| 1 | Med. Hypotheses 2007 -1 69: 849-51 |
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| PMID | 17376600 |
| Title | Cryptochrome1 maybe a candidate gene of schizophrenia. |
| Abstract | During the last 10 years, we have witnessed major progress in the genetic study of schizophrenia, but gene-mapping efforts have been hampered by the complex mode of inheritance and the likelihood of multiple genes of small effect. In view of the complexity, it may be instructive to understand the biological bases for pathogenesis. Extensive disruption in circadian function is known to occur among schizophrenia patients. If circadian dysfunction can be established as an 'endophenotype' for schizophrenia, it may not only enable the identification of more homogenous sub-groups, but also facilitate the genetic analyses. Therefore, circadian dysfunction maybe underlies the pathogenesis of schizophrenia and would be logical to investigate polymorphisms of genes encoding key proteins that mediate circadian rhythms. Cryptochrome1 (CRY1), located in a chromosomal region 12q23-q24.1, performs predominantly regulatory function in circadian clock and which is close to a linkage hotspot (12q24) of schizophrenia. Recent studies also found that CRY1 gene interacted with antipsychotic drugs and dopamine system which played a core role in the pathophysiology of schizophrenia. Based on these findings, we speculate that CRY1 was the candidate gene of schizophrenia. The proposition may have new clues on the development of genetic study on complex diseases. |
| SCZ Keywords | schizophrenia |
| 2 | J. Biol. Rhythms 2011 Aug 26: 305-13 |
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| PMID | 21775289 |
| Title | Interval timing is intact in arrhythmic Cry1/Cry2-deficient mice. |
| Abstract | Localizing 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 Keywords | schizophrenia |
| 3 | Front Behav Neurosci 2014 -1 8: 388 |
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| PMID | 25414651 |
| Title | Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens. |
| Abstract | Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in five of five independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, CRY1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis (WGCNA) identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder (BPD), and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions. |
| SCZ Keywords | schizophrenia |
| 4 | Schizophr. Res. 2016 Apr -1: -1 |
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| PMID | 27132483 |
| 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-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 Keywords | schizophrenia |