title: Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder.
abstract: The neural changes underlying response to antidepressant treatment in adolescents are unknown. Identification of neural change correlates of treatment response could (1) aid in understanding mechanisms of depression and its treatment and (2) serve as target biomarkers for future research.
  
  
  
  Using functional magnetic resonance imaging, we examined changes in brain activation and functional connectivity in 13 unmedicated adolescents with major depressive disorder (MDD) before and after receiving treatment with a selective serotonin reuptake inhibitor medication for 8 weeks. Specifically, we examined brain activation during a negative emotion task and resting-state functional connectivity (RSFC), focusing on the amygdala to capture networks relevant to negative emotion. We conducted whole-brain analyses to identify how symptom improvement was related to change in brain activation during a negative emotion task or amygdala RSFC.
  
  
  
  After treatment, clinical improvement was associated with decreased task activation in rostral and subgenual anterior cingulate cortex and increased activation in bilateral insula, bilateral middle frontal cortices, right parahippocampus, and left cerebellum. Analysis of change in amygdala RSFC showed that treatment response was associated with increased amygdala RSFC with right frontal cortex, but decreased amygdala RSFC with right precuneus and right posterior cingulate cortex.
  
  
  
  The findings represent a foothold for advancing understanding of pathophysiology of MDD in adolescents by revealing the critical neural circuitry changes that underlie a positive response to a standard treatment. Although preliminary, the present study provides a research platform for future work needed to confirm these biomarkers at a larger scale before using them in future target engagement studies of novel treatments.
authors.affiliation: 1 Department of Psychiatry, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Cullen
authors.affiliation: 2 Department of Psychology, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Klimes-Dougan
authors.affiliation: 3 Macalester College , St. Paul, Minnesota.
authors.forename: Dung Pham
authors.initials: DP
authors.lastname: Vu
authors.affiliation: 2 Department of Psychology, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Melinda
authors.initials: M
authors.lastname: Westlund Schreiner
authors.affiliation: 1 Department of Psychiatry, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Bryon A
authors.initials: BA
authors.lastname: Mueller
authors.affiliation: 4 Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Eberly
authors.affiliation: 1 Department of Psychiatry, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Jazmin
authors.initials: J
authors.lastname: Camchong
authors.affiliation: 1 Department of Psychiatry, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Ana
authors.initials: A
authors.lastname: Westervelt
authors.affiliation: 1 Department of Psychiatry, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Kelvin O
authors.initials: KO
authors.lastname: Lim
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000000981:diagnostic imaging; D001921:Brain / Q000000981:diagnostic imaging; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004644:Emotions / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors
keywords: adolescent; antidepressants; depression; fMRI; treatment response