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25 High-resolution MRI Reveals Selective Patterns of Hippocampal Subfield Atrophy in Focal Epilepsy
- Adam Schadler, Erik Kaestner, Alena Stasenko, Christine N. Smith, Catherine Tallman, Nigel P. Pedersen, Shahin Hakimian, Michelle S. Kim, Daniel J Peterson, Thomas J. Grabowski, Daniel L. Drane, Carrie R. McDonald
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 25-26
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Objective:
Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.
Participants and Methods:High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.
Results:Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, p<.005). Contralateral hippocampus did not significantly differ between TLE and HC. Examining individual subfields for the ipsilateral hemisphere revealed significant main-effects for group (F(1, 29)=8.2, p<0.01), subfields (F(4, 115)=550.5, p<0.005), and their interaction (F(4, 115)=8.1, p<0.001). Post-hoc tests revealed that TLE had significantly smaller volume in the ipsilateral CA1 (d=-2.0, p<0.001) and DG (d = -1.4, p<0.005). Longer duration of illness was associated with smaller volume of ipsilateral CA2 (p=-0.492, p<0.05) and larger volume of contralateral whole-hippocampus (p=0.689, p<0.001), CA1 (p=0.614, p < 0.005), and DG (p=0.450, p<0.05).
Conclusions:Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.
Relating Response Inhibition, Brain Connectivity, and Freezing of Gait in People with Parkinson’s Disease
- Daniel S. Peterson, Katrijn Smulders, Martina Mancini, John G. Nutt, Fay B. Horak, Brett W. Fling
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- Journal:
- Journal of the International Neuropsychological Society / Volume 27 / Issue 7 / August 2021
- Published online by Cambridge University Press:
- 09 December 2020, pp. 733-743
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Objective:
Freezing of gait (FoG) in Parkinson’s disease (PD) has been associated with response inhibition. However, the relationship between response inhibition, neural dysfunction, and PD remains unclear. We assessed response inhibition and microstructural integrity of brain regions involved in response inhibition [right hemisphere inferior frontal cortex (IFC), bilateral pre-supplementary motor areas (preSMA), and subthalamic nuclei (STN)] in PD subjects with and without FoG and elderly controls.
Method:Twenty-one people with PD and FoG (PD-FoG), 18 without FoG (PD-noFoG), and 19 age-matched controls (HC) completed a Stop-Signal Task (SST) and MRI scan. Probabilistic fiber tractography assessed structural integrity (fractional anisotropy, FA) among IFC, preSMA, and STN regions.
Results:Stop-signal performance did not differ between PD and HC, nor between PD-FoG and PD-noFoG. Differences in white matter integrity were observed across groups (.001 < p < .064), but were restricted to PD versus HC groups; no differences in FA were observed between PD-FoG and PD-noFoG (p > .096). Interestingly, worse FoG was associated with higher (better) mean FA in the r-preSMA, (β = .547, p = .015). Microstructural integrity of the r-IFC, r-preSMA, and r-STN tracts correlated with stop-signal performance in HC (p ≤ .019), but not people with PD.
Conclusion:These results do not support inefficient response inhibition in PD-FoG. Those with PD exhibited white matter loss in the response inhibition network, but this was not associated with FoG, nor with response inhibition deficits, suggesting FoG-specific neural changes may occur outside the response inhibition network. As shown previously, white matter loss was associated with response inhibition in elderly controls, suggesting PD may disturb this relationship.
Pathway-based polygene risk for severe depression implicates drug metabolism in CONVERGE
- Anna R. Docherty, Arden Moscati, Tim B. Bigdeli, Alexis C. Edwards, Roseann E. Peterson, Daniel E. Adkins, John S. Anderson, Jonathan Flint, Kenneth S. Kendler, Silviu-Alin Bacanu
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- Journal:
- Psychological Medicine / Volume 50 / Issue 5 / April 2020
- Published online by Cambridge University Press:
- 02 April 2019, pp. 793-798
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Background
The Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic. Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways (MPs) proved successful in treating MDD. It is possible that examining polygenicity within specific MPs implicated in MDD can further refine molecular drug targets.
