Searched for: school:SOM
Department/Unit:Child and Adolescent Psychiatry
An fMRI study of cerebrovascular reactivity and perfusion in obstructive sleep apnea patients before and after CPAP treatment
Prilipko, Olga; Huynh, Nelly; Thomason, Moriah E; Kushida, Clete A; Guilleminault, Christian
OBJECTIVE:Cerebrovascular reactivity is impaired in patients suffering from obstructive sleep apnea syndrome (OSAS) as demonstrated by transcranial Doppler studies. We use magnetic resonance imaging techniques to investigate the anatomical distribution of cerebrovascular reactivity changes in patients with OSAS, as well as their evolution after therapeutic and sham continuous positive airway pressure (CPAP) treatment. METHODS:Twenty-three men with moderate or severe obstructive sleep apnea were compared to a healthy control group (n=7) using a breath-holding functional magnetic resonance imaging task and the flow-sensitive alternating inversion recovery (FAIR) imaging before and after 2 months of therapeutic (active) or sub-therapeutic (sham) CPAP treatment. RESULTS:Significantly higher cerebrovascular reactivity was found in healthy controls as compared to patients in bilateral cortical and subcortical brain regions. Cerebrovascular reactivity increased with therapeutic CPAP in the thalamus and decreased with sham CPAP in medial frontal regions in OSAS patients. Duration of nocturnal hypoxemia and body mass index negatively correlated with cerebrovascular reactivity, particularly in the medial temporal lobe structures, suggesting a possible pathophysiological mechanism for hippocampal injury. There was no difference in perfusion between patients and control group, and no effect of CPAP or sham-CPAP treatment on perfusion in patients. CONCLUSIONS:Observed cerebrovascular reactivity changes were neither homogeneous throughout the brain nor followed vascular territories, but rather corresponded to underlying neuronal networks, establishing a relationship between cerebrovascular reactivity and surrounding neuronal activity.
PMID: 24916094
ISSN: 1878-5506
CID: 3149092
Editorial: 'What's up, (R)DoC?' - can identifying core dimensions of early functioning help us understand, and then reduce, developmental risk for mental disorders? [Editorial]
Sonuga-Barke, Edmund J S
In the US the National Institute of Mental Health (NIMH), the main funder of mental health research in the world, has recently changed its funding model to promote a radically new perspective for mental health science. This bold, and for some controversial, initiative, termed the Research Diagnostic Criteria (or RDoC for short), intends to shift the focus of research, and eventually clinical practice, away from existing diagnostic categories, as recently updated in the DSM-5, towards 'new ways of classifying psychopathology based on dimensions of observable behavior and neurobiological measures.' This reorientation from discrete categorical disorder manifestations to underlying cross-cutting dimensions of individual functioning has generated considerable debate across the community of mental health researchers and clinicians (with strong views voiced both pro and con). Given its pivotal role in defining the research agenda globally, there is little doubt that this US science funding initiative will also have ramifications for researchers and clinicians worldwide. In this Editorial we focus specifically on the translational potential of the dimensional RDoC approach, properly extended to developmental models of early risk, in terms of its value as a potential driver of early intervention/prevention models; in the current issue of the JCPP this is exemplified by a number of papers thata address the mapping of underlying dimensions of core functioning to disorder risk, providing evidence for their potential predictive power as early markers of later disorder processes.
PMID: 25039570
ISSN: 0021-9630
CID: 1075562
Perfluorooctanoate exposure and major birth defects
Stein, Cheryl R; Savitz, David A; Elston, Beth; Thorpe, Phoebe G; Gilboa, Suzanne M
Perfluorooctanoate (PFOA) is detectable in umbilical cord blood and amniotic fluid. Some toxicological findings suggest that perfluoroalkyl substances may be teratogenic. Using data from the C8 Health Project, a 2005-2006 survey in a Mid-Ohio Valley community exposed to PFOA through contaminated drinking water, we examined the association between estimated prenatal PFOA concentration and maternally reported birth defects (n=325) among 10,262 live singleton or multiple births from 1990 to 2006. Logistic regression models accounted for siblings using generalized estimating equations. There was generally no association between estimated PFOA concentration and birth defects, with the possible exception of brain defects, where the odds ratio adjusted for year of conception was 2.6 (95% confidence interval 1.3-5.1) for an increase in estimated PFOA exposure from the 25th to 75th percentile. This estimate, however, was based on 13 cases and may represent a chance finding. Further investigation of this potential association may be warranted.
