Membrane phospholipid metabolism and schizophrenia: an in vivo 31P-MR spectroscopy study

Stanley, Jeff; Williamson, Peter C.; Drost, Dick J.; Carr, T.; Rylett, R. Jane; Morrison-Stewart, S. L.; Thompson, R. Terry

doi:10.1016/0920-9964(94)90044-2

Cited by 99 publications

(46 citation statements)

References 21 publications

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“…The development of spatial localization methods, which sample the relative levels of mobile metabolites from a volume of tissue defined from an MR image, has provided a basis for integrating the biochemical information obtained by MRS with the anatomical and pathological information obtained from MRI. In vivo MRS studies of schizophrenia have examined two primary nuclei, phosphorus (Calabrese et al 1992;Deicken et al 1995;Keshavan et al 1993;Pettegrew et al 1993Pettegrew et al , 1995Pettegrew et al , 1991Shioiri et al 1994;Stanley et al 1995b;Stanley et al 1994) and proton (Bertolino et al 1996, Buckley et al 1994Choe et al 1994;Fukuzako et al 1995;Nasrallah et al 1994;Radda and Taylor 1985;Stanley et al 1996;Yurgelun-Todd et al 1996;Yurgelun-Todd et al 1993). Phosphorus MRS can detect alterations in the levels of compounds involved in the bioenergetics of cellular metabolism, such as inorganic phosphate, adenosine triphosphate (ATP), and phosphocreatine.…”

Section: Abstract : Schizophrenia; Proton Magnetic Resonance Spectromentioning

confidence: 99%

“…Spectroscopy studies have reported abnormalities in several brain regions in schizophrenia, including the frontal lobe, temporal lobe, hippocampus-amygdala, and basal ganglia (Bertolino et al 1996;Buckley et al 1994;Calabrese et al 1992;Choe et al 1994;Deicken et al 1995;Fukuzako et al 1995;Keshavan et al 1991;Keshavan et al 1993;Nasrallah et al 1994;Pettegrew et al 1993;Pettegrew et al 1995;Radda and Taylor 1985;Shioiri et al 1994;Stanley et al 1995b;Stanley et al 1994;Stanley et al 1996;Yurgelun-Todd et al 1996;Yurgelun-Todd et al 1993). These metabolic findings converge with reports of volume reduction and aberrant functional activity for glucose metabolism and cerebral blood flow in these brain regions Gur and Pearlson 1993;Kotrla and Weinberger 1995).…”

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confidence: 99%

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Proton Magnetic Resonance Spectroscopy in the Frontal and Temporal Lobes of Neuroleptic Naive Patients with Schizophrenia

Cecil

Lenkinski

Gur

et al. 1999

Neuropsychopharmacology

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Studies with proton magnetic resonance spectroscopy (MRS) have reported abnormalities in N-acetyl-aspartate (NAA), amino acids (AA) and choline (Cho) to creatine (Cr) ratios associated with schizophrenia. We report data on the three ratios in a sample of 18 neuroleptic naive patients with first-episode schizophrenia (eight studied in the dorsolateral prefrontal and 10 in the midtemporal lobe) and 24 healthy controls (14 studied in prefrontal and 10 in midtemporal lobes). Frontal lobe proton spectra were acquired with the stimulated-echo acquisition mode (STEAM) pulse sequence (echo time 21 ms, repetition time 2 s). Temporal lobe proton spectra were acquired with the point-resolved spectroscopy (PRESS) pulse sequence (echo time 16-21 ms, repetition time 2 s). Upon comparison with KEY WORDS : Schizophrenia; Proton magnetic resonance spectroscopyMagnetic resonance imaging (MRI) and spectroscopy (MRS) provide noninvasive, risk-free methods with which to study the origins and the time course of progression of neuropsychiatric disorders. The development of spatial localization methods, which sample the relative levels of mobile metabolites from a volume of tissue defined from an MR image, has provided a basis for integrating the biochemical information obtained by MRS with the anatomical and pathological information obtained from MRI. In vivo MRS studies of schizophrenia have examined two primary nuclei, phosphorus (Calabrese et al. 1992;Deicken et al. 1995;Keshavan et al. 1993;Pettegrew et al. 1993Pettegrew et al. , 1995Pettegrew et al. , 1991Shioiri et al. 1994;Stanley et al. 1995b;Stanley et al. 1994) and proton (Bertolino et al. 1996, Buckley et al. 1994Choe et al. 1994;Fukuzako et al. 1995;Nasrallah et al. 1994;Radda and Taylor 1985;Stanley et al. 1996;Yurgelun-Todd et al. 1996;Yurgelun-Todd et al. 1993). Phosphorus MRS can detect alterations in the levels of compounds involved in the bioenergetics of cellular metabolism, such as inorganic phosphate, adenosine triphosphate (ATP), and phosphocreatine. Additional composite resonances from phosphorus monoesters (PME) and phosphorus diesters (PDE) can also be detected. Phosphorus MRS in schizophrenia research has revealed abnormalities with high-energy phosphates as well as alterations in membrane phospholipid metabolism (Pettegrew et al. 1995 (Birken and Oldendorf 1989), NAA/Cr levels may reflect neuronal viability and integrity. Creatine is a compound involved in the regulation of cellular energy metabolism. The creatine resonance observed by proton MRS, is a combination of creatine and phosphocreatine. Trimethyl ammonium residues primarily representing choline are detected with MRS. The choline resonance is a composite of a number of choline-containing compounds. These include phosphocholine, glycerophosphocholine, acetylcholine, and cytidine diphosphate choline, as well as choline itself. However, the most prominent form of choline in the brain, phosphatidylcholine, is, for the most part, not detected by MRS because of its restricted immobile form . Choline level...

