title: Distinct neurobiological signatures of brain connectivity in depression subtypes during natural viewing of emotionally salient films.
abstract: BACKGROUND
  Establishing an evidence-based diagnostic system informed by the biological (dys)function of the nervous system is a major priority in psychiatry. This objective, however, is often challenged by difficulties in identifying homogeneous clinical populations. Melancholia, a biological and endogenous subtype for major depressive disorder, presents a canonical test case in the search of biological nosology.
  
  
  METHODS
  We employed a unique combination of naturalistic functional magnetic resonance imaging (fMRI) paradigms - resting state and free viewing of emotionally salient films - to search for neurobiological signatures of depression subtypes. fMRI data were acquired from 57 participants; 17 patients with melancholia, 17 patients with (non-melancholic) major depression and 23 matched healthy controls.
  
  
  RESULTS
  Patients with melancholia showed a prominent loss of functional connectivity in hub regions [including ventral medial prefrontal cortex, anterior cingulate cortex (ACC) and superior temporal gyrus] during natural viewing, and in the posterior cingulate cortex while at rest. Of note, the default mode network showed diminished reactivity to external stimuli in melancholia, which correlated with the severity of anhedonia. Intriguingly, the subgenual ACC, a potential target for treating depression with deep brain stimulation (DBS), showed divergent changes between the two depression subtypes, with increased connectivity in the non-melancholic and decreased connectivity in the melancholic subsets.
  
  
  CONCLUSIONS
  These findings reveal neurobiological changes specific to depression subtypes during ecologically valid behavioural conditions, underscoring the critical need to respect differing neurobiological processes underpinning depressive subtypes.
authors.affiliation: QIMR Berghofer Medical Research Institute,Herston, QLD,Australia.
authors.forename: C C
authors.initials: CC
authors.lastname: Guo
authors.affiliation: QIMR Berghofer Medical Research Institute,Herston, QLD,Australia.
authors.forename: M P
authors.initials: MP
authors.lastname: Hyett
authors.affiliation: QIMR Berghofer Medical Research Institute,Herston, QLD,Australia.
authors.forename: V T
authors.initials: VT
authors.lastname: Nguyen
authors.affiliation: School of Psychiatry, University of New South Wales,Sydney,Australia.
authors.forename: G B
authors.initials: GB
authors.lastname: Parker
authors.affiliation: QIMR Berghofer Medical Research Institute,Herston, QLD,Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Breakspear
mesh_terms: D000328:Adult; D000368:Aged; D002540:Cerebral Cortex / Q000503:physiopathology*; D063132:Connectome; D003866:Depressive Disorder / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000503:physiopathology; D004644:Emotions / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D055815:Young Adult
keywords: Depression; emotion; functional connectivity; natural viewing