Reduced hippocampal N-acetyl-aspartate (NAA) as a biomarker for overweight
Open accessAbstract
OBJECTIVE: We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis - a form of neuroplasticity - and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS). METHODS: We combined two previously studied cohorts of GAD and control subjects. Using proton magnetic resonance spectroscopy imaging ((1)H MRSI) in medication-free patients with GAD (n = 29) and a matched healthy control group (n = 22), we determined hippocampal concentrations of (1) NAA (2) choline containing compounds (CHO), and (3) Creatine + phosphocreatine (CR). Data were combined from 1.5 T and 3 T scans by converting values from each cohort to z-scores. Overweight and GAD diagnosis were used as categorical variables while the Penn State Worry Questionnaire (PSWQ) and Anxiety Sensitivity Index (ASI) were used as dependent variables. RESULTS: Overweight subjects (BMI ≥ 25) exhibited lower NAA levels in the hippocampus than normal-weight subjects (BMI < 25) (partial Eta-squared = 0.14) controlling for age, sex and psychiatric diagnosis, and the effect was significant for the right hippocampus in both GAD patients and control subjects. An inverse linear correlation was noted in all subjects between right hippocampal NAA and BMI. High scores on the PSWQ predicted low hippocampal NAA and CR. Both BMI and worry were independent inverse predictors of hippocampal NAA. CONCLUSION: Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A decrease in choline and creatine levels is found in the left hippocampus and centrum semiovale in human adults with anxiety disorder.
“A decrease in choline and creatine levels is also found in the left hippocampus and centrum semiovale in human adults with anxiety disorder [101, 102].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [102]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Development of a Rating Scale for Primary Depressive Illness
Hamilton, M. (1967) · British Journal of Social and Clinical Psychology · doi:10.1111/j.2044-8260.1967.tb00530.x · Cited by 8,410 · see citing works
Measuring the thickness of the human cerebral cortex from magnetic resonance images
Fischl, B. R., & Dale, A. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.200033797 · Cited by 5,789 · see citing works
Development and validation of the Penn State Worry Questionnaire
Meyer, T. J., Miller, M. L., Metzger, R. L., & Borkovec, T. D. (1990) · Behaviour Research and Therapy · doi:10.1016/0005-7967(90)90135-6 · Cited by 5,099 · see citing works
Structured Clinical Interview for DSM-IV Axis I Disorders
Spitzer, R. L., First, M. B., & Gibbon, M. (1997) · Medical Entomology and Zoology · Cited by 3,582 · see citing works
Anxiety, sensitivity, anxiety frequency, and the prediction of fearfulness
Reiss, S., Peterson, R. A., Gursky, D. M., & McNally, R. J. (1986) · Behaviour Research and Therapy · doi:10.1016/0005-7967(86)90143-9 · Cited by 3,169 · see citing works
N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology
MOFFETT, J., Ross, B., Arun, P., Madhavarao, C. N., & Namboodiri, A. M. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.12.003 · Cited by 1,413 · see citing works
Molteni, R., Barnard, R. J., Ying, Z., Roberts, C. K., & Gómez‐Pinilla, F. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00123-9 · Cited by 918 · see citing works
Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells
Rajkowska, G. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00950-1 · Cited by 822 · see citing works
Raji, C. A., Ho, A. J., Parikshak, N., Becker, J. T., López, O. L., Kuller, L. H., Hua, X., Leow, A., Toga, A. W., & Thompson, P. M. (2009) · Human Brain Mapping · doi:10.1002/hbm.20870 · Cited by 685 · see citing works
Essential role of brain-derived neurotrophic factor in adult hippocampal function
Monteggia, L. M., Barrot, M., Powell, C. M., Berton, O., Galanis, V., Gemelli, T., Meuth, S., Nagy, A., Greene, R. W., & Nestler, E. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402141101 · Cited by 685 · see citing works
Brain-Derived Neurotrophic Factor/TrkB Signaling in Memory Processes
Yamada, K., & Nabeshima, T. (2003) · Journal of Pharmacological Sciences · doi:10.1254/jphs.91.267 · Cited by 585 · see citing works
Obesity: Overview of an Epidemic
Mitchell, N. S., Catenacci, V. A., Wyatt, H. R., & Hill, J. O. (2011) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2011.08.005 · Cited by 526 · see citing works
Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo.
