Article
Biochemistry & Molecular Biology
Catherine A. Brownstein, Richard S. Smith, Lance H. Rodan, Mark P. Gorman, Margaret A. Hojlo, Emily A. Garvey, Jianqiao Li, Kristin Cabral, Joshua J. Bowen, Abhijit S. Rao, Casie A. Genetti, Devon Carroll, Emma A. Deaso, Pankaj B. Agrawal, Jill A. Rosenfeld, Weimin Bi, Jennifer Howe, Dimitri J. Stavropoulos, Adam W. Hansen, Hesham M. Hamoda, Ferne Pinard, Annmarie Caracansi, Christopher A. Walsh, Eugene J. D'Angelo, Alan H. Beggs, Mehdi Zarrei, Richard A. Gibbs, Stephen W. Scherer, David C. Glahn, Joseph Gonzalez-Heydrich
Summary: Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants with large effects, offering opportunities for genetic discoveries and early therapeutic interventions. In this study, a stop-gain mutation in the RCL1 gene was identified in an 18-year-old boy with cognitive decline, leading to the discovery of RCL1 copy number variations in multiple patients with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1 contributes to a range of neurological and clinical phenotypes.
MOLECULAR PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Kathleen Rooney, Bekim Sadikovic
Summary: This review discusses the role of large structural chromosome rearrangements in genomic disorders related to neurodevelopmental disorders (NDDs). The review also highlights the significance of DNA methylation (DNAm) and its implications in NDDs and genomic disorders. Additionally, the potential clinical impact of copy number and genomic DNAm testing in the diagnosis of genetic NDDs is discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Clinical Neurology
Clara A. Moreau, Armin Raznahan, Pierre Bellec, Mallar Chakravarty, Paul M. Thompson, Sebastien Jacquemont
Summary: Top-down studies have identified patterns of neuroimaging alterations with extreme polygenic architecture, indicating shared genomic variants and neuroimaging patterns across diagnostic categories. In contrast, bottom-up studies have shown equally large effect sizes of high-risk neuropsychiatric mutations for neuroimaging and behavioral traits, highlighting the surprising discordant effect sizes and the necessity to decompose the heterogeneity hindering case-control studies in idiopathic conditions.
Article
Genetics & Heredity
Kohei Hamanaka, Noriko Miyake, Takeshi Mizuguchi, Satoko Miyatake, Yuri Uchiyama, Naomi Tsuchida, Futoshi Sekiguchi, Satomi Mitsuhashi, Yoshinori Tsurusaki, Mitsuko Nakashima, Hirotomo Saitsu, Kohei Yamada, Masamune Sakamoto, Hiromi Fukuda, Sachiko Ohori, Ken Saida, Toshiyuki Itai, Yoshiteru Azuma, Eriko Koshimizu, Atsushi Fujita, Biray Erturk, Yoko Hiraki, Gaik-Siew Ch'ng, Mitsuhiro Kato, Nobuhiko Okamoto, Atsushi Takata, Naomichi Matsumoto
Summary: The study integrated copy number variants and single-nucleotide variants data, identifying dozens of new candidate genes for NDDs, including 11 high-confidence candidate genes. This research will contribute to the further discovery of novel genes associated with NDDs.
Article
Genetics & Heredity
Brenda Finucane, Matthew T. Oetjens, Alicia Johns, Scott M. Myers, Ciaran Fisher, Lukas Habegger, Evan K. Maxwell, Jeffrey G. Reid, David H. Ledbetter, H. Lester Kirchner, Christa Lese Martin
Summary: The study suggests that adults with pCNVs have increased risk of chronic diseases and higher emergency department visit rates. Early genetic diagnosis and personalized interventions may help improve the health outcomes of adults and reduce healthcare resource consumption.
