4.7 Review

ENIGMA-DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross-diagnostic psychiatric research

Journal

HUMAN BRAIN MAPPING
Volume 43, Issue 1, Pages 194-206

Publisher

WILEY
DOI: 10.1002/hbm.24998

Keywords

big data; cross-disorder; DTI; ENIGMA; RVI; white matter deficit patterns

Funding

  1. National Institutes of Health [R01MH111671, R01MH112180, R01MH116948, S10OD023696, 5T32MH073526, R01EB015611, U01MH108148]
  2. NIMH [R01085953, R21 MH116473, R01MH117601]
  3. NIH Big Data to Knowledge (BD2K) program under consortium [U54 EB020403]
  4. ENIGMA World Aging Center [R56 AG058854]
  5. ENIGMA Sex Differences Initiative [R01 MH116147, R01MH116147]
  6. ENIGMA-PGC PTSD Working Group [R01 MH111671]
  7. ENIGMA Epilepsy Working Group [R01 NS107739]
  8. Kavli Foundation Neuroscience without Borders seed grant
  9. NIH [S10 OD023696]
  10. ENIGMA-COINSTAC: Advanced Worldwide Transdiagnostic Analysis of Valence System Brain Circuits [1R01MH121246-01, R01MH121246]
  11. Italian Ministry of Health [RC 15-16-17-18-19/A]
  12. Fondation pour la recherche medicale Bioinformatics for Biology
  13. ENIGMA's NIH Big Data to Knowledge (BD2K) initiative [U54 EB020403]
  14. T32 Postdoctoral Scholar Fellowship Trainee Grant [5251831121]
  15. NIA [T32AG058507]
  16. Research Council of Norway [223273, 248778, 248980, 249711]
  17. South-East Norway Health Authority [2019108]
  18. Kristian Gerhard Jebsen Stiftelsen [SKGJ-MED-008]
  19. NIH/NIMH [R01 MH085953, R01 MH100900]
  20. SFARI Explorer Award
  21. European Research Council [ERC677467]
  22. Science Foundation Ireland [16ERCS3787]
  23. Health Research Board [CDA-2018-001]
  24. NHMRC [R01 MH117601, 1140764]
  25. VA BLRD [I01BX003477, R01-MH111671]
  26. Chronic Effects of Neurotrauma Consortium
  27. Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) [W81XWH-13-2-0095, 5 I01 RX002174]
  28. South African Medical Research Council
  29. Santa Lucia Foundation in Rome, Italy - Italian Ministry of Health [RC12-13-14-15-16-17-18-19/A]
  30. Dutch Research Council [91717306]
  31. [R01 AG059874]
  32. [K99NS096116]

Ask authors/readers for more resources

The ENIGMA-DTI workgroup investigates the effects of psychiatric, neurological, and developmental disorders on white matter pathways in the human brain. They have identified patterns of white matter deficits in various disorders and demonstrated their reproducibility across different cohorts. Applying the regional vulnerability index (RVI) to individual subjects, they have shown the similarity of deficit patterns among different disorders and discussed the differences between idiopathic schizophrenia and 22q11 deletion syndrome. These findings emphasize the importance of collaborative large-scale research in understanding individual vulnerability and cross-diagnosis features.
The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Psychology, Clinical

Harmonizing PTSD Severity Scales Across Instruments and Sites

Eamonn Kennedy, Emily L. Dennis, Hannah M. Lindsey, Terri deRoon-Cassini, Stefan Du Plessis, Negar Fani, Milissa L. Kaufman, Nastassja Koen, Christine L. Larson, Sarah Laskowitz, Lauren A. M. Lebois, Rajendra A. Morey, Mary R. Newsome, Cori Palermo, Nicholas J. Pastorek, Abigail Powers, Randall Scheibel, Soraya Seedat, Antonia Seligowski, Dan J. Stein, Jennifer Stevens, Delin Sun, Paul Thompson, Maya Troyanskaya, Sanne J. H. van Rooij, Amanda A. Watts, Carissa W. Tomas, Wright Williams, Frank G. Hillary, Mary Jo Pugh, Elisabeth A. Wilde, David F. Tate

Summary: This study uses a multisite mega analysis to derive quantitative recommendations for equating scores across measures of PTSD severity. The results suggest that harmonization and covariate adjustments can significantly improve inference of scores across different instruments.