Bates, T. E., Strangward, M., Keelan, J., Davey, G. P., Munro, P., & Clark, J. B. (1996) · PubMed · Cited by 422 · see citing works
High‐fat diet impairs hippocampal neurogenesis in male rats
Lindqvist, A., Mohapel, P., Bouter, B., Frielingsdorf, H., Pizzo, D., Brundin, P., & Erlanson-Albertsson, C. (2006) · European Journal of Neurology · doi:10.1111/j.1468-1331.2006.01500.x · Cited by 376 · see citing works
Inhibition of N-acetylaspartate production
Bates, T. E., Strangward, M., Keelan, J., Davey, G. P., Munro, P., & Clark, J. B. (1996) · Neuroreport · doi:10.1097/00001756-199605310-00014 · Cited by 365 · see citing works
Multisection proton MR spectroscopic imaging of the brain.
Duyn, J. H., GILLEN, J. S., Sobering, G., van Zijl, P. C. M., & MOONEN, C. T. W. (1993) · Radiology · doi:10.1148/radiology.188.1.8511313 · Cited by 353 · see citing works
Quantitative proton MR spectroscopic imaging of the human brain
Soher, B. J., van Zijl, P. C. M., Duyn, J. H., & Barker, P. B. (1996) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910350313 · Cited by 271 · see citing works
Rozin, P., Dow, S., Moscovitch, M., & Rajaram, S. (1998) · Psychological Science · doi:10.1111/1467-9280.00073 · Cited by 265 · see citing works
Boumezbeur, F., Mason, G. F., de Graaf, R. A., Behar, K. L., Cline, G. W., Shulman, G. I., Rothman, D. L., & Petersen, K. F. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.197 · Cited by 238 · see citing works
Kanoski, S. E., Meisel, R. L., Mullins, A. J., & Davidson, T. L. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.05.004 · Cited by 226 · see citing works
Wu, A., Molteni, R., Ying, Z., & Gómez‐Pinilla, F. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00154-4 · Cited by 223 · see citing works
Hebben, N., Corkin, S., Eichenbaum, H., & Shedlack, K. J. (1985) · Behavioral Neuroscience · doi:10.1037/0735-7044.99.6.1031 · Cited by 220 · see citing works
Hebben, N., Corkin, S., Eichenbaum, H., & Shedlack, K. J. (1985) · Behavioral Neuroscience · doi:10.1037//0735-7044.99.6.1031 · Cited by 218 · see citing works
A role for hippocampus in the utilization of hunger signals
Davidson, T. L., & Jarrard, L. E. (1993) · Behavioral and Neural Biology · doi:10.1016/0163-1047(93)90925-8 · Cited by 216 · see citing works
de Stefano, N., Narayanan, S., Matthews, P. M., Francis, G., Antel, J. P., & Arnold, D. (1999) · Brain : a journal of neurology · doi:10.1093/brain/122.10.1933 · Cited by 196 · see citing works
Brain-Derived Neurotrophic Factor Plays a Critical Role in Contextual Fear Conditioning
Liu, I. Y. C., Lyons, W. E., Mamounas, L. A., & Thompson, R. F. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1948-04.2004 · Cited by 190 · see citing works
Persistence of abnormal neural responses to a meal in postobese individuals
DelParigi, A., Chen, K., Salbe, A. D., Hill, J. O., Wing, R. R., Reiman, E. M., & Tataranni, P. A. (2003) · International Journal of Obesity · doi:10.1038/sj.ijo.0802558 · Cited by 189 · see citing works
A potential role for the hippocampus in energy intake and body weight regulation
Davidson, T. L., Kanoski, S. E., Schier, L. A., Clegg, D. J., & Benoit, S. C. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.10.008 · Cited by 178 · see citing works
Rector, N. A., Szacun-Shimizu, K., & Leybman, M. (2007) · Behaviour Research and Therapy · doi:10.1016/j.brat.2006.09.017 · Cited by 166 · see citing works
Hippocampal volume and total cell numbers in major depressive disorder
