Andrew Zalesky1, Christos Pantelis1, Vanessa Cropley1, Alex Fornito2, Luca Cocchi3, Harrison McAdams4, Liv Clasen4, Deanna Greenstein4, Judith L Rapoport4, Nitin Gogtay4. 1. Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Victoria, Australia. 2. Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Victoria, Australia2Monash Clinical and Imaging Neuroscience, School of Psychology and Psychiatry and Monash Biomedical Imaging, Monash University, Melbourne, Australia. 3. Queensland Brain Institute, The University of Queensland, Brisbane, Australia. 4. Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland.
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.
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.
Authors: Rebecca E Watsky; Stephen J Gotts; Rebecca A Berman; Harrison M McAdams; Xueping Zhou; Dede Greenstein; Francois M Lalonde; Peter Gochman; Liv S Clasen; Lorie Shora; Anna E Ordóñez; Nitin Gogtay; Alex Martin; Deanna M Barch; Judith L Rapoport; Siyuan Liu Journal: Schizophr Res Date: 2018-01-06 Impact factor: 4.939
Authors: Urs Braun; Axel Schaefer; Richard F Betzel; Heike Tost; Andreas Meyer-Lindenberg; Danielle S Bassett Journal: Neuron Date: 2018-01-03 Impact factor: 17.173
Authors: Sheeba Arnold Anteraper; Guusje Collin; Xavier Guell; Timothy Scheinert; Elena Molokotos; Maria Toft Henriksen; Raquelle Mesholam-Gately; Heidi W Thermenos; Larry J Seidman; Matcheri S Keshavan; John D E Gabrieli; Susan Whitfield-Gabrieli Journal: Schizophr Res Date: 2019-12-02 Impact factor: 4.939