1J. Biol. Rhythms 2011 Aug 26: 305-13
TitleInterval timing is intact in arrhythmic Cry1/Cry2-deficient mice.
AbstractLocalizing the self in time is fundamental for daily life functioning and is lacking in severe disabling neuropsychiatric disorders like schizophrenia. Brains keep track of time across an impressive range of scales. Great progress has been made in identifying the molecular machinery of the circadian clock, the brain's master clock that operates on the 24-hour scale and allows animals to know the "time of the day" that important events occur, without referring to external cues. However, the biology of interval timing, the mechanism responsible for durations in the seconds-to-minutes-to-hours range, remains a mystery, and an obvious question is whether there is a common biological solution for keeping track of time across these 2 time scales. To address this, we trained Cry1/CRY2 double knockout mice on an interval timing task with durations that ranged between 3 and 27 seconds. The mice were kept under constant light conditions to avoid any exogenously induced form of daily rhythmicity. We observed that the homozygous knockouts displayed as accurate and precise a temporal memory as the control mice. This suggests that the Cry1 and CRY2 genes are not an important component of the interval timer. Furthermore, proper calibration of the interval timer does not depend on a functional circadian clock. Thus, these 2 timing systems likely rely on different and independent biological mechanisms.
SCZ Keywordsschizophrenia
2Chronobiol. Int. 2015 May 32: 579-84
TitleDepression-associated ARNTL and PER2 genetic variants in psychotic disorders.
AbstractCircadian rhythm disturbances overlap between psychotic disorders, e.g. schizophrenia, and major depression. We hypothesized that circadian gene variants previously associated with unipolar depression would be overrepresented also in patients with psychotic disorder. Six genetic polymorphisms in ARNTL, PER2 and CRY2 were genotyped in 566 schizophrenia spectrum disorder patients and 926 controls. The rs2290036-C variant of ARNTL was over-represented in psychosis patients, and the variants rs934945-G and rs10462023-G of PER2 were associated with a more severe psychotic disorder. The directions of these genetic associations were in line with those previously identified for depression.
SCZ Keywordsschizophrenia
3Schizophr. Res. 2016 Apr -1: -1
TitleAltered circadian clock gene expression in patients with schizophrenia.
AbstractImpaired 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-ERB? 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.
SCZ Keywordsschizophrenia