Cerebral Phosphate Metabolism in First-Degree Relatives of Patients With Schizophrenia

Klemm, Silke; Rzanny, R.; Riehemann, Stephan; Volz, Hans-Peter; Schmidt, Beate; Gerhard, U.-J.; Filz, Christina; Schönberg, Anke; Mentzel, Hans‐Joachim; Kaiser, Werner A.; Blanz, Bernhard

doi:10.1176/appi.ajp.158.6.958

Cited by 47 publications

(27 citation statements)

References 13 publications

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“…However, similar abnormalities in HUFA levels have not been found in patients with bipolar disorder [79]. Studies have found abnormal membrane phospholipid metabolism in first-degree relatives of patients with schizophrenia [80,81] suggesting heightened PLA 2 activity in relatives of schizophrenia. Response to lithium has been shown to follow familial patterns [82].…”

Section: Pla 2 Activity In Psychosesmentioning

confidence: 84%

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

Folley

Doop

Park

2003

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Recent evidence suggests that genetic and biochemical factors associated with psychoses may also provide an increased propensity to think creatively. The evolutionary theories linking brain growth and diet to the appearance of creative endeavors have been made recently, but they lack a direct link to research on the biological correlates of divergent and creative thought. Expanding upon Horrobin's theory that changes in brain size and in neural microconnectivity came about as a result of changes in dietary fat and phospholipid incorporation of highly unsaturated fatty acids, we propose a theory relating phospholipase A 2 (PLA 2 ) activity to the neuromodulatory effects of the noradrenergic system. This theory offers probable links between attention, divergent thinking, and arousal through a mechanism that emphasizes optimal individual functioning of the PLA 2 and NE systems as they interact with structural and biochemical states of the brain. We hope that this theory will stimulate new research in the neural basis of creativity and its connection to psychoses.

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Section: Pla 2 Activity In Psychosesmentioning

confidence: 84%

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

Folley

Doop

Park

2003

Prostaglandins, Leukotrienes and Essential Fatty Acids

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“…[5][6][7][8] In vivo phosphorus magnetic resonance spectroscopy ( 31 P MRS) is a noninvasive technique that can assess the membrane phospholipid and high-energy phosphate metabolism in localized brain regions. The measurable in vivo 31 P metabolites include freely mobile, rapidly tumbling phosphomonoesters leading to narrow spectral resonances (free-PME), freely mobile phosphodiesters (free-PDE), phosphocreatine (PCr), inorganic orthophosphate (Pi) and adenosine triphosphate (ATP). 7,9 The free-PMEs are primarily precursors, and free-PDEs are primarily breakdown products of membrane phospholipids (ie, phosphorylcholine (PC) and phosphorylethanolamine (PE), and glycerolphosphocholine (GPC) and glycerolphosphoethanolamine (GPE), respectively).…”

mentioning

confidence: 99%

“…10 Since cell membranes are continually generated and broken down, expressing the free-PME and free-PDE levels as a ratio provides a measure of turnover equilibrium of membrane phospholipids. In addition to the narrow spectral resonances, in vivo brain 31 P spectra contain broad underlying signals primarily over the PME and PDE spectral regions. Under typical in vivo acquisition conditions, this broad signal comprises of molecules with PDE (and PME) moieties that are less mobile than the free-PDE and free-PME molecules and more mobile than the larger membrane phospholipid-containing bilayer structures.…”

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%

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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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“…This feature of D 9 -THC is crucial, as first-episode schizophrenia patients (Fukuzako, 2001;Keshavan et al, 2000;Stanley et al, 2000) and nonaffected twin siblings and offsprings of schizophrenia patients (Klemm et al, 2001) show alterations of cerebral phospholipid metabolites, suggesting abnormalities of lipid metabolism as part of a genetic vulnerability to develop psychosis. If D 9 -THC has the potential to interact with a pre-existing vulnerability of cerebral lipid metabolism, this could represent a biochemical basis for gene Â environment interaction.…”

Section: Introductionmentioning

confidence: 99%

Cannabinoids Influence Lipid–Arachidonic Acid Pathways in Schizophrenia

Smesny

Rosburg

Baur

et al. 2007

Neuropsychopharmacol

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Increasing evidence suggests modulating effects of cannabinoids on time of onset, severity, and outcome of schizophrenia. Efforts to discover the underlying pathomechanism have led to the assumption of gene Â environment interactions, including premorbid genetical vulnerability and worsening effects of continuing cannabis use. The objective of this cross-sectional study is to investigate the relationship between delta-9-tetrahydrocannabinol intake and niacin sensitivity in schizophrenia patients and healthy controls. Intensity of niacin skin flushing, indicating disturbed prostaglandin-mediated processes, was used as peripheral marker of lipid-arachidonic acid pathways and investigated in cannabis-consuming and nonconsuming schizophrenia patients and in healthy controls. Methylnicotinate was applied in three concentrations onto the forearm skin. Flush response was assessed in 3-min intervals over 15 min using optical reflection spectroscopy. In controls, skin flushing was significantly decreased in cannabis-consuming as compared to nonconsuming individuals. When comparing the nonconsuming subgroups, patients showed significantly decreased flush response. The populations as a whole (patients and controls) showed an inverse association between skin flushing and sum scores of Symptom Check List 90-R. Results demonstrate an impact of long-term cannabis use on lipid-arachidonic acid pathways. Considering pre-existing vulnerability of lipid metabolism in schizophrenia, observed effects of cannabis use support the notion of a gene Â environment interaction.

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Cerebral Phosphate Metabolism in First-Degree Relatives of Patients With Schizophrenia

Abstract: These findings suggest greater phospholipid breakdown even in young first-degree relatives of patients with schizophrenia. This suggestion is discussed with respect to the membrane phospholipid hypothesis of schizophrenia.

Cited by 47 publications

References 13 publications

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

Psychoses and creativity: is the missing link a biological mechanism related to phospholipids turnover?

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

Cannabinoids Influence Lipid–Arachidonic Acid Pathways in Schizophrenia

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