Molecular Pathology in Psychiatric Diseases: Frontiers of Postmortem Brain Research

About this Research Topic

Background

Biological studies of schizophrenia and bipolar disorder have been actively conducted from a variety of directions, including genetic, physiological, imaging, and animal model studies, and the elucidation of their pathophysiology is currently advancing rapidly. In addition, a number of molecular studies using postmortem brains have recently been carried out to validate the findings of the above studies. Postmortem brain studies of schizophrenia, which were rarely reported until around 1970, have increased drastically since the 1990s, especially since 2000. This is because the mechanism of action of antipsychotics has focused attention on brain regions such as the midbrain, striatum, limbic system, and cortical tracts involved in the dopamine neurotransmitter system, and with the progress of structural brain imaging research using CT and MRI, and functional brain imaging research using SPECT and PET, the importance of brain pathology in schizophrenia has gradually been reevaluated. Thus, postmortem brain research on schizophrenia and bipolar disorder is currently very active, and due to recent remarkable technological innovations in the field of basic neuroscience, examinations at the molecular level, such as analysis of mRNA, proteins and lipids, expressed in the brain, and brain-specific genomic polymorphisms such as CNV and DNA methylation are rapidly being conducted. Against the background of these multifaceted developments in neuroscience and the ability to perform comprehensive analyses on small amount of tissue samples, postmortem brain study on psychiatric disorders has shifted from its traditional role of validating results obtained in basic neuroscience studies to a more exploratory role of adding new findings and providing feedback to other approaches. Considering this situation, if postmortem brain research is the final aggregation point for validating findings accumulated in genetic, imaging, and animal model studies, it may indicate that the biological understanding of schizophrenia and bipolar disorder is entering its final phase.

The goal of this Research Topic is to present cutting-edge postmortem brain studies in the molecular pathogenesis of schizophrenia, bipolar disorder, and other psychiatric disorders, and to discuss the potential of these studies to translate to the clinic. This Research Topic will highlight recent advances in molecular pathogenesis, their relevance for clinicians, and their potential for therapeutic development. We will focus on molecular pathways implicated by inflammation-related molecules, carbonyl stress and other oxidative-metabolism-related molecules, lipid-related molecules, and dopamine-, glutamate-, and GABA-related molecules. Furthermore, we will highlight recent findings on genetic risks, environmental stresses and their interactions. We will also focus on advances in bioinformatics, evaluation of the quality of postmortem brain resources and cytohistological approaches. We also aim to highlight relevance of findings from postmortem brain studies to biological findings from diverse animal models, human iPS cells, and gene-associated and clinical imaging studies. Finally, we aim to discuss the potential for these discoveries to inform the development of new treatments as well as the challenges of advancing from basic neurobiological mechanisms to clinical trials. Together, we anticipate that this Research Topic will be broadly informative to clinicians, physician-scientists, and basic scientists interested in understanding the biology of psychiatric disease.

We welcome Original Research articles, Case Reports of pathological autopsy, and Review articles addressing the above aims.

We specifically encourage submissions addressing the following topics:
• inflammation-related molecules in postmortem brain from psychiatric diseases;
• oxidative-metabolism-related molecules in postmortem brain from psychiatric diseases;
• lipid-related molecules in postmortem brain from psychiatric diseases;
• neurotransmission-related molecules in postmortem brain from psychiatric diseases;
• interaction of genetic and environmental factors in postmortem brain from psychiatric diseases;
• bioinformatics based on comprehensive molecular profiling of the postmortem brain from psychiatric diseases (e.g. cluster analysis, pathway analysis);
• evaluation of the quality of postmortem brain resources from psychiatric diseases;
• cytohistological analysis of the postmortem brain from psychiatric diseases; and
• potential clinical applications based on postmortem brain molecular phenotype of psychiatric diseases.

Keywords: schizophrenia, bipolar disorder, neuropsychiatric disorder, genetic, molecular, postmortem brain

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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