previously described in this laboratory. These results indicate that chronic 13-cis-RA treatment in male and female rats has few effects on measures of spatial learning and memory.
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PMID:Oral Accutane (13-cis-retinoic acid) has no effects on spatial learning and memory in male and female Sprague-Dawley rats. 1716 36

In addition to their established role in nervous system development, vitamin A and related retinoids are emerging as regulators of adult brain function. Accutane (13-cis-retinoic acid, isotretinoin) treatment has been reported to increase depression in humans. Recently, we showed that chronic administration of 13-cis-retinoic acid (13-cis-RA) to adolescent male mice increased depression-related behaviors. Here, we have examined whether 13-cis-RA regulates components involved in serotonergic neurotransmission in vitro. We used the RN46A-B14 cell line, derived from rat embryonic raphe nuclei. This cell line synthesizes serotonin (5-hydroxytryptamine, 5-HT) and expresses the 5-HT(1A) receptor and the serotonin reuptake transporter (SERT). Cells were treated with 0, 2.5, or 10 microM 13-cis-RA for 48 or 96 hrs, and the levels of 5-HT; its metabolite, 5-hydroxyindoleacetic acid (5HIAA); 5-HT(1A) receptor; and SERT were determined. Treatment with 13-cis-RA for 96 hrs increased the intracellular levels of 5-HT and tended to increase intra-cellular 5HIAA levels. Furthermore, 48 hrs of treatment with 2.5 and 10 microM 13-cis-RA significantly increased 5-HT(1A) protein to 168.5 +/- 20.0% and 148.7 +/- 2.2% of control respectively. SERT protein levels were significantly increased to 142.5 +/- 11.1% and 119.2 +/- 3.6% of control by 48 hrs of treatment with 2.5 and 10 microM of 13-cis-RA respectively. Increases in both 5-HT(1A) receptor and SERT proteins may lead to decreased serotonin availability at synapses. Such an effect of 13-cis-RA could contribute to the increased depression-related behaviors we have shown in mice.
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PMID:13-cis-Retinoic acid alters intracellular serotonin, increases 5-HT1A receptor, and serotonin reuptake transporter levels in vitro. 1789 27

Vitamin A and its derivatives, the retinoids, have long been studied for their ability to alter central nervous system (CNS) development. Increasingly, it is recognized that sufficient levels of retinoids may also be required for adult CNS function. However, excess dietary vitamin A, due to the consumption of supplements or foods rich in vitamin A, has been reported to induce psychosis. In addition, 13-cis-retinoic acid (13-cis-RA, isotretinoin), the active ingredient in the acne treatment Accutane, has been reported to cause adverse psychiatric events, including depression and suicidal ideation. Nevertheless, epidemiological studies have reported no consistent link between Accutane use and clinical depression in humans. Using an animal model, we have recently shown that 13-cis-RA induces an increase in depression-related behavior. Impairments in spatial learning and memory have also been demonstrated following 13-cis-RA treatment in mice. This review focuses on the behavioral and possible cellular effects of retinoid deficiency or excess in the adult brain in relation to altered mood. Specifically, we discuss the effect of retinoids on depression-related behaviors and whether norepinephrinergic, dopaminergic, or serotonergic neurotransmitter systems may be impaired. In addition, we consider the evidence that adult neurogenesis, a process implicated in the pathophysiology of depression, is reduced by retinoid signaling. We suggest that 13-cis-RA treatment may induce depression-related behaviors by decreasing adult neurogenesis and/or altering the expression of components of serotonergic neurotransmitter system, thereby leading to impaired serotonin signaling.
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PMID:Retinoid-mediated regulation of mood: possible cellular mechanisms. 1829 31

Isotretinoin (13-cis retinoic acid) is an effective treatment for severe cystic or recalcitrant acne vulgaris; however, concerns have been raised regarding its potential association with depression and suicidal behavior. We sought to explore the proposed relationship between isotretinoin use and the risk of depression and attempted and completed suicide in patients with acne vulgaris by performing a systematic literature search for studies reporting primary data on depression and suicidal behavior in patients treated with isotretinoin for acne vulgaris. Nine studies met the qualifying criteria for our analysis. Rates of depression among isotretinoin users ranged from 1% to 11% across studies, with similar rates in oral antibiotic control groups. Overall, studies comparing depression before and after treatment did not show a statistically significant increase in depression diagnoses or depressive symptoms. Some, in fact, demonstrated a trend toward fewer or less severe depressive symptoms after isotretinoin therapy. This decrease was particularly evident in patients with pretreatment scores in the moderate or clinical depression range. No correlation between isotretinoin use and suicidal behavior was reported, although only one retrospective study presented data on this topic. Although the current literature does not support a causative association between isotretinoin use and depression, there are important limitations to many of the studies. The available data on suicidal behavior during isotretinoin treatment are insufficient to establish a meaningful causative association.
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PMID:Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. 1839 69

Retinoids influence cellular processes such as differentiation, proliferation and apoptosis via retinoic acid receptor (RAR) and retinoid X receptor (RXR), and have therapeutic applications in several cancers and dermatologic diseases. Recent reports indicate that depression occasionally occurs in patients using the acne drug Accutane, the active component of which is 13-cis-retinoic acid (13-cis-RA). Although impairment of serotonin (5-HT)-expressing neurons, including morphologic changes, is thought to be associated with depressive symptoms, the effects of 13-cis-RA on 5-HT neurons have not been examined. The present study demonstrated that 13-cis-RA alters the morphology of 5-HT neurons in cultured rat midbrain slices. The 13-cis-RA-induced changes were partially blocked by RXR and RAR antagonists. Furthermore, cotreatment with RAR and RXR agonists altered the morphology of 5-HT neurons to a greater extent than the individual application of each agonist. The morphologic changes were completely blocked by RXR antagonist, whereas RAR antagonist partially blocked the effects. These results suggest that 13-cis-RA exerts its action on slice-cultured 5-HT neurons, at least in part, through specific retinoid receptors. Moreover, RXR has a greater influence on the morphology of 5-HT neurons than RAR. The receptor-mediated actions of 13-cis-RA presented here may provide a clue for further research on depression associated with the use of 13-cis-RA.
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PMID:13-cis-retinoic acid alters the cellular morphology of slice-cultured serotonergic neurons in the rat. 1844 26


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