NEUROPSYCHOLOGY (2023)

Article Psychology, Clinical

Cross-National Harmonization of Neurocognitive Assessment Across Five Sites in a Global Study

Marcelo C. Batistuzzo, Karthik Sheshachala, Daniel M. Alschuler, Dianne M. Hezel, Roberto Lewis-Fernandez, Niels T. de Joode, Chris Vriend, Karolina M. Lempert, Madhuri Narayan, Clara Marincowitz, Christine Lochner, Dan J. Stein, Janardhanan C. Narayanaswamy, Odile A. van den Heuvel, Helen Blair Simpson, Melanie Wall

Summary: To improve the consistency of neurocognitive testing across countries, a prospective harmonization approach was used in a global collaborative study. Five tasks were administered to participants from Brazil, India, the Netherlands, South Africa, and the USA. Despite procedural similarity, the Netherlands and India sites showed differences in cognitive performance, indicating potential selection sampling bias. Future studies should follow similar harmonization procedures and consider measuring additional confounding variables.

NEUROPSYCHOLOGY (2023)

Article Psychology, Clinical

Civilian moral injury: associations with trauma type and high-frequency heart rate variability in two trauma-exposed community-based samples

Emma C. Lathan, Abigail Powers, Anna Kottakis, Alfonsina Guelfo, Greg J. Siegle, Jessica A. Turner, Matthew D. Turner, Vijwala Yakkanti, Jahnvi Jain, Yara Mekawi, Andrew P. Teer, Joseph M. Currier, Negar Fani

Summary: This study found a unique association between moral injury and sexual violence as well as lower hfHRV in civilians.

PSYCHOLOGICAL MEDICINE (2023)

Article Psychiatry

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part II: OCD and PTSD

Borwin Bandelow, Christer Allgulander, David S. Baldwin, Daniel Lucas da Conceicao Costa, Damiaan Denys, Nesrin Dilbaz, Katharina Domschke, Eric Hollander, Siegfried Kasper, Hans-Juergen Moeller, Elias Eriksson, Naomi A. Fineberg, Josef Haettenschwiler, Hisanobu Kaiya, Tatiana Karavaeva, Martin A. Katzman, Yong-Ku Kim, Takeshi Inoue, Leslie Lim, Vasilios Masdrakis, Jose M. Menchon, Euripedes C. Miguel, Antonio E. Nardi, Stefano Pallanti, Giampaolo Perna, Dan Rujescu, Vladan Starcevic, Dan J. Stein, Shih-Jen Tsai, Michael Van Ameringen, Anna Vasileva, Zhen Wang, Joseph Zohar

Summary: According to the guideline by the World Federation of Societies of Biological Psychiatry, OCD and PTSD can be effectively treated with medications and CBT. SSRIs and CBT are first-line treatments for OCD, while SSRIs and venlafaxine are first-line treatments for PTSD.

WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY (2023)

Article Neurosciences

Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study

Emily L. Dennis, Mary R. Newsome, Hannah M. Lindsey, Maheen Adamson, Tara A. Austin, Seth G. Disner, Blessen C. Eapen, Carrie Esopenko, Carol E. Franz, Elbert Geuze, Courtney Haswell, Sidney R. Hinds II, Cooper B. Hodges, Andrei Irimia, Kimbra Kenney, Inga K. Koerte, William S. Kremen, Harvey S. Levin, Rajendra A. Morey, John Ollinger, Jared A. Rowland, Randall S. Scheibel, Martha E. Shenton, Danielle R. Sullivan, Leah D. Talbert, Sophia I. Thomopoulos, Maya Troyanskaya, William C. Walker, Xin Wang, Ashley L. Ware, John Kent Werner, Wright Williams, Paul M. Thompson, David F. Tate, Elisabeth A. Wilde

Summary: Traumatic brain injury (TBI) in military populations can lead to disruptions in brain structure and function, causing cognitive and psychological dysfunction. A study conducted a mega-analysis of neuroimaging and clinical data from military personnel and veterans, finding that deployment-related TBI is associated with increased left lateralization in the cingulum, a white matter tract. This effect was primarily observed in individuals whose worst injury occurred before age 40.

