Proton MRS in twin pairs discordant for schizophrenia

Abstract

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.

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

“…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). Three previous reports have failed to find differences in choline in the cerebellum of patients with schizophrenia (Eluri et al, 1998;Tibbo et al, 2000;Bustillo et al, 2008).…”

“…Fourth, altered NAAG has been described in schizophrenia. Although NAAG could contribute to the quantification of NAA, it could not be differentiated in a reliable way with the methodology employed in our study (Lutkenhoff et al, 2010). Specific techniques to measure NAAG (Edden et al, 2007) could be used in future studies.…”

Glutamatergic and Neuronal Dysfunction in Gray and White Matter: A Spectroscopic Imaging Study in a Large Schizophrenia Sample

“…The glutamate meta-analysis reported increased glutamine and reduced glutamate, in medial frontal single-voxel studies, 6 with progressive reductions with age. These results did not appear related to a more ventral [23][24][25] or dorsal frontal placement. [26][27][28][29][30] However, the quality of the spectral fits is not always clear in these reports (except for [27][28][29] ) and the samples were small (9 to 30 for the schizophrenia groups 6 ).…”

“…[26][27][28][29][30] However, the quality of the spectral fits is not always clear in these reports (except for [27][28][29] ) and the samples were small (9 to 30 for the schizophrenia groups 6 ). More recent studies reported increases, [31][32][33][34][35] reductions 25,[36][37][38] and no differences 39 in Glx or glutamate. Two 33,34 of the 5 recent studies documenting elevations involved more ventral regions.…”

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

“…For example, impaired neurotransmission and excitotoxicity after an ischemic insult lead to transient glutamate decrease and glutamine accumulation (Berthet et al, 2011;Lei et al, 2009). In line with this idea, disturbed glutamatergic neurotransmission in schizophrenia leads to altered levels of glutamine, glutamate, and most notably of Gln/Glu, as observed in translational and clinical 1 H MRS studies (Bustillo et al, 2009;Hashimoto et al, 2005;Lutkenhoff et al, 2008;Shirayama et al, 2010;Tayoshi et al, 2009). …”