GENETICS IN MEDICINE
(2022)
Article
Genetics & Heredity
Ashley Kahen, Haluk Kavus, Alexa Geltzeiler, Catherine Kentros, Cora Taylor, Elizabeth Brooks, LeeAnne Green Snyder, Wendy Chung
Summary: Pathogenic variants in SLC6A1 are associated with a clinical phenotype of developmental delay, behavior problems, and seizures. Understanding the genotype-phenotype correlation within SLC6A1 may provide opportunities to develop new treatments for GABA-related conditions.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Cedrik Tekendo-Ngongang, Angela Grochowsky, Benjamin D. Solomon, Sho T. Yano
Summary: Various variants of the FMR1 gene have been shown to cause disease phenotypes, including splicing variants, missense variants, full deletions, nonsense variants, and frameshift variants. In addition, FMR1 deletions may not only occur in patients with mosaic full mutations, but also in patients with normal-sized CGG repeats, suggesting genomic instability in the CGG repeat region. Clinical tests for potential FMR1-related indications should include methods capable of detecting small coding, noncoding, and copy number variants.
Review
Neurosciences
Josan Gandawijaya, Rosemary A. Bamford, J. Peter H. Burbach, Asami Oguro-Ando
Summary: Autism spectrum disorder (ASD) is a disorder characterized by impaired social interaction, language delay, and repetitive/restrictive behaviors. While the etiology of ASD remains unclear, copy number variations (CNVs) in chromosome 3p have been implicated as a risk locus for ASD development. Specifically, CNVs affecting genes in the 3p26.3 region, which encode neuronal cell adhesion molecules, may play a role in the neurodevelopmental phenotypes observed in individuals with ASD and the rare genetic disorder 3p-deletion syndrome (Del3p).
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemical Research Methods
Fei Qin, Xizhi Luo, Guoshuai Cai, Feifei Xiao
Summary: This study explores the correlation structure of whole-exome sequencing (WES) data and introduces a novel correlation-based CNV detection method, CORRseq, which outperforms existing methods in detecting medium and large CNVs. Modeling genomic correlation structure is advantageous for detecting relatively long CNVs.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Oncology
Cody Ashby, Eileen M. Boyle, Michael A. Bauer, Aneta Mikulasova, Christopher P. Wardell, Louis Williams, Ariel Siegel, Patrick Blaney, Marc Braunstein, David Kaminetsky, Jonathan Keats, Francesco Maura, Ola Landgren, Brian A. Walker, Faith E. Davies, Gareth J. Morgan
Summary: Deciphering genomic architecture helps identify disease drivers and understand myeloma initiation and progression mechanisms. This study demonstrates that structural variants occur nonrandomly in the genome, and their frequencies vary in different genetic contexts. The study also reveals the heterogeneity of transcriptional dysregulation caused by both canonical and novel structural variants, as well as the impact of complex rearrangements on clinical outcomes. Chromothripsis, in particular, has a significant negative effect on clinical outcome.
BLOOD CANCER JOURNAL
(2022)
Article
Endocrinology & Metabolism
Yang Chen, Wei-jia Wu, Li-wei Xing, Xiao-juan Zhang, Jing Wang, Xiao-yan Xia, Rui Zhao, Rong Zhao
Summary: This study examined the correlations between mtDNA D-loop, its haplotypes, and PCOS in the Chinese population, and found that certain mtDNA D-loop mutations and haplotypes may confer protection against PCOS in Chinese women. In addition, elevated mtDNA copy number may serve as an indicator during early stages of PCOS.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biology
Markus Terrey, Scott Adamson, Jeffrey H. Chuang, Susan L. Ackerman
Summary: Translation-dependent quality control pathways, such as NGD, NSD, and NMD, play critical roles in protein synthesis and proteostasis by resolving non-translating ribosomes and preventing the production of potentially toxic peptides. Studies showed that NGD/NSD factors are crucial for cerebellar neurogenesis in mice but not essential for neuron survival post-development. Deletion of the NMD factor Upf2 led to similar effects on signaling pathways, mTOR activation, the translatome, and mouse cerebellar development, suggesting that different quality control pathways in translation can evoke similar cellular responses.
