Highlights
Isotretinoin teratogenicity well established; psychiatric effects documented, controversial
Disturbed retinoid signaling implicated in isotretinoin teratogenic and psychiatric effects
Effect of genetics on susceptibility to psychiatric side effects is possible, not yet known
Postnatal neurocognitive effects of isotretinoin not yet established
Schwannomatosis has been linked to germline mutations in the SMARCB1 and LZTR1 genes, and is frequently associated with pain.In a cohort study, we assessed the mutation status of 37 patients with clinically diagnosed schwannomatosis and compared to clinical data, whole body MRI (WBMRI), visual analog pain scale, and Short Form 36 (SF-36) bodily pain subscale.We identified a germline mutation in LZTR1 in 5 patients (13.5%) and SMARCB1 in 15 patients (40.5%), but found no germline mutation in 17 patients (45.9%). Peripheral schwannomas were detected in 3 LZTR1-mutant (60%) and 10 SMARCB1-mutant subjects (66.7%). Among those with peripheral tumors, the median tumor number was 4 in the LZTR1 group (median total body tumor volume 30 cc) and 10 in the SMARCB1 group (median volume 85cc), (P=.2915 for tumor number and P = .2289 for volume). mutation was associated with an increased prevalence of spinal schwannomas (100% vs 41%, P = .0197). The median pain score was 3.9/10 in the LZTR1 group and 0.5/10 in the SMARCB1 group (P = .0414), and SF-36 pain-associated quality of life was significantly worse in the LZTR1 group (P = .0106). Pain scores correlated with total body tumor volume (rho = 0.32471, P = .0499), but not with number of tumors (rho = 0.23065, P = .1696).We found no significant difference in quantitative tumor burden between mutational groups, but spinal schwannomas were more common in LZTR1-mutant patients. Pain was significantly higher in LZTR1-mutant than in SMARCB1-mutant patients, though spinal tumor location did not significantly correlate with pain. This suggests a possible genetic association with schwannomatosis-associated pain.
Background: An association between isotretinoin (13-cis-retinoic acid, sold under trade names including Accutane [Hoffmann-La Roche Inc, Basel, Switzerland]) and birth defects, depression, and suicide is well documented but controversial. A link to psychosis and exacerbation of bipolar symptoms is less extensively addressed in the literature. Objective: Given recent conceptualization of psychotic disorders as neurodevelopmental, and current interest in possible shared etiology of different neurodevelopmental disorders such as psychosis, autism, and intellectual disability, this review concurrently examines the literature on developmental (primarily teratogenic) and psychiatric side effects of isotretinoin exposure. The goal of concurrent review is to identify shared mechanisms in the literature that may inform future effort s to clarify the neurocognitive and psychiatric effects of isotretinoin exposure at different developmental stages or given different genetic backgrounds. Methods: Literature was obtained by PubMed search for the term isotretinoin in combination with each of the terms psychosis , psychiatric , and teratogenic . Resulting articles met inclusion criteria for review if they addressed psychiatric side effects of isotretinoin treatment or the neurobehavioral teratology of isotretinoin. Results: The association of isotretinoin exposure with prenatal developmental toxicity is well established. Although numerous reports also link isotretinoin treatment with psychiatric side effects, this association remains controversial.
Conclusions:The extent to which isotretinoin influences pediatric and adult development and cognition, and whether and why certain individuals may be susceptible to psychiatric side effects, remains to be clarified.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.