This competing renewal for an independent scientist award (1 K02 MHO 1180) seeks to further elucidate the premorbid indicators of biological risk for schizophrenia and continue scientific development of the applicant through coursework, collaborations and consultations with other scientists. The central hypothesis of the proposed study is that an abnormality in late neurodevelopmental maturation of the thalamocortical circuits underlies the vulnerability to schizophrenia. During the first funding cycle of this award, the investigator has recruited a well-characterized cohort of child and adolescent relatives of schizophrenia patients (HR-S) who show evidence of impaired structural and functional integrity of the cortical and thalamic brain structures. These impairments appear to progressively evolve during adolescence. In the proposed study he will seek to confirm these observations in an independent cohort of HR-S subjects, and to examine structural and functional integrity of cortical and the thalamic structures in the HR-S subjects by neurobehavioral, neuroimaging and P50 studies. He will also follow up the original cohort of HR-S subjects to seek evidence of continuing brain dysmaturation and its relation to emergence of psychopathology. These studies will establish a cohort of HR-S subjects for further follow-up studies of developmental vulnerability to schizophrenia. The candidate also intends to enhance his scientific development by collaborations with other clinical and neuroscience investigators at the University of Pittsburgh and at other Universities. Specifically, he seeks to further his skills in developmental neuroscience, genetics, neuroimaging as well as clinical and design issues for studies of high risk subjects. The proposed studies will facilitate the applicant's continued involvement in mentoring activities, and develop collaborations for a multi-site study of HR-S subjects proposed to be submitted in the near future. This professional enhancement plan and the research project are likely to help the candidate realize his full potential and contribute to our further understanding of the pathogenesis of schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH001180-11
Application #
6846307
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Meinecke, Douglas L
Project Start
1995-07-01
Project End
2007-01-31
Budget Start
2005-03-14
Budget End
2007-01-31
Support Year
11
Fiscal Year
2005
Total Cost
$117,223
Indirect Cost
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Cai, HuaLin; Zhou, Xiang; Dougherty, George G et al. (2018) Pregnenolone-progesterone-allopregnanolone pathway as a potential therapeutic target in first-episode antipsychotic-naïve patients with schizophrenia. Psychoneuroendocrinology 90:43-51
Shah, Jai L; Tandon, Neeraj; Montrose, Debra M et al. (2017) Clinical psychopathology in youth at familial high risk for psychosis. Early Interv Psychiatry :
Padmanabhan, Jaya L; Shah, Jai L; Tandon, Neeraj et al. (2017) The ""polyenviromic risk score"": Aggregating environmental risk factors predicts conversion to psychosis in familial high-risk subjects. Schizophr Res 181:17-22
Lizano, Paulo L; Keshavan, Matcheri S; Tandon, Neeraj et al. (2016) Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study. Schizophr Res 170:115-22
Shah, J L; Tandon, N; Howard, E R et al. (2015) Pituitary volume and clinical trajectory in young relatives at risk for schizophrenia. Psychol Med 45:2813-24
Ramanathan, Seethalakshmi; Miewald, Jean; Montrose, Debra et al. (2015) Can age at sexual maturity act as a predictive biomarker for prodromal negative symptoms? Schizophr Res 164:35-9
Shah, Jai L; Tandon, Neeraj; Keshavan, Matcheri S (2013) Psychosis prediction and clinical utility in familial high-risk studies: selective review, synthesis, and implications for early detection and intervention. Early Interv Psychiatry 7:345-60
Francis, Alan N; Bhojraj, Tejas S; Prasad, Konasale M et al. (2013) Alterations in the cerebral white matter of genetic high risk offspring of patients with schizophrenia spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry 40:187-92
Tandon, Neeraj; Montrose, Debra; Shah, Jai et al. (2012) Early prodromal symptoms can predict future psychosis in familial high-risk youth. J Psychiatr Res 46:105-10
Bhojraj, Tejas S; Francis, Alan N; Montrose, Debra M et al. (2011) Grey matter and cognitive deficits in young relatives of schizophrenia patients. Neuroimage 54 Suppl 1:S287-92

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