MethodsUsing a large case–control GWAS based on low-coverage whole genome sequencing (N = 10 640) in Han Chinese women, we derived polygenic risk scores (PRS) for MDD and for MDD specific to each of over 300 MPs previously shown to be relevant to psychiatric diagnoses. We then identified sets of PRSs, accounting for critical covariates, significantly predictive of case status.
ResultsOver and above global MDD polygenic risk, polygenic risk within the GO: 0017144 drug metabolism pathway significantly predicted recurrent depression after multiple testing correction. Secondary transcriptomic analysis suggests that among genes in this pathway, CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1) might be most relevant to MDD. Within the cases, pathway-based risk was additionally associated with age at onset of MDD.
ConclusionsResults indicate that pathway-based risk might inform etiology of recurrent major depression. Future research should examine whether polygenicity of the drug metabolism gene pathway has any association with clinical presentation or treatment response. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.
Polygenic prediction of the phenome, across ancestry, in emerging adulthood
- Anna R. Docherty, Arden Moscati, Danielle Dick, Jeanne E. Savage, Jessica E. Salvatore, Megan Cooke, Fazil Aliev, Ashlee A. Moore, Alexis C. Edwards, Brien P. Riley, Daniel E. Adkins, Roseann Peterson, Bradley T. Webb, Silviu A. Bacanu, Kenneth S. Kendler
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- Journal:
- Psychological Medicine / Volume 48 / Issue 11 / August 2018
- Published online by Cambridge University Press:
- 27 November 2017, pp. 1814-1823
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Background
Identifying genetic relationships between complex traits in emerging adulthood can provide useful etiological insights into risk for psychopathology. College-age individuals are under-represented in genomic analyses thus far, and the majority of work has focused on the clinical disorder or cognitive abilities rather than normal-range behavioral outcomes.
MethodsThis study examined a sample of emerging adults 18–22 years of age (N = 5947) to construct an atlas of polygenic risk for 33 traits predicting relevant phenotypic outcomes. Twenty-eight hypotheses were tested based on the previous literature on samples of European ancestry, and the availability of rich assessment data allowed for polygenic predictions across 55 psychological and medical phenotypes.
ResultsPolygenic risk for schizophrenia (SZ) in emerging adults predicted anxiety, depression, nicotine use, trauma, and family history of psychological disorders. Polygenic risk for neuroticism predicted anxiety, depression, phobia, panic, neuroticism, and was correlated with polygenic risk for cardiovascular disease.
ConclusionsThese results demonstrate the extensive impact of genetic risk for SZ, neuroticism, and major depression on a range of health outcomes in early adulthood. Minimal cross-ancestry replication of these phenomic patterns of polygenic influence underscores the need for more genome-wide association studies of non-European populations.
Contributors
