title: 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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden.
authors.forename: Anne-Sofie
authors.initials: AS
authors.lastname: Johansson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Section of Psychiatry at Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Owe-Larsson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Section of Psychiatry at Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors.forename: Jerker
authors.initials: J
authors.lastname: Hetta
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. Electronic address: gabriella.lundkvist@ki.se.
authors.forename: Gabriella B
authors.initials: GB
authors.lastname: Lundkvist
mesh_terms: D000293:Adolescent; D000328:Adult; D056926:CLOCK Proteins / Q000378:metabolism; D002478:Cells, Cultured; D057906:Circadian Clocks / Q000502:physiology*; D056931:Cryptochromes / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D056950:Period Circadian Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000150:complications / Q000378:metabolism*; D012890:Sleep / Q000502:physiology; D012893:Sleep Wake Disorders / Q000150:complications / Q000378:metabolism; D055815:Young Adult
chemical_list: C538963:CRY1 protein, human; D056931:Cryptochromes; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D056926:CLOCK Proteins; C538943:CLOCK protein, human
keywords: Biological clock; Circadian rhythm; Human; Molecular clock; Psychiatric disorder; Schizophrenia; Sleep