title: Development of White Matter Microstructure and Intrinsic Functional Connectivity Between the Amygdala and Ventromedial Prefrontal Cortex: Associations With Anxiety and Depression.
abstract: BACKGROUND
  Connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) is compromised in multiple psychiatric disorders, many of which emerge during adolescence. To identify to what extent the deviations in amygdala-vmPFC maturation contribute to the onset of psychiatric disorders, it is essential to characterize amygdala-vmPFC connectivity changes during typical development.
  
  
  METHODS
  Using an accelerated cohort longitudinal design (1-3 time points, 10-25 years old, n = 246), we characterized developmental changes of the amygdala-vmPFC subregion functional and structural connectivity using resting-state functional magnetic resonance imaging and diffusion-weighted imaging.
  
  
  RESULTS
  Functional connectivity between the centromedial amygdala and rostral anterior cingulate cortex (rACC), anterior vmPFC, and subgenual cingulate significantly decreased from late childhood to early adulthood in male and female subjects. Age-associated decreases were also observed between the basolateral amygdala and the rACC. Importantly, these findings were replicated in a separate cohort (10-22 years old, n = 327). Similarly, structural connectivity, as measured by quantitative anisotropy, significantly decreased with age in the same regions. Functional connectivity between the centromedial amygdala and the rACC was associated with structural connectivity in these same regions during early adulthood (22-25 years old). Finally, a novel time-varying coefficient analysis showed that increased centromedial amygdala-rACC functional connectivity was associated with greater anxiety and depression symptoms during early adulthood, while increased structural connectivity in centromedial amygdala-anterior vmPFC white matter was associated with greater anxiety/depression during late childhood.
  
  
  CONCLUSIONS
  Specific developmental periods of functional and structural connectivity between the amygdala and the prefrontal systems may contribute to the emergence of anxiety and depressive symptoms and may play a critical role in the emergence of psychiatric disorders in adolescence.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh. Electronic address: mjalbrzikowski@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Jalbrzikowski
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh.
authors.forename: Bart
authors.initials: B
authors.lastname: Larsen
authors.affiliation: Department of Psychology (MNH), Pennsylvania State University, State College, Pennsylvania.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Hallquist
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh.
authors.forename: William
authors.initials: W
authors.lastname: Foran
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh.
authors.forename: Finnegan
authors.initials: F
authors.lastname: Calabro
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh; Department of Psychology, University of Pittsburgh, Pittsburgh; Department of Pediatrics, University of Pittsburgh, Pittsburgh.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Luna
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging* / Q000254:growth & development; D001007:Anxiety / Q000000981:diagnostic imaging*; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000000981:diagnostic imaging*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging* / Q000254:growth & development; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000254:growth & development; D011569:Psychiatric Status Rating Scales; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
keywords: Amygdala; Anxiety; Depression; Development; Diffusion spectrum imaging; Resting-state functional neuroimaging; Ventromedial prefrontal cortex