title: Abnormal hippocampal structure and function in clinical anxiety and comorbid depression.
abstract: Given the high prevalence rates of comorbidity of anxiety and depressive disorders, identifying a common neural pathway to both disorders is important not only for better diagnosis and treatment, but also for a more complete conceptualization of each disease. Hippocampal abnormalities have been implicated in anxiety and depression, separately; however, it remains unknown whether these abnormalities are also implicated in their comorbidity. Here we address this question by testing 32 adults with generalized anxiety disorder (15 GAD only and 17 comorbid MDD) and 25 healthy controls (HC) using multimodal MRI (structure, diffusion and functional) and automated hippocampal segmentation. We demonstrate that (i) abnormal microstructure of the CA1 and CA2-3 is associated with GAD/MDD comorbidity and (ii) decreased anterior hippocampal reactivity in response to repetition of the threat cue is associated with GAD (with or without MDD comorbidity). In addition, mediation-structural equation modeling (SEM) reveals that our hippocampal and dimensional symptom data are best explained by a model describing a significant influence of abnormal hippocampal microstructure on both anxiety and depression-mediated through its impact on abnormal hippocampal threat processing. Collectively, our findings show a strong association between changes in hippocampal microstructure and threat processing, which together may present a common neural pathway to comorbidity of anxiety and depression.
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Jiook
authors.initials: J
authors.lastname: Cha
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, New York.
authors.forename: Tsafrir
authors.initials: T
authors.lastname: Greenberg
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Song
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Helen
authors.initials: H
authors.lastname: Blair Simpson
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Posner
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York.
authors.forename: Lilianne R
authors.initials: LR
authors.lastname: Mujica-Parodi
mesh_terms: D001007:Anxiety / Q000453:epidemiology* / Q000473:pathology*; D001245:Association Learning / Q000502:physiology; D015897:Comorbidity; D003863:Depression / Q000453:epidemiology* / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D057566:Self Report; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000473:pathology; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: cue-repetition effect; hippocampal grey matter diffusivity; hippocampal subdivision segmentation; structural equation modeling