4.4 Article

Altered circadian clock gene expression in patients with schizophrenia

Journal

SCHIZOPHRENIA RESEARCH
Volume 174, Issue 1-3, Pages 17-23

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.schres.2016.04.029

Keywords

Biological clock; Human; Psychiatric disorder; Schizophrenia; Circadian rhythm; Sleep; Molecular clock

Categories

Funding

  1. Stanley Medical Research Institute
  2. Foundation of Soderstrom Konigska sjukhemmet [SLS-230721]
  3. Swedish Society of Medical Research [SLS-100171]
  4. Swedish Society of Medicine [SLS-178551]
  5. Foundation of Magnus Bergvall [4-422/2014, 24942-1/2011]
  6. Foundation of Marta Lundkvist
  7. Foundation of Rut and Astrid Wolff
  8. Foundation of Fredrik and Ingrid Thuring
  9. Foundation of Golje [LA2011-0481]
  10. Foundation of ALF [20060679]

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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 48 h of the clock genes CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERB alpha 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. (C) 2016 Elsevier B.V. All rights reserved.

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