Abstract
Reduced N-acetyl-aspartate (NAA) levels have been reported in the prefrontal cortex (PFC) in patients with schizophrenia using proton magnetic resonance spectroscopy. However, it is unclear whether this NAA reduction predates the illness onset and is reported in subjects at-risk for developing schizophrenia (HRS). The aim of this study was to assess NAA levels in the PFC in HRS. We hypothesized that HRS display lower NAA levels than healthy controls in the PFC. Studies assessing levels of NAA/Creatine (NAA/Cr) in the PFC in HRS were extracted from literature. Meta-analysis tools were used to compute effect sizes of nine selected studies meeting our inclusion criteria (clinical and/or genetic HRS, groups of HRS, and healthy controls matched for age and gender, spectral acquisition in the PFC). We reported that HRS exhibited a significant lower NAA/Cr level (2.15 ± 0.29; n = 208) than healthy controls (2.21 ± 0.32; n = 234) in the PFC with a medium pooled effect size [Hedges’s g = −0.42; 95% confidence interval: (−0.61; −0.23); p < 0.0001] corresponding to an average 5.7% of NAA/Cr decrease. Secondary analysis revealed that this reduction was observed in young HRS (<40 years old) who have not reached the peak age of risk for schizophrenia (−11%, g = −0.82, p < 0.00001) but not in old HRS (>40 years old) who have already passed the peak age (g = 0.11, p = 0.56), when they are compared with their matched healthy controls. Our findings suggest that the NAA/Cr reduction in the PFC reported in patients with schizophrenia is observable only in HRS who have not passed the peak age of risk for schizophrenia. NAA/Cr level in the PFC could therefore be considered as a biological vulnerability marker of schizophrenia.
Highlights
The prefrontal cortex (PFC) is crucially involved in schizophrenia [1]
We reported that HRS exhibited a significant lower NAA/Cr level (2.15 ± 0.29; n = 208) than healthy controls (2.21 ± 0.32; n = 234) in the PFC with a medium pooled effect size [Hedges’s g = −0.42; 95% confidence interval: (−0.61; −0.23); p < 0.0001] corresponding to an average 5.7% of NAA/Cr decrease
Secondary analysis revealed that this reduction was observed in young HRS (40 years old) who have already passed the peak age (g = 0.11, p = 0.56), when they are compared with their matched healthy controls
Summary
The prefrontal cortex (PFC) is crucially involved in schizophrenia [1]. Morphological and functional abnormalities have been reported in the PFC at different stages of the illness [2, 3]. In a recent review and metaanalysis of 64 studies including 1256 patients and 1209 healthy controls, Steen and colleagues [5] have reported a 10% NAA reduction in the PFC in patients with schizophrenia, compared with healthy controls. Such a NAA reduction may reflect neuronal or axonal loss and may account for neuronal and molecular perturbations leading to abnormal brain activity often reported in patients with schizophrenia [6]. Antipsychotic medication have been reported to modulate NAA concentration leading to the hypothesis that the changes observed in NAA levels in the PFC in patients may be due primarily to treatment [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
