ReviewNovel Approaches to the Study of Postmortem Brain in Psychiatric Illness: Old Limitations and New Challenges
Section snippets
Long-Standing Challenges
The selection of samples for postmortem brain studies includes consideration of manner of death, age, sex, tissue pH, mRNA integrity (RIN), postmortem interval (PMI), diagnostic certainty, comorbid substance use, and prior medication treatment status. Despite attempts to rigorously characterize samples, studies of a particular illness often find inconsistent results for the same dependent variable. For example, postmortem studies of the NR1 subunit of the N-methyl-D-aspartate glutamate receptor
Summary
Although there have been important advances in the field of mental health research, a full accounting of the etiologies of severe mental illnesses such as schizophrenia and the mood disorders remains to be achieved. Postmortem studies have a critical role, along with animal models and studies of living patients, in the search for causes and cures for these diseases. Promising innovative methodologies combined with increasingly bigger and better characterized subjects cohorts have the postmortem
References (100)
- et al.
Human postmortem tissue: What quality markers matter?
Brain Res
(2006) - et al.
Postmortem studies in schizophrenic brain
J Psychiatr Res
(1997) The human brain revisited: Opportunities and challenges in postmortem studies of psychiatric disorders
Neuropsychopharmacology
(2002)- et al.
Critical factors in gene expression in postmortem human brain: Focus on studies in schizophrenia
Biol Psychiatry
(2006) - et al.
Gene expression profiling in the post-mortem human brain—no cause for dismay
J Chem Neuroanat
(2001) Tissue preparation and banking
Prog Brain Res
(2006)- et al.
Effect of agonal and postmortem factors on gene expression profile: Quality control in microarray analyses of postmortem human brain
Biol Psychiatry
(2004) - et al.
Terminal coma affects messenger RNA detection in post mortem human temporal cortex
Brain Res Mol Brain Res
(1991) - et al.
The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: Selective mRNA vulnerability and comparison with their encoded proteins
Neurosci Lett
(1995) - et al.
Tissue pH as an indicator of mRNA preservation in human post-mortem brain
Brain Res Mol Brain Res
(1995)
Evaluation of isolation methods and RNA integrity for bacterial RNA quantitation
J Microbiol Methods
RNA integrity and the effect on the real-time qRT-PCR performance
Mol Aspects Med
Quality control for microarray analysis of human brain samples: the impact of postmortem factors, RNA characteristics, and histopathology
J Neurosci Methods
Postmortem stability of dopamine D1 receptor mRNA and D1 receptors
Brain Res Mol Brain Res
Biological stability of mRNA isolated from human postmortem brain collections
Biol Psychiatry
Stability of gene expression in postmortem brain revealed by cDNA gene array analysis
Brain Res
Altered vesicular glutamate transporter expression in the anterior cingulate cortex in schizophrenia
Biol Psychiatry
Decreased density of tyrosine hydroxylase-immunoreactive axons in the entorhinal cortex of schizophrenic subjects
Biol Psychiatry
Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys
Biol Psychiatry
Deficient attentional modulation of startle eyeblink is associated with symptom severity in the schizophrenia spectrum
Schizophr Res
Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder
Neuropsychopharmacology
Methodological considerations for gene expression profiling of human brain
J Neurosci Methods
A noncoding antisense RNA in Tie-1 locus regulates Tie-1 function in vivo
Blood
A microarray study of post-mortem mRNA degradation in mouse brain tissue
Brain Res Mol Brain Res
Recovery and expression of messenger RNA from postmortem human brain tissue
Mod Pathol
Recovery of high-integrity mRNA from brains of rats killed by high-energy focused microwave irradiation
Brain Res Brain Res Protoc
Oligodendrocyte dysfunction in schizophrenia and bipolar disorder
Lancet
Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia
Schizophr Res
Combining laser capture microdissection with quantitative real-time PCR: Effects of tissue manipulation on RNA quality and gene expression
J Neurosci Methods
Schizophrenia and sex associated differences in the expression of neuronal and oligodendrocyte-specific genes in individual thalamic nuclei
Schizophr Res
Epigenetic regulation in human brain-focus on histone lysine methylation
Biol Psychiatry
Decreased synaptophysin in the medial temporal lobe in schizophrenia demonstrated using immunoautoradiography
Neuroscience
Influence of freezer storage time on cerebral biogenic amine and metabolite concentrations and receptor ligand binding characteristics
Brain Res
Biochemical and molecular studies using human autopsy brain tissue
J Neurochem
N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia
Am J Psychiatry
Increased levels of expression of an NMDARI splice variant in the superior temporal gyrus in schizophrenia
Neuroreport
Expression of NMDAR1, GluR1, GluR7, and KA1 glutamate receptor mRNAs is decreased in frontal cortex of “neuroleptic-free” schizophrenics: Evidence on reversible up-regulation by typical neuroleptics
J Neurochem
Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics
J Neurosci
Agonal respirations during cardiac arrest
Curr Opin Crit Care
Selection of reference gene expression in a schizophrenia brain cohort
Aust N Z J Psychiatry
Pre- and postmortem influences on brain RNA
J Neurochem
Mitochondrial-related gene expression changes are sensitive to agonal-pH state: Implications for brain disorders
Mol Psychiatry
Effects of ante mortem and postmortem variables on human brain mRNA quality: A BrainNet Europe study
J Neuropathol Exp Neurol
The RIN: An RNA integrity number for assigning integrity values to RNA measurements
BMC Mol Biol
The patients dying after long terminal phase have acidotic brains; implications for biochemical measurements on autopsy tissue
J Neural Transm
Postmortem delay has minimal effect on brain RNA integrity
J Neuropathol Exp Neurol
Evaluating RNA status for RT-PCR in extracts of postmortem human brain tissue
BioTechniques
Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces
Nucleic Acids Res
High-resolution quantification of specific mRNA levels in human brain autopsies and biopsies
Genome Res
Selective postmortem degradation of inducible heat shock protein70 (hsp70) mRNAs in rat brain
Cell Mol Neurobiol
Cited by (66)
A characteristic cerebellar biosignature for bipolar disorder, identified with fully automatic machine learning
2023, IBRO Neuroscience ReportsPostmortem, in silico, and clinical studies focused on perturbations of glutamate neurobiology in schizophrenia
2022, Schizophrenia ResearchA bioinformatic inquiry of the EAAT2 interactome in postmortem and neuropsychiatric datasets
2022, Schizophrenia ResearchA review and meta-analysis of gene expression profiles in suicide
2022, European NeuropsychopharmacologyThe role of glutamatergic neurotransmission in the motor and non-motor symptoms in Parkinson's disease: Clinical cases and a review of the literature
2021, Journal of Clinical NeuroscienceNo changes of expression of GPR56 protein in the parietal cortex, cerebellum, and liver from psychiatric disorders
2021, Journal of Affective Disorders Reports