Negative symptoms in schizophrenia present a challenge to treatment and are associated with profound functional impairment. Characterizing the developmental trajectory of these symptoms and their relation to the emergence of schizophrenia and psychosis during adolescence and early adulthood is an essential prerequisite for early identification and clinical intervenfion. The overall goal of this Project is to probe brain circuitry that underlies the core domain of negative symptoms of diminished emotional expressivity and social drive, in informative youths at risk for psychosis and early in the course of illness. By applying deep phenotyping of clinical, neurobehavioral, physiologic and anatomic measures that complement the rodent studies (Projects II, 111) and can be integrated with cellular, molecular and genomic data (Projects IV, V), we hope to propel the field and elucidate key features of schizophrenia that require better understanding leading to new treatments. Project I will specifically contribute to elucidafing how neural responses are modulated by aversive conditioning and extinction and how these processes are impaired in affected and at risk youths. Complementary EEG and fMRI methods will help test the hypothesis that dysregulation of amgydala and its role in circuits mediating negative emofion processing contribute to schizophrenia risk, negative symptoms, and social dysfunction. The sample will include 225 youths characterized in Core A. There will be 75 participants in each group of patients with schizophrenia, clinical risk and healthy controls. They will each undergo an fMRI and an EEG experiment in a counter-balanced order. Complementary tasks that probe amygdala circuitry will be administered in the studies. The EEG procedure will include more refined gradation of timing parameters and the fMRI will provide 3-D anatomical resolution and amygdala integrity and activation measures. Basal and activation parameteres will be related to dimensional measures of negative symptomatology, social function and social learning of positive and negative value.

Public Health Relevance

Project I will integrate key dimensional clinical phenotypes with neurobehavioral measures, multi-modal neuroimaging, electrophysiology and genomics. This effort will cohere with the NIMH strategic plan for Conte Centers and for the Research Domain Criteria approach. The Project will augment current knowledge on amygdala circuitry functioning and the effects of psychosis and risk for psychosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
1P50MH096891-01
Application #
8443527
Study Section
Special Emphasis Panel (ZMH1-ERB-S (02))
Project Start
2012-09-01
Project End
2017-05-31
Budget Start
2012-09-01
Budget End
2013-05-31
Support Year
1
Fiscal Year
2012
Total Cost
$372,276
Indirect Cost
$142,476
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Gennatas, Efstathios D; Avants, Brian B; Wolf, Daniel H et al. (2017) Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood. J Neurosci 37:5065-5073
Schoch, Hannah; Kreibich, Arati S; Ferri, Sarah L et al. (2017) Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene. Biol Psychiatry 81:193-202
Chang, X; Liu, Y; Hahn, C-G et al. (2017) RNA-seq analysis of amygdala tissue reveals characteristic expression profiles in schizophrenia. Transl Psychiatry 7:e1203
Agrawal, A; Chou, Y-L; Carey, C E et al. (2017) Genome-wide association study identifies a novel locus for cannabis dependence. Mol Psychiatry :
White, Lauren K; Moore, Tyler M; Calkins, Monica E et al. (2017) An Evaluation of the Specificity of Executive Function Impairment in Developmental Psychopathology. J Am Acad Child Adolesc Psychiatry 56:975-982.e3
Mihara, Takuma; Mensah-Brown, Kobina; Sobota, Rosanna et al. (2017) Amygdala activity associated with social choice in mice. Behav Brain Res 332:84-89
Kaczkurkin, A N; Moore, T M; Calkins, M E et al. (2017) Common and dissociable regional cerebral blood flow differences associate with dimensions of psychopathology across categorical diagnoses. Mol Psychiatry :
Ciric, Rastko; Wolf, Daniel H; Power, Jonathan D et al. (2017) Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity. Neuroimage 154:174-187
Honnorat, N; Satterthwaite, T D; Gur, R E et al. (2017) sGraSP: A graph-based method for the derivation of subject-specific functional parcellations of the brain. J Neurosci Methods 277:1-20
Moore, Tyler M; Risbrough, Victoria B; Baker, Dewleen G et al. (2017) Effects of military service and deployment on clinical symptomatology: The role of trauma exposure and social support. J Psychiatr Res 95:121-128

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