HUMAN BRAIN MAPPING (2023)

Article Psychology, Clinical

Measurement Fidelity of Clinical Assessment Methods in a Global Study on Identifying Reproducible Brain Signatures of Obsessive-Compulsive Disorder

Roseli G. Shavitt, Karthik Sheshachala, Dianne M. Hezel, Melanie M. Wall, Srinivas Balachander, Christine Lochner, Janardhanan C. Narayanaswamy, Daniel L. C. Costa, Maria Alice de Mathis, Anton J. L. M. van Balkom, Niels T. de Joode, Madhuri Narayan, Odile A. van den Heuvel, Dan J. Stein, Euripedes C. Miguel, Helen Blair Simpson, Y. C. Janardhan Reddy

Summary: This study describes the steps taken to ensure measurement fidelity of core clinical measures in a five-country study on brain signatures of obsessive-compulsive disorder (OCD). The researchers used standardized instruments and implemented techniques such as translating instruments, developing a clinical decision manual, and providing reliability training to evaluators. The results showed high interrater reliability for most scales and consistent factor structures across sites.

NEUROPSYCHOLOGY (2023)

Review Psychiatry

Within-individual variability in cognitive performance in schizophrenia: A narrative review of the key literature and proposed research agenda

Olivia Wootton, Shareefa Dalvie, Ezra Susser, Ruben C. Gur, Dan J. Stein

Summary: Schizophrenia, a neurodevelopmental disorder, is a leading cause of disability globally. Cognitive deficits are a characteristic of schizophrenia and can predict functional outcomes. Within-individual variability (WIV) in cognitive performance is higher in schizophrenia, and it provides additional insight into cognitive function beyond mean performance measures. Despite limited research, this narrative review summarizes the clinical, neural, and genetic correlates of WIV in schizophrenia and identifies knowledge gaps and future research directions.

SCHIZOPHRENIA RESEARCH (2023)

Review Psychiatry

Middle-income country perspectives on global mental health

Amy S. Adams, Goodman Sibeko, Dan J. Stein

Summary: Despite being a new discipline, global mental health has made significant advances in optimizing mental health services in low- and middle-income countries. This review focuses on middle-income countries such as Brazil, China, India, and South Africa, examining key issues including mental health legislation, burden of disease, task-sharing, and capacity-building.

CURRENT OPINION IN PSYCHIATRY (2023)

Article Biochemistry & Molecular Biology

Pruning and thresholding approach for methylation risk scores in multi-ancestry populations

Junyu Chen, Evan Gatev, Todd Everson, Karen N. Conneely, Nastassja Koen, Michael P. Epstein, Michael S. Kobor, Heather J. Zar, Dan J. Stein, Anke Huels

Summary: Recent studies have focused on developing methylation risk scores (MRS), which use weighted sums of DNA methylation (DNAm) values at pre-selected CpG sites. Most current MRS approaches only include genome-wide significant CpG sites and do not consider co-methylation. New methods that relax the p-value threshold and account for DNAm inter-correlation show promise in improving predictive performance of MRS.