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- By Tod C. Aeby, Melanie D. Altizer, Ronan A. Bakker, Meghann E. Batten, Anita K. Blanchard, Brian Bond, Megan A. Brady, Saweda A. Bright, Ellen L. Brock, Amy Brown, Ashley Carroll, Jori S. Carter, Frances Casey, Weldon Chafe, David Chelmow, Jessica M. Ciaburri, Stephen A. Cohen, Adrianne M. Colton, PonJola Coney, Jennifer A. Cross, Julie Zemaitis DeCesare, Layson L. Denney, Megan L. Evans, Nicole S. Fanning, Tanaz R. Ferzandi, Katie P. Friday, Nancy D. Gaba, Rajiv B. Gala, Andrew Galffy, Adrienne L. Gentry, Edward J. Gill, Philippe Girerd, Meredith Gray, Amy Hempel, Audra Jolyn Hill, Chris J. Hong, Kathryn A. Houston, Patricia S. Huguelet, Warner K. Huh, Jordan Hylton, Christine R. Isaacs, Alison F. Jacoby, Isaiah M. Johnson, Nicole W. Karjane, Emily E. Landers, Susan M. Lanni, Eduardo Lara-Torre, Lee A. Learman, Nikola Alexander Letham, Rachel K. Love, Richard Scott Lucidi, Elisabeth McGaw, Kimberly Woods McMorrow, Christopher A. Manipula, Kirk J. Matthews, Michelle Meglin, Megan Metcalf, Sarah H. Milton, Gaby Moawad, Christopher Morosky, Lindsay H. Morrell, Elizabeth L. Munter, Erin L. Murata, Amanda B. Murchison, Nguyet A. Nguyen, Nan G. O’Connell, Tony Ogburn, K. Nathan Parthasarathy, Thomas C. Peng, Ashley Peterson, Sarah Peterson, John G. Pierce, Amber Price, Heidi J. Purcell, Ronald M. Ramus, Nicole Calloway Rankins, Fidelma B. Rigby, Amanda H. Ritter, Barbara L. Robinson, Danielle Roncari, Lisa Rubinsak, Jennifer Salcedo, Mary T. Sale, Peter F. Schnatz, John W. Seeds, Kathryn Shaia, Karen Shelton, Megan M. Shine, Haller J. Smith, Roger P. Smith, Nancy A. Sokkary, Reni A. Soon, Aparna Sridhar, Lilja Stefansson, Laurie S. Swaim, Chemen M. Tate, Hong-Thao Thieu, Meredith S. Thomas, L. Chesney Thompson, Tiffany Tonismae, Angela M. Tran, Breanna Walker, Alan G. Waxman, C. Nathan Webb, Valerie L. Williams, Sarah B. Wilson, Elizabeth M. Yoselevsky, Amy E. Young
- Edited by David Chelmow, Virginia Commonwealth University, Christine R. Isaacs, Virginia Commonwealth University, Ashley Carroll, Virginia Commonwealth University
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- Book:
- Acute Care and Emergency Gynecology
- Published online:
- 05 November 2014
- Print publication:
- 30 October 2014, pp ix-xiv
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- By Lenard A. Adler, Pinky Agarwal, Rehan Ahmed, Jagga Rao Alluri, Fawaz Al-Mufti, Samuel Alperin, Michael Amoashiy, Michael Andary, David J. Anschel, Padmaja Aradhya, Vandana Aspen, Esther Baldinger, Jee Bang, George D. Baquis, John J. Barry, Jason J. S. Barton, Julius Bazan, Amanda R. Bedford, Marlene Behrmann, Lourdes Bello-Espinosa, Ajay Berdia, Alan R. Berger, Mark Beyer, Don C. Bienfang, Kevin M. Biglan, Thomas M. Boes, Paul W. Brazis, Jonathan L. Brisman, Jeffrey A. Brown, Scott E. Brown, Ryan R. Byrne, Rina Caprarella, Casey A. Chamberlain, Wan-Tsu W. Chang, Grace M. Charles, Jasvinder Chawla, David Clark, Todd J. Cohen, Joe Colombo, Howard Crystal, Vladimir Dadashev, Sarita B. Dave, Jean Robert Desrouleaux, Richard L. Doty, Robert Duarte, Jeffrey S. Durmer, Christyn M. Edmundson, Eric R. Eggenberger, Steven Ender, Noam Epstein, Alberto J. Espay, Alan B. Ettinger, Niloofar (Nelly) Faghani, Amtul Farheen, Edward Firouztale, Rod Foroozan, Anne L. Foundas, David Elliot Friedman, Deborah I. Friedman, Steven J. Frucht, Oded Gerber, Tal Gilboa, Martin Gizzi, Teneille G. Gofton, Louis J. Goodrich, Malcolm H. Gottesman, Varda Gross-Tsur, Deepak Grover, David A. Gudis, John J. Halperin, Maxim D. Hammer, Andrew R. Harrison, L. Anne Hayman, Galen V. Henderson, Steven Herskovitz, Caitlin Hoffman, Laryssa A. Huryn, Andres M. Kanner, Gary P. Kaplan, Bashar Katirji, Kenneth R. Kaufman, Annie Killoran, Nina Kirz, Gad E. Klein, Danielle G. Koby, Christopher P. Kogut, W. Curt LaFrance, Patrick