Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11507
Subject order-independent group ICA (SOI-GICA) for functional MRI data analysis
Independent component analysis (ICA) is a data-driven approach to study functional magnetic resonance imaging (fMRI) data. Particularly, for group analysis on multiple subjects, temporally concatenation group ICA (TC-GICA) is intensively used. However, due to the usually limited computational capability, data reduction with principal component analysis (PCA: a standard preprocessing step of ICA decomposition) is difficult to achieve for a large dataset. To overcome this, TC-GICA employs multiple-stage PCA data reduction. Such multiple-stage PCA data reduction, however, leads to variable outputs due to different subject concatenation orders. Consequently, the ICA algorithm uses the variable multiple-stage PCA outputs and generates variable decompositions. In this study, a rigorous theoretical analysis was conducted to prove the existence of such variability. Simulated and real fMRI experiments were used to demonstrate the subject-order-induced variability of TC-GICA results using multiple PCA data reductions. To solve this problem, we propose a new subject order-independent group ICA (SOI-GICA). Both simulated and real fMRI data experiments demonstrated the high robustness and accuracy of the SOI-GICA results compared to those of traditional TC-GICA. Accordingly, we recommend SOI-GICA for group ICA-based fMRI studies, especially those with large data sets
PMID: 20338245
ISSN: 1095-9572
CID: 122714
Functional impact of global rare copy number variation in autism spectrum disorders
The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways
PMCID:3021798
PMID: 20531469
ISSN: 1476-4687
CID: 133515
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2010:107(28):12692-7.DOI: 10.1073/pnas.1002418107
Optical activation of lateral amygdala pyramidal cells instructs associative fear learning
Humans and animals can learn that specific sensory cues in the environment predict aversive events through a form of associative learning termed fear conditioning. This learning occurs when the sensory cues are paired with an aversive event occurring in close temporal proximity. Activation of lateral amygdala (LA) pyramidal neurons by aversive stimuli is thought to drive the formation of these associative fear memories; yet, there have been no direct tests of this hypothesis. Here we demonstrate that viral-targeted, tissue-specific expression of the light-activated channelrhodopsin (ChR2) in LA pyramidal cells permitted optical control of LA neuronal activity. Using this approach we then paired an auditory sensory cue with optical stimulation of LA pyramidal neurons instead of an aversive stimulus. Subsequently presentation of the tone alone produced behavioral fear responses. These results demonstrate in vivo optogenetic control of LA neurons and provide compelling support for the idea that fear learning is instructed by aversive stimulus-induced activation of LA pyramidal cells
PMCID:2906568
PMID: 20615999
ISSN: 1091-6490
CID: 135007
Latent Regression Analysis
Finite mixture models have come to play a very prominent role in modelling data. The finite mixture model is predicated on the assumption that distinct latent groups exist in the population. The finite mixture model therefore is based on a categorical latent variable that distinguishes the different groups. Often in practice distinct sub-populations do not actually exist. For example, disease severity (e.g. depression) may vary continuously and therefore, a distinction of diseased and not-diseased may not be based on the existence of distinct sub-populations. Thus, what is needed is a generalization of the finite mixture's discrete latent predictor to a continuous latent predictor. We cast the finite mixture model as a regression model with a latent Bernoulli predictor. A latent regression model is proposed by replacing the discrete Bernoulli predictor by a continuous latent predictor with a beta distribution. Motivation for the latent regression model arises from applications where distinct latent classes do not exist, but instead individuals vary according to a continuous latent variable. The shapes of the beta density are very flexible and can approximate the discrete Bernoulli distribution. Examples and a simulation are provided to illustrate the latent regression model. In particular, the latent regression model is used to model placebo effect among drug treated subjects in a depression study
PMCID:2897159
PMID: 20625443
ISSN: 1471-082x
CID: 138266
Tourette's Disorder
OPINION STATEMENT: Tourette's disorder (TD) is a common childhood-onset neuropsychiatric disorder characterized by chronic motor and vocal tics. TD frequently occurs with other neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), and may contribute to reduced quality of life and disability. Currently available treatments to reduce tics are limited by variable clinical response and frequent adverse effects. They include alpha-2 agonists, antipsychotics (first and second generation), tetrabenazine, benzodiazepines, and habit reversal therapy. Some new and emerging (but unproven) treatments are also discussed, including topiramate and dopamine agonists. In addition, there is increasing interest in deep brain stimulation, but this is not yet ready for general use.
