Abstract
Background
The hippocampus is a core region of interest for all major mental disorders, and its
subfields implement distinctive functions. It is unclear whether the mental disorders
exhibit common patterns of hippocampal impairments, and we lack knowledge on whether
and how hippocampal subfields represent deficit spectra across mental disorders.
Methods
Using brain images of 1123 individuals scanned on a single magnetic resonance imaging
scanner, we examined the commonality, specificity, and symptom associations of the
volume of hippocampal subfields across patients with schizophrenia, patients with
obsessive-compulsive disorder, patients with bipolar disorder, patients with major
depressive disorder, and healthy control subjects. We further performed a transdiagnostic
analysis of the individual variability of the volume of hippocampal subfields to reflect
cross-disease gradients in the hippocampus.
Results
We found common and disease-specific abnormalities in a few hippocampal fields and
identified 2 reliable transdiagnostic factors in the hippocampal subfields, each reflecting
a spectrum of mental disorders. The plane spanned by the 2 most reliable factors provided
a clearer view of hippocampal volume abnormality spectra among the major mental disorders.
In addition, functional and genetic enrichment analyses supported the different roles
of the 2 hippocampal factors in mental disorders.
Conclusions
The volume of hippocampal subfields reflected some commonality and specificity among
the 3 major mental disorders. We propose a new pathophysiological dimensional view
of the hippocampus, reflecting at least 2 spectra of mental disorders, suggesting
multivariate links among the diseases. This work highlights the value of the complementary
categorical and dimensional views of the hippocampal deficits in mental disorders.
Keywords
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References
- Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017.Lancet. 2018; 392: 1789-1858
- Identification of common neural circuit disruptions in cognitive control across psychiatric disorders.Am J Psychiatry. 2017; 174: 676-685
- Analysis of shared heritability in common disorders of the brain.Science. 2018; 360eaap8757
- Psychiatric genetics and the structure of psychopathology.Mol Psychiatry. 2019; 24: 409-420
- Classifying major mental disorders genetically.Prog Neuropsychopharmacol Biol Psychiatry. 2021; 112110410
- Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders.Cell. 2019; 179: 1469-1482.e11
- Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: Evidence from voxel-based meta-analysis.Mol Psychiatry. 2017; 22: 1455-1463
- Cross-disorder analysis of brain structural abnormalities in six major psychiatric disorders: A secondary analysis of mega- and meta-analytical findings from the ENIGMA Consortium.Biol Psychiatry. 2020; 88: 678-686
- Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: Findings from the ENIGMA ADHD, ASD, and OCD Working Groups.Am J Psychiatry. 2020; 177: 834-843
- Hippocampal subfield volumes in major depressive disorder and bipolar disorder.Eur Psychiatry. 2019; 57: 70-77
- Limbic-cortical dysregulation: A proposed model of depression.J Neuropsychiatry Clin Neurosci. 1997; 9: 471-481
- Antidepressants recruit new neurons to improve stress response regulation.Mol Psychiatry. 2011; 16: 1177-1188
- Subcortical volumetric abnormalities in bipolar disorder.Mol Psychiatry. 2016; 21: 1710-1716
- Distinct subcortical volume alterations in pediatric and adult OCD: A worldwide meta- and mega-analysis.Am J Psychiatry. 2017; 174: 60-69
- Hippocampal volume and cell number in depression, schizophrenia, and suicide subjects.Brain Res. 2020; 1727146546
- Postmortem transcriptional profiling reveals widespread increase in inflammation in schizophrenia: A comparison of prefrontal cortex, striatum, and hippocampus among matched tetrads of controls with subjects diagnosed with schizophrenia, bipolar or major depressive disorder.Transl Psychiatry. 2019; 9: 151
- Multimodal mapping and analysis of the cyto- and receptorarchitecture of the human hippocampus.Brain Struct Funct. 2020; 225: 881-907
- The many dimensions of human hippocampal organization and (dys)function.Trends Neurosci. 2021; 44: 977-989
- A pathophysiological framework of hippocampal dysfunction in ageing and disease.Nat Rev Neurosci. 2011; 12: 585-601
- Hippocampal subfields differentially correlate with chronic pain in older adults.Brain Res. 2014; 1573: 54-62
- Abnormalities of hippocampal shape and subfield volumes in medication-free patients with obsessive-compulsive disorder.Hum Brain Mapp. 2019; 40: 4105-4113
- Region-specific sex differences in the hippocampus.Neuroimage. 2020; 215116781
- Atrophy of hippocampal subfield CA2/3 in healthy elderly men is related to educational attainment.Neurobiol Aging. 2019; 80: 21-28
- Genomic anatomy of the hippocampus.Neuron. 2008; 60: 1010-1021
- Heritability of hippocampal formation sub-region volumes.J Neurol Neurosci. 2016; 7: 159
- Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes.Mol Psychiatry. 2020; 25: 3053-3065
- Hippocampal subfield transcriptome analysis in schizophrenia psychosis.Mol Psychiatry. 2020; 26: 2577-2589
- In vivo hippocampal subfield volumes in schizophrenia and bipolar disorder.Biol Psychiatry. 2015; 77: 581-588