Review
Biochemical Research Methods
Mian Umair Ahsan, Qian Liu, Jonathan Elliot Perdomo, Li Fang, Kai Wang
Summary: As long-read sequencing technologies become more popular, various methods have been developed for detecting and analyzing structural variants (SVs) from long reads. These methods are needed to adapt to the unique challenges and opportunities presented by long-read sequencing. This review summarizes more than 50 long-read-based methods for SV detection, genotyping, and visualization, and discusses how new telomere-to-telomere genome assemblies and pangenome efforts can enhance accuracy and drive the development of SV callers in the future.
Article
Genetics & Heredity
Saloni Sharma, Brenna Hourigan, Zain Patel, Jill A. Rosenfeld, Katie M. Chan, Michael F. Wangler, Joanna S. Yi, Anna Lehman, Causes Study, Gabriella Horvath, Paul A. Cloos, Qiumin Tan
Summary: This study describes three novel and one previously reported CIC variants in individuals with neurodevelopmental delay. The results suggest that partial loss of CIC-L leads to transcriptional derepression of CIC target genes, and a missense variant may result in partial loss of CIC transcriptional repressor activity.
Article
Genetics & Heredity
Tina O. Findley, Alyssa K. Crain, Smridhi Mahajan, Ahmed Deniwar, Jessica Davis, Ana S. Solis Zavala, Antonio F. Corno, David Rodriguez-Buritica
Summary: Genetic etiology can be identified in 20%-30% of CHD patients, with CMA detecting pathogenic CNV. Among neonates with CHD, CMA had a diagnostic yield of 4%-28%. Pathogenic CNVs associated with NDI were found in 21.3% of neonates with CHD, with atrioventricular septal defects and conotruncal defects showing the highest diagnostic yield by CMA. Neonates with pathogenic CNV were more likely to have NDI, be smaller in length at birth, and require enteral feeding tubes upon discharge.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Psychology, Clinical
Rachael L. Adams, Alister Baird, Jacqueline Smith, Nigel Williams, Marianne B. M. van den Bree, David E. J. Linden, Michael J. Owen, Jeremy Hall, Stefanie C. Linden
Summary: Adult CNV carriers have a significantly increased rate of anxiety and personality disorders. In addition, they have a high rate of psychiatric multimorbidity. These findings support comprehensive psychiatric and medical assessments for CNV carriers and the establishment of multidisciplinary clinical services.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Neurosciences
Clara A. Moreau, Annabelle Harvey, Kuldeep Kumar, Guillaume Huguet, Sebastian G. W. Urchs, Elise A. Douard, Laura M. Schultz, Hanad Sharmarke, Khadije Jizi, Charles-Olivier Martin, Nadine Younis, Petra Tamer, Thomas Rolland, Jean-Louis Martineau, Pierre Orban, Ana Isabel Silva, Jeremy Hall, Marianne B. M. van den Bree, Michael J. Owen, David E. J. Linden, Aurelie Labbe, Sarah Lippe, Carrie E. Bearden, Laura Almasy, David C. Glahn, Paul M. Thompson, Thomas Bourgeron, Pierre Bellec, Sebastien Jacquemont
Summary: Polygenicity and genetic heterogeneity pose challenges in studying psychiatric disorders. This study estimated and compared the effect sizes on brain connectivity of different genetic risk factors and found that psychiatric CNVs had the largest effect sizes, followed by psychiatric conditions, neuroticism and fluid intelligence, and PRSs. The effect sizes of CNVs on connectivity were correlated with their effects on cognition and disease risk.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Clinical Neurology
Clara A. Moreau, Kuldeep Kumar, Annabelle Harvey, Guillaume Huguet, Sebastian G. W. Urchs, Laura M. Schultz, Hanad Sharmarke, Khadije Jizi, Charles-Olivier Martin, Nadine Younis, Petra Tamer, Jean-Louis Martineau, Pierre Orban, Ana Isabel Silva, Jeremy Hall, Marianne B. M. van den Bree, Michael J. Owen, David E. J. Linden, Sarah Lippe, Carrie E. Bearden, Laura Almasy, David C. Glahn, Paul M. Thompson, Thomas Bourgeron, Pierre Bellec, Sebastien Jacquemont
Summary: This study uses large-scale resting-state functional MRI data to investigate the influence of genetic variants on large-scale brain networks and their correlations with psychiatric disorders and cognitive traits. The findings suggest a substantial genetic component for shared connectivity profiles across conditions and traits, providing new avenues for understanding and treating psychiatric disorders.