PMID: 20842587
ISSN: 1092-8480
CID: 167354
Brain volumes in psychotic youth with schizophrenia and mood disorders
BACKGROUND: We sought to test the hypothesis that deficits in grey matter volume are characteristic of psychotic youth with early-onset schizophrenia-spectrum disorders (EOSS) but not of psychotic youth with early-onset mood disorders (EOMD). METHODS: We used magnetic resonance imaging to examine brain volume in 24 psychotic youth (13 male, 11 female) with EOSS (n = 12) or EOMD (n = 12) and 17 healthy controls (10 male, 7 female). We measured the volume of grey and white matter using an automated segmentation program. RESULTS: After adjustment for age and intracranial volume, whole brain volume was lower in the EOSS patients than in the healthy controls (p = 0.001) and EOMD patients (p = 0.002). The EOSS patients had a deficit in grey matter volume (p = 0.005), especially in the frontal (p = 0.003) and parietal (p = 0.006) lobes, with no significant differences in white matter volume. LIMITATIONS: The main limitations of our study were its small sample size and the inclusion of patients with depression and mania in the affective group. CONCLUSION: Adolescents with EOSS have grey matter deficits compared with healthy controls and psychotic adolescents with EOMD. Our results suggest that grey matter deficits are not generally associated with psychosis but may be specifically associated with schizophrenia. Larger studies with consistent methods are needed to reconcile the contradictory findings among imaging studies involving psychotic youth.
PMCID:2895153
PMID: 20569649
ISSN: 1488-2434
CID: 1780422
Journal of the American Academy of Child & Adolescent Psychiatry. 2010:49(7):686-98.DOI: 10.1016/j.jaac.2010.03.018
Prevalence of DSM-IV disorder in a representative, healthy birth cohort at school entry: sociodemographic risks and social adaptation
OBJECTIVE: The aims of this paper are as follows: to present past-year prevalence data for DSM-IV disorders in the early elementary school years; to examine the impact of impairment criteria on prevalence estimates; to examine the relation of sociodemographic and psychosocial risk factors to disorders; and to explore associations between "internalizing" and "externalizing" disorders and social competence and family burden as further validation of the impairing nature of these disorders. METHOD: As part of a longitudinal representative population study of children born healthy between July 1995 and September 1997 in the New Haven-Meriden Standard Metropolitan Statistical Area of the 1990 Census (n = 1,329), parents of a subsample enriched for child psychopathology (n = 442; 77.6% response rate, 69.5% of eligible sample) were interviewed in the child's kindergarten or first-grade year with the Diagnostic Interview Schedule for Children, Version IV (DISC-IV). Parents were surveyed about sociodemographic and psychosocial characteristics, and both parents and teachers were surveyed about social competence. RESULTS: Approximately one in five (21.6 %) children met criteria for psychiatric disorder(s) with impairment. Sociodemographic and psychosocial correlates included persistent poverty beginning in early childhood, limited parental education, low family expressiveness, stressful life events, and violence exposure. Finally, diagnostic status was significantly associated with poorer social competence and family burden. CONCLUSIONS: That approximately one in five children evidenced a psychiatric disorder with impairment during the transition to formal schooling highlights the importance of integrating psychiatric epidemiological and developmental approaches to inform conversations about school readiness and intervention planning.
PMCID:3166638
PMID: 20610138
ISSN: 0890-8567
CID: 177348
Amygdala activation in response to facial expressions in pediatric obsessive-compulsive disorder
BACKGROUND: Exaggerated amygdala activation to threatening faces has been detected in adults and children with anxiety disorders, compared to healthy comparison (HC) subjects. However, the profile of amygdala activation in response to facial expressions in obsessive-compulsive disorder (OCD) may be a distinguishing feature; a prior study found that compared with healthy adults, adults with OCD exhibited less amygdala activation to emotional and neutral faces, relative to fixation [Cannistraro et al. (2004). Biological Psychiatry 56:916-920]. METHODS: In the current event-related functional magnetic resonance imaging (fMRI) study, a pediatric OCD sample (N=12) and a HC sample (N=17) performed a gender discrimination task while viewing emotional faces (happy, fearful, disgusted) and neutral faces. RESULTS: Compared to the HC group, the OCD group showed less amygdala/hippocampus activation in all emotion and neutral conditions relative to fixation. CONCLUSIONS: Like previous reports in adult OCD, pediatric OCD may have a distinct neural profile from other anxiety disorders, with respect to amygdala activation in response to emotional stimuli that are not disorder specific.
PMCID:2951127
PMID: 20602430
ISSN: 1091-4269
CID: 161840
Issues for DSM-5: whither melancholia? The case for its classification as a distinct mood disorder [Editorial]
PMCID:3733615
PMID: 20595426
ISSN: 0002-953x
CID: 998202
The clinical utility of the Social Responsiveness Scale and Social Communication Questionnaire in tuberous sclerosis complex
Tuberous sclerosis complex (TSC) is often associated with epilepsy, mental retardation, and autism spectrum disorders (ASDs). Thus, screening for ASDs is important when evaluating these individuals. We examined the utility of the Social Responsiveness Scale (SRS) and Social Communication Questionnaire (SCQ), two measures for screening for ASDs, in a TSC population. Twenty-one children were evaluated, with 52.4% classified as having ASDs on the SRS and 42.9% classified as such on the SCQ. Number of antiepileptic drugs significantly correlated with SRS Total score, as did level of intellectual functioning. Evidence for convergent validity was obtained between the SRS and SCQ Total scores (r=0.605). Moreover, all SRS subscales correlated with SCQ Total score (r>0.400). All SCQ subscales except for Communication correlated with SRS total. Overall, the results demonstrate that these questionnaires appear to be effective screens for ASDs in a TSC population and are measuring similar constructs
PMID: 20554253
ISSN: 1525-5069
CID: 110875
