Brain morphology does not clearly map to cognition in individuals on the bipolar-schizophrenia-spectrum: a cross-diagnostic study of cognitive subgroups

doi:10.1016/j.jad.2020.11.064

Journal of Affective Disorders

Volume 281, 15 February 2021, Pages 776-785

https://doi.org/10.1016/j.jad.2020.11.064 Get rights and content

Highlights

•
The patterns of brain morphology in cognitive subgroups were not consistent across global, regional, and vertex-wise analyses.
•
Contrary to expectations, the subgroup with the greatest cognitive impairments demonstrated relative increases in volume and cortical thickness.
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Our findings suggest that variation in cognitive performance may not map cleanly onto variation in brain morphology in SSD and BD.

Abstract

Background

Characterisation of brain morphological features common to cognitively similar individuals with bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) may be key to understanding their shared neurobiological deficits. In the current study we examined whether three previously characterised cross-diagnostic cognitive subgroups differed among themselves and in comparison to healthy controls across measures of brain morphology.

Method

T1-weighted structural magnetic resonance imaging scans were obtained for 143 individuals; 65 healthy controls and 78 patients (SSD, n = 40; BD I, n = 38) classified into three cross-diagnostic cognitive subgroups: Globally Impaired (n = 24), Selectively Impaired (n = 32), and Superior/Near-Normal (n = 22). Cognitive subgroups were compared to each other and healthy controls on three separate analyses investigating (1) global, (2) regional, and (3) vertex-wise comparisons of brain volume, thickness, and surface area.

Results

No significant subgroup differences were evident in global measures of brain morphology. In region of interest analyses, the Selectively Impaired subgroup had greater right accumbens volume than those Superior/Near-Normal subgroup and healthy controls, and the Superior/Near-Normal subgroup had reduced volume of the left entorhinal region compared to all other groups. In vertex-wise comparisons, the Globally Impaired subgroup had greater right precentral volume than the Selectively Impaired subgroup, and thicker cortex in the postcentral region relative to the Superior/Near-Normal subgroup.

Limitations

Exploration of medication effects was limited in our data.

Conclusions

Although some differences were evident in this sample, generally cross-diagnostic cognitive subgroups of individuals with SSD and BD did not appear to be clearly distinguished by patterns in brain morphology.

Section snippets

Method

This study was approved by the relevant Human Ethics Review Board and abided by the Declaration of Helsinki.

Demographics

The outcomes of the demographic and clinical analyses comparing cross-diagnostic cognitive subgroups and controls are presented in Table 1a. The healthy control group was significantly younger than the Globally and Selectively Impaired subgroup. The Globally Impaired subgroup comprised the greatest number of SSD patients, while the Superior/Near-Normal subgroup comprised the greatest number of BD patients. Finally, the percentage of patients on atypical antipsychotics was the highest in the

Discussion

This study aimed to provide further insight into the relationship between brain structure and cognition in BD and SSD, as well as the extent of neurobiological overlap of these disorders that may be associated with shared cognitive deficits. This was achieved by analysing differences in brain morphology between three cross-diagnostic cognitive subgroups and healthy controls, and comparing the outcomes to that of analyses comparing traditional diagnostic subgroups and healthy controls. Our key

Declaration of Competing Interest

Over the last four years, Prof Pantelis has been on advisory boards for AstraZeneca, Janssen-Cilag, Lundbeck, and Servier; and he has received honoraria for talks presented at educational meetings organized by AstraZeneca, Eli Lilly, Janssen-Cilag, Lundbeck, Pfizer, and Shire. The other authors report no financial relationships with commercial interests.

Financial support

Financial support from the National Health and Medical Research Council (NHMRC) provided salary support to TVR (Early Career Fellowship 1088785), SR (Senior Research Fellowship 1154651) and CP (Senior Principal Research Fellowships 628386 and 1105825); and Swinburne University/the Australian Government provided postgraduate scholarships to JK, SC and PS. The authors would also like to acknowledge project specific financial support of the NHMRC (1060664), Henry Freeman Trust, Jack Brockhoff

Ethical standards

The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Data availability

Data is available upon request. Enquires can be directed to the corresponding author.

