In this RSDA application, the candidate seeks to enhance his career development by pursuing studies of putative neurodevelopmental markers in young first-episode schizophrenic patients an subjects at high risk for this disorder, i.e. offspring of schizophrenic parents. The candidate, who has conducted research into the biology of schizophrenia for several years, needs to devote more time to research and gain additional experience and skills for his professional development in the field of neurodevelopmental biology of schizophrenic disorders. The central hypothesis of the proposed study is that an exaggerated pruning of the prefrontal cortex and related neural circuits underlies the vulnerability to schizophrenia.
The aim of the study is to test this hypothesis by comparing putative indices of brain maturation [slow wave sleep (polysomnographic studies), volume of prefrontal cortex add other related brain structures (MR imaging studies), and prefrontal membrane phospholipid metabolism (magnetic resonance spectroscopy studies)] in adolescent schizophrenic patients, of offspring of schizophrenic parents and matched controls. These measures will also be examined in relation to biological measures known to be frequent among relatives of schizophrenic patients, such as eye tracking abnormalities and cognitive impairment, and other clinical measures relevant to neural development, such as perinatal history, neurological signs, and family history. The proposed studies will build on existing resources to establish a well characterized cohort of patients and high risk subjects which could be used for further studies of biological vulnerability to schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research (K02)
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Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
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Meinecke, Douglas L
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University of Pittsburgh
Schools of Medicine
United States
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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; Yao, Jeffrey K; Tandon, Neeraj et al. (2017) Association of sFlt-1 and worsening psychopathology in relatives at high risk for psychosis: A longitudinal study. Schizophr Res 183:75-81
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
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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
Bhojraj, Tejas S; Sweeney, John A; Prasad, Konasale M et al. (2011) Gray matter loss in young relatives at risk for schizophrenia: relation with prodromal psychopathology. Neuroimage 54 Suppl 1:S272-9

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