Polygenic risk for depression and the neural correlates of working memory in healthy subjects

AbstractThe Corsi Block-Tapping test (CBT) is a measure of spatial working memory (WM) in clinical practice, requiring an examinee to reproduce sequences of cubes tapped by an examiner. CBT implies complementary behaviors in the examiners and the examinees, as they have to attend a precise turn taking. Previous studies demonstrated that the Prefrontal Cortex (PFC) is activated during CBT, but scarce evidence is available on the neural correlates of CBT in the real setting. We assessed PFC activity in dyads of examiner–examinee participants while completing the real version of CBT, during conditions of increasing and exceeding workload. This procedure allowed to investigate whether brain activity in the dyads is coordinated. Results in the examinees showed that PFC activity was higher when the workload approached or reached participants’ spatial WM span, and lower during workload conditions that were largely below or above their span. Interestingly, findings in the examiners paralleled the ones in the examinees, as examiners’ brain activity increased and decreased in a similar way as the examinees’ one. In the examiners, higher left-hemisphere activity was observed suggesting the likely activation of non-spatial WM processes. Data support a bell-shaped relationship between cognitive load and brain activity, and provide original insights on the cognitive processes activated in the examiner during CBT.

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Effects of polygenic risk for major mental disorders and cross-disorder on cortical complexity

Psychological Medicine ◽

10.1017/s0033291721001082 ◽

2021 ◽

pp. 1-12

Author(s):

Simon Schmitt ◽

Tina Meller ◽

Frederike Stein ◽

Katharina Brosch ◽

Kai Ringwald ◽

...

Keyword(s):

Bipolar Disorder ◽

Mental Disorders ◽

Cortical Thickness ◽

Genetic Risk ◽

Right Hemisphere ◽

Autism Spectrum ◽

Risk Scores ◽

Grey Matter Volume ◽

Polygenic Risk ◽

Risk For Depression

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.

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Discovery of breast cancer risk genes and establishment of a prediction model based on estrogen metabolism regulation

BMC Cancer ◽

10.1186/s12885-021-07896-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Feng Zhao ◽

Zhixiang Hao ◽

Yanan Zhong ◽

Yinxue Xu ◽

Meng Guo ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Healthy Subjects ◽

Metabolic Enzyme ◽

Estrogen Metabolism ◽

Polygenic Risk Score ◽

Risk Genes ◽

Polygenic Risk ◽

Enzyme Gene

Abstract Background Multiple common variants identified by genome-wide association studies have shown limited evidence of the risk of breast cancer in Chinese individuals. In this study, we aimed to uncover the relationship between estrogen levels and the genetic polymorphism of estrogen metabolism-related enzymes in breast cancer (BC) and establish a risk prediction model composed of estrogen-metabolizing enzyme genes and GWAS-identified breast cancer-related genes based on a polygenic risk score. Methods Unrelated BC patients and healthy subjects were recruited for analysis of estrogen levels and single nucleotide polymorphisms (SNPs) in genes encoding estrogen metabolism-related enzymes. The polygenic risk score (PRS) was used to explore the combined effect of multiple genes, which was calculated using a Bayesian approach. An independent sample t-test was used to evaluate the differences between PRS scores of BC and healthy subjects. The discriminatory accuracy of the models was compared using the area under the receiver operating characteristic (ROC) curve. Results The estrogen homeostasis profile was disturbed in BC patients, with parent estrogens (E1, E2) and carcinogenic catechol estrogens (2/4-OHE1, 2-OHE2, 4-OHE2) significantly accumulating in the serum of BC patients. We then established a PRS model to evaluate the role of SNPs in multiple genes. PRS model 1 (M1) was established from SNPs in 6 GWAS-identified high risk genes. On the basis of M1, we added SNPs from 7 estrogen metabolism enzyme genes to establish PRS model 2 (M2). The independent sample t-test results showed that there was no difference between BC and healthy subjects in M1 (P = 0.17); however, there was a significant difference between BC and healthy subjects in M2 (P = 4.9*10− 5). The ROC curve results showed that the accuracy of M2 (AUC = 62.18%) in breast cancer risk identification was better than that of M1 (AUC = 54.56%). Conclusion Estrogen and related metabolic enzyme gene polymorphisms are closely related to BC. The model constructed by adding estrogen metabolic enzyme gene SNPs has a good predictive ability for breast cancer risk, and the accuracy is greatly improved compared with that of the PRS model that only includes GWAS-identified gene SNPs.

