PT-026 - EXPLORING THE RELATIONSHIP BETWEEN ANTIDEPRESSANT TREATMENT, NEUROCHEMICALS IN THE BRAIN AND ANXIETY/DEPRESSION SYMPTOMS IN YOUTH

T. Stephens^1,2, I. Choi³, P. Lee³, W. Brooks³, J. Tumberger^4,5, M. Bartkoski^1,2, J. Leeder⁶, S. Stancil^6,5,7; ¹University of Kansas Medical Center, University of Kansas Medical Center- Kansas City, Kansas, USA, ²Children's Mercy Kansas City, ³University of Kansas Medical Center, Kansas City, KS, USA, ⁴Children's Mercy Kansas City, Kansas City, MO, USA, ⁵University of Kansas School of Medicine, Kansas City, KS, USA, ⁶Children's Mercy Kansas City, Kansas City, MO, USA, ⁷University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.

Background: Pediatric mood and anxiety disorders are common and associated with significant morbidity and mortality, including suicidality. Investigating factors influencing symptom presentation and treatment response will aid in developing targeted therapies and optimizing outcomes. Neurochemical levels serve as proxies for neurobiological processes altered in depressive and anxiety disorders. While the impact of antidepressant treatment on brain metabolism has been studied in adults, there is limited data in pediatric populations. This study aims to evaluate the relationship between neurochemical concentrations and anxiety and depressive symptoms in fluoxetine-treated youth.

Methods: Adolescents and young adults aged 12-21 years, on steady state fluoxetine, underwent proton magnetic resonance spectroscopy (1H-MRS) at 3 T to measure glutamate (Glu), glutamine (Gln), myo-inositol (mI), choline-containing products (Cho), N-acetylaspartate (NAA) and creatine (Cr). Neurochemicals were reported as ratios relative to Cr. Depressive and anxiety symptoms were assessed using the PHQ-9 and PROMIS Anxiety scales, respectively. Participants with PHQ-9 scores ≥ 11 or PROMIS Anxiety t-scores ≥ 60 (moderate anxiety) were considered non-responders. Statistical analyses included Student’s t-test, Cohen’s d, and Spearman’s rho, performed using JMP Pro v17.

Results: In 46 youth (mean age 16.1 ± 1.9 years, range 12-21, 67% female), NAA levels did not correlate with anxiety symptom severity (Spearman’s ρ= -0.146, p=0.333). When stratified by response to fluoxetine, NAA was significantly higher in fluoxetine responders compared to non-responders (NAA mean 1.67 ± 0.09 vs1.57 ± 0.11, p = 0.004, Cohen’s d = 0.94). Glx, Glu, Gln, mI, and Cho levels did not differ between responders and non-responders, nor did they correlate with anxiety or depression symptom severity scores.

Conclusion: In fluoxetine-treated youth, fluoxetine anxiety responders had increased NAA levels compared to non-responders. NAA, a marker of neuronal integrity, is typically lower in certain psychiatric disorders relative to healthy controls, with some evidence suggesting normalization following successful treatment. Our pilot findings support the need for further research into NAA as a potential biomarker for fluoxetine response.