PMCID:4117925
PMID: 24803403
ISSN: 1873-1708
CID: 3143272
Multimodal MR Imaging of Brain Iron in Attention Deficit Hyperactivity Disorder: A Noninvasive Biomarker That Responds to Psychostimulant Treatment?
Adisetiyo, Vitria; Jensen, Jens H; Tabesh, Ali; Deardorff, Rachael L; Fieremans, Els; Di Martino, Adriana; Gray, Kevin M; Castellanos, Francisco X; Helpern, Joseph A
Purpose To comprehensively assess brain iron levels in typically developing control subjects and patients with attention deficit hyperactivity disorder (ADHD) when psychostimulant medication history is accounted for. Materials and Methods This prospective study was approved by the institutional review board, and informed consent was obtained. Brain iron was indexed noninvasively by using magnetic resonance (MR) imaging relaxation rates (R2, R2*, R2') and magnetic field correlation (MFC) in the globus pallidus, putamen, caudate nucleus, and thalamus for 22 patients with ADHD (12 medication-naive patients and 10 with a history of psychostimulant treatment) and 27 control subjects (age range, 8-18 years). Serum iron measures were also collected. Subgroup differences were analyzed with data-appropriate omnibus tests followed by post hoc pairwise comparisons; false discovery rate correction was conducted to control for multiple comparisons. Results Medication-naive ADHD patients had significantly lower striatal and thalamic MFC indexes of brain iron than did control subjects (putamen, P = .012; caudate nucleus, P = .008; thalamus, P = .012) and psychostimulant-medicated ADHD patients (putamen, P = .006; caudate nucleus, P = .010; thalamus, P = .021). Conversely, the MFC indexes in medicated patients were comparable to those in control subjects. No significant differences were detected with R2, R2*, R2', or serum measures. Conclusion Lower MFC indexes of striatal and thalamic brain iron in medication-naive ADHD patients and lack of differences in psychostimulant-medicated patients suggest that MFC indexes of brain iron may represent a noninvasive diagnostic biomarker that responds to psychostimulant treatment. (c) RSNA, 2014 Online supplemental material is available for this article.
PMCID:4263268
PMID: 24937545
ISSN: 0033-8419
CID: 1065442
A Dose-Ranging Study of Behavioral and Pharmacological Treatment in Social Settings for Children with ADHD
Pelham, William E; Burrows-Maclean, Lisa; Gnagy, Elizabeth M; Fabiano, Gregory A; Coles, Erika K; Wymbs, Brian T; Chacko, Anil; Walker, Kathryn S; Wymbs, Frances; Garefino, Allison; Hoffman, Martin T; Waxmonsky, James G; Waschbusch, Daniel A
Placebo and three doses of methylphenidate (MPH) were crossed with 3 levels of behavioral modification (no behavioral modification, NBM; low-intensity behavioral modification, LBM; and high-intensity behavior modification, HBM) in the context of a summer treatment program (STP). Participants were 48 children with ADHD, aged 5-12. Behavior was examined in a variety of social settings (sports activities, art class, lunch) that are typical of elementary school, neighborhood, and after-school settings. Children received each behavioral condition for 3 weeks, order counterbalanced across groups. Children concurrently received in random order placebo, 0.15 mg/kg/dose, 0.3 mg/kg/dose, or 0.6 mg/kg/dose MPH, 3 times daily with dose manipulated on a daily basis in random order for each child. Both behavioral and medication treatments produced highly significant and positive effects on children's behavior. The treatment modalities also interacted significantly. Whereas there was a linear dose-response curve for medication in NBM, the dose-response curves flattened considerably in LBM and HBM. Behavior modification produced effects as large as moderate doses, and on some measures, high doses of medication. These results replicate and extend to social-recreational settings previously reported results in a classroom setting from the same sample (Fabiano et al., School Psychology Review, 36, 195-216, 2007). Results illustrate the importance of taking dosage/intensity into account when evaluating combined treatments; there were no benefits of combined treatments when the dosage of either treatment was high but combination of the low-dose treatments produced substantial incremental improvement over unimodal treatment.
