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)

Use of the acne drug Accutane (13-cis retinoic acid, [13-cis RA]) has been associated with severe depression. This association has been considered controversial because no causative link has been found between 13-cis RA and this disorder. A recent hypothesis has suggested that atrophy of the hippocampus can result in depression. We now show, in a mouse model, that endogenous RA generated by synthetic enzymes in the meninges acts on hippocampal granule neurons, and chronic (3-week) exposure to a clinical dose of 13-cis RA may result in hippocampal cell loss. In humans this may be conjectured to be the mechanism by which Accutane contributes to depression.
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PMID:13-cis Retinoic acid (accutane) suppresses hippocampal cell survival in mice. 1525 24

Isotretinoin (Accutane) is a drug closely related to the chemical structure of Vitamin A. The pharmacology and toxicology of these two retinoids is similar enough to warrant comparison. Accutane is a powerful drug which its manufacturer, Roche, indicates is limited for severe recalcitrant nodular acne. This potency is also reflected in Accutane's well-known ability to produce severe birth defects if taken during pregnancy. Less well-known is the risk of this lipid soluble chemical to affect the Central Nervous System. Reports of intracranial hypertension, depression, and suicidal indeation with Accutane use have prompted an examination of this serious and life threatening potential. Though Roche has added a warning to its product label for signs of depression and suicidal ideation, this product is being overprescribed for all forms of acne, including mild cases and moderate acne that have not been treated with alternative medications, which have a lesser risk of depression and suicide. There is no contesting that this drug is effective at clearing up the most severe forms of acne, but the public must be informed of its proper, limited indication for use; depression and suicide can follow in patients with no prior history of psychiatric symptoms or suicide attempts.
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PMID:Polar hysteria: an expression of hypervitaminosis A. 1554 93

Isotretinoin (Accutane) ranks in the top 10 of the US Food and Drug Administration's database of drugs associated with reports of depression and suicide attempts. However, this association is still controversial because up to 5.6% of patients with moderate acne may have pre-existing suicidal ideations, improvement of acne often reduces associated depression, and isotretinoin users are reportedly no more likely than those taking antibiotics for acne to have depression or commit suicide. We describe a series of cases of manic psychosis that developed in a 1-year period (2003) in association with isotretinoin treatment and resulted in suicidality and progression to long-standing psychosis. Cases were drawn from 500 soldiers who had been evaluated in a military specialists dermatology clinic for severe acne. Data were summarized from medical records of five severe acne patients treated by isotretinion during their compulsory military service. Data from their draft board examinations and service records, as well as repeated clinical assessments by certified psychiatrists at the Israel Defense Forces (IDF) Mental Health Department clinic, were evaluated. Five young adults developed manic psychosis within a mean of 7.6 months of exposure to isotretinoin. In three cases, this was accompanied by a suicide attempt, and in three cases, psychosis lasted for longer than 6 months. Either a personal history of obsessive-compulsive disorder, neurological insult or family history of a major psychiatric illness were present in all cases. The present case-series is suggestive of an increase in the likelihood of an association between exposure to isotretinion and manic psychosis. Associated risk factors were both family and personal history of psychiatric morbidity. Further studies are needed to establish our findings.
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PMID:Affective psychosis following Accutane (isotretinoin) treatment. 1560 15

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


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