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Neural correlates of working memory deficits and associations to response inhibition in obsessive compulsive disorder

NeuroImage Clinical ◽

10.1016/j.nicl.2017.10.039 ◽

2018 ◽

Vol 17 ◽

pp. 426-434 ◽

Cited By ~ 8

Author(s):

Stephan Heinzel ◽

Christian Kaufmann ◽

Rosa Grützmann ◽

Robert Hummel ◽

Julia Klawohn ◽

...

Keyword(s):

Working Memory ◽

Obsessive Compulsive Disorder ◽

Response Inhibition ◽

Memory Deficits ◽

Neural Correlates ◽

Obsessive Compulsive ◽

Compulsive Disorder

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Neural Correlates of Impaired Cognitive Control over Working Memory in Schizophrenia

Biological Psychiatry ◽

10.1016/j.biopsych.2013.09.032 ◽

2014 ◽

Vol 76 (2) ◽

pp. 146-153 ◽

Cited By ~ 23

Author(s):

Teal S. Eich ◽

Derek Evan Nee ◽

Catherine Insel ◽

Chara Malapani ◽

Edward E. Smith

Keyword(s):

Working Memory ◽

Cognitive Control ◽

Neural Correlates

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Neural Correlates of Visuospatial Working Memory in Healthy Young Adults at Risk for Hypertension

Brain Imaging and Behavior ◽

10.1007/s11682-008-9025-4 ◽

2008 ◽

Vol 2 (3) ◽

pp. 192-199 ◽

Cited By ~ 23

Author(s):

Andreana P. Haley ◽

John Gunstad ◽

Ronald A. Cohen ◽

Beth A. Jerskey ◽

Richard C. Mulligan ◽

...

Keyword(s):

At Risk ◽

Working Memory ◽

Young Adults ◽

Neural Correlates ◽

Visuospatial Working Memory

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Neural correlates of visuospatial working memory in attention-deficit/hyperactivity disorder and healthy controls

Psychiatry Research Neuroimaging ◽

10.1016/j.pscychresns.2015.07.003 ◽

2015 ◽

Vol 233 (2) ◽

pp. 233-242 ◽

Cited By ~ 20

Author(s):

Hanneke van Ewijk ◽

Wouter D. Weeda ◽

Dirk J. Heslenfeld ◽

Marjolein Luman ◽

Catharina A. Hartman ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Working Memory ◽

Attention Deficit ◽

Neural Correlates ◽

Healthy Controls ◽

Visuospatial Working Memory ◽

Hyperactivity Disorder

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Neural correlates of deficits in subcomponents of working memory in schizophrenia: An fMRI study

Neuroscience Research ◽

10.1016/j.neures.2011.07.1729 ◽

2011 ◽

Vol 71 ◽

pp. e394

Author(s):

Tatsunobu Natsubori ◽

Hidenori Yamasue ◽

Noriaki Yahata ◽

Norichika Iwashiro ◽

Yosuke Takano ◽

...

Keyword(s):

Working Memory ◽

Neural Correlates ◽

Fmri Study

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The Neural Correlates of Spatial and Object Working Memory in Elderly and Parkinson’s Disease Subjects

Behavioural Neurology ◽

10.1155/2015/123636 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Silvia P. Caminiti ◽

Chiara Siri ◽

Lucia Guidi ◽

Angelo Antonini ◽

Daniela Perani

Keyword(s):

Parkinson’S Disease ◽

Working Memory ◽

Parkinson's Disease ◽

Neural Correlates ◽

Elderly Subjects ◽

Task Execution ◽

Compensatory Mechanisms ◽

Frontoparietal Network ◽

Fmri Study ◽

Comparable Performance

This fMRI study deals with the neural correlates of spatial and objects working memory (SWM and OWM) in elderly subjects (ESs) and idiopathic Parkinson’s disease (IPD). Normal aging and IPD can be associated with a WM decline. In IPD population, some studies reported similar SWM and OWM deficits; others reported a greater SWM than OWM impairment. In the present fMRI research, we investigated whether compensated IPD patients and elderly subjects with comparable performance during the execution of SWM and OWM tasks would present differences in WM-related brain activations. We found that the two groups recruited a prevalent left frontoparietal network when performing the SWM task and a bilateral network during OWM task execution. More specifically, the ESs showed bilateral frontal and subcortical activations in SWM, at difference with the IPD patients who showed a strict left lateralized network, consistent with frontostriatal degeneration in IPD. The overall brain activation in the IPD group was more extended as number of voxels with respect to ESs, suggesting underlying compensatory mechanisms. In conclusion, notwithstanding comparable WM performance, the two groups showed consistencies and differences in the WM activated networks. The latter underline the compensatory processes of normal typical and pathological aging.

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