1. Ebstein RP, Mankuta D, Yirmiya N, Malavasi F. {{Are retinoids potential therapeutic agents in disorders of social cognition including autism?}}. {FEBS Lett};2011 (Jun 6);585(11):1529-1536.
Increasing evidence suggests that the nonapeptide, oxytocin (OT), helps shape social and affiliative behaviors not only in lower mammals but also in humans. Recently, an essential mediator of brain OT release has been discovered, ADP-ribosyl cyclase and/or CD38. We have subsequently shown that polymorphisms across the CD38 gene are associated with autism spectrum disorders (ASD). Notably, CD38 expression in lymphoblastoid cells (LBC) is reduced in cell lines derived from ASD subjects compared to parental cell lines. Intriguingly, a correlation was observed between CD38 expression and measures of social function in ASD. Finally, we have shown that all-trans retinoic acid (ATRA), a known inducer of CD38 transcription, can rescue low CD38 expressing LBC lines derived from ASD subjects and restore normal levels of transcription of this ectoenzyme providing ‘proof of principle’ in a peripheral model that retinoids are potential therapeutic agents in ASD.
2. Karimov CB, Moragianni VA, Cronister A, Srouji S, Petrozza J, Racowsky C, Ginsburg E, Thornton KL, Welt CK. {{Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function}}. {Hum Reprod};2011 (Jun 6)
BACKGROUND The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). However, its prevalence in women with occult POI (i.e. menstrual cycles, but impaired ovarian response) has not been examined. We hypothesized that both the FMR1 premutation and intermediate allele is more frequent in infertile women with occult POI than in controls, and that a repeat length cutoff might predict occult POI. METHODS All subjects were menstruating women <42 years old and with no family history of unexplained mental retardation, autism or fragile X syndrome. Cases had occult POI defined by elevated FSH or poor response to gonadotrophin therapy (n= 535). Control subjects (n= 521) had infertility from other causes or were oocyte donors. Prevalence of the FMR1 premutation and intermediate alleles was examined and allele length was compared between controls and women with occult POI. RESULTS The frequency of the premutation (7/535 versus 1/521; P< 0.05) and intermediate alleles (17/535 versus 7/521; P< 0.05) was higher in women with occult POI than in controls. The allele with the greatest number of CGG repeats was longer in women with occult POI compared with controls (32.7 +/- 7.1 versus 31.6 +/- 4.3; P< 0.01). A receiver operating characteristic curve examining repeat length as a test for occult POI had an area of 0.56 +/- 0.02 (P< 0.01). A repeat cutoff of 45 had a specificity of 98%, but a sensitivity of only 5% to identify occult POI. The positive predictive value was only 21% for a fertility population that has approximately 22% of its patients with occult POI. CONCLUSIONS The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragileX-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI.