J.M. Lavin, Susan W. Law, James L. Levenson, Richard B. Lipton, Glenn Lopate, Daniel J. Luciano, Reema Maindiratta, Robert M. Mallery, Georgios Manousakis, Alan Mazurek, Luis J. Mejico, Dragana Micic, Ali Mokhtarzadeh, Walter J. Molofsky, Heather E. Moss, Mark L. Moster, Manpreet Multani, Siddhartha Nadkarni, George C. Newman, Rolla Nuoman, Paul A. Nyquist, Gaia Donata Oggioni, Odi Oguh, Denis Ostrovskiy, Kristina Y. Pao, Juwen Park, Anastas F. Pass, Victoria S. Pelak, Jeffrey Peterson, John Pile-Spellman, Misha L. Pless, Gregory M. Pontone, Aparna M. Prabhu, Michael T. Pulley, Philip Ragone, Prajwal Rajappa, Venkat Ramani, Sindhu Ramchandren, Ritesh A. Ramdhani, Ramses Ribot, Heidi D. Riney, Diana Rojas-Soto, Michael Ronthal, Daniel M. Rosenbaum, David B. Rosenfield, Durga Roy, Michael J. Ruckenstein, Max C. Rudansky, Eva Sahay, Friedhelm Sandbrink, Jade S. Schiffman, Angela Scicutella, Maroun T. Semaan, Robert C. Sergott, Aashit K. Shah, David M. Shaw, Amit M. Shelat, Claire A. Sheldon, Anant M. Shenoy, Yelizaveta Sher, Jessica A. Shields, Tanya Simuni, Rajpaul Singh, Eric E. Smouha, David Solomon, Mehri Songhorian, Steven A. Sparr, Egilius L. H. Spierings, Eve G. Spratt, Beth Stein, S.H. Subramony, Rosa Ana Tang, Cara Tannenbaum, Hakan Tekeli, Amanda J. Thompson, Michael J. Thorpy, Matthew J. Thurtell, Pedro J. Torrico, Ira M. Turner, Scott Uretsky, Ruth H. Walker, Deborah M. Weisbrot, Michael A. Williams, Jacques Winter, Randall J. Wright, Jay Elliot Yasen, Shicong Ye, G. Bryan Young, Huiying Yu, Ryan J. Zehnder
- Edited by Alan B. Ettinger, Albert Einstein College of Medicine, New York, Deborah M. Weisbrot, State University of New York, Stony Brook
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- Book:
- Neurologic Differential Diagnosis
- Published online:
- 05 June 2014
- Print publication:
- 17 April 2014, pp xi-xx
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Psychosocial outcome and psychiatric comorbidity in older adolescents with Tourette syndrome: controlled study
- Daniel A. Gorman, Nancy Thompson, Kerstin J. Plessen, Mary M. Robertson, James F. Leckman, Bradley S. Peterson
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- Journal:
- The British Journal of Psychiatry / Volume 197 / Issue 1 / July 2010
- Published online by Cambridge University Press:
- 02 January 2018, pp. 36-44
- Print publication:
- July 2010
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Background
Children with Tourette syndrome generally experience improvement of tics by age 18 years, but psychosocial and comorbidity outcomes at this age are unclear.
AimsTo compare psychosocial outcomes and lifetime comorbidity rates in older adolescents with Tourette syndrome and controls. We hypothesised a priori that individuals with Tourette syndrome would have lower Children's Global Assessment Scale (CGAS) scores.
MethodA total of 65 individuals with Tourette syndrome, identified in childhood, and 65 matched community controls without tic or obsessive–compulsive disorder (OCD) symptoms were assessed around 18 years of age regarding psychosocial functioning and lifetime psychiatric disorders.
ResultsCompared with controls, individuals with Tourette syndrome had substantially lower CGAS scores (P=10−8) and higher rates of attention-deficit hyperactivity disorder (ADHD), major depression, learning disorder and conduct disorder (P⩽0.01). In the participants with Tourette syndrome, poorer psychosocial outcomes were associated with greater ADHD, OCD and tic severity.
