Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10−8, 5.18 × 10−7 and 1.25 × 10−9, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology

Adult-Age Inflammatory Pain Experience Enhances Long-Term Pain Vigilance in Rats

Background: Previous animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent painrelated behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear. Methodology/Principal Findings: In the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain. Conclusions/Significance: These results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight th

A 'snip' in time: what is the best age to circumcise?

<p>Abstract</p> <p>Background</p> <p>Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves.</p> <p>Discussion</p> <p>We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used.</p> <p>Summary</p> <p>Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.</p

Prenatal Antipsychotic Exposure and Neuromotor Performance During Infancy

CONTEXT: Despite the expanding clinical utility of antipsychotics beyond psychotic disorders to include depressive, bipolar, and anxiety disorders, reproductive safety data regarding the neurodevelopmental sequelae of fetal antipsychotic exposure are scarce. OBJECTIVE: To examine whether intrauterine antipsychotic exposure is associated with deficits in neuromotor performance and habituation in 6-month-old infants. DESIGN, SETTING, AND PARTICIPANTS: A prospective controlled study was conducted from December 1999 through June 2008 at the Infant Development Laboratory of the Emory Psychological Center examining maternal-infant dyads (N=309) at 6 months postpartum with pregnancy exposure to antipsychotics (n=22), antidepressants (n = 202), or no psychotropic agents (n = 85). Examiners masked to maternal-infant exposure status administered a standardized neuromotor examination (Infant Neurological International Battery [INFANIB]) that tests posture, tone, reflexes, and motor skills and a visual habituation paradigm using a neutral female face. MAIN OUTCOME MEASURES: The INFANIB composite score; number of trials required to achieve a 50% decrease in infant fixation during a visual habituation task; and mean time looking at the stimulus across 10 trials. RESULTS: Infants prenatally exposed to antipsychotics (mean=64.71) showed significantly lower INFANIB scores than those with antidepressant (mean=68.57) or no psychotropic (mean=71.19) exposure, after controlling for significant covariates (F(2,281)=4.51; P =.01; partial η(2)=0.033). The INFANIB scores were also significantly associated with maternal psychiatric history, including depression, psychosis, and overall severity/chronicity (P’s<.05) and maternal depression during pregnancy was associated with less efficient habituation (r(245)=0.16; P <.02). There were no significant differences regarding habituation between medication exposure groups. CONCLUSIONS: Among 6-month-old infants, a history of intrauterine antipsychotic exposure, compared with antidepressant or no psychotropic exposure, was associated with significantly lower scores on a standard test of neuromotor performance, highlighting the need for further scrutiny of the reproductive safety and neurodevelopmental sequelae of fetal antipsychotic exposure. Disentangling medication effects from maternal illness effects, which also contributed, remains a critical challenge