Cobb, J. A., Simpson, J., Mahajan, G., Overholser, J. C., Jurjus, G., Dieter, L., Herbst, N. P., May, W., Rajkowska, G., & Stockmeier, C. A. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.10.020 · Cited by 144 · see citing works
Apfel, B. A., Ross, J., Hlavin, J., Meyerhoff, D. J., Metzler, T. J., Marmar, C. R., Weiner, M. W., Schuff, N., & Neylan, T. C. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.044 · Cited by 139 · see citing works
N -Acetylaspartate and N -acetylaspartylglutamate
Benarroch, E. E. (2008) · Neurology · doi:10.1212/01.wnl.0000311267.63292.6c · Cited by 119 · see citing works
Lin, A., Shic, F., Enriquez, C. M., & Ross, B. D. (2003) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/s10334-003-0004-x · Cited by 115 · see citing works
Magnetic resonance spectroscopy: current and future applications in psychiatric research
Lyoo, I. K., & Renshaw, P. F. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01313-0 · Cited by 104 · see citing works
Quantitative spectroscopic imaging of the human brain
Pan, J. W., Twieg, D. B., & Hetherington, H. P. (1998) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910400305 · Cited by 100 · see citing works
Pilot multimodal twin imaging study of generalized anxiety disorder
Hettema, J. M., Kettenmann, B., Ahluwalia, V., McCarthy, C., Kates, W. R., Schmitt, J. E., Silberg, J. L., Neale, M. C., Kendler, K. S., & Fatouros, P. P. (2011) · Depression and Anxiety · doi:10.1002/da.20901 · Cited by 91 · see citing works
Mathew, S. J., Mao, X., Keegan, K. A., Levine, S. M., Smith, E. L., Heier, L., Otcheretko, V., Coplan, J. D., & Shungu, D. C. (2008) · NMR in Biomedicine · doi:10.1002/nbm.1315 · Cited by 85 · see citing works
Self-citationKing, B. M. (2012) · American Psychologist · doi:10.1037/a0030684 · Cited by 80 · see citing works
Gazdzinski, S. P., Millin, R., Kaiser, L. G., Durazzo, T. C., Mueller, S. G., Weiner, M. W., & Meyerhoff, D. J. (2009) · Obesity · doi:10.1038/oby.2009.325 · Cited by 79 · see citing works
Mathew, S. J., Mao, X., Coplan, J. D., Smith, E. L., Sackeïm, H. A., Gorman, J. M., & Shungu, D. C. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.6.1119 · Cited by 79 · see citing works
Self-citation(2002) · PubMed · Cited by 74 · see citing works
Characteristics of worry in Generalized Anxiety Disorder
Hirsch, C. R., Mathews, A., Lequertier, B., Perman, G., & Hayes, S. (2013) · Journal of Behavior Therapy and Experimental Psychiatry · doi:10.1016/j.jbtep.2013.03.004 · Cited by 72 · see citing works
Learned and cognitive controls of food intake
Benoit, S. C., Davis, J. F., & Davidson, T. L. (2010) · Brain Research · doi:10.1016/j.brainres.2010.06.009 · Cited by 70 · see citing works
Hippocampal N-Acetylaspartate Concentration and Response to Riluzole in Generalized Anxiety Disorder
Mathew, S. J., Price, R. B., Mao, X., Smith, E. L., Coplan, J. D., Charney, D. S., & Shungu, D. C. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.09.012 · Cited by 68 · see citing works
Self-citationAbdallah, C. G., Coplan, J. D., Jackowski, A. P., Sato, J. R., Mao, X., Shungu, D. C., & Mathew, S. J. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.05.009 · Cited by 66 · see citing works
Self-citationPerinatal Maternal Fat Intake Affects Metabolism and Hippocampal Function in the Offspring
Walker, C., Naef, L., D’Asti, E., Long, H., Xu, Z., Moreau, A., & Azeddine, B. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1418.023 · Cited by 64 · see citing works
Ursache, A., Wedin, W., Tirsi, A., & Convit, A. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.12.020 · Cited by 61 · see citing works
