Lack of Gender Influence on Cortical and Subcortical Gray Matter Development in Childhood-Onset Schizophrenia

Weisinger, Brian; Greenstein, Deanna; Mattai, Anand; Clasen, Liv S.; Lalonde, François; Feldman, Sara; Miller, Rachel; Tossell, Julia W.; Vyas, Nora S.; Stidd, Reva; David, Christopher N.; Gogtay, Nitin

doi:10.1093/schbul/sbr049

Cited by 17 publications

(11 citation statements)

References 64 publications

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“…This is consistent with previous findings in our group, which indicated no gender differences in cortical thickness, subcortical volume development, 34,35 or cortical gray matter development 36 . These findings also corroborate findings of AOS studies 27 .…”

Section: Discussionsupporting

confidence: 94%

“…A small longitudinal study (n=21) found males with early-onset schizophrenia (EOS) to have more frontal gray matter loss compared to controls than females with EOS, although that study was underpowered to detect change in women due to small sample size (23.81% female n=5) 33 . Earlier studies in our group have found no gender differences in cortical thickness and subcortical volume development 34,35 or development of total cortical gray matter 36 in patients with COS. Nevertheless, while changes in cortical brain volume are among the most consistently reported abnormalities in both AOS and COS, a thorough and systematic evaluation of potential gender differences remains lacking 37,38 .…”

Section: Introductioncontrasting

confidence: 60%

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Lack of Gender-Related Differences in Childhood-Onset Schizophrenia

Ordóñez¹,

Loeb

Zhou

et al. 2016

Journal of the American Academy of Child & Adolescent Psych

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Objective Gender differences, including younger age of onset and greater premorbid deficits in men, have been reported in adult-onset schizophrenia (AOS). This study comprehensively evaluated gender differences in childhood-onset schizophrenia (COS), a rare variant of the disorder. Method We examined demographic, premorbid, clinical, familial, and cognitive characteristics, as well as presence of chromosomal abnormalities and brain magnetic resonance imaging (MRI) cortical volumes, in 133 patients with COS. Cortical analyses included age- and gender-matched healthy volunteers (n=124). Results Males with COS (n=72) had a slight but significant earlier age of onset than females with COS (mean age 9.51± 2.28 vs. 10.29 ± 1.63, t[131] = 2.21, p = .03), higher verbal IQ scores (83.00 ± 15.97 vs. 75.58 ± 15.10, t[89] = 2.24, p = .03), and higher rates of comorbid pervasive developmental disorder (PDD; 28.17% vs. 6.90%, χ2[1] = 9.54, p < .01) and attention-deficit/hyperactivity disorder (ADHD; 43.86% vs. 21.43%, χ2[1] = 5.40, p = .02). There were no significant gender differences across other demographic, IQ, or clinical measures, frequency of chromosomal abnormalities, family clinical measures, premorbid functioning, or in gender by disorder interactions for MRI brain measures. Conclusion After a comprehensive examination, we found few remarkable gender differences in COS. Although less striking than that seen in AOS, males with COS had an earlier age of onset. ADHD and PDD rates were high in COS overall, suggesting greater neurodevelopmental vulnerability in COS. However, the gender ratios of these comorbidities in COS mirror those of the general populations, indicating that these gender differences may be unrelated to COS.

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Section: Discussionsupporting

confidence: 94%

Section: Introductioncontrasting

confidence: 60%

Lack of Gender-Related Differences in Childhood-Onset Schizophrenia

Ordóñez¹,

Loeb

Zhou

et al. 2016

Journal of the American Academy of Child & Adolescent Psych

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“…In a meta-analysis of longitudinal MRI studies in children and adolescents with early onset psychosis, the proportion of males in each study was not found to significantly impact regional brain volume effect sizes [140]. Likewise, a longitudinal sample of youth with childhood-onset schizophrenia found no sex differences for either cortical thickness or subcortical volumes [160]. Moving forward, it will be important for future research to determine when sex differences in regional volumes emerge during development in youth at risk for psychosis symptoms.…”

Section: Psychosismentioning

confidence: 93%

Sex differences in the developing brain: insights from multimodal neuroimaging

Kaczkurkin

Raznahan

Satterthwaite

2018

Neuropsychopharmacol

273

213

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Youth (including both childhood and adolescence) is a period when the brain undergoes dramatic remodeling and is also a time when neuropsychiatric conditions often emerge. Many of these illnesses have substantial sex differences in prevalence, suggesting that sex differences in brain development may underlie differential risk for psychiatric symptoms between males and females. Substantial evidence documents sex differences in brain structure and function in adults, and accumulating data suggests that these sex differences may be present or emerge during development. Here we review the evidence for sex differences in brain structure, white matter organization, and perfusion during development. We then use these normative differences as a framework to understand sex differences in brain development associated with psychopathology. In particular, we focus on sex differences in the brain as they relate to anxiety, depression, psychosis, and attention-deficit/hyperactivity symptoms. Finally, we highlight existing limitations, gaps in knowledge, and fertile avenues for future research.

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“…It has also been established that COS probands do not differ from healthy controls with regards to sex differences in cortical thickness (Weisinger et al, 2013), or with regards to cross-sectional or longitudinal developmental changes in asymmetry (Bakalar et al, 2009). Cortical thickness deficits in COS probands are also largely uninfluenced by clozapine versus olanzapine intake, aside from a small area of the right prefrontal cortex (Mattai et al, 2010).…”

Section: 2 Structural Neuroimagingmentioning

confidence: 99%

Neuroimaging findings from childhood onset schizophrenia patients and their non-psychotic siblings

Ordóñez

Luscher

Gogtay

2016

Schizophrenia Research

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Childhood onset schizophrenia (COS), with onset of psychosis before age 13, is a rare form of schizophrenia that represents a more severe and chronic form of the adult onset illness. In this review we examine structural and functional magnetic resonance imaging (MRI) studies of COS and non-psychotic siblings of COS patients in the context of studies of schizophrenia as a whole. Studies of COS to date reveal progressive loss of gray matter volume and cortical thinning, ventricular enlargement, progressive decline in cerebellar volume and a significant but fixed deficit in hippocampal volume. COS is also associated with a slower rate of white matter growth and disrupted local connectivity strength. Sibling studies indicate that non-psychotic siblings of COS patients share many of these brain abnormalities, including decreased cortical thickness and disrupted white matter growth, yet these abnormalities normalize with age. Cross-sectional and longitudinal neuroimaging studies remain some of the few methods for assessing human brain function and play a pivotal role in the quest for understanding the neurobiology of schizophrenia as well as other psychiatric disorders. Parallel studies in non-psychotic siblings provide a unique opportunity to understand both risk and resilience in schizophrenia.

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Lack of Gender Influence on Cortical and Subcortical Gray Matter Development in Childhood-Onset Schizophrenia

Abstract: Sex appears to play a similar role in cortical and subcortical GM development in COS as it does in normally developing children.

Cited by 17 publications

References 64 publications

Lack of Gender-Related Differences in Childhood-Onset Schizophrenia

Lack of Gender-Related Differences in Childhood-Onset Schizophrenia

Sex differences in the developing brain: insights from multimodal neuroimaging

Neuroimaging findings from childhood onset schizophrenia patients and their non-psychotic siblings

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