PMCID:4090274
PMID: 24429997
ISSN: 0091-0627
CID: 786042
Asthma and mental health among youth in high risk service settings
Goodwin, Renee D; Hottinger, Kate; Pena, Lillian; Chacko, Anil; Feldman, Jonathan; Wamboldt, Marianne Z; Hoven, Christina
Abstract Objective: To investigate the prevalence of asthma and mental health problems among representative samples of youth in high risk service settings and the community, and to examine the relationship between asthma and mental health in these groups. Methods: Data were drawn from the Alternative Service Use Patterns of Youth with Serious Emotional Disturbance Study (SED) (n=1,181), a combined representative, cross-sectional sample of youth in various clinical settings and the community. Multiple logistic regression analyses were used to examine the association between asthma and mental disorders. Demographic characteristics were investigated as potential confounders. Results: Asthma was common among 15.2% of youth in service settings and 18.8% of youth in the community. The prevalence of mental disorders was extremely high among youth with and without asthma in all service settings, and asthma was associated with increased prevalence of mental disorders among youth in the community, but not among youth in service settings. The relationship between asthma and internalizing disorders among youth in the community does not appear entirely attributable to confounding by demographics. Conclusions: Findings are consistent with and extend previous data by showing that both asthma and mental disorders are disproportionately common among youth in high risk service settings. Almost half of youth with asthma in service settings meet diagnostic criteria for a mental disorder. Clinicians and policy makers who are responsible for the health care of youth in these high risk groups should be aware that asthma is common, and that the prevalence of internalizing disorders are especially common among those with asthma.
PMID: 24628526
ISSN: 0277-0903
CID: 889472
Behavioral Interventions in Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials Across Multiple Outcome Domains
Daley, David; van der Oord, Saskia; Ferrin, Maite; Danckaerts, Marina; Doepfner, Manfred; Cortese, Samuele; Sonuga-Barke, Edmund J S
OBJECTIVE: Behavioral interventions are recommended as attention-deficit/hyperactivity disorder (ADHD) treatments. However, a recent meta-analysis found no effects on core ADHD symptoms when raters were probably blind to treatment allocation. The present analysis is extended to a broader range of child and parent outcomes. METHOD: A systematic search in PubMed, Ovid, Web of Knowledge, ERIC, and CINAHAL databases (up to February 5, 2013) identified published randomized controlled trials measuring a range of patient and parent outcomes for children and adolescents diagnosed with ADHD (or who met validated cutoffs on rating scales). RESULTS: Thirty-two of 2,057 nonduplicate screened records were analyzed. For assessments made by individuals closest to the treatment setting (usually unblinded), there were significant improvements in parenting quality (standardized mean difference [SMD] for positive parenting 0.68; SMD for negative parenting 0.57), parenting self-concept (SMD 0.37), and child ADHD (SMD 0.35), conduct problems (SMD 0.26), social skills (SMD 0.47), and academic performance (SMD 0.28). With probably blinded assessments, significant effects persisted for parenting (SMD for positive parenting 0.63; SMD for negative parenting 0.43) and conduct problems (SMD 0.31). CONCLUSION: In contrast to the lack of blinded evidence of ADHD symptom decrease, behavioral interventions have positive effects on a range of other outcomes when used with patients with ADHD. There is blinded evidence that they improve parenting and decrease childhood conduct problems. These effects also may feed through into a more positive parenting self-concept but not improved parent mental well-being.