Article
Neurosciences
Chaira Serrarens, Sriranga Kashyap, Laura Riveiro-Lago, Maarten Otter, Bea C. M. Campforts, Constance T. R. M. Stumpel, Henk Jansma, David E. J. Linden, Therese A. M. J. van Amelsvoort, Claudia Vingerhoets
Summary: This study investigated the effects of triple X syndrome (47,XXX) on functional connectivity in the brain. The results showed abnormal increase in resting-state functional connectivity in patients. However, these changes were not associated with intelligence quotient (IQ) or social cognition function.
Article
Neurosciences
Xi Yang, Xinqi Zhou, Fei Xin, Benjamin Becker, David Linden, Dennis Hernaus
Summary: Age-related changes in brain function have an important role in neurodegenerative diseases. Previous studies have mainly focused on static functional connectivity, but emerging evidence suggests that aging is associated with dynamic changes in brain interactions and transitions. This study replicates the finding of age-associated changes in dynamic functional connectivity using fMRI data from two cultures (Western European and Chinese). Older participants consistently exhibit a lower occurrence and duration of a specific connectivity state (state I) compared to younger participants, as well as more transitions between networks and greater variance in global efficiency.
Article
Clinical Neurology
Ruben L. Andriessen, Mayke Oosterloo, Angelique Hollands, David E. J. Linden, Bianca T. A. de Greef, Albert F. G. Leentjens
Summary: The study found that psychotropic medication is widely prescribed in HD patients, with antidepressant use decreasing proportionally and antipsychotic use increasing with advancing disease stages. This suggests a relative decrease in prevalence of anxiety and depression, and a relative increase in irritability and delusions over disease stages.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Neurosciences
Duncan James McLauchlan, David E. J. Linden, Anne E. Rosser
Summary: In Huntington's disease, irritability is mainly mediated by excessive response to provocation rather than a failure of motor inhibition, while impulsive behavior is associated with irritability.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Psychology, Biological
Jakub Kopal, Kuldeep Kumar, Karin Saltoun, Claudia Modenato, Clara A. Moreau, Sandra Martin-Brevet, Guillaume Huguet, Martineau Jean-Louis, Charles-Olivier Martin, Zohra Saci, Nadine Younis, Petra Tamer, Elise Douard, Anne M. Maillard, Borja Rodriguez-Herreros, Aurelie Pain, Sonia Richetin, Leila Kushan, Ana I. Silva, Marianne B. M. van den Bree, David E. J. Linden, Michael J. Owen, Jeremy Hall, Sarah Lippe, Bogdan Draganski, Ida E. Sonderby, Ole A. Andreassen, David C. Glahn, Paul M. Thompson, Carrie E. Bearden, Sebastien Jacquemont, Danilo Bzdok
Summary: The researchers built computational bridges between rare CNVs in a clinical dataset and their deep phenotypic profiling in a large population. The results showed that CNVs are associated with various organ systems across the body, with implications for major brain disorders.
NATURE HUMAN BEHAVIOUR
(2023)
Article
Neurosciences
Joanne L. Doherty, Adam C. Cunningham, Samuel J. R. A. Chawner, Hayley M. Moss, Diana C. Dima, David E. J. Linden, Michael J. Owen, Marianne B. M. van den Bree, Krish D. Singh
Summary: The study utilized magnetoencephalography to investigate the electrophysiological markers of brain activity in individuals with 22q11.2 deletion syndrome. The findings revealed alterations in local and global network function, which may contribute to the increased vulnerability to neurodevelopmental and psychiatric disorders in this population.
