Faculty Bibliography

(Reprinted with permission from Schizophrenia Research 2013; 150:11-14).

Transcranial magnetic stimulation (TMS) is a powerful investigational tool for in vivo manipulation of regional or network activity, with a growing number of potential clinical applications. Unfortunately, the vast majority of targeting strategies remain limited by their reliance on non-realistic brain models and assumptions that anatomo-functional relationships are 1:1. Here, we present an integrated framework that combines anatomically realistic finite element models of the human head with resting functional MRI to predict functional networks targeted via TMS at a given coil location and orientation. Using data from the Human Connectome Project, we provide an example implementation focused on dorsolateral prefrontal cortex (DLPFC). Three distinct DLPFC stimulation zones were identified, differing with respect to the network to be affected (default, frontoparietal) and sensitivity to coil orientation. Network profiles generated for DLPFC targets previously published for treating depression revealed substantial variability across studies, highlighting a potentially critical technical issue.

OBJECTIVE:Disruptive mood dysregulation disorder (DMDD) is a novel diagnosis listed in Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) to encompass chronic and impairing irritability in youth, and to help its differentiation from bipolar disorders. Because it is a new entity, treatment guidelines, as well as its sociodemographic and clinical features among diverse populations, are still not elucidated. Here, DMDD cases from three centers in Turkey are reported and the implications are discussed. METHODS:The study was conducted at the Abant Izzet Baysal University Medical Faculty Department of Child and Adolescent Psychiatry (Bolu), and American Hospital and Bengi Semerci Institute (Istanbul) between August 2014 and October 2014. Records of patients were reviewed and features of patients who fulfilled criteria for DMDD were recorded. Data were analyzed with SPS Version 17.0 for Windows. Descriptive analyses, χ(2) test, and Mann-Whitney U test were used for analyses. Diagnostic consensus was determined via Cohen's κ constants. p was set at 0.01. RESULTS:Thirty-six patients (77.8 % male) fulfilled criteria for DMDD. κ value for consensus between clinicians was 0.68 (p = 0.00). Mean age of patients was 9.0 years (S.D. = 2.5) whereas the mean age of onset for DMDD symptoms was 4.9 years (S.D. = 2.2). Irritability, temper tantrums, verbal rages, and physical aggression toward family members were the most common presenting complaints. CONCLUSIONS:Diagnostic consensus could not be reached for almost one fourth of cases. Most common reasons for lack of consensus were problems in clarification of moods of patients in between episodes, problems in differentiation of normality and pathology (i.e., symptoms mainly reported in one setting vs. pervasiveness), and inability to fulfill frequency criterion for tantrums.

OBJECTIVE:To evaluate whether a psychosocial screening program that included free and flexible access to mental health (MH) consultation resulted in increased rate of consultations. STUDY DESIGN/METHODS:This is a post hoc review of a clinical screening program in a pediatric food allergy clinic in New York City. Screening was limited to 2 days per week, providing an opportunity to compare screened and nonscreened cohorts. Previous results from more than 1000 other families were analyzed to create the 1-page screening questionnaire. Participants were children with allergies and their parents who sought care at the clinic between March and September 2013. Parents were screened for distress and quality of life burden related to their child's allergy, and children were screened for anxiety, bullying, and quality of life. The predefined primary outcome was the percentage of families who received the free MH consultation after screening vs no-screening days in the allergy clinic. RESULTS:The 3143 encounters during the study period included 1171 on screening days and 1972 on no-screening days. Most (86%) eligible families completed the screen. Almost one-half (44%) met the initial screening thresholds. A total of 71 families (6.1% of screening days encounters) were referred to a MH consultation after a secondary review, but only 11 (1% of screening days encounters) scheduled a MH appointment. Eighteen families from the no-screening days came to a MH evaluation (1% of no-screening days encounters). CONCLUSION/CONCLUSIONS:Screening did not lead to enhanced MH follow-up. Resources may be better used on ensuring the availability of MH care rather than on screening in pediatric specialty clinics.