EPIGENETICS (2023)

Article Multidisciplinary Sciences

Country-level gender inequality is associated with structural differences in the brains of women and men

Andre Zugman, Luz Maria Alliende, Vicente Medel, Richard A. I. Bethlehem, Jakob Seidlitz, Grace Ringlein, Celso Arango, Aurina Arnatkeviciute, Laila Asmal, Mark Bellgrove, Vivek Benegal, Miquel Bernardo, Pablo Billeke, Jorge Bosch-Bayard, Rodrigo Bressan, Geraldo F. Busatto, Mariana N. Castro, Tiffany Chaim-Avancini, Albert Compte, Monise Costanzi, Leticia Czepielewski, Paola Dazzan, Camilo de la Fuente-Sandoval, Marta Di Forti, Covadonga M. Diaz-Caneja, Ana Maria Diaz-Zuluaga, Stefan Du Plessis, Fabio L. S. Duran, Sol Fittipaldi, Alex Fornito, Nelson B. Freimer, Ary Gadelha, Clarissa S. Gama, Ranjini Garani, Clemente Garcia-Rizo, Cecilia Gonzalez Campo, Alfonso Gonzalez-Valderrama, Salvador Guinjoan, Bharath Holla, Agustin Ibanez, Daniza Ivanovic, Andrea Jackowski, Pablo Leon-Ortiz, Christine Lochner, Carlos Lopez-Jaramillo, Hilmar Luckhoff, Raffael Massuda, Philip McGuire, Jun Miyataaaa, Romina Mizrahi, Robin Murray, Aysegul Ozerdem, Pedro M. Pan, Mara Parellada, Lebogan Phahladira, Juan P. Ramirez-Mahalu, Ramiro Reckziegel, Tiago Reis Marques, Francisco Reyes-Madrigal, Annerine Roos, Pedro Rosa, Giovanni Salum, Freda Scheffler, Gunter Schumann, Mauricio Serpa, Dan J. Stein, Angeles Tepper, Jeggan Tiego, Tsukasa Ueno, Juan Undurraga, Eduardo A. Undurrag, Pedro Valdes-Sosaooo, Isabel Valliy, Mirta Villarrealu, Toby T. Winton-Brownrrr, Nefize Yalin, Francisco Zamorano, Marcus V. Zanetti, Anderson M. Winkler, Daniel S. Pine, Sara Evans-Lacko, Nicolas A. Crossley

Summary: Gender inequality has been linked to higher mental health risks and lower academic achievement for women globally. Differences in brain structure between men and women may be partially explained by unequal exposure to harsher conditions in gender-unequal countries, leading to worse outcomes for women. A meta-analysis of MRI scans from 139 samples across 29 countries revealed that women in gender-equal countries had no differences or even thicker cortical regions, while those in countries with greater gender inequality had thinner cortices. These findings highlight the potential negative impact of gender inequality on women's brains and the need for policies based on neuroscience for gender equality.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

Article Clinical Neurology

PTSD and comorbid MDD is associated with activation of the right frontoparietal network

Sheri-Michelle Koopowitz, Heather J. Zar, Dan J. Stein, Jonathan C. Ipser

Summary: There is growing evidence of abnormalities in intrinsic functional connectivity (FC) in both PTSD and MDD. However, there has been limited research on their co-occurrence. Characterizing these abnormalities in this clinical population is crucial for understanding the impairments associated with different networks.

PSYCHIATRY RESEARCH-NEUROIMAGING (2023)

Article Psychology, Clinical

Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants

Sean R. McWhinney, Christoph Abe, Martin Alda, Francesco Benedetti, Erlend Boen, Caterina del Mar Bonnin, Tiana Borgers, Katharina Brosch, Erick J. Canales-Rodriguez, Dara M. Cannon, Udo Dannlowski, Ana M. Diaz-Zuluaga, Lorielle M. F. Dietze, Torbjorn Elvsashagen, Lisa T. Eyler, Janice M. Fullerton, Jose M. Goikolea, Janik Goltermann, Dominik Grotegerd, Bartholomeus C. M. Haarman, Tim Hahn, Fleur M. Howells, Martin Ingvar, Neda Jahanshad, Tilo T. J. Kircher, Axel Krug, Rayus T. Kuplicki, Mikael Landen, Hannah Lemke, Benny Liberg, Carlos Lopez-Jaramillo, Ulrik F. Malt, Fiona M. Martyn, Elena Mazza, Colm McDonald, Genevieve McPhilemy, Sandra Meier, Susanne Meinert, Tina Meller, Elisa M. T. Melloni, Philip B. Mitchell, Leila Nabulsi, Igor Nenadic, Nils Opel, Roel A. Ophoff, Bronwyn J. Overs, Julia-Katharina Pfarr, Julian A. Pineda-Zapata, Edith Pomarol-Clotet, Joaquim Radua, Jonathan Repple, Maike Richter, Kai G. Ringwald, Gloria Roberts, Alex Ross, Raymond Salvador, Jonathan Savitz, Simon Schmitt, Peter R. Schofield, Kang Sim, Dan J. Stein, Frederike Stein, Henk S. Temmingh, Katharina Thiel, Sophia I. Thomopoulos, Neeltje E. M. van Haren, Cristian Vargas, Eduard Vieta, Annabel Vreeker, Lena Waltemate, Lakshmi N. Yatham, Christopher R. K. Ching, Ole A. Andreassen, Paul M. Thompson, Tomas Hajek