NEUROPSYCHOPHARMACOLOGY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Yanq Xiao, Tijs Louwies, Kristen Smith-Edwards, Arthur Beyder, David Linden, Gianrico Farrugia, Purna Kashyap
Article
Clinical Neurology
Duncan James McLauchlan, Thomas Lancaster, David Craufurd, David E. J. Linden, Anne E. Rosser
Summary: Depression is more common in neurodegenerative diseases like Huntington's disease, and the choice of antidepressant treatment for Huntington's disease lacks sufficient evidence. This study used propensity score analyses and cognitive battery assessments to determine the best treatment choices for depression in Huntington's disease and identified the main mechanisms underlying depression.
BRAIN COMMUNICATIONS
(2022)
Article
Geochemistry & Geophysics
Han V. Nguyen, Magnus O. Ulfarsson, Johannes R. Sveinsson, Mauro Dalla Mura
Summary: Image fusion is widely used in various applications. This article proposes a fusion framework using an unsupervised convolutional neural network and Stein's unbiased risk estimate, which achieves high-quality fused images.
IEEE TRANSACTIONS ON GEOSCIENCE AND REMOTE SENSING
(2022)
Article
Engineering, Electrical & Electronic
Bin Zhao, Haukur Isfeld Ragnarsson, Magnus O. Ulfarsson, Gabriele Cavallaro, Jon Atli Benediktsson
Summary: This article proposes an approach to classify hyperspectral images using only metadata and demonstrates that it outperforms other methods in quantitative assessments.
IEEE JOURNAL OF SELECTED TOPICS IN APPLIED EARTH OBSERVATIONS AND REMOTE SENSING
(2022)
Review
Neurosciences
Maya Jammoul, Dareen Jammoul, Kevin K. Wang, Firas Kobeissy, Ralph G. Depalma
Summary: This article reviews the possible mechanisms by which traumatic brain injury (TBI) may stimulate the development of opioid use disorder (OUD) and discusses the interaction between these two processes. CNS damage due to TBI appears to drive adverse effects of subsequent OUD, with pain being a risk factor for opioid use after TBI.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Danusa Mar Arcego, Jan-Paul Buschdorf, Nicholas O'Toole, Zihan Wang, Barbara Barth, Irina Pokhvisneva, Nirmala Arul Rayan, Sachin Patel, Euclides Jose de Mendonca Filho, Patrick Lee, Jennifer Tan, Ming Xuan Koh, Chu Ming Sim, Carine Parent, Randriely Merscher Sobreira de Lima, Andrew Clappison, Kieran J. O'Donnell, Carla Dalmaz, Janine Arloth, Nadine Provencal, Elisabeth B. Binder, Josie Diorio, Patricia Pelufo Silveira, Michael J. Meaney
Summary: This study investigates the impact of environmental influences on mental health by integrating transcriptomic data from animal models with human data. The results suggest that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Milenna T. van Dijk, Ardesheer Talati, Pratik Kashyap, Karan Desai, Nora C. Kelsall, Marc J. Gameroff, Natalie Aw, Eyal Abraham, Breda Cullen, Jiook Cha, Christoph Anacker, Myrna M. Weissman, Jonathan Posner
Summary: This study found that maternal stress is associated with future depressive symptoms and alterations in microstructure of the dentate gyrus (DG) in offspring. These results were consistent across two independent cohorts.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Josephine C. McGowan, Liliana R. Ladner, Claire X. Shubeck, Juliana Tapia, Christina T. LaGamma, Amanda Anqueira-Gonzalez, Ariana DeFrancesco, Briana K. Chen, Holly C. Hunsberger, Ezra J. Sydnor, Ryan W. Logan, Tzong-Shiue Yu, Steven G. Kernie, Christine A. Denny
Summary: Traumatic brain injury (TBI) leads to fear generalization by altering fear memory traces, and this symptom can be improved with (R,S)-ketamine.
BIOLOGICAL PSYCHIATRY
(2024)