INTERACTIVE EFFECTS OF FAMILY HISTORY, POLYGENIC RISK AND AGE ON CORTICAL THICKNESS IN YOUNG PEOPLE AT HIGH GENETIC RISK OF BIPOLAR DISORDER

2019 ◽  
Vol 29 ◽  
pp. S924
Author(s):  
Rhoshel K. Lenroot ◽  
Bronwyn Overs ◽  
Gloria Roberts ◽  
Andrew Frankland ◽  
Florence Levy ◽  
...  
2021 ◽  
pp. 1-12
Author(s):  
Simon Schmitt ◽  
Tina Meller ◽  
Frederike Stein ◽  
Katharina Brosch ◽  
Kai Ringwald ◽  
...  

Abstract Background MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood. Methods We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness. Results The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing. Conclusions Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.


2019 ◽  
Vol 29 ◽  
pp. S129
Author(s):  
Philip Mitchell ◽  
Gloria Roberts ◽  
Rhoshel K. Lenroot ◽  
Bronwyn Overs ◽  
Janice Fullerton ◽  
...  

2017 ◽  
Vol 81 (10) ◽  
pp. S318-S319 ◽  
Author(s):  
Philip Mitchell ◽  
Michael Breakspear ◽  
Gloria Roberts ◽  
Alistair Perry ◽  
Andrew Frankland ◽  
...  

2016 ◽  
Vol 23 (2) ◽  
pp. 413-421 ◽  
Author(s):  
G Roberts ◽  
A Perry ◽  
A Lord ◽  
A Frankland ◽  
V Leung ◽  
...  

2018 ◽  
Vol 19 ◽  
pp. 71-81 ◽  
Author(s):  
Jayson Jeganathan ◽  
Alistair Perry ◽  
Danielle S. Bassett ◽  
Gloria Roberts ◽  
Philip B. Mitchell ◽  
...  

2019 ◽  
Vol 245 ◽  
pp. 228-236 ◽  
Author(s):  
Riya Wadhwa ◽  
Wei Wen ◽  
Andrew Frankland ◽  
Vivian Leung ◽  
Carina Sinbandhit ◽  
...  

2019 ◽  
Vol 50 (10) ◽  
pp. 1653-1662 ◽  
Author(s):  
Mathew A. Harris ◽  
Xueyi Shen ◽  
Simon R. Cox ◽  
Jude Gibson ◽  
Mark J. Adams ◽  
...  

AbstractBackgroundSubstantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.MethodsThe present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.ResultsThere was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.ConclusionsOur significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.


2016 ◽  
Vol 46 (11) ◽  
pp. 2385-2396 ◽  
Author(s):  
G. Roberts ◽  
W. Wen ◽  
A. Frankland ◽  
T. Perich ◽  
E. Holmes-Preston ◽  
...  

BackgroundWhite matter (WM) impairments have been reported in patients with bipolar disorder (BD) and those at high familial risk of developing BD. However, the distribution of these impairments has not been well characterized. Few studies have examined WM integrity in young people early in the course of illness and in individuals at familial risk who have not yet passed the peak age of onset.MethodWM integrity was examined in 63 BD subjects, 150 high-risk (HR) individuals and 111 participants with no family history of mental illness (CON). All subjects were aged 12 to 30 years.ResultsThis young BD group had significantly lower fractional anisotropy within the genu of the corpus callosum (CC) compared with the CON and HR groups. Moreover, the abnormality in the genu of the CC was also present in HR participants with recurrent major depressive disorder (MDD) (n = 16) compared with CON participants.ConclusionsOur findings provide important validation of interhemispheric abnormalities in BD patients. The novel finding in HR subjects with recurrent MDD – a group at particular risk of future hypo/manic episodes – suggests that this may potentially represent a trait marker for BD, though this will need to be confirmed in longitudinal follow-up studies.


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