Abstract
Background
A decline in cortical thickness during early life appears to be a normal neuromaturational
process. Accelerated cortical thinning has been linked with conversion to psychosis
among individuals at clinical high risk for psychosis (CHR-P). Previous research indicates
that exposure to life event stress (LES) is associated with exaggerated cortical thinning
in both healthy and clinical populations, and LES is also linked with conversion to
psychosis in CHR-P. To date, there are no reports on the relationship of LES with
cortical thickness in CHR-P. This study examines this relationship and whether LES
is linked with cortical thinning to a greater degree in individuals at CHR-P who convert
to psychosis compared with individuals at CHR-P who do not convert and healthy control
subjects.
Methods
Controlling for age and gender (364 male, 262 female), this study examined associations
between LES and baseline cortical thickness in 436 individuals at CHR-P (375 nonconverters
and 61 converters) and 190 comparison subjects in the North American Prodrome Longitudinal
Study.
Results
Findings indicate that prebaseline cumulative LES is associated with reduced baseline
cortical thickness in several regions among the CHR-P and control groups. Evidence
suggests that LES is a risk factor for thinner cortex to the same extent across diagnostic
groups, while CHR-P status is linked with thinner cortex in select regions after accounting
for LES.
Conclusions
This research provides additional evidence to support the role of LES in cortical
thinning in both healthy youth and those at CHR-P. Potential underlying mechanisms
of the findings and implications for future research are discussed.
Keywords
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References
- Stressful life events and schizophrenia. I: A review of the research.Br J Psychiatry. 1993; 162: 161-166
- Schizophrenia: A neural diathesis-stress model.Psychol Rev. 1997; 104: 667-685
- Stress and the progression of the developmental hypothesis of schizophrenia.Br J Psychiatry. 2002; 181: 363-365
- Allostatic load and reduced cortical thickness in schizophrenia.Psychoneuroendocrinology. 2017; 77: 105-111
- The prevalence and correlates of trauma-related symptoms in schizophrenia spectrum disorder.Compr Psychiatry. 2008; 49: 330-334
- The history of childhood trauma among individuals with ultra high risk for psychosis is as common as among patients with first-episode schizophrenia.Early Interv Psychiatry. 2013; 7: 414-420
- History of trauma and the association with baseline symptoms in an ultra-high risk for psychosis cohort.Psychiatry Res. 2013; 210: 75-81
- Childhood trauma in schizophrenia: Current findings and research perspectives.Front Neurosci. 2019; 13: 274
- Childhood adversities increase the risk of psychosis: A meta-analysis of patient-control, prospective- and cross-sectional cohort studies.Schizophr Bull. 2012; 38: 661-671
- Stress exposure and sensitivity in the clinical high-risk syndrome: Initial findings from the North American Prodrome Longitudinal Study (NAPLS).Schizophr Res. 2014; 160: 104-109
- The role of trauma and stressful life events among individuals at clinical high risk for psychosis: A review.Front Psychiatry. 2017; 8: 55
- Ten surprising facts about stressful life events and disease risk.Annu Rev Psychol. 2019; 70: 577-597
- Revisiting the stress concept: Implications for affective disorders.J Neurosci. 2020; 40: 12-21
- Stress and the developing adolescent brain.Neuroscience. 2013; 249: 162-171
- Chronic social defeat stress induces sustained synaptic structural changes in the prefrontal cortex and amygdala.Behav Brain Res. 2019; 373: 112079
- Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis.Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29: 1201-1213
- Evidence for similar prefrontal structural and functional alterations in male and female rats following chronic stress or glucocorticoid exposure.Cereb Cortex. 2020; 30: 353-370
- Stress and neurodevelopmental processes in the emergence of psychosis.Neuroscience. 2013; 249: 172-191
- HPA axis and memory.Best Pract Res Clin Endocrinol Metab. 2003; 17: 287-299
- Socioeconomic disparities in chronic physiologic stress are associated with brain structure in children.Biol Psychiatry. 2019; 86: 921-929
- How does your cortex grow?.J Neurosci. 2011; 31: 7174-7177
- Unique developmental trajectories of cortical thickness and surface area.Neuroimage. 2014; 87: 120-126
- The contribution of cortical thickness and surface area to gray matter asymmetries in the healthy human brain.Hum Brain Mapp. 2014; 35: 6011-6022
- Age-related effects and sex differences in gray matter density, volume, mass, and cortical thickness from childhood to young adulthood.J Neurosci. 2017; 37: 5065-5073
