Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium

Horiuchi, Yasue; Kondo, Mari A.; Okada, Kinya; Takayanagi, Yoichiro; Tanaka, Teppei; Ho, Tang; Varvaris, Mark; Tajinda, Katsunori; Hiyama, Hideki; Ni, K; Colantuoni, Carlo; Schretlen, David J.; Cascella, Nicola G.; Pevsner, Jonathan; Ishizuka, Koko; Sawa, Akira

doi:10.1038/tp.2016.154

Cited by 30 publications

(31 citation statements)

References 61 publications

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“…The olfactory neural epithelium has received increasing interest as a surrogate tissue to study brain disorders . Multiple studies have shown that the molecular profiles of brain cells are much closer to those of the olfactory epithelium, compared to those of blood cells . The olfactory epithelium harbors olfactory receptor neurons at different stages of development, and offers a unique resource for investigating both state and trait biomarkers for psychiatric disorders .…”

Section: Patient Neuronal Sample Collectionmentioning

confidence: 99%

“…One significant limitation to the use of the olfactory epithelium is the lack of purity of nasal biopsies, as the tissue contains a number of non‐neuronal cells. To enrich neuronal cell populations, endoscope‐guided nasal punch is combined with laser‐capture microdissection (LCM) to dissect the neuronal tissue . Nevertheless, glia‐like sustentacular (non‐neuronal) cells cannot be excluded with this method.…”

Section: Patient Neuronal Sample Collectionmentioning

confidence: 99%

“…19,26 Multiple studies have shown that the molecular profiles of brain cells are much closer to those of the olfactory epithelium, compared to those of blood cells. [27][28][29] The olfactory epithelium harbors olfactory receptor neurons at different stages of development, and offers a unique resource for investigating both state and trait biomarkers for psychiatric disorders. 30 In particular, the capacity of the olfactory epithelium to regenerate allows for repeated biopsies to study state changes over time.…”

Section: Utility Of the Olfactory Epithelium To Detect State Biomarkersmentioning

confidence: 99%

“…To enrich neuronal cell populations, endoscope-guided nasal punch is combined with laser-capture microdissection (LCM) to dissect the neuronal tissue. 28,32 Nevertheless, glia-like sustentacular (non-neuronal) cells cannot be excluded with this method. Furthermore, the punch biopsy is invasive, and the LCM technique is laborious and timeconsuming.…”

Section: Utility Of the Olfactory Epithelium To Detect State Biomarkersmentioning

confidence: 99%

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Trait and state biomarkers for psychiatric disorders: Importance of infrastructure to bridge the gap between basic and clinical research and industry

Lema

Gamo

Yang

et al. 2018

Psychiatry Clin Neurosci

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To further improve clinical activities in psychiatry by early diagnosis and early intervention with novel mechanism-guided treatments, there is a great need for biomarkers that reflect 'trait' and 'state' in major mental disorders. Stable trait biomarkers would allow early diagnosis, prognosis, and hopefully early intervention in these disorders, while dynamic state markers that reflect symptomatic changes would help to develop treatments that target these molecular mechanisms. However, in the search for such biomarkers, and eventually translating them to the clinic and industry, challenges currently exist at multiple levels, from basic scientific understanding, patient sample collection, and sample and data management, to bridging the gap between basic and clinical research and industry. To address these challenges, we propose an infrastructure that emphasizes: (i) a research and educational framework to facilitate translation between basic neuroscience, clinical research, and industry; (ii) patient recruitment and collection of disease-relevant samples to study trait and state biomarkers; and (iii) a comprehensive database to integrate patient and sample information with biological and clinical data. We believe that such an approach would bolster: research into the biological mechanisms of psychiatric disorders; and collaboration among the laboratory, clinic, and industry to translate these findings into successful treatments.

