Dataset Information

In memory of Professor Iain Wilkinson: cognitive and neuroimaging endophenotypes in a consanguineous schizophrenia multiplex family.

ABSTRACT:

Background

Schizophrenia endophenotypes may help elucidate functional effects of genetic risk variants in multiply affected consanguineous families that segregate recessive risk alleles of large effect size. We studied the association between a schizophrenia risk locus involving a 6.1Mb homozygous region on chromosome 13q22-31 in a consanguineous multiplex family and cognitive functioning, haemodynamic response and white matter integrity using neuroimaging.

Methods

We performed CANTAB neuropsychological testing on four affected family members (all homozygous for the risk locus), ten unaffected family members (seven homozygous and three heterozygous) and ten healthy volunteers, and tested neuronal responses on fMRI during an n-back working memory task, and white matter integrity on diffusion tensor imaging (DTI) on four affected and six unaffected family members (four homozygous and two heterozygous) and three healthy volunteers. For cognitive comparisons we used a linear mixed model (Kruskal-Wallis) test, followed by posthoc Dunn's pairwise tests with a Bonferroni adjustment. For fMRI analysis, we counted voxels exceeding the p < 0.05 corrected threshold. DTI analysis was observational.

Results

Family members with schizophrenia and unaffected family members homozygous for the risk haplotype showed attention (p < 0.01) and working memory deficits (p < 0.01) compared with healthy controls; a neural activation laterality bias towards the right prefrontal cortex (voxels reaching p < 0.05, corrected) and observed lower fractional anisotropy in the anterior cingulate cortex and left dorsolateral prefrontal cortex.

Conclusions

In this family, homozygosity at the 13q risk locus was associated with impaired cognition, white matter integrity, and altered laterality of neural activation.

SUBMITTER: Wilkinson ID

PROVIDER: S-EPMC10235651 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

In memory of Professor Iain Wilkinson: cognitive and neuroimaging endophenotypes in a consanguineous schizophrenia multiplex family.

Wilkinson Iain D ID Mahmood Tariq T Yasmin Sophia Faye SF Tomlinson Anneka A Nazari Jamshid J Alhaj Hamid H El Din Soumaya Nasser SN Neill Joanna J Pandit Chhaya C Ashraf Shahzad S Cardno Alastair G AG Clapcote Steven J SJ Inglehearn Chris F CF Woodruff Peter W PW

Psychological medicine 20220207 7

<h4>Background</h4>Schizophrenia endophenotypes may help elucidate functional effects of genetic risk variants in multiply affected consanguineous families that segregate recessive risk alleles of large effect size. We studied the association between a schizophrenia risk locus involving a 6.1Mb homozygous region on chromosome 13q22-31 in a consanguineous multiplex family and cognitive functioning, haemodynamic response and white matter integrity using neuroimaging.<h4>Methods</h4>We performed CA ...[more]

PMID: 35125130

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Project description:BackgroundThe cognitive deficits of schizophrenia are largely resistant to current treatments and thus are a lifelong illness burden. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition across major cognitive domains; however, the multimodal brain alterations specifically associated with MCCB in schizophrenia have not been examined.MethodsThe interrelationships between MCCB and the abnormalities seen in three types of neuroimaging-derived maps-fractional amplitude of low-frequency fluctuations (fALFF) from resting-state functional magnetic resonance imaging (MRI), gray matter (GM) density from structural MRI, and fractional anisotropy from diffusion MRI-were investigated by using multiset canonical correlation analysis in data from 47 schizophrenia patients treated with antipsychotic medications and 50 age-matched healthy control subjects.ResultsOne multimodal component (canonical variant 8) was identified as both group differentiating and significantly correlated with the MCCB composite. It demonstrated 1) increased cognitive performance associated with higher fALFF (intensity of regional spontaneous brain activity) and higher GM volumes in thalamus, striatum, hippocampus, and the mid-occipital region, with co-occurring fractional anisotropy changes in superior longitudinal fascicules, anterior thalamic radiation, and forceps major; 2) higher fALFF but lower GM volume in dorsolateral prefrontal cortex related to worse cognition in schizophrenia; and 3) distinct domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased fALFF in inferior parietal lobule particularly correlated with decreased social cognition. Medication dose did not relate to these findings in schizophrenia.ConclusionsOur results suggest linked functional and structural deficits in distributed cortico-striato-thalamic circuits may be closely related to MCCB-measured cognitive impairments in schizophrenia.

Dataset Information

In memory of Professor Iain Wilkinson: cognitive and neuroimaging endophenotypes in a consanguineous schizophrenia multiplex family.

Background

Methods

Results

Conclusions

Publications

In memory of Professor Iain Wilkinson: cognitive and neuroimaging endophenotypes in a consanguineous schizophrenia multiplex family.

Similar Datasets

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