A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

Yang, Kun; Longo, Luisa; Narita, Zui; Cascella, Nicola G.; Nucifora, Frederick C.; Coughlin, Jennifer M.; Nestadt, Gerald; Sedlak, Thomas W.; Mihaljević, Marina; Wang, M.; Kenkare, Anshel; Nagpal, Anisha; Sethi, Mehk; Kelly, Alexandra; Carlo, Pasquale Di; Kamath, Vidyulata; Faria, Andréia V.; Barker, Peter B.; Sawa, Akira

doi:10.1101/2021.05.03.442450

Cited by 4 publications

(1 citation statement)

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“…To demonstrate the validity and utility of ONCs as surrogate neuronal cells, in the present study, we used clinical data and biospecimens collected from study participants recruited by clinical cohorts [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] established at Johns Hopkins Schizophrenia Center under approval of the Johns Hopkins Medicine Institutional Review Boards. All study participants provided written informed consent.…”

Section: Study Participantsmentioning

confidence: 99%

Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science

Yang

Ishizuka

Lane

et al. 2022

Preprint

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Biopsy is an essential procedure of clinical medicine in which we obtain tissues and cells that are supposed to directly reflect pathological changes of each disease. Biopsy from the brain is difficult at both practical and ethical levels. Nasal biopsy that captures tissues with olfactory neurons has been considered as an alternative method of obtaining neurons from living patients with brain disorders. However, insufficient characterization of biopsied cells/tissues has hampered a wider use of nasal tissues as surrogate resources for the brain. By conducting single cell and bulk RNA-sequence analysis of olfactory neuronal cells (ONCs) enriched from nasal biopsied tissues and using multiple pubic datasets in comparison, we now report precise characterization of ONCs at the molecular levels. These cells are easily and reproducibly prepared and have two major strengths. They are homogeneous and neuronal, resembling excitatory neurons in the dorsolateral prefrontal cortex and anterior cingulate cortex in molecular signatures.

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Section: Study Participantsmentioning

confidence: 99%

Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science

Yang

Ishizuka

Lane

et al. 2022

Preprint

Self Cite

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Central oxidative stress and early vocational outcomes in first episode psychosis: A 7-Tesla Magnetic Resonance Spectroscopy study of glutathione

Mackinley

Ford²,

Jeon

et al. 2021

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Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Several lines of evidence from preclinical, genetic and biochemical studies suggest a role for high oxidative stress in poor functional outcomes. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) provides an opportunity to investigate the relationship between central antioxidant tone and functional outcomes at the time of first episode psychosis (FEP). A body of epidemiological studies indicates better functional outcomes in patients at early stages of schizophrenia compared to patients at a chronic, established phase of illness. We scanned 57 patients with FEP and 30 matched healthy controls and estimated GSH resonance using 7-Tesla MRS. We minimised the confounding effects of illness chronicity, long-term treatment exposure and metabolic complications by recruiting patients with <2 weeks of lifetime antipsychotic exposure on average and followed up this cohort for the next 1 year to determine functional outcomes. Patients with FEP who achieved employment/education or training status (EET) in the first year, had higher GSH at the baseline than healthy controls. Social and occupational functioning assessment scale (SOFAS) scores were also significantly higher in patients with higher GSH levels at the outset, after adjusting for various confounds including baseline SOFAS. Patients who were not in employment, education or training (NEET) did not differ from healthy subjects in their GSH levels. Our observations support a key role for the central antioxidant tone in the functional outcomes of early psychosis.

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Neuroimaging alterations and relapse in early-stage psychosis

Mihaljević

Nagpal

Etyemez

et al. 2021

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Recent reports have indicated that the occurrence of symptom exacerbation in early-stage psychosis could result in brain changes, which are likely to underlie the poorer disease outcome. Thus, it is important to identify neuroimaging signature associated with symptom exacerbation in early-stage psychosis. We studied 85 patients with psychosis within two years after onset and 94 healthy controls (HC). The patient group was subdivided into two groups: 54 patients who did not experience major symptom exacerbation between the onset and study enrollment (P1), and 31 patients who experienced major symptom exacerbation (P2). We analyzed three brain imaging measures derived from resting-state functional MRI, such as global efficiency, nodal efficiency, and resting-state functional connectivity (rs-FC). After excluding some brain imaging measures that were potentially affected by clinical variables, we conducted a comparison between overall patient group and HC group as well as comparsions between HC, P1, and P2 groups for these three types of brain imaging measures, respectively. By integrating the information, we pinned down the dorsal anterior cingulate cortex and thalamus as key hubs in the context of several large-scale brain networks associated with symptom exacerbations in early-stage psychosis. Our study implies the importance of considering neural mechanism associated with symptom exacerbations in early stages of psychotic disorders.

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A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

Cited by 4 publications

References 71 publications

Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science

Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science

Central oxidative stress and early vocational outcomes in first episode psychosis: A 7-Tesla Magnetic Resonance Spectroscopy study of glutathione

Neuroimaging alterations and relapse in early-stage psychosis

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