Correlations between Hippocampal Neurogenesis and Metabolic Indices in Adult Nonhuman Primates
Perera, T. D., Lu, D., Thirumangalakudi, L., Smith, E. L., Yaretskiy, A., Rosenblum, L. A., Kral, J. G., & Coplan, J. D. (2011) · Neural Plasticity · doi:10.1155/2011/875307 · Cited by 55 · see citing works
Self-citationCoplan, J. D., Mathew, S. J., Mao, X., Smith, E. L. P., Hof, P. R., Coplan, P. M., Rosenblum, L. A., Gorman, J. M., & Shungu, D. C. (2006) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2005.12.011 · Cited by 45 · see citing works
Self-citationMassana, G., Gastó, C., Junqué, C., Mercader, J. M., Gómez‐Ansón, B., Massana, J., Torres, X., & Salamero, M. (2002) · NeuroImage · doi:10.1006/nimg.2002.1083 · Cited by 41 · see citing works
Gallinat, J., Ströhle, A., Lang, U. E., Bajbouj, M., Kalus, P., Montag, C., Seifert, F. C., Wernicke, C., Rommelspacher, H., Rinneberg, H. H., et al. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.01.001 · Cited by 35 · see citing works
Gazdzinski, S. P., Durazzo, T. C., Mon, A., & Meyerhoff, D. J. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01305.x · Cited by 28 · see citing works
Orsi, G., Perlaki, G., Kovács, N., Aradi, M., Papp, Z., Karádi, K., Szalay, C., Karádi, Z., Lénárd, L., Tényi, T., et al. (2011) · Brain Imaging and Behavior · doi:10.1007/s11682-011-9119-2 · Cited by 20 · see citing works
Metabolic syndrome and neurometabolic asymmetry of hippocampus in adult bonnet monkeys
Coplan, J. D., Abdallah, C. G., Mathew, S. J., Shungu, D. C., Mao, X., Smith, E. L., Kaufman, D., Gorman, J. M., Owens, M. J., Nemeroff, C. B., et al. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.03.020 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Wu, Y., Lu, Y.-C., Jacobs, M., Pradhan, S., Kapse, K., Zhao, L., Niforatos-Andescavage, N., Vezina, G., du Plessis, A. J., & Limperopoulos, C. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.19940 · Cited by 218 · see citing works
Wu, Y., De Asis-Cruz, J., & Limperopoulos, C. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02449-0 · Cited by 124 · see citing works
“A decrease in choline and creatine levels is also found in the left hippocampus and centrum semiovale in human adults with anxiety disorder [101, 102].”
Background
- Authors
- Coplan, J. D., Fathy, H. M., Abdallah, C. G., Ragab, S. A., Kral, J. G., Mao, X., Shungu, D. C., & Mathew, S. J.
- Affiliations
- State University of New York (US)
- Yale University (US)
- SUNY Downstate Health Sciences University (US)
- Cornell University (US)
- Baylor College of Medicine (US)
- Corresponding author
- Coplan, Jeremy D.
- ORCID
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2014
- Volume
- 4
- Pages
- 326-335
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC3913836
- OpenAlex
- W2040855376
- Cited by
- 28
- References
- 54
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 2 · 2015: 3 · 2014: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- N-acetylaspartate, hippocampus, overweight, body mass index, neuroplasticity, neuronal integrity, worry, generalized anxiety disorder, anxiety sensitivity, choline-containing compounds, creatine, biomarkers
- MeSH terms
- Adult, Anxiety Disorders, Aspartic Acid, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Sensitivity and Specificity, Reproducibility of Results, Biomarkers, Down-Regulation, Overweight, Proton Magnetic Resonance Spectroscopy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