C-tactile (CT) afferents encode caress-like touch that supports social-emotional development, and stimulation of the CT system engages the insula and cortical circuitry involved in social-emotional processing. Very few neuroimaging studies have investigated the neural mechanisms of touch processing in people with autism spectrum disorder (ASD), who often exhibit atypical responses to touch. Using functional magnetic resonance imaging, we evaluated the hypothesis that children and adolescents with ASD would exhibit atypical brain responses to CT-targeted touch. Children and adolescents with ASD, relative to typically developing (TD) participants, exhibited reduced activity in response to CT-targeted (arm) versus non-CT-targeted (palm) touch in a network of brain regions known to be involved in social-emotional information processing including bilateral insula and insular operculum, the right posterior superior temporal sulcus, bilateral temporoparietal junction extending into the inferior parietal lobule, right fusiform gyrus, right amygdala, and bilateral ventrolateral prefrontal cortex including the inferior frontal and precentral gyri, suggesting atypical social brain hypoactivation. Individuals with ASD (vs. TD) showed an enhanced response to non-CT-targeted versus CT-targeted touch in the primary somatosensory cortex, suggesting atypical sensory cortical hyper-reactivity.

Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high-, and low-impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome-wide association study (GWAS)-implicated BMD variants. We used dual-energy X-ray absorptiometry to estimate femoral neck, total hip, and spine areal-BMD and total body less head (TBLH) bone mineral content (BMC) Z-scores. The BMD genetic score was negatively associated with each bone Z-score (eg, TBLH-BMC: estimate = -0.03, p = 1.3 × 10(-6) ). Total PA was positively associated with bone Z-scores; these associations were driven by time spent in high-impact PA (eg, TBLH-BMC: estimate = 0.05, p = 4.0 × 10(-10) ) and were observed even for children with lower than average bone Z-scores. We found no evidence of PA-adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA-genetic score-Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH-BMC in males (p interaction = 7.1 × 10(-5) ), where PA was associated with higher TBLH-BMC Z-score among the BMD-lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10(-9) ). In conclusion, the beneficial effect of PA on bone, especially high-impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS-implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.

Using adult identified bone mineral density (BMD) loci, we calculated genetic risk scores (GRS) to determine if they were associated with changes in BMD during childhood. Longitudinal data from the Bone Mineral Density in Childhood Study were analyzed (N = 798, 54% female, all European ancestry). Participants had up to 6 annual dual energy X-ray scans, from which areal BMD (aBMD) Z-scores for the spine, total hip, and femoral neck were estimated, as well as total body less head bone mineral content (TBLH-BMC) Z-scores. Sixty-three single-nucleotide polymorphisms (SNPs) were genotyped, and the percentage of BMD-lowering alleles carried was calculated (overall adult GRS). Subtype GRS that include SNPs associated with fracture risk, pediatric BMD, WNT signaling, RANK-RANKL-OPG, and mesenchymal stem cell differentiation were also calculated. Linear mixed effects models were used to test associations between each GRS and bone Z-scores, and if any association differed by sex and/or chronological age. The overall adult, fracture, and WNT signaling GRS were associated with lower Z-scores (eg, spine aBMD Z-score: βadult  = -0.04, p = 3.4 × 10(-7) ; βfracture = -0.02, p = 8.9 × 10(-6) ; βWNT  = -0.01, p = 3.9 × 10(-4) ). The overall adult GRS was more strongly associated with lower Z-scores in females (p-interaction ≤ 0.05 for all sites). The fracture GRS was more strongly associated with lower Z-scores with increasing age (p-interaction ≤ 0.05 for all sites). The WNT GRS associations remained consistent for both sexes and all ages (p-interaction > 0.05 for all sites). The RANK-RANKL-OPG GRS was more strongly associated in females with increasing age (p-interaction < 0.05 for all sites). The mesenchymal stem cell GRS was associated with lower total hip and femoral neck Z-scores, in both boys and girls, across all ages. No associations were observed between the pediatric GRS and bone Z-scores. In conclusion, adult identified BMD loci associated with BMD and BMC in the pediatric setting, especially in females and in loci involved in fracture risk and WNT signaling.