Prefrontal NAA and Glx Levels in Different Stages of Psychotic Disorders: a 3T 1H-MRS Study.

Edith Liemburg,Lex Wunderink,Henderikus Knegtering,Leonie Bais,Gerdina Pijnenborg,André Aleman,Jozarni Dlabac-De Lange,Jorien Van Der Velde,Anita Sibeijn-Kuiper,Esther Opmeer,Annerieke De Vos

doi:10.1038/srep21873

Edith Liemburg, Lex Wunderink + Show 9 more

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https://doi.org/10.1038/srep21873

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Abstract

H-Magnetic Resonance Spectroscopy (1H-MRS) can offer insights in various neuropathologies by measuring metabolite levels in the brain. In the current study we investigated the levels of glutamate + glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate + glutamic acid (NAA + NAAG; neuronal viability) in the prefrontal cortex of patients with a psychotic disorder and people at Ultra High Risk (UHR) for psychosis. A 1H-MRS spectrum was acquired in 31 patients with a recent onset psychotic disorder and 60 with a chronic state, 16 UHR patients and 36 healthy controls. Absolute metabolite levels were calculated using LCModel with a reference water peak. Groups were compared while taking into account age and partial volume effects. Moreover, we investigated associations with positive and negative symptoms, duration of illness, and antipsychotic treatment in patients. The most notable finding is that chronicity of schizophrenia was related to decreased levels of Glx and NAA. On the other hand, although on an exploratory note, UHR showed increased levels of prefrontal Glx and NAA levels with increasing age. Our results may indicate an initial Glx and NAA increase and subsequent decrease during illness progression that may be related to the neurotoxic effects of glutamate.

Highlights

Proton Magnetic Resonance Spectroscopy (1H-MRS) is a non-invasive MR technique that can offer insights in altered metabolite levels caused by various neuropathologies[14,15,16,17]
One chronic patient was excluded because metabolite concentrations had a standard deviation higher than 20% of the estimated concentration, and one patient and one Ultra High Risk (UHR) subject were excluded because the metabolite concentrations deviated more than 3 standard deviations (SDs) from the group mean
These findings are in line with a meta-analysis showing that glutamate and N-Acetyl Aspartate (NAA) had a stronger decline with age in patients than in healthy controls[12], and with reviews showing some evidence for lower Glx and NAA levels in chronically ill schizophrenia patients[16,17] and lower NAA levels in patients with earlier onset of illness[19]

Summary

Introduction

Proton Magnetic Resonance Spectroscopy (1H-MRS) is a non-invasive MR technique that can offer insights in altered metabolite levels caused by various neuropathologies[14,15,16,17]. The few available studies on the effect of antipsychotics have shown both increases and decreases of metabolite levels, that may be dependent on type, dose or duration of treatment[13,16,22], but reduced Glx and NAA levels have been related to stronger D2 antagonists[16,17,19]. We aim to investigate lateral prefrontal white matter Glx and NAA levels in recent onset patients and chronic patients as well as subjects with an UHR state compared to matched healthy controls. We tested the hypothesis whether subjects with UHR would have increased levels of Glx and decreased levels of NAA and whether psychotic patients have lower Glx and NAA levels than healthy controls, related to duration of illness. We investigated absolute levels (instead of ratios) and we corrected for cerebral spinal fluid (CSF) and gray matter (GM) volume

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