title: Major depressive disorder is associated with abnormal interoceptive activity and functional connectivity in the insula.
abstract: BACKGROUND
  Somatic complaints and altered interoceptive awareness are common features in the clinical presentation of major depressive disorder (MDD). Recently, neurobiological evidence has accumulated demonstrating that the insula is one of the primary cortical structures underlying interoceptive awareness. Abnormal interoceptive representation within the insula may thus contribute to the pathophysiology and symptomatology of MDD.
  
  
  METHODS
  We compared functional magnetic resonance imaging blood oxygenation level-dependent responses between 20 unmedicated adults with MDD and 20 healthy control participants during a task requiring attention to visceral interoceptive sensations and also assessed the relationship of this blood oxygenation level-dependent response to depression severity, as rated using the Hamilton Depression Rating Scale. Additionally, we examined between-group differences in insula resting-state functional connectivity and its relationship to Hamilton Depression Rating Scale ratings of depression severity.
  
  
  RESULTS
  Relative to the healthy control subjects, unmedicated MDD subjects exhibited decreased activity bilaterally in the dorsal mid-insula cortex (dmIC) during interoception. Activity within the insula during the interoceptive attention task was negatively correlated with both depression severity and somatic symptom severity in depressed subjects. Major depressive disorder also was associated with greater resting-state functional connectivity between the dmIC and limbic brain regions implicated previously in MDD, including the amygdala, subgenual prefrontal cortex, and orbitofrontal cortex. Moreover, functional connectivity between these regions and the dmIC was positively correlated with depression severity.
  
  
  CONCLUSIONS
  Major depressive disorder and the somatic symptoms of depression are associated with abnormal interoceptive representation within the insula.
authors.affiliation: Laureate Institute for Brain Research, The University of Tulsa, Tulsa, Oklahoma; Department of Biological Sciences, The University of Tulsa, Tulsa, Oklahoma.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Avery
authors.affiliation: Laureate Institute for Brain Research, The University of Tulsa, Tulsa, Oklahoma; Johnson & Johnson, Inc., New Brunswick, New Jersey.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
authors.affiliation: Laureate Institute for Brain Research, The University of Tulsa, Tulsa, Oklahoma; Laureate Psychiatric Clinics and Hospital, The University of Oklahoma Tulsa, Oklahoma.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Moseman
authors.affiliation: Laureate Institute for Brain Research, The University of Tulsa, Tulsa, Oklahoma; College of Engineering, The University of Oklahoma, Tulsa, Oklahoma.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bodurka
authors.affiliation: Laureate Institute for Brain Research, The University of Tulsa, Tulsa, Oklahoma.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barcalow
authors.affiliation: Laureate Institute for Brain Research, The University of Tulsa, Tulsa, Oklahoma; Faculty of Community Medicine, The University of Tulsa, Tulsa, Oklahoma. Electronic address: wksimmons@gmail.com.
authors.forename: W Kyle
authors.initials: WK
authors.lastname: Simmons
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology*; D001921:Brain / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D006801:Humans; D065812:Interoception / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D055815:Young Adult
keywords: Depression severity; fMRI; functional connectivity; insula; interoception; major depressive disorder