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PreprintCited by 42Treatment of Major DepressionAdvanced MRI Techniques and ApplicationsTryptophan and brain disorders

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Proton magnetic resonance spectroscopy of N-acetyl aspartate in first depressive episode and chronic major depressive disorder: a systematic review and meta-analysis

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Saccaro, Luigi F., Tassone, Matteo, Tozzi, Francesca, Rutigliano, Grazia·2022·Journal of Affective Disorders
DOI 10.1101/2022.07.01.22277107

Preprint — published as 10.1016/j.jad.2024.03.150 · Paper page

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Abstract

N-acetyl aspartate (NAA) is a marker of neuronal integrity and metabolism. Deficiency in neuronal plasticity and hypometabolism are implicated in the pathophysiology of Major Depressive Disorder (MDD). To test if cerebral NAA concentrations decrease progressively over the MDD course, we conducted a meta-analysis of Proton Magnetic Resonance Spectroscopy ( 1 H-MRS) studies comparing NAA concentrations in chronic MDD (cMDD) and first episode of depression (FED) to healthy controls. We searched Scopus® and Web of Knowledge □ using search terms related to depression and NAA. Hedges’ g was used as effect size measure, together with heterogeneity analyses, test of moderators and publication bias and quality assessment. The protocol is registered in PROSPERO (CRD42020221050). Sixty-two studies were included and meta-analyzed using a random-effect model for each brain region. NAA concentrations were significantly reduced in cMDD compared to healthy controls within the frontal lobe (n=26, Hedges’ g= -0.330, 95% CI -0.598 to -0.062; p= 0.018), the occipital lobe (n = 4, Hedges’ g= -0.677, 95% CI -1.013 to -0.341; p = 0.007), the thalamus (n= 4, Hedges’ g= -0.673, 95% CI -1.108 to -0.238; p = 0.016) and the frontal (n = 6, Hedges’ g= -0.471, 95% CI -0.891 to -0.052; p= 0.034) and periventricular white matter (n= 3, Hedges’ g= -0.478, 95% CI -0.938 to -0.018; p= 0.047). We highlighted a gap of knowledge regarding NAA levels in FED. Sensitivity analyses indicated that antidepressant treatment may reverse NAA alterations in the frontal lobe. Our findings are in line with previous evidence showing alterations in the aforementioned brain areas in MDD. Future studies should assess NAA alterations in the early stages of the illness and their longitudinal progression, also considering our preliminary results on the modifying effect of antidepressant treatment.

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Metadata

Authors
Saccaro, L. F., Tassone, M., Tozzi, F., & Rutigliano, G.
Affiliations
  • University of Geneva (CH)
  • University of Pisa (IT)
  • Scuola Normale Superiore (IT)
Corresponding author
Saccaro, Luigi F.
ORCID
Venue
Journal of Affective Disorders
Publisher
openRxiv
Published
2022-07-02
Volume
355
Pages
265-282
ISSN
0165-0327 (ISSN-L)
DOI
10.1101/2022.07.01.22277107
OpenAlex
W4393258906
Cited by
42
References
1
Citations by year
2026: 15 · 2025: 18 · 2024: 8 · 2023: 1
FWCI
2.57
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Affective Disorders (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • European Commission (HORIZON2020, 101026235)
  • Università di Pisa (Ateneo 2019)
  • HORIZON EUROPE Framework Programme
  • Horizon 2020
  • Marine Stewardship Council
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
N-acetylaspartate, major depressive disorder, first-episode depression, chronic depression, 1H NMR, brain metabolites, neuronal integrity, frontal lobe, occipital lobe, thalamus, white matter, antidepressant treatment, field strength
MeSH terms
Aspartic Acid, Brain, Chronic Disease, Major Depressive Disorder, Frontal Lobe, Humans, Occipital Lobe, Thalamus, White Matter, Proton Magnetic Resonance Spectroscopy

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