Poster No:
459
Submission Type:
Abstract Submission
Authors:
Cecilie Lemvigh1,2, Rachel Brouwer3, Jayachandra Raghava4, Tina Kristensen5, Birte Glenthøj5, Bjørn Ebdrup5
Institutions:
1Centre for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital, Glostrup, Capital Region of Denmark, 2Mental Health Centre Glostrup, Glostrup, Capital Region, Denmark, 3Vrije Universiteit Amsterdam, Faculty of Science, Complex Trait Genetics, Amsterdam, Amsterdam Metropolitan Area, 4Center for Neuropsychiatric Schizophrenia Research, Glostrup, Capital Region of Denmark, 5Centre for Neuropsychiatric Schizophrenia Research, CNSR, Glostrup, Capital Region of Denmark
First Author:
Cecilie Lemvigh, PhD
Centre for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital|Mental Health Centre Glostrup
Glostrup, Capital Region of Denmark|Glostrup, Capital Region, Denmark
Co-Author(s):
Rachel Brouwer
Vrije Universiteit Amsterdam, Faculty of Science, Complex Trait Genetics
Amsterdam, Amsterdam Metropolitan Area
Jayachandra Raghava
Center for Neuropsychiatric Schizophrenia Research
Glostrup, Capital Region of Denmark
Tina Kristensen, PhD
Centre for Neuropsychiatric Schizophrenia Research, CNSR
Glostrup, Capital Region of Denmark
Bjørn Ebdrup, Professor
Centre for Neuropsychiatric Schizophrenia Research, CNSR
Glostrup, Capital Region of Denmark
Introduction:
Schizophrenia is a heritable illness (Hilker et al., 2018) associated with altered white matter microstructure (Cetin-Karayumak et al., 2020). There is also evidence that white matter microstructure itself is heritable (Kochunov et al., 2015), and a previous study has indicated a shared genetic basis with schizophrenia (Bohlken et al., 2016). In addition, the experience of trauma during childhood is a well-established risk factor for schizophrenia that has also been linked to white matter alterations (Asmal et al., 2019). We aim to delineate the genetic relationships between schizophrenia liability, white matter microstructure and childhood trauma to increase our understanding of these etiologically different pathological processes.
Methods:
Participants were recruited from 2011-2017 in Denmark by linking two nationwide registers; The Danish Twin Registry and The Danish Psychiatric Registry. Monozygotic (MZ) and dizygotic (DZ) proband pairs (concordant or discordant for schizophrenia spectrum disorders) and healthy controls twin pairs (HCs) matched on sex and age were included.
Diffusion weighted magnetic resonance imaging scans were conducted on a single Philips 3T Achieva whole-body scanner with a 32-channel SENSE head coil. A diffusion tensor model was applied to derive measures of fractional anisotropy (FA). For these analyses we included 7 FA measures combining the left and right hemisphere: Global FA, superior longitudinal fasciculus (SLF), superior fronto-occipital fasciculus (SFOF), inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), cingulate gyrus (CG) and corpus callosum. FA values were normalized by ROI size. Childhood trauma was examined using the Childhood Trauma Questionnaire (CTQ) assessing physical, emotional, and sexual abuse, and physical and emotional neglect.
Group differences were examined using ANOVA/t-tests for FA and the Kruskal-Wallis/Mann-Whitney U test for CTQ. Differences between patients and their unaffected co-twins were examined using paired t-tests. Associations between FA and CTQ were explored using Spearman's correlations.
Results:
216 twins participated (age 41.7 ±10.3, 49% females), covering 32 complete MZ and 24 complete DZ proband pairs, 29 complete MZ 20 complete DZ HC pairs. Further, six individuals from proband pairs participated without their twin. Of the total sample, 177 participants completed the MRI scan (43 patients, 43 unaffected co-twins, 91 HCs).
We observed a significant effect of group on IFOF (p=.02), with both patients (p=.007) and unaffected co-twins (p=.018) showing lower levels compared to HCs. Interestingly, in discordant DZ proband pairs, patients had lower levels of global FA (p=.038), SLF (p=.019) and SFOF (p=.03) compared to their unaffected co-twins, while there were no significant differences within MZ proband pairs.
For trauma we observed significant group effects in CTQ total and all five subdomains (all p's<.001), with both patients (all p's<.001) and unaffected co-twins (all p's<.04) reporting higher levels compared to HCs.
In the whole group, CTQ total was not associated with the included FA measures. When splitting the sample according to diagnosis, we observed a significant negative correlation between CTQ total and FA in SLF (p=.043) in HCs. In unaffected co-twins we saw a positive correlation between CTQ total and FA in CG (p=.047) and UF (p=.010). In patients there were no significant associations between CTQ and FA.
Conclusions:
Preliminary results suggest that patients with schizophrenia have lower FA in the IFOF compared to HCs. In DZ proband pairs, patients also had lower levels of FA in several tracts compared to their unaffected co-twins. In addition, patients with schizophrenia and their unaffected co-twins reported higher levels of childhood trauma compared to matched HCs. Finally, the preliminary results suggest a different relationship between white matter microstructure and childhood trauma in patients compared to their unaffected co-twins and HCs.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Genetics:
Genetics Other
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 2
Keywords:
Psychiatric
Psychiatric Disorders
Schizophrenia
Trauma
White Matter
Other - Twin
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Other
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
Diffusion MRI
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
FSL
Provide references using APA citation style.
1. Asmal, L. et al. (2019). Childhood Trauma Associated White Matter Abnormalities in First-Episode Schizophrenia. Schizophrenia Bulletin, 45(2), 369–376. https://doi.org/10.1093/schbul/sby062
2. Bohlken, M. et al. (2016). Structural Brain Connectivity as a Genetic Marker for Schizophrenia. JAMA Psychiatry, 73(1), 11–19. https://doi.org/10.1001/jamapsychiatry.2015.1925
3. Cetin-Karayumak, S. et al. (2020). White matter abnormalities across the lifespan of schizophrenia: a harmonized multi-site diffusion MRI study. Molecular Psychiatry, 25(12), 3208–3219. https://doi.org/10.1038/s41380-019-0509-y
4. Hilker, R. et al. (2018). Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register. Biological Psychiatry, 83(6), 492–498. https://doi.org/10.1016/j.biopsych.2017.08.017
5. Kochunov, P. et al. (2015). Heritability of fractional anisotropy in human white matter: A comparison of Human Connectome Project and ENIGMA-DTI data. NeuroImage, 111, 300–311. https://doi.org/10.1016/j.neuroimage.2015.02.050
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