Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11288
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
Does the cortisol response to stress mediate the link between expressed emotion and oppositional behavior in Attention-Deficit/Hyperactivity-Disorder (ADHD)?
BACKGROUND: Expressed Emotions (EE) are associated with oppositional behavior (OPB) in children with Attention Deficit/Hyperactivity Disorder (ADHD). EE has been linked to altered stress responses in some disorders, but ADHD has not been studied. We test the hypothesis that OPB in ADHD is mediated by altered stress-related cortisol reactivity to EE. METHODS: Two groups of children (with/without ADHD) and their respective parents were randomly assigned to two different conditions with/without negative emotion and participated in an emotion provocation task. Parents' EE, their ratings of their children's OPB and their children's salivary cortisol levels were measured. RESULTS: Low parental warmth was associated with OPB in ADHD. High levels of parental EE elicited a larger cortisol response. Stress-related cortisol reactivity mediated the EE-OPB link for all children. This highlights the general importance of parent-child interactions on externalizing behavior problems. CONCLUSION: High EE is a salient stressor for ADHD children that leads to increased levels of cortisol and OPB. The development of OPB might be mediated by the stress-response to high EE
PMCID:2917389
PMID: 20633268
ISSN: 1744-9081
CID: 145839
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
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 child psychology & psychiatry & allied disciplines. 2010:51(7):755-62.DOI: 10.1111/j.1469-7610.2010.02249.x
5HTT genotype moderates the influence of early institutional deprivation on emotional problems in adolescence: evidence from the English and Romanian Adoptee (ERA) study
BACKGROUND: A common polymorphism in the serotonin transporter gene (SLC6A4, 5HTT) has been repeatedly shown to moderate the influence of childhood adversity and stressful life events on the development of psychopathology. Using data from the English and Romanian Adoptee Study, a prospective-longitudinal study of individuals (n = 125) exposed to severe early institutional deprivation (ID), we tested whether the effect of ID on adolescent emotional problems is moderated by 5HTT genotype and stressful life events in adolescence. METHODS: Emotional problems were assessed using questionnaire data (age 11), and on the basis of the CAPA diagnostic interview (age 15). Additionally, the number of stressful life events was measured. RESULTS: There was a significant effect for genotype (p = .003) and a gene x environment interaction (p = .008) that was independent of age at testing. Carriers of the s/l and s/s genotype who experienced severe ID showed the highest emotional problem scores, while l/l homozygotes in the severe ID group showed the lowest overall levels. Furthermore, s/s carriers in the severe ID group who experienced a high number of stressful life events between 11 and 15 years had the largest increases in emotional problem scores, while a low number of stressful life events was associated with the largest decrease (4-way interaction: p = .05). CONCLUSIONS: The effects of severe early ID on emotional problems in adolescence are moderated by 5HTT genotype, and influenced by stressful life events in adolescence
PMID: 20345836
ISSN: 1469-7610
CID: 145841
Effect of sex and estrogen therapy on the aging brain: a voxel-based morphometry study
OBJECTIVE: It is still a matter of debate whether estrogen can have a protective effect on brain integrity and against age- and Alzheimer-related assaults. Evidence points toward selective sparing of gray matter (GM) in postmenopausal women using hormone therapy. In the current study, the effect of sex and estrogen therapy (ET) exposure on GM density using voxel-based morphometry was assessed. METHODS: High-resolution structural magnetic resonance imaging scans of 46 healthy participants were analyzed using voxel-based morphometry. A total of 15 men and 31 healthy postmenopausal women were included: 15 ET-naive women (never users) and 16 current ET users with an average duration of use of 11 years. RESULTS: Sex differences were found in fronto-temporo-parietal areas, with postmenopausal women having greater GM concentration in the medial prefrontal cortex, temporal cortices, angular gyrus, and precuneus, whereas the men had greater GM density in the superior frontal, inferior temporal gyri, and inferior parietal lobules. ET users compared with never users had greater GM density in the superior frontal gyrus and less GM density in the posterior part of the hippocampus and parahippocampal gyrus, posterior cingulate, and angular gyri. In the group of ET users, a negative association was found between duration of ET use and posterior hippocampus and parahippocampal GM density, whereas a positive association was found in the hypothalamus, striatum, precunei, and inferior parietal lobules. CONCLUSIONS: These results point toward a potential regional- and duration-dependent estrogen exposure effect on cerebral areas known to be involved in age-related cognitive functions and Alzheimer and Parkinson diseases
PMID: 20616671
ISSN: 1530-0374
CID: 143001
Defining age limits of the sensitive period for attachment learning in rat pups
Enhanced odor preference learning and attenuated fear learning characterizes rat pups' attachment learning Sensitive Period for learning the maternal odor. This period terminates at 10 days old (PN10) with increasing endogenous levels of the stress hormone, corticosterone. Increasing Sensitive Period pups' corticosterone prematurely terminates the Sensitive Period, while decreasing corticosterone in older pups delays Sensitive Period termination. Here we extend these findings and define the age range corticosterone alters learning and question whether corticosterone permanently terminates the Sensitive Period. Pups were odor-0.5 mA shock conditioned with either corticosterone increased (PN5-6; 4 mg/kg vs. saline) or decreased (PN15-16; naturally by maternal presence or corticosterone synthesis blocker, Metyrapone). Finally, PN7-8 pups were conditioned with corticosterone and reconditioned without corticosterone to assess whether the Sensitive Period was permanently terminated. Results indicate developmental limits for corticosterone regulation of pup learning are PN6 through PN15. Furthermore, inducing precocious corticosterone induced fear learning was not permanent, since reconditioning without corticosterone enabled odor preference learning. Results suggest pups are protected from learning aversions to maternal odor until approaching weaning
PMCID:3602827
PMID: 20583142
ISSN: 1098-2302
CID: 139563
Behavioural phenotyping assays for mouse models of autism
Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100-150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of autism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders
PMCID:3087436
PMID: 20559336
ISSN: 1471-0048
CID: 143002
