The membrane hypothesis of schizophrenia

Horrobin, David F.; Glen, A.I.M.; Vaddadi, Krishna S

doi:10.1016/0920-9964(94)90043-4

Cited by 311 publications

(168 citation statements)

References 60 publications

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“…Elevated choline containing compounds levels (represented collectively as GPC + PCh) have been interpreted as supportive of the 'membrane hypothesis' of schizophrenia (Horrobin et al, 1994), suggesting that phospholipid disturbances and an increased myelin degradation supports a generalized membrane disorder in patients with schizophrenia (Auer et al, 2001). Our results in elevated choline containing compounds (GPC + PCh) found in the dorsal caudate of FEP patients agrees with previous reports in patients with schizophrenia (Bustillo et al, 2002;Lutkenhoff et al, 2010), and in childhood-onset schizophrenia (O'Neill et al, 2004).…”

Section: Other Metabolitessupporting

confidence: 82%

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Fuente‐Sandoval

León-Ortíz

Favila

et al. 2011

Neuropsychopharmacol

208

157

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The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy ( 1 H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first-episode psychosis patients (FEP), and (3) 40 age-and sex-matched healthy controls. All subjects underwent a 1 H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia.

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Section: Other Metabolitessupporting

confidence: 82%

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Fuente‐Sandoval

León-Ortíz

Favila

et al. 2011

Neuropsychopharmacol

208

157

View full text Add to dashboard Cite

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“…The Cho signal is thought to rise in tissues 392 undergoing enhanced throughput of phospholipid membrane con-393 stituents, as during times of membrane build-up or degradation 394 (Gill et al, 1990;Speck et al, 1996). In this sense, the present 395 results support the notion of membrane abnormalities in schizo-396 phrenia (Fenton et al, 2000;Horrobin et al, 1994) 2001), however, we 398 observed above-normal Cho in superior anterior cingulate, frontal 399 cortex, and caudate head, rather than in left thalamus and left 400 parietal white matter. A recent report (Yamasue et al, 2002) 401 documents below-normal NAA/Cho and above-normal Cho/Cr 402 in the anterior cingulate in adult schizophrenia.…”

supporting

confidence: 57%

1H MRSI evidence of metabolic abnormalities in childhood-onset schizophrenia

et al. 2004

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In adult schizophrenia, magnetic resonance imaging (MRI) and 14 magnetic resonance spectroscopy (MRS) have revealed volumetric 15 and metabolic defects in multiple brain regions, among them the 16 anterior cingulate, frontal cortex, striatum, thalamus, parietal cortex, 17 and frontal and parietal white matter. This study used proton magnetic 18 resonance spectroscopic imaging (s 1 H MRSI) to identify potential 19 metabolic abnormalities in these regions in childhood-onset schizo-20 phrenia.1 H MRSI was acquired at 1.5 T and 272 ms echo time in 11 21 children and adolescents with schizophrenia (aged 7 -18 years; seven 22 boys, four girls; all but two medicated) and 20 age-matched healthy 23 controls (10 boys, 10 girls). Absolute levels of N-acetyl compounds 24 (NAA), creatine plus phosphocreatine (Cr), and choline compounds 25 (Cho) were compared among groups in each region. In schizophrenic 26 patients relative to controls, Cr was 14.3% higher in superior anterior 27 cingulate (mean of left and right hemispheres). Cho was higher in 28 superior anterior cingulate (30.3%), frontal cortex (13.3%), and 29 caudate head (13.5%). In the thalamus, there was also a diagnosis-30 by-gender interaction, whereby NAA was lower in patients for male but 31 not for female subjects. Elevated Cr suggests abnormal local cell-32 energy demand and elevated Cho is consistent with a prior proposal 33 that patients with early age-of-onset schizophrenia exhibit phospholipid 34 membrane disturbances. Low NAA may reflect diminished neuronal 35 integrity. 36 D

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“…Cho findings in schizophrenia (reviewed in Wobrock et al, 17 ) are less consistent than those for NAA. Elevated Cho levels have been interpreted as supportive of the 'membrane hypothesis' of schizophrenia 35,36 with more severe phospholipid disturbances resulting in an earlier disease onset. 37 Theberge et al 38 found that Cho correlated positively with duration of untreated psychosis and suggested that untreated psychosis may increase membrane turnover, perhaps on account of excitotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Proton MRS in twin pairs discordant for schizophrenia

et al. 2008

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Proton magnetic resonance spectroscopy ( 1 H MRS) neurometabolite abnormalities have been detected widely in subjects with and at risk for schizophrenia. We hypothesized that such abnormalities would be present both in patients with schizophrenia and in their unaffected twin siblings. We acquired magnetic resonance spectra (TR/TE = 3000/30 ms) at voxels in the mesial prefrontal gray matter, left prefrontal white matter and left hippocampus in 14 twin pairs discordant for schizophrenia (2 monozygotic, 12 dizygotic), 13 healthy twin pairs (4 monozygotic, 9 dizygotic) and 1 additional unaffected co-twin of a schizophrenia proband. In the mesial prefrontal gray matter voxel, N-acetylaspartate (NAA), creatine þ phosphocreatine (Cr), glycerophosphocholine þ phosphocholine (Cho) and myo-inositol (mI) did not differ significantly between patients with schizophrenia, their unaffected co-twins or healthy controls. However, glutamate (Glu) was significantly lower in patients with schizophrenia (31%, percent difference) and unaffected co-twins (21%) than in healthy controls (collapsed across twin pairs). In the left hippocampus voxel, levels of NAA (23%), Cr (22%) and Cho (36%) were higher in schizophrenia patients compared with controls. Hippocampal NAA (25%), Cr (22%) and Cho (37%) were also significantly higher in patients than in their unaffected co-twins. Region-to-region differences in metabolite levels were also notable within all three diagnosis groups. These findings suggest that 1 H MRS neurometabolite abnormalities are present not only in patients with schizophrenia, but also in their unaffected co-twins. Thus, reduced mesial prefrontal cortical Glu and elevated hippocampal NAA, Cr and Cho may represent trait markers of schizophrenia risk and, when exacerbated, state markers of schizophrenia itself.

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The membrane hypothesis of schizophrenia

Cited by 311 publications

References 60 publications

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

1H MRSI evidence of metabolic abnormalities in childhood-onset schizophrenia

Proton MRS in twin pairs discordant for schizophrenia

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