Searched for: school:SOM
Department/Unit:Child and Adolescent Psychiatry
Testosterone rapidly increases neural reactivity to threat in healthy men: a novel two-step pharmacological challenge paradigm
Goetz, Stefan M M; Tang, Lingfei; Thomason, Moriah E; Diamond, Michael P; Hariri, Ahmad R; Carré, Justin M
BACKGROUND:Previous research suggests that testosterone (T) plays a key role in shaping competitive and aggressive behavior in humans, possibly by modulating threat-related neural circuitry. However, this research has been limited by the use of T augmentation that fails to account for baseline differences and has been conducted exclusively in women. Thus, the extent to which normal physiologic concentrations of T affect threat-related brain function in men remains unknown. METHODS:In the current study, we use a novel two-step pharmacologic challenge protocol to overcome these limitations and to evaluate causal modulation of threat- and aggression-related neural circuits by T in healthy young men (n = 16). First, we controlled for baseline differences in T through administration of a gonadotropin releasing hormone antagonist. Once a common baseline was established across participants, we then administered T to within the normal physiologic range. During this second step of the protocol we acquired functional neuroimaging data to examine the impact of T augmentation on neural circuitry supporting threat and aggression. RESULTS:Gonadotropin releasing hormone antagonism successfully reduced circulating concentrations of T and brought subjects to a common baseline. Administration of T rapidly increased circulating T concentrations and was associated with heightened reactivity of the amygdala, hypothalamus, and periaqueductal grey to angry facial expressions. CONCLUSIONS:These findings provide novel causal evidence that T rapidly potentiates the response of neural circuits mediating threat processing and aggressive behavior in men.
PMID: 24576686
ISSN: 1873-2402
CID: 3149072
Use of outpatient mental health services among children of different ages: are younger children more seriously ill?
Horwitz, Sarah M; Storfer-Isser, Amy; Demeter, Christine; Youngstrom, Eric A; Frazier, Thomas W; Fristad, Mary A; Arnold, L Eugene; Axelson, David; Birmaher, Boris; Kowatch, Robert A; Findling, Robert L
OBJECTIVE: The study compared use of specialty outpatient mental services among children ages six and seven and children ages eight through 12 and investigated predictors of differences in the patterns of service use by age. METHODS: Eligible children were first-time patients of clinics participating in the Longitudinal Assessment of Manic Symptoms who were between ages six and 12 and who were English speaking. Children who screened positive for symptoms of mania (N=1,124) were invited to participate, and families of 621 (55%) children consented. A matched sample of 86 children without a positive screen for mania also participated. Baseline interviews assessed sociodemographic characteristics of the child and family and the child's functioning, diagnoses, and use of services. RESULTS: Of the 707 children, 30% were younger, and 50% used multiple types of specialty outpatient services. Younger children were more likely to be male, have Medicaid insurance, and have two parents with mental health problems. Use of multiple types of services was related to study site, high depression scores, fewer minor health issues, and fewer stressful life events among younger children and with parental stress, primary diagnosis, poor functioning, and not living with both parents among older children. Younger children were much more likely than older children to have used services before age six. CONCLUSIONS: Younger children showed very early use of multiple types of services for mental health problems and a pattern of persistent impairment despite long-standing use of services. These data argue strongly for focusing on emotional and behavioral issues among young children.
PMCID:4121963
PMID: 24789735
ISSN: 1075-2730
CID: 1291452
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
Somatic Complaints in Anxious Youth
Crawley, Sarah A; Caporino, Nicole E; Birmaher, Boris; Ginsburg, Golda; Piacentini, John; Albano, Anne Marie; Sherrill, Joel; Sakolsky, Dara; Compton, Scott N; Rynn, Moira; McCracken, James; Gosch, Elizabeth; Keeton, Courtney; March, John; Walkup, John T; Kendall, Philip C
This study examined (a) demographic and clinical characteristics associated with physical symptoms in anxiety-disordered youth and (b) the impact of cognitive-behavioral therapy (Coping Cat), medication (sertraline), their combination, and pill placebo on physical symptoms. Youth (N = 488, ages 7-17 years) with a principal diagnosis of generalized anxiety disorder, separation anxiety disorder, or social phobia participated as part of a multi-site, randomized controlled trial and received treatment delivered over 12 weeks. Diagnostic status, symptom severity, and impairment were assessed at baseline and week 12. The total number and severity of physical symptoms was associated with age, principal diagnosis, anxiety severity, impairment, and the presence of comorbid internalizing disorders. Common somatic complaints were headaches, stomachaches, head cold or sniffles, sleeplessness, and feeling drowsy or too sleepy. Physical symptoms decreased over the course of treatment, and were unrelated to treatment condition. Clinical implications and directions for future research are discussed (ClinicalTrials.gov number, NCT00052078).
PMCID:3989467
PMID: 24129543
ISSN: 0009-398x
CID: 907322
Commercial sexual exploitation of children and the role of the child psychiatrist [Editorial]
Ijadi-Maghsoodi, Roya; Todd, Emily J; Bath, Eraka P J
PMID: 25062588
ISSN: 1527-5418
CID: 2313492
Impairment in emotional modulation of attention and memory in schizophrenia
Walsh-Messinger, Julie; Ramirez, Paul Michael; Wong, Philip; Antonius, Daniel; Aujero, Nicole; McMahon, Kevin; Opler, Lewis A; Malaspina, Dolores
Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a Rapid Serial Visual Presentation of pictures. Target stimuli were either positive or negative, or neutral images presented at either 200ms or 700ms lag. Additionally, a visual hedonic task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200ms and 700ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700ms lag condition and fewer negative images under the 200ms lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder.
PMCID:4098815
PMID: 24910446
ISSN: 1573-2509
CID: 1033492
Coping with asymmetry: how infants and adults walk with one elongated leg
Cole, Whitney G; Gill, Simone V; Vereijken, Beatrix; Adolph, Karen E
The stability of a system affects how it will handle a perturbation: The system may compensate for the perturbation or not. This study examined how 14-month-old infants-notoriously unstable walkers-and adults cope with a perturbation to walking. We attached a platform to one of participants' shoes, forcing them to walk with one elongated leg. At first, the platform shoe caused both age groups to slow down and limp, and caused infants to misstep and fall. But after a few trials, infants altered their gait to compensate for the platform shoe whereas adults did not; infants recovered symmetrical gait whereas adults continued to limp. Apparently, adult walking was stable enough to cope with the perturbation, but infants risked falling if they did not compensate. Compensation depends on the interplay of multiple factors: The availability of a compensatory response, the cost of compensation, and the stability of the system being perturbed.
PMCID:4096352
PMID: 24857934
ISSN: 1934-8800
CID: 1651502
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
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
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