ConclusionsClinically ascertained children with Tourette syndrome typically have impaired psychosocial functioning and high comorbidity rates in late adolescence.
Contributors
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- By Kateri Berasi, Carol A. Boyer, Diane R. Brown, Robyn Lewis Brown, Tony N. Brown, Padraic J. Burns, Cleopatra Howard Caldwell, Daniel L. Carlson, Cheryl Corcoran, Manuela Costa, Stephen Crystal, Gary S. Cuddeback, William W. Eaton, Adrianne Frech, Virginia Aldigé Hiday, Stevan E. Hobfoll, Allan V. Horwitz, Robert J. Johnson, Verna M. Keith, Ronald C. Kessler, Corey L. M. Keyes, Jacinta P. Leavell, Harriet P. Lefley, Mary Clare Lennon, Laura Limonic, Bruce G. Link, Athena McLean, David Mechanic, Elizabeth G. Menaghan, Barret Michalec, John Mirowsky, Shirin Montazer, Joseph P. Morrissey, Carles Muntaner, Bernice A. Pescosolido, Christopher Peterson, Jo C. Phelan, Michael Polgar, Sarah Rosenfield, Catherine E. Ross, Ebony Sandusky, Jaime C. Sapag, Teresa L. Scheid, Mark F. Schmitz, Sharon Schwartz, Dena Smith, David T. Takeuchi, Peggy A. Thoits, R. Jay Turner, Edwina S. Uehara, Jerome C. Wakefield, James Walkup, Emily Walton, Blair Wheaton, David R. Williams, Kristi Williams
- Edited by Teresa L. Scheid, University of North Carolina, Charlotte, Tony N. Brown, Vanderbilt University, Tennessee
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- Book:
- A Handbook for the Study of Mental Health
- Published online:
- 05 June 2012
- Print publication:
- 16 November 2009, pp xi-xiv
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12 - Disturbances of fronto-striatal circuits in Tourette syndrome and obsessive-compulsive disorder
- from Section 2 - Atypical processes in developmental neuropsychiatric disorders
- Edited by Judith M. Rumsey, National Institute of Mental Health, Bethesda, Maryland, Monique Ernst, National Institute of Mental Health, Bethesda, Maryland
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- Book:
- Neuroimaging in Developmental Clinical Neuroscience
- Published online:
- 04 August 2010
- Print publication:
- 19 February 2009, pp 199-216
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- By James M. Bjork, Hilary P. Blumberg, Nathalie Boddaert, Susan Bookheimer, Silvia A. Bunge, Beata Buzas, B. J. Casey, Nadia Chabane, Eveline A. Crone, Mirella Dapretto, John A. Detre, Vaibhav A. Diwadkar, Jeffery N. Epstein, Monique Ernst, Guido K. W. Frank, David C. Glahn, David Goldman, Daniel A. Gorman, Ian H. Gotlib, Michael G. Hardin, Clinton D. Hermes, Rebecca M. Jones, Jutta Joormann, Jessica H. Kalmar, Walter H. Kaye, Matcheri S. Keshavan, Dae-Shik Kim, Liat Levita, Lisa H. Lu, Rachel Marsh, Kristin McNealy, Kevin A. Pelphrey, Susan B. Perlman, Bradley S. Peterson, Daniel S. Pine, Steven R. Pliszka, Konasale Prasad, Hengyi Rao, Allan L. Reiss, Perry Renshaw, Susan M. Rivera, Jason Royal, Judith M. Rumsey, Maulik P. Shah, Marisa M. Silveri, Elizabeth R. Sowell, Jeffrey A. Stanley, Henning U. Voss, Jiong-Jiong Wang, Ke Xu, Deborah Yurgelun-Todd, Monica Zilbovicius
- Edited by Judith M. Rumsey, National Institute of Mental Health, Bethesda, Maryland, Monique Ernst, National Institute of Mental Health, Bethesda, Maryland
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- Book:
- Neuroimaging in Developmental Clinical Neuroscience
- Published online:
- 04 August 2010
- Print publication:
- 19 February 2009, pp vii-xii
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