title: Reduced hippocampal N-acetyl-aspartate (NAA) as a biomarker for overweight.
abstract: 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.
  
  
  CONCLUSIONS
  Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted.
authors: Department of Psychiatry, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
authors: Jeremy D
authors: JD
authors: Coplan
authors: Department of Psychiatry, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
authors: Hassan M
authors: HM
authors: Fathy
authors: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors: Chadi G
authors: CG
authors: Abdallah
authors: Department of Psychiatry, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
authors: Sherif A
authors: SA
authors: Ragab
authors: Department of Surgery and Medicine, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
authors: John G
authors: JG
authors: Kral
authors: Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA ; Department of Psychiatry, Weill Medical College of Cornell University, New York, NY, USA ; Department of Biophysics, Weill Medical College of Cornell University, New York, NY, USA.
authors: Xiangling
authors: X
authors: Mao
authors: Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA ; Department of Psychiatry, Weill Medical College of Cornell University, New York, NY, USA ; Department of Biophysics, Weill Medical College of Cornell University, New York, NY, USA.
authors: Dikoma C
authors: DC
authors: Shungu
authors: Menninger Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
authors: Sanjay J
authors: SJ
authors: Mathew
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000175:diagnosis* / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D050177:Overweight / Q000175:diagnosis* / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: Body mass index; Creatine (CR); Generalized anxiety disorder; Neuronal integrity; Obesity; Penn State Worry Questionnaire