Delayed development of brain connectivity in adolescents with schizophrenia and their unaffected siblings

Zalesky, Andrew., Pantelis, Christos., Cropley, Vanessa., Fornito, Alex., Cocchi, Luca., McAdams, Harrison., Clasen, Liv., Greenstein, Deanna., Rapoport, Judith L. and Gogtay, Nitin. (2015) Delayed development of brain connectivity in adolescents with schizophrenia and their unaffected siblings. JAMA Psychiatry, 72 9: 900-908. doi:10.1001/jamapsychiatry.2015.0226

Author Zalesky, Andrew.
Pantelis, Christos.
Cropley, Vanessa.
Fornito, Alex.
Cocchi, Luca.
McAdams, Harrison.
Clasen, Liv.
Greenstein, Deanna.
Rapoport, Judith L.
Gogtay, Nitin.
Title Delayed development of brain connectivity in adolescents with schizophrenia and their unaffected siblings
Journal name JAMA Psychiatry   Check publisher's open access policy
ISSN 2168-622X
Publication date 2015-09
Year available 2015
Sub-type Article (original research)
DOI 10.1001/jamapsychiatry.2015.0226
Open Access Status Not Open Access
Volume 72
Issue 9
Start page 900
End page 908
Total pages 9
Place of publication Chicago, Illinois, United States
Publisher American Medical Association
Collection year 2016
Language eng
Formatted abstract
Importance Abnormalities in structural brain connectivity have been observed in patients with schizophrenia. Mapping these abnormalities longitudinally and understanding their genetic risk via sibship studies will provide crucial insight into progressive developmental changes associated with schizophrenia.

Objectives To identify corticocortical connections exhibiting an altered developmental trajectory in adolescents with childhood-onset schizophrenia (COS) and to determine whether similar alterations are found in patients’ unaffected siblings.

Design, Setting, and Participants Using prospective structural brain magnetic resonance imaging, large-scale corticocortical connectivity was mapped from ages 12 to 24 years in 109 patients with COS (272 images), 86 of their unaffected siblings (184 images), and 102 healthy controls (262 images) over a 20-year period beginning January 1, 1991, through April 30, 2011, as part of the ongoing COS study at the National Institute of Mental Health.

Main Outcomes and Measures Structural connectivity between pairs of cortical regions was estimated using a validated technique based on across-subject covariation in magnetic resonance imaging–derived cortical thickness measurements.

Results Compared with normally developing controls, significant left-hemisphere occipitotemporal deficits in cortical thickness correlations were found in patients with COS as well as their healthy siblings (P < .05). Deficits in siblings normalized by mid-adolescence, whereas patients with COS showed significantly longer maturational delays, with cortical thickness correlations between the left temporal lobe and left occipital cortex not showing evidence of development until early adulthood. The normalization of deficits with age in patients with COS correlated with improvement in symptoms. Compared with controls, left-hemisphere occipitotemporal thickness correlations in a subgroup of patients with high positive symptoms were significantly reduced from age 14 to 18 years (P < .05); however, other patients with low positive symptoms showed no significant deficits.

Conclusions and Relevance Delayed maturation of occipitotemporal connectivity appears to be a trait marker in patients with COS, with a milder endophenotype in unaffected siblings associated with resilience to developing schizophrenia. These findings indicate genetically influenced and connection-specific developmental abnormalities in the schizophrenia connectome, and lead to the hypothesis that visual hallucinations in patients with COS may be because of delayed development of the inferior longitudinal fasciculus, a prominent occipitotemporal fiber.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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