title: Infant brain development and vulnerability to later internalizing difficulties: the Generation R study.
abstract: OBJECTIVE
  Although clinical studies have demonstrated smaller subcortical volumes in structures such as the amygdala, hippocampus, caudate nucleus, and thalamus in adults and adolescents with depressive disorders and anxiety, no study has assessed such structures in babies, long before the development of the disorders. This study examined whether the size of the "gangliothalamic ovoid" (encompassing the basal ganglia and thalamus) assessed during infancy is associated with increased internalizing problems in early childhood.
  
  
  METHODS
  Cranial ultrasounds were used to assess gangliothalamic ovoid diameter and ventricular volume at 6 weeks of postnatal age; moreover, head circumference was measured. Outcome data included ratings of internalizing and externalizing problems using the Child Behavior Checklist (reported by mothers and fathers) at 18 and/or 36 months. Analyses were based on a total of 651 children.
  
  
  RESULTS
  Smaller gangliothalamic diameter was associated with higher Child Behavior Checklist Internalizing scores at ages 18 and 36 months. Results remained significant after correcting for head circumference and were evident for the DSM-oriented subscales of anxiety problems and affective problems. Total ventricular volume was not consistently associated with Internalizing scores.
  
  
  CONCLUSIONS
  Findings associating infant brain measurements with Child Behavior Checklist mother and father reports at two time points are consistent with previous cross-sectional reports of smaller subcortical volumes in depression. Results were not simply reflective of overall brain development, because the pattern held after adjustment for head circumference. This is the first study to point toward a biological vulnerability evident in infancy, involved in the development of internalizing problems in childhood.
authors.affiliation: Ste-Justine's Hospital Research Center, the University of Montreal.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Herba
authors.forename: Sabine J
authors.initials: SJ
authors.lastname: Roza
authors.forename: Paul
authors.initials: P
authors.lastname: Govaert
authors.forename: Joram
authors.initials: J
authors.lastname: van Rossum
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Vincent
authors.initials: V
authors.lastname: Jaddoe
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
mesh_terms: D000342:Affective Symptoms / Q000503:physiopathology / Q000523:psychology; D001479:Basal Ganglia / Q000254:growth & development*; D002508:Cephalometry; D057189:Checklist; D002653:Child Behavior Disorders / Q000503:physiopathology / Q000523:psychology; D002675:Child, Preschool; D015331:Cohort Studies; D004453:Echoencephalography; D005260:Female; D006801:Humans; D007223:Infant; D007389:Internal-External Control; D008137:Longitudinal Studies; D008297:Male; D009415:Nerve Net / Q000254:growth & development*; D010552:Personality Assessment / Q000706:statistics & numerical data; D011594:Psychometrics; D012307:Risk Factors; D013223:Statistics as Topic; D013694:Temperament / Q000502:physiology; D013788:Thalamus / Q000254:growth & development*