- A longitudinal study: Changes in cortical thickness and surface area during pubertal maturation.PLoS One. 2015; 10e0119774
- Thinner prefrontal cortex in veterans with posttraumatic stress disorder.Neuroimage. 2008; 41: 675-681
- Reduced cortical thickness as an outcome of differential sensitivity to environmental risks in schizophrenia.Biol Psychiatry. 2011; 69: 487-494
- Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing.J Child Psychol Psychiatry. 2016; 57: 1154-1164
- Neonatal pain-related stress predicts cortical thickness at age 7 years in children born very preterm.PLoS One. 2013; 8e76702
- Neural alterations in ADHD children as indicated by voxel-based cortical thickness and morphometry analysis.Brain Dev. 2017; 39: 403-410
- Cortical thickness in major depressive disorder: A systematic review and meta-analysis.Prog Neuropsychopharmacol Biol Psychiatry. 2019; 88: 287-302
- Cortical thickness in bipolar disorder: A systematic review.Bipolar Disord. 2016; 18: 4-18
- The contributions of disease and genetic factors towards regional cortical thinning in schizophrenia: The UCLA family study.Schizophr Res. 2010; 123: 116-125
- Cortical thickness reduction in individuals at ultra-high-risk for psychosis.Schizophr Bull. 2011; 37: 839-849
- Reduced cortical thickness in subjects at clinical high risk for psychosis and clinical attributes.Aust N Z J Psychiatry. 2019; 53: 219-227
- Alterations in white matter microstructure and cortical thickness in individuals at ultra-high risk of psychosis: A multimodal tractography and surface-based morphometry study.Psychiatry Res Neuroimaging. 2019; 289: 26-36
- Age-related cortical thickness differences in adolescents with early-onset schizophrenia compared with healthy adolescents.Psychiatry Res. 2013; 214: 190-196
- Lack of evidence for regional brain volume or cortical thickness abnormalities in youths at clinical high risk for psychosis: Findings from the longitudinal youth at risk study.Schizophr Bull. 2015; 41: 1285-1293
- Progressive reduction in cortical thickness as psychosis develops: A multisite longitudinal neuroimaging study of youth at elevated clinical risk.Biol Psychiatry. 2015; 77: 147-157
- Cortical thickness gradients in structural hierarchies.Neuroimage. 2015; 111: 241-250
- Cortical thickness alterations linked to somatoform and psychological dissociation in functional neurological disorders.Hum Brain Mapp. 2018; 39: 428-439
- Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence.Hum Brain Mapp. 2009; 30: 163-174
- Impact of polygenic risk for schizophrenia on cortical structure in UK Biobank.Biol Psychiatry. 2019; 86: 536-544
- Brain heterogeneity in schizophrenia and its association with polygenic risk.JAMA Psychiatry. 2019; 76: 739-748
- Age-related differences in cortical thickness vary by socioeconomic status.PLoS One. 2016; 11e0162511
- Association between stressful life events and psychotic experiences in adolescence: Evidence for gene-environment correlations.Br J Psychiatry. 2016; 208: 532-538
- Effects of environmental risks and polygenic loading for schizophrenia on cortical thickness.Schizophr Res. 2017; 184: 128-136
- Longitudinal changes in cortisol secretion and conversion to psychosis in at-risk youth.J Abnorm Psychol. 2010; 119: 401-408
- The neural diathesis-stress model of schizophrenia revisited: An update on recent findings considering illness stage and neurobiological and methodological complexities.Neurosci Biobehav Rev. 2017; 73: 191-218
- North American Prodrome Longitudinal Study (NAPLS 2): Overview and recruitment.Schizophr Res. 2012; 142: 77-82
- Exemplification of a method for scaling life events: The Peri Life Events Scale.J Health Soc Behav. 1978; 19: 205-229
- Comorbid diagnoses for youth at clinical high risk of psychosis.Schizophr Res. 2017; 190: 90-95
- Reliability of neuroanatomical measurements in a multisite longitudinal study of youth at risk for psychosis.Hum Brain Mapp. 2014; 35: 2424-2434
- Use of machine learning to determine deviance in neuroanatomical maturity associated with future psychosis in youths at clinically high risk.JAMA Psychiatry. 2018; 75: 960-968
- FreeSurfer.Neuroimage. 2012; 62: 774-781
- Measuring the thickness of the human cerebral cortex from magnetic resonance images.Proc Natl Acad Sci U S A. 2000; 97: 11050-11055
- Determining the optimal level of smoothing in cortical thickness analysis: A hierarchical approach based on sequential statistical thresholding.Neuroimage. 2010; 52: 158-171
- Permutation inference for the general linear model.Neuroimage. 2014; 92: 381-397
- Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference.Neuroimage. 2009; 44: 83-98
- Mediation: R package for causal mediation analysis.J Stat Soft. 2014; 59: 1-38
- Gender difference analysis of cortical thickness in healthy young adults with surface-based methods.Neuroimage. 2006; 31: 31-38