PMID: 25062591
ISSN: 0890-8567
CID: 1089542
Maternal familismo and early childhood functioning in Mexican and Dominican immigrant families
Calzada, Esther J; Huang, Keng-Yen; Linares-Torres, Heliana; Singh, S Diana; Brotman, Laurie
A large theoretical and empirical literature documents the central role of familismo (i.e., a strong emphasis on family) in the functioning of Latino youth. Few studies, however, have examined its association with early childhood functioning. The present study explored the potential risk and protective effects of maternal familismo on the adaptive and mental health functioning of 4 - 5 year old Latino children. A sample of 205 Mexican and 147 Dominican immigrant families was recruited from New York City. Mothers reported on their level of familismo, and acculturative status. Mothers and teachers rated child adaptive behavior and internalizing and externalizing problems. Findings suggest that maternal familismo is not uniformly associated with positive or negative early developmental outcomes but that its effects are moderated by child gender, family poverty and cultural (e.g., maternal ethnic and US American identity) characteristics. In addition, different mechanisms were identified for each ethnic group. Familismo was associated both positively (for boys) and negatively (for poor children) with adaptive behavior in the Mexican American sample. In the Dominican American sample, familismo showed a wide range of positive, albeit moderated, effects. Prevention efforts that help parents critically evaluate the impact of familismo on family processes, and preserve those manifestations of familismo that are protective, may best promote Latino child well-being.
PMCID:4244907
PMID: 25436179
ISSN: 2168-1678
CID: 1369922
Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study
McGrath, Lauren M; Yu, Dongmei; Marshall, Christian; Davis, Lea K; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A; Osiecki, Lisa; O'Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Cath, Danielle C; Cavallini, Maria C; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, Damiaan; Derks, Eske M; Dion, Yves; Rosario, Maria C; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas V; Garrido, Helena; Geller, Daniel; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grunblatt, Edna; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hounie, Ana G; Jankovic, Joseph; Kennedy, James L; King, Robert A; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L; Lyon, Gholson J; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T; McMahon, William; Murphy, Dennis L; Naarden, Allan L; Neale, Benjamin M; Nurmi, Erika; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I; Richter, Margaret A; Riddle, Mark; Robertson, Mary M; Rosenberg, David; Rouleau, Guy A; Ruhrmann, Stephan; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H; Stein, Dan J; Tischfield, Jay A; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R; Shugart, Yin Yao; Miguel, Euripedes C; Nicolini, Humberto; Oostra, Ben A; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A; Cox, Nancy J; Hanna, Gregory L; Brentani, Helena; Scherer, Stephen W; Arnold, Paul D; Stewart, S Evelyn; Mathews, Carol A; Knowles, James A; Cook, Edwin H; Pauls, David L; Wang, Kai; Scharf, Jeremiah M
OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. METHOD: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. RESULTS: Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). CONCLUSION: Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.
PMCID:4218748
PMID: 25062598
ISSN: 0890-8567
CID: 1089552
Quality concerns in antipsychotic prescribing for youth: a review of treatment guidelines
Kealey, Edith; Scholle, Sarah Hudson; Byron, Sepheen C; Hoagwood, Kimberly; Leckman-Westin, Emily; Kelleher, Kelly; Finnerty, Molly
BACKGROUND: Antipsychotic prescribing for youth has increased rapidly, is linked with serious health concerns, and lacks clear measures of quality for pediatric care. We reviewed treatment guidelines relevant to 7 quality concepts for appropriate use and management of youth on antipsychotics: 1) use in very young children, 2) multiple concurrent antipsychotics, 3) higher-than-recommended doses, 4) use without a primary indication, 5) access to psychosocial interventions, 6) metabolic screening, and 7) follow-up visits with a prescriber. METHODS: We searched for clinical practice guidelines meeting the following criteria: developed or endorsed by a national body, published after 2000, and specific treatment recommendations made related to 1 or more of the 7 quality concepts. Sources included electronic databases, the American Academy of Child and Adolescent Psychiatry Web site, and stakeholder and expert advisory committee recommendations. Two raters reviewed the 11 guidelines identified, extracting treatment recommendations, including details that could support measure definitions, and ratings of strength of recommendation and evidence. RESULTS: All 7 quality concepts were strongly endorsed by 1 or more guidelines, and 2 or more guidelines assigned their highest strength of recommendation ratings to 6 of the 7 concepts. Two guidelines rated evidence, providing high strength of evidence for 2 quality concepts: psychosocial interventions and metabolic monitoring. CONCLUSIONS: Guidelines provide support for 7 quality concepts addressing antipsychotic prescribing for youth. However, guideline support is often based on strong clinical consensus rather than a robust evidence base.
PMCID:4486323
PMID: 25169461
ISSN: 1876-2867
CID: 1173692