Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.

Students helping students: vertical peer mentoring to enhance the medical school experience.

BACKGROUND: Effective mentoring is an important component of medical student professional development. We provide a description of the mentoring program at our institution. METHODS: Our institution UTHSCSA implemented a student-advising program (Veritas) with clinical faculty mentors and senior students (MiMs). The MiMs provided vertical peer mentoring to more junior students as an adjunct to faculty advising. The MiMs lead small group discussions that foster camaraderie, share academic and career information and promote professional identity. An optional MiM elective more intensively develops mentorship and leadership skills through a formal curriculum. The authors used annual survey data of all students as well as student mentors to evaluate program effectiveness. RESULTS: Overall, student perception of the program improved each year across multiple domains, including feeling more prepared, supported and satisfied with their overall experience in medical school. Student mentors also found the process rewarding and helpful to their future careers as physicians. CONCLUSIONS: The authors suggest implementing a vertical peer-mentoring program can be an effective adjunct to faculty mentoring.

Cumulative effective doses delivered by radiographs to preterm infants in a neonatal intensive care unit.

OBJECTIVE: We sought to determine the number and distribution of radiographs and the cumulative effective radiograph doses (cED) received by a population of preterm infants (PIs) hospitalized in an NICU. STUDY DESIGN: We reviewed the files of all preterm infants (gestational age: <34 weeks) who were admitted to an NICU during an 18-month period and were discharged alive. A generalized additive model was used to study the relationship between cED and patient characteristics. RESULTS: Four hundred fifty files were analyzed. The median gestational age was 30.1 weeks (range: 24.1-33.9 weeks), and the median birth weight was 1250 g (range: 520-2760 g). The median number of radiographs per infant was 10.6 (range: 0-95), and the median cED was 138 microSv (range: 0-1450 microSv). The cumulative dose exceeded 500 microSv in 7.6% of the cases. Factors that influenced the cumulative effective dose were gestational age, birth weight, care procedures, and clinical adverse events. CONCLUSIONS: Given the potentially life-threatening complications of PIs, cumulative radiograph doses received in the ICU seem low with regard to environmental exposure and international recommendations. Additional studies are needed to evaluate the possible lifetime consequences of exposure to ionizing radiation at this age.

Does asymptomatic septal agenesis exist? A review of 34 cases.

BACKGROUND: Primary septal agenesis (PSA) is a rare brain malformation that can be isolated or part of developmental brain abnormalities (holoprosencephaly, septo-optic dysplasia or cortical malformation). Such associated malformation can be subtle, leading to difficulties in the prenatal management of PSA. Moreover, the neurological prognosis of isolated PSA remains debatable. OBJECTIVE: The aims of the study were to specify the patterns and frequency of brain malformations associated with septal agenesis (SA), to identify the clinical prognosis, and to discuss the aetiology of PSA with the new insights provided by molecular genetics. MATERIALS AND METHODS: The study consisted of a 14-year retrospective review of brain MRI in 34 patients having PSA (mean age, 5 years). Chiasm and optic nerves were not evaluated. Post-hydrocephalus SA or incomplete data were excluded. The clinical data were correlated to the MRI patterns. RESULTS: The study disclosed 82.5% associated lesions with MRI (28/34): 11 neuronal migration disorders, 9 holoprosencephalies (HP), 7 pituitary stalk interruptions, 1 corpus callosum partial agenesis; 17.5% (6/34) of cases were apparently isolated PAS. Clinically, the patients had motor dysfunction in 68% (23/34), mental retardation in 65% (22/34), blindness in 24% (8/34), endocrinological defects in 21% (7/34) and epilepsy in 18% (6/34) of cases. Nine percent of patients (3/34) were neurologically normal (including one with scoliosis and two infants younger than 2 years at the last follow-up). Patients with bilateral cortical anomalies and HP (even if mild) had the worst neurological prognosis. A severe motor impairment was present without evidence of hemispheric anomaly in 12% of patients (4/34). Interestingly, the frontal lobes were involved in 90% of cortical anomalies and HP, supporting the malformative aetiology of PSA. CONCLUSIONS: PSA rarely appears isolated and severe psychomotor impairment may occur in apparently isolated forms. These unfavourable results should be highlighted and need to be confirmed by a prospective study.

MRI of the fetal posterior fossa.

MRI is a useful tool to complement US for imaging of the fetal posterior fossa (PF). In France, the discovery of a PF malformation in the fetus frequently leads to termination of pregnancy (80% in a personal series). However, despite improved accuracy in the diagnosis of PF abnormalities, prognosis remains uncertain. The first objective of this review is to document the normal MRI landmarks of the developing fetal PF. Because of their thinness, the visibility of the cerebellar fissures is dramatically delayed on MRI compared to macroscopic data. An important landmark is identification of the primary fissure of the vermis, normally seen at around 25-26 weeks' gestation (WG) on the sagittal slice, separating the larger posterior lobe from the anterior lobe (volume ratio around 2:1). The prepyramidal and secondary fissures are usually only identifiable after 32 WG and the hemispheric fissures are difficult to see until the end of pregnancy. Considering the signal changes, high signal on T2-weighted (T2-W) sequences is seen from 25 WG in the posterior part of the brain stem (tegmentum and ascending sensory tracts) related to myelination. The low signal intensities seen within the cerebellum on T2-W images correspond to high cellularity of grey matter (deep nuclei), as there is no myelination within the white matter before 38 WG. The second objective is to highlight the signs highly predictive of a poor neurological prognosis. Lack of pontine curvature or vermian agenesis without a PF cyst (small volume of PF) is greatly associated with poor neurological status. The third objective is to propose a diagnostic strategy in difficult cases where prognosis is important, e.g. the Dandy Walker continuum. Analysis of the cerebellum is often impossible if a PF cyst is present (whatever its nature) as the mass effect usually blurs the foliation and even impairs evaluation of the normal ratio between the posterior and anterior lobes of the vermis. Isolated cerebellar hypoplasias raise the question of prognosis and genetic counselling. Such uncertainties require an amniocentesis and a careful search for other anomalies (cerebral and extracerebral). Unilateral abnormalities of a cerebellar hemisphere can be associated with good neurological status if they are isolated. The final objective is to discuss other rare PF fetal abnormalities, such as vascular malformations and tumours.

Sedation in children undergoing CT scan or MRI: effect of time-course and tolerance of rectal chloral hydrate.

The aim of this paper was to describe the time-course of the sedative effect of rectal chloral hydrate (75 mg/kg) in children undergoing CT scan or MRI. Twenty children (2.13 +/- 1.43 years old) were administered 75 mg/kg chloral hydrate rectally (chloralhydrat-rectiole rectal formulation, Dr Mann-Pharma Lab, Berlin, Germany), before a CT scan or an NMR imaging. Sedation was measured at specific times using a sedation score of 1-6. Patients were continuously monitored for respiratory and heart rate, systolic and diastolic blood pressures, and oxygen saturation. About 82.35 and 94.11% of the patients had a score of sedation > or = 3 within 15 and 30 min, respectively. The mean time to effective sedation (score > or = 3) was of 0.30 +/- 0.14 h (median time, 0.25 h). The mean duration of effective sedation (score > or = 3) was 1.29 +/- 1.05 h (median duration, 0.75 h). A total of 93.1% of the X-ray sections were obtained without artifact and sedation was considered by radiologists to be efficient for 83.3% of the procedures. This sedation procedure appeared efficient and safe during ambulatory CT scan and NMR imaging. The long-term effect of chloral hydrate, however, remains to be evaluated.