Common and specific large-scale brain changes in major depressive disorder, anxiety disorders, and chronic pain: a transdiagnostic multimodal meta-analysis of structural and functional MRI studies

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Abstract

Major depressive disorder (MDD), anxiety disorders (ANX), and chronic pain (CP) are closely-related disorders with both high degrees of comorbidity among them and shared risk factors. Considering this multi-level overlap, but also the distinct phenotypes of the disorders, we hypothesized both common and disorder-specific changes of large-scale brain systems, which mediate neural mechanisms and impaired behavioral traits, in MDD, ANX, and CP. To identify such common and disorder-specific brain changes, we conducted a transdiagnostic, multimodal meta-analysis of structural and functional MRI-studies investigating changes of gray matter volume (GMV) and intrinsic functional connectivity (iFC) of large-scale intrinsic brain networks across MDD, ANX, and CP. The study was preregistered at PROSPERO (CRD42019119709). 320 studies comprising 10,931 patients and 11,135 healthy controls were included. Across disorders, common changes focused on GMV-decrease in insular and medial-prefrontal cortices, located mainly within the so-called default-mode and salience networks. Disorder-specific changes comprised hyperconnectivity between default-mode and frontoparietal networks and hypoconnectivity between limbic and salience networks in MDD; limbic network hyperconnectivity and GMV-decrease in insular and medial-temporal cortices in ANX; and hypoconnectivity between salience and default-mode networks and GMV-increase in medial temporal lobes in CP. Common changes suggested a neural correlate for comorbidity and possibly shared neuro-behavioral chronification mechanisms. Disorder-specific changes might underlie distinct phenotypes and possibly additional disorder-specific mechanisms.

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Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Theo Vos, Stephen S Lim, Cristiana Abbafati … (2023)

Summary Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding Bill & Melinda Gates Foundation.

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Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.

D F Stroup, J A Berlin, S C Morton … (2000)

Because of the pressure for timely, informed decisions in public health and clinical practice and the explosion of information in the scientific literature, research results must be synthesized. Meta-analyses are increasingly used to address this problem, and they often evaluate observational studies. A workshop was held in Atlanta, Ga, in April 1997, to examine the reporting of meta-analyses of observational studies and to make recommendations to aid authors, reviewers, editors, and readers. Twenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedical editing. Deliberations of the workshop were open to other interested scientists. Funding for this activity was provided by the Centers for Disease Control and Prevention. We conducted a systematic review of the published literature on the conduct and reporting of meta-analyses in observational studies using MEDLINE, Educational Research Information Center (ERIC), PsycLIT, and the Current Index to Statistics. We also examined reference lists of the 32 studies retrieved and contacted experts in the field. Participants were assigned to small-group discussions on the subjects of bias, searching and abstracting, heterogeneity, study categorization, and statistical methods. From the material presented at the workshop, the authors developed a checklist summarizing recommendations for reporting meta-analyses of observational studies. The checklist and supporting evidence were circulated to all conference attendees and additional experts. All suggestions for revisions were addressed. The proposed checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion. Use of the checklist should improve the usefulness of meta-analyses for authors, reviewers, editors, readers, and decision makers. An evaluation plan is suggested and research areas are explored.

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The organization of the human cerebral cortex estimated by intrinsic functional connectivity.

B T Thomas Yeo, Fenna M Krienen, Jorge Sepulcre … (2011)

Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.

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Author and article information

Contributors

Felix Brandl:

ORCID: http://orcid.org/0000-0003-3719-9263

felix.brandl@tum.de

Journal

Journal ID (nlm-ta): Neuropsychopharmacology

Journal ID (iso-abbrev): Neuropsychopharmacology

Title: Neuropsychopharmacology

Publisher: Springer International Publishing (Cham )

ISSN (Print): 0893-133X

ISSN (Electronic): 1740-634X

Publication date (Electronic): 20 January 2022

Publication date PMC-release: 20 January 2022

Publication date (Print): April 2022

Volume: 47

Issue: 5

Pages: 1071-1080

Affiliations

[1 ]GRID grid.6936.a, ISNI 0000000123222966, Technical University of Munich, School of Medicine, Department of Psychiatry, ; 81675 Munich, Germany

[2 ]GRID grid.6936.a, ISNI 0000000123222966, Technical University of Munich, School of Medicine, Department of Neuroradiology, ; 81675 Munich, Germany

[3 ]GRID grid.6936.a, ISNI 0000000123222966, Technical University of Munich, School of Medicine, TUM-NIC Neuroimaging Center, ; 81675 Munich, Germany

[4 ]GRID grid.8647.d, ISNI 0000 0004 0637 0731, University of Maribor, Faculty of Arts, Department of Psychology, ; Koroska cesta 160, 2000 Maribor, Slovenia

[5 ]GRID grid.6936.a, ISNI 0000000123222966, Technical University of Munich, School of Medicine, Department of Neurology, ; 81675 Munich, Germany

Author information

Felix Brandl http://orcid.org/0000-0003-3719-9263

Markus Ploner http://orcid.org/0000-0002-7767-7170

Article

Publisher ID: 1271

DOI: 10.1038/s41386-022-01271-y

PMC ID: 8938548

PubMed ID: 35058584

SO-VID: 81c9b822-2ac5-4735-83a9-82c03de41eb7

License:

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