title: A neural substrate for behavioral inhibition in the risk for major depressive disorder.
abstract: OBJECTIVE
  Behavioral inhibition (BI) is an early developing trait associated with cautiousness and development of clinical depression and anxiety. Little is known about the neural basis of BI and its predictive importance concerning risk for internalizing disorders. We looked at functional connectivity of the default-mode network (DMN) and salience network (SN), given their respective roles in self-relational and threat processing, in the risk for internalizing disorders, with an emphasis on determining the functional significance of these networks for BI.
  
  
  METHODS
  We used functional magnetic resonance imaging to scan, during the resting state, children and adolescents 8 to 17 years of age who were either at high familial risk (HR; n = 16) or low familial risk (LR; n = 18) for developing clinical depression and/or anxiety. Whole-brain DMN and SN functional connectivity were estimated for each participant and compared across groups. We also compared the LR and HR groups on levels of BI and anxiety, and incorporated these data into follow-up neurobehavioral correlation analyses.
  
  
  RESULTS
  The HR group, relative to the LR group, showed significantly decreased DMN connectivity with the ventral striatum and bilateral sensorimotor cortices. Within the HR group, trait BI increased as DMN connectivity with the ventral striatum and sensorimotor cortex decreased. The HR and LR groups did not differ with respect to SN connectivity.
  
  
  CONCLUSIONS
  Our findings show, in the risk for internalizing disorders, a negative functional relation between brain regions supporting self-relational processes and reward prediction. These findings represent a potential neural substrate for behavioral inhibition in the risk for clinical depression and anxiety.
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK.
authors.forename: Julie
authors.initials: J
authors.lastname: Frost Bellgowan
authors.affiliation: Haskins Laboratories, New Haven, CT.
authors.forename: Peter
authors.initials: P
authors.lastname: Molfese
authors.affiliation: Stanford University, Stanford, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Marx
authors.affiliation: Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, Detroit.
authors.forename: Moriah
authors.initials: M
authors.lastname: Thomason
authors.affiliation: Scientific and Statistical Computing Core, National Institute of Mental Health, Bethesda, MD.
authors.forename: Daniel
authors.initials: D
authors.lastname: Glen
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Santiago
authors.affiliation: Stanford University, Stanford, CA.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gotlib
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK; Janssen Pharmaceuticals, Beerse, Belgium.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK; Center for Social and Affective Neuroscience, Linköping University, Linköping, Sweden. Electronic address: paul.hamilton@cal.berkeley.edu.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Hamilton
mesh_terms: D000293:Adolescent; D001008:Anxiety Disorders / Q000503:physiopathology*; D000067290:Behavior Rating Scale; D001931:Brain Mapping; D002648:Child; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D057566:Self Report; D066328:Ventral Striatum / Q000473:pathology*
keywords: behavioral inhibition; default-mode; depression risk; fMRI; ventral striatum