- Neuroimaging hippocampal subfields in schizophrenia and bipolar disorder: A systematic review and meta-analysis.J Psychiatr Res. 2018; 104: 217-226
- Hippocampal volume in first-episode schizophrenia and longitudinal course of the illness.World J Biol Psychiatry. 2016; 17: 429-438
- Increased hippocampal tail volume predicts depression status and remission to anti-depressant medications in major depression.Mol Psychiatry. 2018; 23: 1737-1744
- FreeSurfer-based segmentation of hippocampal subfields: A review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts.Hum Brain Mapp. 2022; 43: 207-233
- The P-factor and its genomic and neural equivalents: An integrated perspective.Mol Psychiatry. 2022; 27: 38-48
- Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders.Am J Psychiatry. 2010; 167: 748-751
- Three approaches to understanding and classifying mental disorder: ICD-11, DSM-5, and the National Institute of Mental Health's Research Domain Criteria (RDoC).Psychol Sci Public Interest. 2017; 18: 72-145
- Identification of common neural circuit disruptions in emotional processing across psychiatric disorders.Am J Psychiatry. 2020; 177: 411-421
- The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.J Clin Psychiatry. 1998; 59 (quiz 34-57): 22-33
- The positive-negative dimension in schizophrenia: Its validity and significance.Psychiatr Dev. 1987; 5: 79-103
- Development of a rating scale for primary depressive illness.Br J Soc Clin Psychol. 1967; 6: 278-296
- INCloud: Integrated neuroimaging cloud for data collection, management, analysis and clinical translations.Gen Psychiatry. 2021; 34e100651
- FreeSurfer. Neuroimage. 2012; 62: 774-781
- A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI.Neuroimage. 2015; 115: 117-137
- Statistical adjustments for brain size in volumetric neuroimaging studies: Some practical implications in methods.Psychiatry Res. 2011; 193: 113-122
- Head size, age and gender adjustment in MRI studies: A necessary nuisance?.Neuroimage. 2010; 53: 1244-1255
- Correction for intracranial volume in analysis of whole brain atrophy in multiple sclerosis: The proportion vs. residual method.Neuroimage. 2004; 22: 1732-1743
- Brain annotation toolbox: Exploring the functional and genetic associations of neuroimaging results.Bioinformatics. 2019; 35: 3771-3778
- Smaller hippocampal volume in posttraumatic stress disorder: A multisite ENIGMA-PGC study: Subcortical volumetry results from posttraumatic stress disorder consortia.Biol Psychiatry. 2018; 83: 244-253
- Heritability and reliability of automatically segmented human hippocampal formation subregions.Neuroimage. 2016; 128: 125-137
- Test-retest reliability of FreeSurfer automated hippocampal subfield segmentation within and across scanners.Neuroimage. 2020; 210116563
- Toward the future of psychiatric diagnosis: The seven pillars of RDoC.BMC Med. 2013; 11: 126
- Comparative anatomy of the prosubiculum, subiculum, presubiculum, postsubiculum, and parasubiculum in human, monkey, and rodent.J Comp Neurol. 2013; 521: 4145-4162
- ENIGMA MDD: Seven years of global neuroimaging studies of major depression through worldwide data sharing.Transl Psychiatry. 2020; 10: 172
- The mechanisms for pattern completion and pattern separation in the hippocampus.Front Syst Neurosci. 2013; 7: 74
- The hippocampal formation in schizophrenia.Am J Psychiatry. 2010; 167: 1178-1193
- Regional specific evidence for memory-load dependent activity in the dorsal subiculum and the lateral entorhinal cortex.Front Syst Neurosci. 2017; 11: 51
- Functional connectivity evidence for state-independent executive function deficits in patients with major depressive disorder.J Affect Disord. 2021; 291: 76-82
- Executive functioning deficits among adults with Bipolar Disorder (types I and II): A systematic review and meta-analysis.J Affect Disord. 2017; 218: 407-427
- Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD.Psychol Bull. 1997; 121: 65-94
- Genome-wide association study of suicide attempts in mood disorder patients.Am J Psychiatry. 2010; 167: 1499-1507
- Influence of kynurenine 3-monooxygenase (KMO) gene polymorphism on cognitive function in schizophrenia.Schizophr Res. 2014; 160: 80-87
- Reduced hippocampal subfield volume in schizophrenia and clinical high-risk state for psychosis.Front Psychiatry. 2021; 12642048
- Hippocampal subfield volumes in mood disorders.Mol Psychiatry. 2017; 22: 1352-1358
- Embryology of the human fetal hippocampus: MR imaging, anatomy, and histology.AJNR Am J Neuroradiol. 1997; 18: 525-532
- The development of the human hippocampal fissure.J Anat. 1967; 101: 655-676
- Developmental abnormalities of the hippocampus in first-episode schizophrenia.Biol Psychiatry. 2003; 53: 555-561
- Medial temporal lobe structures and hippocampal subfields in psychotic disorders: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study.JAMA Psychiatry. 2014; 71: 769-777
- Higher volumes of hippocampal subfields in pediatric obsessive-compulsive disorder.Psychiatry Res Neuroimaging. 2021; 307111200
Article info
Publication history
Published online: July 04, 2022
Accepted:
June 22,
2022
Received in revised form:
June 19,
2022
Received:
October 10,
2021
Identification
Copyright
© 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
