Glutamatergic Correlates of Bipolar Symptoms in Adolescents

A. Irem Sonmez, Charles P. Lewis, John D. Port, Alejandra Cabello-Arreola, Caren J. Blacker, Bhedita J. Seewoo, Alastair J. Mckean, Jarrod M. Leffler, Mark A. Frye, Paul E. Croarkin

Research output: Contribution to journalArticlepeer-review


Objectives: Prior studies demonstrate elevated cortical glutamate (Glu) in patients with bipolar disorder (BD). Studies assessing neurochemistry in early stages of bipolar illness before the emergence of manic symptoms are lacking. This study aimed to examine neurochemical correlates measured by proton magnetic resonance spectroscopy (1H-MRS) and a dimensional measure of bipolarity in a sample of depressed adolescents. Methods: Adolescent participants (aged 13-21 years) underwent a semistructured diagnostic interview and clinical assessment, which included the General Behavior Inventory Parent Version (P-GBI), a 73-item, parent-rated assessment of symptoms and behaviors. 1H-MRS scans of a left dorsolateral prefrontal cortex (L-DLPFC) voxel (8 cm3) were collected using a two-dimensional J-averaged sequence to assess N-acetylaspartate (NAA), Glu, Glx (glutamate + glutamine), and NAA/Glx concentrations. We used generalized linear models to assess the relationships between P-GBI scores and metabolite levels in L-DLPFC. Results: Thirty-six participants (17 healthy controls, 19 depressed) underwent 1H-MRS scans and clinical evaluation with the P-GBI. There was a significant negative relationship between P-GBI score and L-DLPFC NAA/Glx in the whole sample. However, the magnitude of the effect was small and statistical significance was lost after correcting for multiple comparisons. Conclusions: These preliminary results suggest that NAA/Glx may have utility as a marker of bipolar traits in healthy and depressed adolescents. If replicated, 1H-MRS measures of glutamatergic metabolism anomalies might have a role in identifying depressed adolescents at risk for mixed symptom presentations or BD. Identifying bipolarity in the early stages of the disease would have a significant impact on treatment planning and prognosis. Further longitudinal studies should examine neurochemical correlates of mood state during the developmental emergence of BD.

Original languageEnglish (US)
Pages (from-to)599-605
Number of pages7
JournalJournal of Child and Adolescent Psychopharmacology
Issue number10
StatePublished - Dec 2020


  • H-MRS
  • NAA
  • adolescent
  • bipolar disorder
  • glutamate

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health
  • Pharmacology (medical)


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