title: Structural connectivity and response to ketamine therapy in major depression: A preliminary study.
abstract: BACKGROUND
  Ketamine elicits an acute antidepressant effect in patients with major depressive disorder (MDD). Here, we used diffusion imaging to explore whether regional differences in white matter microstructure prior to treatment may predict clinical response 24h following ketamine infusion in 10 MDD patients.
  
  
  METHODS
  FSL's Tract-Based Spatial Statistics (TBSS) established voxel-level differences in fractional anisotropy (FA) between responders (patients showing >50% improvement in symptoms 24h post-infusion) and non-responders in major white matter pathways. Follow-up regions-of-interest (ROI) analyses examined differences in FA and radial (RD), axial (AD) and mean diffusivity (MD) between responders and non-responders and 15 age- and sex-matched controls, with groups compared pairwise.
  
  
  RESULTS
  Whole brain TBSS (p<0.05, corrected) and confirmatory tract-based regions-of-interest analyses showed larger FA values in the cingulum and forceps minor in responders compared to non-responders; complementary decreases in RD occurred in the cingulum (p<0.05). Only non-responders differed from controls showing decreased FA in the forceps minor, increased RD in the cingulum and forceps minor, and increased MD in the forceps minor (p<0.05).
  
  
  CONCLUSIONS
  Non-responders showed an earlier age of onset and longer current depressive episode than responders. Though these factors did not interact with diffusion metrics, results may be impacted by the limited sample size.
  
  
  CONCLUSIONS
  Though findings are considered preliminary, significant differences in FA, RD and MD shown in non-responders compared to responders and controls in fronto-limbic and ventral striatal pathways suggest that the structural architecture of specific functional networks mediating emotion may predict ketamine response in MDD.
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Megha M
authors.initials: MM
authors.lastname: Vasavada
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Amber M
authors.initials: AM
authors.lastname: Leaver
authors.affiliation: Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Randall T
authors.initials: RT
authors.lastname: Espinoza
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Shantanu H
authors.initials: SH
authors.lastname: Joshi
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Njau
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA; Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
authors.forename: Roger P
authors.initials: RP
authors.lastname: Woods
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA; Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, CA, USA. Electronic address: narr@ucla.edu.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Narr
mesh_terms: D000328:Adult; D016880:Anisotropy; D000928:Antidepressive Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D003337:Corpus Callosum / Q000502:physiology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000502:physiology; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000502:physiology; D016896:Treatment Outcome; D066127:White Matter / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine
keywords: Biomarkers; Diffusion Tensor Imaging (DTI); Fractional anisotropy (FA); Glutamate; Treatment response