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Inflammation, hippocampal volume, and cognition in schizophrenia: results from the Northern Finland Birth Cohort 1966

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Abstract

Increased blood interleukin-6 (IL-6) levels are a replicated abnormality in schizophrenia, and may be associated with smaller hippocampal volumes and greater cognitive impairment. These findings have not been investigated in a population-based birth cohort. The general population Northern Finland Birth Cohort 1966 was followed until age 43. Subjects with schizophrenia were identified through the national Finnish Care Register. Blood IL-6 levels were measured in n = 82 subjects with schizophrenia and n = 5373 controls at age 31. Additionally, 31 patients with schizophrenia and 63 healthy controls underwent brain structural MRI at age 34, and cognitive testing at ages 34 and 43. Patients with schizophrenia had significantly higher median (interquartile range) blood IL-6 levels than controls (5.31, 0.85–17.20, versus 2.42, 0.54–9.36, p = 0.02) after controlling for potential confounding factors. In both schizophrenia and controls, higher blood IL-6 levels were predictors of smaller hippocampal volumes, but not cognitive performance at age 34. We found evidence for increased IL-6 levels in patients with midlife schizophrenia from a population-based birth cohort, and replicated associations between IL-6 levels and hippocampal volumes. Our results complement and extend the previous findings, providing additional evidence that IL-6 may play a role in the pathophysiology of schizophrenia and associated brain alterations.

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Authors and Affiliations

  1. Department of Psychiatry and Health Behavior, Augusta University, 997 Saint Sebastian Way, Augusta, GA, 30912, USA

    Brian J. Miller

  2. Research Unit of Biomedicine, University of Oulu, Oulu, Finland

    Karl-Heinz Herzig & Toni Karhu

  3. Medical Research Center (MRC) and Oulu University Hospital, Oulu, Finland

    Karl-Heinz Herzig, Jari Jokelainen, Sirkka Keinänen-Kiukaanniemi, Marjo-Riitta Järvelin & Juha Veijola

  4. Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland

    Karl-Heinz Herzig & Sirkka Keinänen-Kiukaanniemi

  5. Center for Life Course Health Research, University of Oulu, Oulu, Finland

    Jari Jokelainen, Sirkka Keinänen-Kiukaanniemi, Marjo-Riitta Järvelin, Matti Isohanni & Markku Timonen

  6. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

    Marjo-Riitta Järvelin

  7. MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

    Marjo-Riitta Järvelin & Heimo Viinamäki

  8. Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland

    Juha Veijola & Erika Jääskeläinen

  9. Psychiatry, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland

    Heimo Viinamäki

  10. Department of Pediatric Radiology, University of Oulu, Oulu, Finland

    Päivikki Tanskanen

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  1. Brian J. Miller
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Correspondence to Brian J. Miller.

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Conflict of interest

Dr. Miller has nothing to disclose for this study. In the past 12 months, Dr. Miller received research support from the National Institute of Mental Health, NARSAD, the Stanley Medical Research Institute, Acadia, Alkermes, and Augusta University; and Honoraria from Psychiatric Times. Dr. Herzig declares no conflict of interest. Mr. Jokelainen declares no conflict of interest. Mr. Karhu declares no conflict of interest. Dr. Keinänen-Kiukaanniemi declares no conflict of interest. Dr. Järvelin declares no conflict of interest. Dr. Veijola declares no conflict of interest. Dr. Viinamäki declares no conflict of interest. Dr. Jääskeläinen declares no conflict of interest. Dr. Isohanni declares no conflict of interest. Dr. Timonen declares no conflict of interest.

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Miller, B.J., Herzig, KH., Jokelainen, J. et al. Inflammation, hippocampal volume, and cognition in schizophrenia: results from the Northern Finland Birth Cohort 1966. Eur Arch Psychiatry Clin Neurosci 271, 609–622 (2021). https://doi.org/10.1007/s00406-020-01134-x

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