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Section: Patient Neuronal Sample Collectionmentioning

confidence: 99%

Section: Patient Neuronal Sample Collectionmentioning

confidence: 99%

Section: Utility Of the Olfactory Epithelium To Detect State Biomarkersmentioning

confidence: 99%

Section: Utility Of the Olfactory Epithelium To Detect State Biomarkersmentioning

confidence: 99%

See 2 more Smart Citations

Trait and state biomarkers for psychiatric disorders: Importance of infrastructure to bridge the gap between basic and clinical research and industry

Lema

Gamo

Yang

et al. 2018

Psychiatry Clin Neurosci

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“…For example, by using neural layers from biopsied OE enriched by LCM, the SMAD pathway was found to be downregulated and potentially associated with cognitive deficits in SZ [16]. A significant decrease in the density of p75-NGFR- positive basal cells in SZ OE nasal biopsies was also observed, suggesting dysregulation in the development of ORNs [11].…”

Section: Findings From Oe-derived Tissue/cell Models Obtained From Szmentioning

confidence: 99%

Application of olfactory tissue and its neural progenitors to schizophrenia and psychiatric research

Lavoie

Sawa²,

Ishizuka³

2017

Current Opinion in Psychiatry

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Purpose of review The goal of this review article is to introduce olfactory epithelium (OE)-derived cell/tissue models as a promising surrogate system to study the molecular mechanisms implicated in schizophrenia (SZ) and other neuropsychiatric disorders. Here we particularly focus the utility of their neural progenitors. Recent findings Recent investigations of the pathophysiology of SZ using OE-derived tissue/cell models have provided insights about SZ-associated alterations in neurodevelopment, stress response, and gene/protein expression regulatory pathways. Summary The OE retains the capacity for lifelong neurogenesis and regeneration, because of the presence of neural stem cells and progenitors. Thus, both mature neurons and neural progenitors can be obtained from the OE without the need for genetic reprogramming and related confounds. Furthermore, the OE is highly scalable resource in translational settings. Here we also demonstrate recent findings from research using OE-derived tissue/cell models in SZ and other brain disorders. In summary, we propose that the OE as a promising resource to study neural molecular and cellular signatures relevant to the pathology of SZ and other mental disorders.

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SMAD genes are up‐regulated in brain and blood samples of individuals with schizophrenia

Wolf

Yitzhaky

Hertzberg

2023

J of Neuroscience Research

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Schizophrenia is a severe psychiatric disorder, with heritability around 80%, but a not fully understood pathophysiology. Signal transduction through the mothers against decapentaplegic (SMADs) are eight different proteins involved in the regulation of inflammatory processes, cell cycle, and tissue patterning. The literature is not consistent regarding the differential expression of SMAD genes among subjects with schizophrenia. In this article, we performed a systematic meta‐analysis of the expression of SMAD genes in 423 brain samples (211 schizophrenia vs. 212 healthy controls), integrating 10 datasets from two public repositories, following the PRISMA guidelines. We found a statistically significant up‐regulation of SMAD1, SMAD4, SMAD5, and SMAD7, and a tendency for up‐regulation of SMAD3 and SMAD9 in brain samples of patients with schizophrenia. Overall, six of the eight genes showed a tendency for up‐regulation, and none of them was found to have a tendency for down‐regulation. SMAD1 and SMAD4 were up‐regulated also in blood samples of 13 individuals with schizophrenia versus eight healthy controls, suggesting the SMAD genes' potential role as biomarkers of schizophrenia. Furthermore, SMAD genes' expression levels were significantly correlated with those of Sphingosine‐1‐phosphate receptor‐1 (S1PR1), which is known to regulate inflammatory processes. Our meta‐analysis supports the involvement of SMAD genes in the pathophysiology of schizophrenia through their role in inflammatory processes, as well as demonstrates the importance of gene expression meta‐analysis for improving our understanding of psychiatric diseases.

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Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium

Cited by 30 publications

References 61 publications

Trait and state biomarkers for psychiatric disorders: Importance of infrastructure to bridge the gap between basic and clinical research and industry

Trait and state biomarkers for psychiatric disorders: Importance of infrastructure to bridge the gap between basic and clinical research and industry

Application of olfactory tissue and its neural progenitors to schizophrenia and psychiatric research

SMAD genes are up‐regulated in brain and blood samples of individuals with schizophrenia

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