This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The first generation of neuroimaging studies showed that anatomic pathology is present at the first episode (FE) of schizophrenia but left major unanswered questions about the initial pathology and its longitudinal course. Answers are critically needed to distinguish deficits reflecting static encephalopathy from those that progress with the illness. Most knowledge comes from cross-sectional studies of chronic patients, but evidence suggests that pathology is less severe in FE patients, and that there may be illness-associated deterioration. It is now suspected also that some antipsychotic drugs (APDs) affect brain structure. These findings highlight the need to study first episode patients, enabling accurate identification of pathology that cannot reflect treatment or long-term illness effects. The findings further point to the need for longitudinal follow-up of sufficient duration that anatomic changes and related functional changes can be expected to occur. New research must also include adequate control over treatments and assessments of nutritional status to help distinguish initial and ongoing illness-related pathologies from factors unrelated to the illness. To enable relevance to current practice, changes in brain structure and structure-function relations must be evaluated in patients receiving novel APDs as first-line treatments. The proposed research uses magnetic resonance imaging (MRI) methods in a unique sample of antipsychotic-na ve, first-episode patients (N = 116), and demographically matched healthy volunteers (N = 84), who are participating in a study now supported by the NIMH. Patients will be randomized to first-line treatment with one of three new APDs (olanzapine, risperidone, or ziprasidone), and followed intensively for 3 years with a broad range of clinical, neurocognitive, and functional outcomes assessments. MRI exams with multiple acquisition sequences will be conducted before treatment, after 16 weeks of controlled treatment, and after 3 years. Both established and innovative approaches to morphometric analysis will be used, enabling detailed mapping of neuroanatomic variations that are associated with group differences, longitudinal changes, and functional indices. The data obtained will have major implications for segregating initial from ongoing anatomic pathology, and specifying the relations of initial and ongoing pathologic processes to multidimensional response patterns and long-term outcomes.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR013642-10
Application #
7627729
Study Section
Special Emphasis Panel (ZRG1-SBIB-L (40))
Project Start
2007-09-30
Project End
2008-07-31
Budget Start
2007-09-30
Budget End
2008-07-31
Support Year
10
Fiscal Year
2007
Total Cost
$20,077
Indirect Cost
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Green, Shulamite A; Hernandez, Leanna M; Bowman, Hilary C et al. (2018) Sensory over-responsivity and social cognition in ASD: Effects of aversive sensory stimuli and attentional modulation on neural responses to social cues. Dev Cogn Neurosci 29:127-139
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