TY - JOUR
T1 - Convergent evidence of the contribution of TP53 genetic variation (Pro72Arg) to metabolic activity and white matter volume in the frontal lobe in schizophrenia patients
AU - Molina, Vicente
AU - Papiol, Sergi
AU - Sanz, Javier
AU - Rosa, Araceli
AU - Arias, Bárbara
AU - Fatjó-Vilas, Mar
AU - Calama, Julia
AU - Hernández, Ana I.
AU - Bécker, Joemir
AU - Fañanás, Lourdes
N1 - Funding Information:
The authors would like to thank the participating patients, their families and healthy controls, whose generous contributions have made this study possible. This study was supported by grants from Fundació “La Caixa” ( 99-111-00 ), ( 99-042-00 ), FIS ( 02/3095 and PI 080017 ), Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III , Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) , the Spanish Ministerio of Science and Innovation ( SAF2008-05674-C03-01 ) and Generalitat de Catalunya, DURSI ; Grant Number: 2005SGR00608 . Sergi Papiol was supported by a grant of the Ministry of Education and Culture of Spain .
PY - 2011/5/1
Y1 - 2011/5/1
N2 - Abnormalities in white matter (WM) volumes and integrity in schizophrenia, together with post-mortem studies showing reduced expression of oligodendrocyte/myelination genes and apoptotic processes taking place in oligodendrocytes, suggest the interest of major regulators of apoptosis as candidate genes for some features related to myelin integrity in schizophrenia. Protein p53, encoded by TP53 gene, has a central role in the control of apoptosis and is involved in oligodendrocyte development. TP53 gene polymorphisms may account for variability in WM features, metabolic activity and biochemical markers of neuronal integrity and membrane turnover. Pro72Arg and Ins16bp polymorphisms at TP53 gene were analyzed in 20 DSM-IV schizophrenia patients. T1/T2-weighted sequences of these patients were acquired using a 1.5. T Philips Gyroscan system. Scans were transformed into Talairach space and segmented into gray matter (GM), WM and cerebrospinal fluid (CSF) using Statistical Parametric Mapping under a ROI approach. Likewise dorsolateral prefrontal cortex (DLPFC) metabolic activity was measured using a procedure based on MRI/PET image fusion. In 13 of these patients proton magnetic resonance spectroscopy was used to examine N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) levels in dorsolateral-medial prefrontal cortex (DLMPFC). MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n = 45). Patients Pro/Arg heterozygous (Pro72Arg polymorphism) showed a generalized deficit in whole-brain WM that was especially prominent in frontal lobe and a lower metabolic activity in the DLPFC as compared to Pro/Pro homozygous. Pro/Arg subjects also showed decreased NAA/Cho and increased Cho/Cr ratios in right DLMPFC. TP53 genetic variability influences WM volumes in frontal lobes and it seems to modulate the metabolic activity in this region. Our results suggest that TP53 might influence aspects of myelin and white matter integrity which may account for some of the frontal dysfunction features commonly described in these patients.
AB - Abnormalities in white matter (WM) volumes and integrity in schizophrenia, together with post-mortem studies showing reduced expression of oligodendrocyte/myelination genes and apoptotic processes taking place in oligodendrocytes, suggest the interest of major regulators of apoptosis as candidate genes for some features related to myelin integrity in schizophrenia. Protein p53, encoded by TP53 gene, has a central role in the control of apoptosis and is involved in oligodendrocyte development. TP53 gene polymorphisms may account for variability in WM features, metabolic activity and biochemical markers of neuronal integrity and membrane turnover. Pro72Arg and Ins16bp polymorphisms at TP53 gene were analyzed in 20 DSM-IV schizophrenia patients. T1/T2-weighted sequences of these patients were acquired using a 1.5. T Philips Gyroscan system. Scans were transformed into Talairach space and segmented into gray matter (GM), WM and cerebrospinal fluid (CSF) using Statistical Parametric Mapping under a ROI approach. Likewise dorsolateral prefrontal cortex (DLPFC) metabolic activity was measured using a procedure based on MRI/PET image fusion. In 13 of these patients proton magnetic resonance spectroscopy was used to examine N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) levels in dorsolateral-medial prefrontal cortex (DLMPFC). MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n = 45). Patients Pro/Arg heterozygous (Pro72Arg polymorphism) showed a generalized deficit in whole-brain WM that was especially prominent in frontal lobe and a lower metabolic activity in the DLPFC as compared to Pro/Pro homozygous. Pro/Arg subjects also showed decreased NAA/Cho and increased Cho/Cr ratios in right DLMPFC. TP53 genetic variability influences WM volumes in frontal lobes and it seems to modulate the metabolic activity in this region. Our results suggest that TP53 might influence aspects of myelin and white matter integrity which may account for some of the frontal dysfunction features commonly described in these patients.
UR - http://www.scopus.com/inward/record.url?scp=79953054744&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2011.01.076
DO - 10.1016/j.neuroimage.2011.01.076
M3 - Article
C2 - 21296169
AN - SCOPUS:79953054744
SN - 1053-8119
VL - 56
SP - 45
EP - 51
JO - NeuroImage
JF - NeuroImage
IS - 1
ER -