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We found widespread differences in cortical thickness in frontal, temporal and parietal regions in cognitive subgroups and healthy controls. Widespread reduced cortical thickness in similar regions has been reported before in SSD (Hanford et al., 2019; Karantonis et al., 2021b; van Erp et al., 2018; Van Haren et al., 2011; Van Rheenen et al., 2018). In general, more severely impaired individuals show more widespread cortical thinning (Fernández-Linsenbarth et al., 2021; Geisler et al., 2015; Guimond et al., 2016; Ho et al., 2020).
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Research paperBrain morphology does not clearly map to cognition in individuals on the bipolar-schizophrenia-spectrum: a cross-diagnostic study of cognitive subgroups

Highlights

Abstract

Background

Method

Results

Limitations

Conclusions

Section snippets

Method

Demographics

Discussion

Declaration of Competing Interest

Financial support

Ethical standards

Data availability

Psychiatry Research: Neuroimaging

European Neuropsychopharmacology

Neuroanatomic Differences Among Cognitive and Symptom Subtypes of Schizophrenia

The Journal of Nervous and Mental Disease

Structural and Functional Brain Correlates of Cognitive Impairment in Euthymic Patients with Bipolar Disorder

PLoS One

Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis

Psychological Medicine

Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis

Br J Psychiatry

Volumetric analysis of frontal lobe regions in schizophrenia: relation to cognitive function and symptomatology

Biological Psychiatry

Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume

Transl Psychiatry

Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder-a systematic review of the magnetic resonance neuroimaging literature

NPJ Schizophr

Characterising cognitive heterogeneity in schizophrenia spectrum disorders—A systematic review and narrative synthesis

Neuroscience & Biobehavioural Reviews

Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs

American Journal of Psychiatry

Striatal shape abnormalities as novel neurodevelopmental endophenotypes in schizophrenia: A longitudinal study

Human Brain Mapping

Neurobiological Commonalities and Distinctions Among Three Major Psychiatric Diagnostic Categories: A Structural MRI Study

Schizophr Bull

Anatomical Abnormalities in Gray and White Matter of the Cortical Surface in Persons with Schizophrenia

PLoS One

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Schizophr Bull

An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest

NeuroImage

Whole brain segmentation: automated labelling of neuroanatomical structures in the human brain

Neuron

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Biological Psychiatry

Brain structure and function correlates of cognitive subtypes in schizophrenia

Psychiatry Res

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Neuroimage: Clinical

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Neuropsychology Review

Verbal memory impairments in schizophrenia associated with cortical thinning

Neuroimage: Clinical

Hippocampal and orbital inferior frontal gray matter volume abnormalities and cognitive deficit in treatment-naive, first-episode patients with schizophrenia

Schizophr Res

Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain

Hum Brain Mapp

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Prog Neuropsychopharmacol Biol Psychiatry

The genetics of functional disability in schizophrenia and bipolar illness: Methods and initial results for VA cooperative study #572

Am J Med Genet B Neuropsychiatr Genet

In vivo hippocampal subfield volumes in schizophrenia and bipolar disorder

Biological Psychiatry

More powerful procedures for multiple significance testing

Statistics in Medicine

Neural correlates of global and specific cognitive deficits in schizophrenia

Schizophrenia Research

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Journal of Affective Disorders, 266

The positive and negative syndrome scale (PANSS) for schizophrenia

Schizophr Bull

Amygdala volume and verbal memory performance in schizophrenia and bipolar disorder

Cognitive Behavioural Neurology

Cortical thinning in bipolar disorder and schizophrenia

Schizophrenia Research

Research paper
Brain morphology does not clearly map to cognition in individuals on the bipolar-schizophrenia-spectrum: a cross-diagnostic study of cognitive subgroups