Resilience to Schizophrenia in Siblings of Those With the Disease

Fundamental differences between how the brain forms during adolescence have been discovered in children with schizophrenia and their siblings, a new study shows. The study opens up new avenues for researchers to explore when developing treatment for the illness, which can be hugely debilitating for children.

Researchers from the University of Melbourne and the National Institute of Mental Health in Washington DC used structural brain magnetic resonance imaging (MRI) to map the brains of 109 children with childhood-onset schizophrenia (COS), from ages 12 to 24.

They compared the images with scans taken of the participants’ brothers and sisters without COS to see if similar brain changes took place over time.

The siblings without COS showed similar delays in brain connectivity while growing up, but these connections tended to normalise or ‘catch up’ to those of normally developing adolescents.

The findings are published in the July edition of a Journal of the American Medical Association Network, JAMA Psychiatry.

Lead researcher, Dr. Andrew Zalesky is a University of Melbourne electrical engineer who lends his expertise to understanding the brain’s wiring. He divides his time between the Faculties of Medicine and Engineering at the Melbourne Neuropsychiatry Centre.

Dr. Zalesky says the ability of the siblings to catch up and develop important brain circuitry means there is a degree of resilience to their risk for schizophrenia.

“We’ve looked at the development of brain networks over the adolescent period, from childhood to early adulthood. Abnormalities detected early in the unaffected children normalise by age 16,” Dr. Zalesky said.

“The greatest risk for schizophrenia is family history, but the majority of siblings of individuals with the disorder are unaffected.

“So why are these brothers and sisters able to overcome the risk? Looking for these biological factors that protect a person from developing schizophrenia opens up a new direction in the search for treatments.”

This image shows a woman sitting on the floor and holding her head.

Researchers compared the images with scans taken of the participants’ brothers and sisters without COS to see if similar brain changes took place over time. Image is for illustrative purposes only.

Co-author, Professor Christos Pantelis, heads the Melbourne Neuropsychiatry Centre at the University of Melbourne. He treats patients with severe forms of schizophrenia at NorthWestern Mental Health.

He says examining the biological, social and psychological protective factors that can improve resilience to mental disorders will help researchers to develop new approaches to treatment.

“New generation medications can help young patients manage their symptoms, but can have significant side effects. Our work has the potential to open up avenues towards earlier intervention with fewer side-effects that improve a child’s resilience to becoming ill,” Prof Pantelis said.

“This is an interesting new direction, as it suggests the search for targeted psychiatric treatments for schizophrenia and psychosis requires following young people over time.”

About this schizophrenia research

Source: Jane Gardner – University of Melbourne
Image Source: The image is in the public domain
Original Research: Abstract for “Delayed Development of Brain Connectivity in Adolescents With Schizophrenia and Their Unaffected Siblings” by Andrew Zalesky, PhD; Christos Pantelis, MD; Vanessa Cropley, PhD; Alex Fornito, PhD; Luca Cocchi, PhD; Harrison McAdams, PhD; Liv Clasen, PhD; Deanna Greenstein, PhD; Judith L. Rapoport, MD; and Nitin Gogtay, MD in JAMA Psychiatry. Published online July 15 2015 doi:10.1001/jamapsychiatry.2015.0226


Abstract

Delayed Development of Brain Connectivity in Adolescents With Schizophrenia and Their Unaffected Siblings

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.

“Delayed Development of Brain Connectivity in Adolescents With Schizophrenia and Their Unaffected Siblings” by Andrew Zalesky, PhD; Christos Pantelis, MD; Vanessa Cropley, PhD; Alex Fornito, PhD; Luca Cocchi, PhD; Harrison McAdams, PhD; Liv Clasen, PhD; Deanna Greenstein, PhD; Judith L. Rapoport, MD; and Nitin Gogtay, MD in JAMA Psychiatry. Published online July 15 2015 doi:10.1001/jamapsychiatry.2015.0226

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