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Investigating whole-brain MRI markers in neuropsychiatric disorders – separating disease duration from medication effects in schizophrenia and bipolar disorder

João V. Duarte1, 2, 3*, Nuno Madeira4, 5, Ricardo Martins1, 2, 3, Gabriel N. Costa1, 2, 3, António Macedo5, 6 and Miguel Castelo-Branco1, 2, 3
  • 1 Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Portugal
  • 2 Institute of Nuclear Sciences Applied to Health, University of Coimbra, Portugal
  • 3 CNC.IBILI Consortium, University of Coimbra, Portugal
  • 4 Hospital and University Center of Coimbra, Department of Psychiatry, Portugal
  • 5 Institute of Psychological Medicine, Faculty of Medicine, University of Coimbra, Portugal
  • 6 Department of Psychiatry, Hospital and University Center of Coimbra, Portugal

Background and Aims Numerous imaging studies show regional volume changes in patients with schizophrenia (SCZ) and bipolar disorder (BPD). However, the effects of disease duration and medication are difficult to separate [1]. We intend to investigate structural differences in patients with early SCZ and BPD in homogeneous samples matched for age and disease duration. Established markers like cortical thickness and grey matter volume are heavily influenced by post-onset changes, providing limited access to early pathologies. As schizophrenia is believed to be a neurodevelopmental disease with high heritability, another aim of the study is to compare different morphometric features in psychiatric disorders, including gyrification which is assumed to be more specifically determined by genetic and early developmental factors. Methods We compared MRI scans of 20 SCZ and 20 BPD patients with 20 age- and sex-matched controls. Clinical groups statistically differed in medication (chlorpromazine equivalent dose, p=0.032) but not in disease duration (SCZ 5.15±0.97 years; BPD 6.00±1.78 years), allowing to study their effects separately. We used CAT12/SPM12 to analyze whole brain GM/WM volume, cortical thickness and gyrification. We used age, gender and total intracranial volume (TIV) as covariates. Results We observed a main group effect on regional GM volume in the right globus pallidus (F=4.423, p<0.002), which was higher in SCZ compared to healthy controls (post-hoc analysis p<0.001, Bonferroni corrected). There was no significant correlation between the volume of globus pallidus and age, disease duration or medication in any of the study groups. There was no group effect on WM volume when correcting for multiple comparisons, although we observed differences near the superior frontal gyrus (BA9/10) and superior temporal gyrus (BA38), neither showing differences on cortical thickness. Interestingly, gyrification was altered between clinical groups in supramarginal gyrus (BA40) and inferior frontal gyrus (BA47), although at uncorrected p<0.001. Conclusions Volume of the globus pallidus is a significant marker of early SCZ but not BPD although there is no correlation with age, disease duration or medication. Different morphometric features might help to elucidate distinct phenotypes in psychiatric disorders. Morphological alterations with different etiologies can serve as neuroimaging-derived biomarkers that can discriminate schizophrenia from bipolar disease. Further investigation is warranted to relate these changes with clinical phenotype.

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Acknowledgements

This research work was funded by the Portuguese Foundation for Science and Technology (FCT) (grants: COMPETE UID/NEU/04539/2013, SAICTPAC/0010/2015, BIGDATIMAGE-CENTRO-01-0145-FEDER-000016, FCT/COMPETE 2020, QREN CENTRO-07-ST24-FEDER-00205).

References

[1] N. Hashimoto et al., “The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects,” NeuroImage Clin., vol. 17, no. August 2017, pp. 563–569, 2018.

Keywords: Schizophrenia, Bipolar Disorder, MRI, Neuroimaging, biomarkers

Conference: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.

Presentation Type: Poster presentation

Topic: Psychiatric Disorders / Addiction

Citation: Duarte JV, Madeira N, Martins R, Costa GN, Macedo A and Castelo-Branco M (2019). Investigating whole-brain MRI markers in neuropsychiatric disorders – separating disease duration from medication effects in schizophrenia and bipolar disorder. Front. Cell. Neurosci. Conference Abstract: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019). doi: 10.3389/conf.fncel.2019.01.00048

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Received: 28 Feb 2019; Published Online: 27 Sep 2019.

* Correspondence: PhD. João V Duarte, Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Coimbra, Portugal, joao.v.duarte@fmed.uc.pt