Abstract
In vivo 31P magnetic resonance spectroscopy (31P MRS) studies have shown abnormal membrane phospholipid metabolism in the prefrontal cortex (PF) in the early course of schizophrenia. It is unclear, however, whether these alterations also represent premorbid risk indicators in schizophrenia. In this paper, we report in vivo 31P MRS data on children and adolescents at high risk (HR) for schizophrenia. In vivo 31P MRS studies of the PF were conducted on 16 nonpsychotic HR offspring of parents with schizophrenia or schizoaffective disorder, and 37 age-matched healthy comparison (HC) subjects. While 11 of the HR subjects had evidence of Axis I psychopathology (HR-P), five HR subjects had none (HR-NP). We quantified the freely mobile phosphomonoester (PME) and phosphodiester (PDE) levels reflecting membrane phospholipid precursors and breakdown products, respectively, and the relatively broad signal underlying PDE and PME peaks, comprised of less mobile molecules with PDE and PME moieties (eg, synaptic vesicles and phosphorylated proteins). Compared to HC subjects, HR subjects had reductions in freely mobile PME; the differences were accounted for mainly by the HR-P subjects. Additionally, HR-P subjects showed increases in the broad signal underlying the PME and PDE peaks in the PF. To conclude, these data demonstrate new evidence for decreased synthesis of membrane phospholipids and possibly altered content or the molecular environment of synaptic vesicles and/or phosphoproteins in the PF of young offspring at risk for schizophrenia. Follow-up studies are needed to examine the predictive value of these measures for future emergence of schizophrenia in at-risk individuals.
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Acknowledgements
This work was supported in part by NIMH Grants MH45203, MH45156, MH01180, MH01433 and a NARSAD Established Investigator Award (MSK); NS #33355 (NJM) and MH #46614 (JWP). We gratefully acknowledge the help of Melissa Zeigler and Mandayam Sujata in clinical assessments, and Germaine Miller and Dennis McKeag in postprocessing of data. We are also grateful for the time-domain fitting software package, which was provided by Dr Drost's laboratory, University of Western Ontario, London, Ontario, Canada.
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Keshavan, M., Stanley, J., Montrose, D. et al. Prefrontal membrane phospholipid metabolism of child and adolescent offspring at risk for schizophrenia or schizoaffective disorder: an in vivo 31P MRS study. Mol Psychiatry 8, 316–323 (2003). https://doi.org/10.1038/sj.mp.4001325
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DOI: https://doi.org/10.1038/sj.mp.4001325
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