Altered circadian clock gene expression in patients with schizophrenia
Abstract
Impaired circadian rhythmicity has been reported in several psychiatric disorders. Schizophrenia is commonly associated with aberrant sleep-wake cycles and insomnia. It is not known if schizophrenia is associated with disturbances in molecular rhythmicity. We cultured fibroblasts from skin samples obtained from patients with chronic schizophrenia and from healthy controls, respectively, and analyzed the circadian expression during 48h of the clock genes CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBα and DBP. In fibroblasts obtained from patients with chronic schizophrenia, we found a loss of rhythmic expression of CRY1 and PER2 compared to cells from healthy controls. We also estimated the sleep quality in these patients and found that most of them suffered from poor sleep in comparison with the healthy controls. In another patient sample, we analyzed mononuclear blood cells from patients with schizophrenia experiencing their first episode of psychosis, and found decreased expression of CLOCK, PER2 and CRY1 compared to blood cells from healthy controls. These novel findings show disturbances in the molecular clock in schizophrenia and have important implications in our understanding of the aberrant rhythms reported in this disease.
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Mononuclear blood cells from schizophrenia patients experiencing their first episode of psychosis have decreased expression of CLOCK, PER2, and CRY1 relative to non-schizophrenia individuals.
“Similarly, mononuclear blood cells from SZ patients experiencing their first episode of psychosis, have decreased expression of CLOCK, PER2, and CRY1 relative to non-SZ individuals164.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [164]
Fibroblasts enriched from skin biopsies of schizophrenia patients exhibit loss of rhythmic expression of CRY1 and PER2 compared to cells from healthy controls, while rhythms in BMAL1 and REV-ERBα persist in a manner comparable to cells from healthy individuals.
“Specifically, fibroblasts enriched from skin biopsies of SZ patients exhibit loss of rhythmic expression of CRY1 and PER2 compared to cells from healthy controls, while rhythms in BMAL1, REV-ERBα persist in a manner comparable to the cells from healthy individuals164.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [164]
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- Authors
- Johansson, A.-S., Owe-Larsson, B., Hetta, J., & Lundkvist, G. B.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Lundkvist, Gabriella B.
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 174
- Issue
- 1-3
- Pages
- 17-23
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2344601571
- Cited by
- 120
- References
- 38
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 9 · 2022: 16 · 2021: 17 · 2020: 13 · 2019: 13 · 2018: 12 · 2017: 8 · 2016: 1 · 2013: 1
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- The Stanley Medical Research Institute
- Foundations of Söderström Königska sjukhemmet (SLS-230721)
- Magnus Bergvall (4-422/2014, 24942-1/2011)
- Märta Lundkvist
- Rut and Astrid Wolff (2008-09)
- Fredrik and Ingrid Thuring (2009-12)
- Golje (LA2011-0481)
- ALF (20060679)
- Swedish Society of Medical Research (SLS-100171)
- Swedish Society of Medicine (SLS-178551)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- schizophrenia, clock genes
- MeSH terms
- Adolescent, Adult, Cells, Cultured, Female, Fibroblasts, Gene Expression Regulation, Humans, Male, Middle Aged, RNA, Messenger, Schizophrenia, Sleep, Sleep Wake Disorders, Young Adult, CLOCK Proteins, Cryptochromes, Period Circadian Proteins, Circadian Clocks
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