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Eotaxin, an Endogenous Cognitive Deteriorating Chemokine (ECDC), Is a Major Contributor to Cognitive Decline in Normal People and to Executive, Memory, and Sustained Attention Deficits, Formal Thought Disorders, and Psychopathology in Schizophrenia Patients

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Abstract

Eotaxin is increased in neurodegenerative disorders and schizophrenia, and preclinical studies indicate that eotaxin may induce cognitive deficits. This study aims to examine whether peripheral levels of eotaxin impact cognitive functioning in healthy volunteers and formal thought disorder (FTD) and psychopathology in schizophrenia patients. Serum levels of eotaxin were assayed and cognitive tests were performed on a sample of 40 healthy participants and 80 schizophrenia patients. Among healthy participants, eotaxin levels were significantly associated with episodic/semantic memory, executive functions, Mini Mental State Examination, emotion recognition, and sustained attention. In addition, age-related effects on these cognitive measures were partly mediated by eotaxin. The super-variable “age-eotaxin” predicted a large part of the variance in cognitive functions among healthy participants, and hence, eotaxin may act as an “accelerated brain aging chemokine” (ABAC). In schizophrenia, eotaxin levels had a strong impact on formal thought disorders and psychopathology. In schizophrenia, increased eotaxin strongly impacts memory and sustained attention, which together to a large extent determine FTD. FTD together with memory deficits predicts around 92.5% of the variance in psychopathology. Moreover, the effects of eotaxin are partially mediated by executive functioning, while the effects of male sex on FTD and psychopathology are mediated by eotaxin. In healthy subjects, eotaxin strongly impacts executive functioning and multiple cognitive domains. In schizophrenia, peripheral levels of eotaxin strongly impact both negative symptoms and psychosis (hallucinations and delusions), and these eotaxin effects are mediated by impairments in frontal functioning, memory, sustained attention, and FTD. Eotaxin is an endogenous cognitive deteriorating chemokine (ECDC) and a novel therapeutic target for age-related cognitive decline and schizophrenia as well.

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Funding

The study was supported by the Asahi Glass Foundation, Chulalongkorn University Centenary Academic Development Project, and Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, grant number RA60/042.

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Authors and Affiliations

  1. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Sunee Sirivichayakul & Michael Maes

  2. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Buranee Kanchanatawan & Supaksorn Thika

  3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    André F. Carvalho

  4. Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada

    André F. Carvalho

  5. Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria

    Michael Maes

  6. IMPACT Strategic Research Center, Barwon Health, Deakin University, Geelong, VIC, Australia

    Michael Maes

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  1. Sunee Sirivichayakul
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Contributions

All the contributing authors have participated in the manuscript. MM and BK designed the study. BK recruited patients and completed diagnostic interviews and rating scale measurements. MM carried out the statistical analyses. ST carried out the cognitive tests. SS performed the eotaxin assays. All authors (BK, ST, SS, AC, and MM) contributed to the interpretation of the data and writing of the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Michael Maes.

Ethics declarations

The study was conducted according to Thai and International ethics and privacy laws. Approval for the study was obtained from the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, which is in compliance with the International Guideline for Human Research protection as required by the Declaration of Helsinki, The Belmont Report, CIOMS Guideline, and International Conference on Harmonization in Good Clinical Practice (ICH-GCP).

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The authors declare that they have no conflict of interest.

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Sirivichayakul, S., Kanchanatawan, B., Thika, S. et al. Eotaxin, an Endogenous Cognitive Deteriorating Chemokine (ECDC), Is a Major Contributor to Cognitive Decline in Normal People and to Executive, Memory, and Sustained Attention Deficits, Formal Thought Disorders, and Psychopathology in Schizophrenia Patients. Neurotox Res 35, 122–138 (2019). https://doi.org/10.1007/s12640-018-9937-8

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