Widespread Reductions of Cortical Thickness in Schizophrenia and Spectrum Disorders and Evidence of Heritability

Goldman, Aaron L.; Pezawas, Lukas; Mattay, Venkata S.; Fischl, Bruce; Verchinski, Beth A.; Chen, Qiang; Weinberger, Daniel R.; Meyer‐Lindenberg, Andreas

doi:10.1001/archgenpsychiatry.2009.24

Cited by 241 publications

(206 citation statements)

References 68 publications

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“…Studies have shown widespread cortical thickness reductions across the brain in patients with schizophrenia compared with healthy controls with frontal and temporal regions being generally more affected than others areas (Nesvåg et al 2008;Goldman, 2009;Schultz et al 2010). In line with prior work, Ehrlich et al (2012) and Geisler et al (2015) recently reported marked reductions of cortical thickness in patients with schizophrenia, which were also related to executive functioning.…”

Section: Introductionsupporting

confidence: 72%

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

et al. 2017

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Background. Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. Results. Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.Conclusions. Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

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Section: Introductionsupporting

confidence: 72%

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

et al. 2017

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“…Increased average head size, childhood brain volume, or cortical thickness in individuals with: (i) idiopathic autism (50-53), (ii) the autism-associated duplications at 1q21.1 (17) and 16p13.1 (32) and the autism-associated deletions at 16p11.2 (31), and (iii) autism due to loss of function (or haploinsufficiency) of FMR1 (54), NF1 (55), PTEN (56) and RNF135 (57). By contrast, reduced average values for brain size and cortical thickness, due to some combination of reduced growth and accelerated gray matter loss, have been demonstrated with notable consistency across studies of schizophrenia (58)(59)(60)(61)(62), and such reduced head or brain size has also been associated with the schizophrenia-linked CNVs at 1q21.1 and 22q11.21 (17,63,64), and with deletions of 16p13.1 (65).…”

Section: Discussionmentioning

confidence: 99%

Comparative genomics of autism and schizophrenia

Crespi

Stead

Elliot

2010

Proc. Natl. Acad. Sci. U.S.A.

236

138

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We used data from studies of copy-number variants (CNVs), singlegene associations, growth-signaling pathways, and intermediate phenotypes associated with brain growth to evaluate four alternative hypotheses for the genomic and developmental relationships between autism and schizophrenia: (i) autism subsumed in schizophrenia, (ii) independence, (iii) diametric, and (iv) partial overlap. Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other. Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance. However, differentiation between the partial overlap and diametric hypotheses using these data is precluded by limited overlap in the specific genetic markers analyzed in both autism and schizophrenia. Evidence from the effects of risk variants on growth-signaling pathways shows that autism-spectrum conditions tend to be associated with upregulation of pathways due to loss of function mutations in negative regulators, whereas schizophrenia is associated with reduced pathway activation. Finally, data from studies of head and brain size phenotypes indicate that autism is commonly associated with developmentally-enhanced brain growth, whereas schizophrenia is characterized, on average, by reduced brain growth. These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurodevelopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain.genetics | evolution | psychiatry T he Swiss psychiatrist Eugen Bleuler coined the terms "schizophrenia", for the splitting of psychic functions, and "autism", for withdrawal from external reality in patients with schizophrenia, almost exactly a century ago (1). Ever since 1943, when Leo Kanner (2) coopted autism to refer to a new condition involving "disturbance of affective contact" manifested in children, the relationship between schizophrenia and Kanner's autism has remained unclear (3). Kanner originally conceived autism as an early, distinct subtype of schizophrenia (model 1A) (Fig. 1A), a view he later renounced in favor of a model, which was also supported by Rutter (4) with the conditions as distinct, separate, and unrelated (model 1B) (Fig. 1B). Under each of these two hypotheses, autism and schizophrenia may each grade more or less smoothly, and independently, into so-called normality. Schizophrenia and autism have also been considered as diametric, or opposite sets of conditions (model 1C) (Fig. 1C) along a spectrum of social-brain phenotypes from hypodevelopment in autism, to normality, to hyperdevelopment in schizophrenia (5). By a fourth model, autism overlaps broadly yet...

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“…In fact, one of the principal pathological findings in the brains of those affected with schizophrenia involves abnormal cortical thinning (Cannon et al, 2015). Reduced cortical thickness has also been demonstrated in the unaffected siblings of patients with the disorder (Goldman et al, 2009;Goghari, Rehm, Carter, & MacDonald, 2007;Gogtay et al, 2007), suggesting a possible relationship of these cortical changes to the genetic liability for developing the illness. Indeed, schizophrenia's strongest genetic association involves variation in the major histocompatibility complex (MHC) locus, which mediates synapse elimination during postnatal development in mice (Sekar et al, 2016).…”

Section: Structural Abnormalities In Schizophreniamentioning

confidence: 99%

Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia.

Ammari¹,

Heinrichs²,

Pinnock³

et al. 2014

Neuropsychology

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Objective: Although impaired general intellectual ability is a prevalent feature in schizophrenia, patterns suggesting preserved, deteriorated, and premorbidly impaired intellect have also been identified. The main purpose of this investigation was to examine the clinical, cognitive, and neuroanatomical characteristics of these intellectual subtypes, and to establish the value and validity of this approach for reducing the heterogeneity of schizophrenia. Methods: A total of 71 patients with a diagnosis of schizophrenia or schizoaffective disorder and 66 healthy controls were assessed. A 'preserved' performance pattern (n=29) was defined by average-range estimated premorbid and current IQ with no evidence of decline (premorbid-current IQ difference <10 points). A 'deteriorated' pattern (n=14) was defined by a difference between estimated premorbid and current IQ estimates of 10 points or more. A 'premorbidly impaired' pattern (n=14) was defined by below average estimated premorbid and current IQ and no evidence of decline greater than 10 points. The groups were compared on demographic,

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Widespread Reductions of Cortical Thickness in Schizophrenia and Spectrum Disorders and Evidence of Heritability

Cited by 241 publications

References 68 publications

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

Comparative genomics of autism and schizophrenia

Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia.

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