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Section: Abstract : Schizophrenia; Proton Magnetic Resonance Spectromentioning

confidence: 99%

mentioning

confidence: 99%

Proton Magnetic Resonance Spectroscopy in the Frontal and Temporal Lobes of Neuroleptic Naive Patients with Schizophrenia

Cecil

Lenkinski

Gur

et al. 1999

Neuropsychopharmacology

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“…5,7,8,30 To further investigate possible trait-related markers of the underlying neurodevelopmental pathogenesis of schizophrenia, one can conduct 31 P spectroscopy studies in individuals at increased genetic risk, such as child and adolescent offspring of parents with this illness. In view of previous in vivo 31 P spectroscopy studies showing alterations of membrane phospholipid metabolites in the PF of schizophrenia subjects 7,[23][24][25] and relatives at risk for this disorder, 31 we hypothesized that high-risk (HR) child and adolescent offspring of parents with schizophrenia would show alterations in membrane phospholipid metabolites, in the PF region, compared to matched healthy comparison (HC) subjects. Considering our specific predictions on the PF regions suggested by our prior work, we focus this report on the PF; data on other brain regions will be reported elsewhere.…”

mentioning

confidence: 99%

“…Early in postnatal brain development, levels of membrane phospholipid precursors are high and breakdown products are low; this is followed by dramatic decreases in precursor levels and increases in breakdown products, which then plateau, as the brain reaches late adolescence. [17][18][19][20][21][22] In vivo 31 P MRS studies have shown lower PME levels and higher PDE levels in the PF 7,[23][24][25] and temporal lobe 26 of first-episode, neuroleptic naïve schizophrenia subjects, compared to matched controls. Reduced PME correlate with Wisconsin Cart Sorting test performance 27 and negative symptoms 28 in schizophrenia, implicating the PF in the pathogenesis of this disorder (for a review, see Keshavan et al…”

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confidence: 99%

Prefrontal membrane phospholipid metabolism of child and adolescent offspring at risk for schizophrenia or schizoaffective disorder: an in vivo 31P MRS study

et al. 2003

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In vivo31 P magnetic resonance spectroscopy ( 31 P 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 31 P MRS data on children and adolescents at high risk (HR) for schizophrenia. In vivo 31 P 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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“…Alterations in phosphodiesters have also been reported in patients with schizophrenia (107)(108)(109)(110)(111), but with some studies in disagreement (112)(113)(114)(115). As discussed by Stanley (102), some of the variability may arise from differing detection efficiencies of broad vs narrow phosphodiester peaks.…”

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confidence: 99%

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Mason

Krystal

2006

NMR Biomed.

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Magnetic resonance spectroscopy (MRS) is likely in the near future to play a key role in the process of drug discovery and evaluation. As the pharmaceutical industry seeks biochemical markers of drug delivery, efficacy and toxicity, this non-invasive technique offers numerous ways to study adults and children repeatedly and without ionizing radiation. In this article, we survey an array of the information that MRS offers about neurochemistry in general and psychiatric disorders and their treatment in particular. We also present growing evidence of glial abnormalities in neuropsychiatric disorders and discuss what MRS is contributing to that line of investigation. The third major direction of this article is the discussion of where MRS techniques are headed and how those new techniques can contribute to studies of mechanisms of psychiatric disease and drug discovery.

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Membrane phospholipid metabolism and schizophrenia: an in vivo 31P-MR spectroscopy study

Cited by 99 publications

References 21 publications

Proton Magnetic Resonance Spectroscopy in the Frontal and Temporal Lobes of Neuroleptic Naive Patients with Schizophrenia

Proton Magnetic Resonance Spectroscopy in the Frontal and Temporal Lobes of Neuroleptic Naive Patients with Schizophrenia

Prefrontal membrane phospholipid metabolism of child and adolescent offspring at risk for schizophrenia or schizoaffective disorder: an in vivo 31P MRS study

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

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