MH049716

Virginia Institute for Psychiatric and Behavioral Genetics

The Transmission of Vulnerability Factors for Schizophrenia

Grant number
5R01
MH049716

Principal Investigator:
Kenneth Kendler (PI subcontract) PI: Keith Nuechterlein

Co-investigators:
Michael Neale
Kristen Jacobson

Years:
1994-2007

Abstract

This project is designed to test key hypotheses regarding the transmission of measurable nonsymptomatic characteristics of individuals that reflect their predisposition to schizophrenia. Identification of such vulnerability factors and of their interrelationships within and across biological relatives of patients with schizophrenia should allow us to accelerate our progress in detecting the nature of genetic contributions to schizophrenia. The next project phase will primarily focus on the interrelationships among neurocognitive dysfunctions mediated partially by the prefrontal cortex and the medial temporal region, subtle structural anomalies in these two regions, and liability to schizophrenia. Our search for vulnerability factors in neurocognitive functioning and regional brain structure is an attempt to identify intermediate phenotypes or "endophenotypes" that are closer in causal chains to the effects of genes than is schizophrenia itself. Neurocognitive measures will involve the domains of attention, working memory, and consolidation of declarative memory. Morphometric indices from MRI will emphasize subtle volume and gray matter density alterations in the prefrontal cortex and medial temporal structures. Using family data, we will test whether the relationships between these brain structural anomalies, their hypothesized associated neurocognitive deficits, and schizophrenia spectrum disorder across first-degree relatives are consistent with one common underlying familial/genetic factor, or an alternative model in which there is more than one dimension of familial/genetic liability to schizophrenia. These goals will be addressed through data collection with schizophrenic probands and their first-degree relatives as well as with demographically matched community controls and their first-degree relatives.

Keywords

brain morphology, cognition, disease /disorder proneness /risk, family genetics, neuroanatomy, schizophrenia, attention, memory, personality, phenotype, prefrontal lobe /cortex, short term memory, human subject, magnetic resonance imaging, morphometry, patient oriented research

Funding Agency

NIMH: National Institute of Mental Health, National Institute of Health

information	mission \| history \| relations \| contact	research	resources \| projects \| collaborations \| publications \| software
people	faculty \| trainees \| staff \| jobs	education	seminars \| training program \| training record \| courses \| workshops