Abnormal hippocampal structure and function in clinical anxiety and comorbid depression.
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.
['Cha|Jiook|J|', 'Greenberg|Tsafrir|T|', 'Song|Inkyung|I|', 'Blair Simpson|Helen|H|', 'Posner|Jonathan|J|', 'Mujica-Parodi|Lilianne R|LR|']
D001007:Anxiety D001245:Association Learning D015897:Comorbidity D003863:Depression D005260:Female D006624:Hippocampus D006801:Humans D021621:Imaging, Three-Dimensional D008279:Magnetic Resonance Imaging D008297:Male D010100:Oxygen D011569:Psychiatric Status Rating Scales D057566:Self Report D013702:Temporal Lobe D055815:Young Adult
cue-repetition effect hippocampal grey matter diffusivity hippocampal subdivision segmentation structural equation modeling