Summary: This study found that body mass index (BMI) and bipolar disorder (BD) have an impact on brain structure, particularly in cortical thickness. Both BMI and BD negatively affect the same brain regions, and BMI has a greater effect on brain alterations in individuals with BD. It is important to assess the neuroanatomical changes in BD caused by BMI and the effects of psychiatric medications on the brain.

PSYCHOLOGICAL MEDICINE (2023)

Article Psychiatry

Efficacy of a dialogic book-sharing intervention in a South African birth cohort: A randomized controlled trial

Sheri-Michelle Koopowitz, Karen Thea Mare, Marilyn Lake, Christopher du Plooy, Nadia Hoffman, Kirsten A. Donald, Susan Malcolm-Smith, Lynne Murray, Heather J. Zar, Peter Cooper, Dan J. Stein

Summary: This study investigated the effects of dialogic book-sharing on language development, neurocognitive function, and socio-emotional domains in 3.5-year-old children from low-income South African communities. The results showed no significant differences between the intervention and control groups after 4 months post-intervention.

COMPREHENSIVE PSYCHIATRY (2024)

Article Clinical Neurology

Case-controlled field study of the ICD-11 clinical descriptions and diagnostic requirements for Bodily Distress Disorders

Jared Keeley, Geoffrey M. Reed, Tahilia Rebello, Julia Brechbiel, Jose Angel Garcia-Pacheco, Kazeem Adebayo, Oluyomi Esan, Oluyinka Majekodunmi, Akin Ojagbemi, Lucky Onofa, Rebeca Robles, Chihiro Matsumoto, Maria Elena Medina-Mora, Cary S. Koganl, Maya Kulygina, Wolfgang Gaebel, Min Zhao, Michael C. Roberts, Pratap Sharanr, Jose Luis Ayuso-Mateos, Brigitte Khoury, Dan J. Steinu, Anne M. Lovell, Kathleen Pike, Francis Creedxd, Oye Gureje

Summary: The ICD-11 diagnostic guidelines for Bodily Distress Disorder (BDD) show improvement in clinicians' diagnostic accuracy and perceived clinical utility compared to the guidelines for Somatoform Disorders in ICD-10.

JOURNAL OF AFFECTIVE DISORDERS (2023)

Article Neurosciences

1H-MRS neurometabolite profiles and motor development in school-aged children who are HIV-exposed uninfected: a birth cohort study

Simone R. Williams, Frances C. Robertson, Catherine J. Wedderburn, Jessica E. Ringshaw, Layla Bradford, Charmaine N. Nyakonda, Nadia Hoffman, Shantanu H. Joshi, Heather J. Zar, Dan J. Stein, Kirsten A. Donald

Summary: This study found that decreased levels of glutamate in the parietal gray matter and lower choline ratios in the parietal white matter were observed in children who are HIV-exposed uninfected (CHEU), suggesting regional alterations and myelin loss. Additionally, the study revealed associations between neurometabolite profiles and motor developmental outcomes in CHEU.

FRONTIERS IN NEUROSCIENCE (2023)

No Data Available