- Gender effects on cortical thickness and the influence of scaling.Hum Brain Mapp. 2006; 27: 314-324
- Age and gender as determinants of stress exposure, generation, and reactions in youngsters: A transactional perspective.Child Dev. 1999; 70: 660-677
- Sex differences in the HPA axis.Compr Physiol. 2014; 4: 1121-1155
- Sex differences in brain anatomy.Prog Brain Res. 2010; 186: 3-12
- Sex matters during adolescence: Testosterone-related cortical thickness maturation differs between boys and girls.PLoS One. 2012; 7e33850
- Clinical high risk for psychosis: Gender differences in symptoms and social functioning.Early Interv Psychiatry. 2017; 11: 306-313
- Gender differences in schizophrenia and first-episode psychosis: A comprehensive literature review.Schizophr Res Treatment. 2012; 2012: 916198
- Toward understanding how early-life stress reprograms cognitive and emotional brain networks.Neuropsychopharmacology. 2016; 41: 197-206
- A mosaic of sex-related structural changes in the human brain following exposure to real-life stress.Brain Struct Funct. 2020; 225: 461-466
- Grey matter volume and thickness abnormalities in young people with a history of childhood abuse.Psychol Med. 2018; 48: 1034-1046
- Developmental trajectories of early life stress and trauma: A narrative review on neurobiological aspects beyond stress system dysregulation.Front Psychiatry. 2019; 10: 118
- The long-term impact of early life stress on orbitofrontal cortical thickness.Cereb Cortex. 2020; 30: 1307-1317
- Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis.Psychol Med. 2014; 44: 489-498
- Resilience and cortical thickness: A MRI study.Eur Arch Psychiatry Clin Neurosci. 2020; 270: 533-539
- Early life stress-induced alterations in rat brain structures measured with high resolution MRI.PLoS One. 2017; 12e0185061
- The dynamics of stress: A longitudinal MRI study of rat brain structure and connectome.Mol Psychiatry. 2018; 23: 1998-2006
- The adrenal cortex and life.Mol Cell Endocrinol. 2009; 300: 2-6
- Stress- and allostasis-induced brain plasticity.Annu Rev Med. 2011; 62: 431-445
- Combat exposure, posttraumatic stress disorder, and head injuries differentially relate to alterations in cortical thickness in military veterans.Neuropsychopharmacology. 2020; 45: 491-498
- Postnatal ontogeny of expression of the corticosteroid receptor genes in mammalian brains: Inter-species and intra-species differences.Brain Res Rev. 2008; 57: 596-605
- Shifts in hormonal stress reactivity during adolescence are not associated with changes in glucocorticoid receptor levels in the brain and pituitary of male rats.Dev Neurosci. 2014; 36: 261-268
- Risk factors for psychosis: Impaired social and role functioning.Schizophr Bull. 2012; 38: 1247-1257
- Changes in cortical thickness during the course of illness in schizophrenia.Arch Gen Psychiatry. 2011; 68: 871-880
- Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis.Psychol Med. 2015; 45: 515-527
- Amygdalar reactivity is associated with prefrontal cortical thickness in a large population-based sample of adolescents.PLoS One. 2019; 14e0216152
- Influence of childhood trauma and brain-derived neurotrophic factor Val66Met polymorphism on posttraumatic stress symptoms and cortical thickness.Nature. 2019; 9: 6028
- Polygenic risk score contribution to psychosis prediction in a target population of persons at clinical high risk.Am J Psychiatry. 2020; 177: 155-163
- Impulsivity as a mediating factor in the association between posttraumatic stress disorder symptoms and substance use.Psychol Trauma. 2020; 12: 659-668
- From vulnerability to neurotoxicity: A developmental approach to the effects of stress on the brain and behavior.in: Spengler D. Binder E. Epigenetics and Neuroendocrinology. Springer, Cham2016: 3-48
- The impact of stress on the structure of the adolescent brain: Implications for adolescent mental health.Brain Res. 2017; 1654: 185-191
- Effects of stress throughout the lifespan on the brain, behaviour and cognition.Nat Rev Neurosci. 2009; 10: 434-445
- Effects of early life stress on cognitive and affective function: An integrated review of human literature.Psychopharmacology. 2011; 214: 55-70
- Adolescence and aging: Impact of adolescence inflammatory stress and microbiota alterations on brain development, aging, and neurodegeneration.J Gerontol A Biol Sci Med Sci. 2020; 75: 1251-1257
- Inter-regional variations in gene expression and age-related cortical thinning in the adolescent brain.Cereb Cortex. 2018; 28: 1272-1281
Article Info
Publication History
Published online: April 27, 2021
Accepted:
April 20,
2021
Received in revised form:
March 21,
2021
Received:
December 15,
2020
Identification
Copyright
© 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
