Format

Send to

Choose Destination
Biol Psychiatry. 2014 Sep 15;76(6):438-46. doi: 10.1016/j.biopsych.2014.02.010. Epub 2014 Feb 22.

Abnormal cortical growth in schizophrenia targets normative modules of synchronized development.

Author information

1
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland; Brain Mapping Unit, Behavioural & Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address: aalexanderbloch@gmail.com.
2
New York University School of Medicine, New York, New York; Nathan S. Kline Institute for Psychiatric Research, New York, New York.
3
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland.
4
Brain Mapping Unit, Behavioural & Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; Cambridgeshire & Peterborough National Health Service Foundation Trust, Cambridge; ImmunoPsychiatry, Alternative Discovery & Development, GlaxoSmithKline, Stevenage, United Kingdom.

Abstract

BACKGROUND:

Schizophrenia is a disorder of brain connectivity and altered neurodevelopmental processes. Cross-sectional case-control studies in different age groups have suggested that deficits in cortical thickness in childhood-onset schizophrenia may normalize over time, suggesting a disorder-related difference in cortical growth trajectories.

METHODS:

We acquired magnetic resonance imaging scans repeated over several years for each subject, in a sample of 106 patients with childhood-onset schizophrenia and 102 age-matched healthy volunteers. Using semiparametric regression, we modeled the effect of schizophrenia on the growth curve of cortical thickness in ~80,000 locations across the cortex, in the age range 8 to 30 years. In addition, we derived normative developmental modules composed of cortical regions with similar maturational trajectories for cortical thickness in typical brain development.

RESULTS:

We found abnormal nonlinear growth processes in prefrontal and temporal areas that have previously been implicated in schizophrenia, distinguishing for the first time between cortical areas with age-constant deficits in cortical thickness and areas whose maturational trajectories are altered in schizophrenia. In addition, we showed that when the brain is divided into five normative developmental modules, the areas with abnormal cortical growth overlap significantly only with the cingulo-fronto-temporal module.

CONCLUSIONS:

These findings suggest that abnormal cortical development in schizophrenia may be modularized or constrained by the normal community structure of developmental modules of the human brain connectome.

KEYWORDS:

Neuroimaging; penalized splines; psychosis; system; topology

PMID:
24690112
PMCID:
PMC4395469
DOI:
10.1016/j.biopsych.2014.02.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center