| 1 | Dialogues Clin Neurosci 2007 -1 9: 333-42 |
|---|---|
| PMID | 17969870 |
| Title | The role of circadian clock genes in mental disorders. |
| Abstract | The study of molecular clock mechanisms in psychiatric disorders is gaining significant interest due to data suggesting that a misalignment between the endogenous circadian system and the sleep-wake cycle might contribute to the clinical status of patients suffering from a variety of psychiatric disorders. Sleep disturbances in major depressive disorder (MDD) are characterized by increased sleep latency, poorer sleep efficiency reduced latency to the first rapid eye movement (REM) sleep episode, and early-morning awakening, but there is little data to indicate a role of circadian clock genes in MDD. There is also relatively little information regarding the role of clock genes in anxiety. In contrast, a significant amount of evidence gathered in bipolar disorder (BPD) patients suggests a circadian rhythm disorder, namely an advanced circadian rhythm and state-dependent alterations of REM sleep latency. Most research on the role of clock genes in BPD has focused on polymorphisms of CLOCK, but the lithium target GSK3 may also play a significant role. A circadian phase shift is also theorized to contribute to the pathophysiology of winter seasonal affective disorder (SAD). Certain allelic combinations of NPAS2, PER3, and BMAL1 appear to contribute to the risk of SAD. In chronic schizophrenia, disturbances of sleep including insomnia and reduced sleep efficiency have been observed. Genetic studies have found associations with CLOCK, PER1, PER3, and TIMELESS. Sleep and circadian changes associated with dementia due to Alzheimer's disease suggest a functional change in the circadian master clock, which is supported by postmortem studies of clock gene expression in the brain. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Bipolar Disord 2010 Dec 12: 875-6 |
| PMID | 21176035 |
| Title | Association of Per3 gene with bipolar disorder: comment on "Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia". |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Transl Psychiatry 2012 -1 2: e73 |
| PMID | 22832735 |
| Title | A promoter polymorphism in the Per3 gene is associated with alcohol and stress response. |
| Abstract | The period homolog genes Per1, Per2 and PER3 are important components of the circadian clock system. In addition to their role in maintaining circadian rhythm, these genes have been linked to mood disorders, stress response and vulnerability to addiction and alcoholism. In this study, we combined high-resolution sequence analysis and quantitative trait locus (QTL) mapping of gene expression and behavioral traits to identify PER3 as a compelling candidate for the interaction between circadian rhythm, alcohol and stress response. In the BXD family of mouse strains, sequence variants in PER3 have marked effects on steady-state mRNA and protein levels. As a result, the transcript maps as a cis-acting expression QTL (eQTL). We found that an insertion/deletion (indel) variant in a putative stress response element in the promoter region of PER3 causes local control of transcript abundance. This indel results in differences in protein binding affinities between the two alleles through the Nrf2 transcriptional activator. Variation in PER3 is also associated with downstream differences in the expression of genes involved in circadian rhythm, alcohol, stress response and schizophrenia. We found that the PER3 locus is linked to stress/anxiety traits, and that the basal expression of PER3 is also correlated with several anxiety and addiction-related phenotypes. Treatment with alcohol results in increased expression of PER3 in the hippocampus, and this effect interacts with acute restraint stress. Our data provide strong evidence that variation in the PER3 transcript is causally associated with and also responsive to stress and alcohol. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Neuropsychiatr Dis Treat 2014 -1 10: 2325-30 |
| PMID | 25525361 |
| Title | Association of Per3 length polymorphism with bipolar I disorder and schizophrenia. |
| Abstract | Sleep-wake disturbances have frequently been reported in bipolar disorder and schizophrenia, and are considered to be caused by an underlying circadian rhythm disorder. The study presented here was designed to investigate the existence of PER3 polymorphism in bipolar disorder type I (BD-I) and schizophrenic patients in South India. Blood samples were collected from 311 BD-I patients, 293 schizophrenia patients, and 346 age- and sex-matched normal controls. PER3 genotyping was performed on DNA by polymerase chain reaction using specific primers. An increased prevalence of five repeat homozygotes was seen in BD-I patients as compared with healthy controls (odds ratio =1.72 [95% confidence interval: 1.08-2.76, P=0.02]). In BD-I patients, the frequency of the five repeat allele was higher (allele frequency =0.41), and that of the four repeat allele lower (allele frequency =0.36) (? (2)=4.634; P<0.03) than in the control group. No significant association was observed in the allele frequencies of four and five repeat alleles in schizophrenia patients when compared with controls. The occurrence of the five repeat allele of PER3 may be a risk factor for BD-I onset in this ethnic group. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Neuropsychiatr Dis Treat 2014 -1 10: 2325-30 |
| PMID | 25525361 |
| Title | Association of Per3 length polymorphism with bipolar I disorder and schizophrenia. |
| Abstract | Sleep-wake disturbances have frequently been reported in bipolar disorder and schizophrenia, and are considered to be caused by an underlying circadian rhythm disorder. The study presented here was designed to investigate the existence of PER3 polymorphism in bipolar disorder type I (BD-I) and schizophrenic patients in South India. Blood samples were collected from 311 BD-I patients, 293 schizophrenia patients, and 346 age- and sex-matched normal controls. PER3 genotyping was performed on DNA by polymerase chain reaction using specific primers. An increased prevalence of five repeat homozygotes was seen in BD-I patients as compared with healthy controls (odds ratio =1.72 [95% confidence interval: 1.08-2.76, P=0.02]). In BD-I patients, the frequency of the five repeat allele was higher (allele frequency =0.41), and that of the four repeat allele lower (allele frequency =0.36) (? (2)=4.634; P<0.03) than in the control group. No significant association was observed in the allele frequencies of four and five repeat alleles in schizophrenia patients when compared with controls. The occurrence of the five repeat allele of PER3 may be a risk factor for BD-I onset in this ethnic group. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Chronobiol. Int. 2015 Jun 32: 591-5 |
| PMID | 25798540 |
| Title | Differences in planning performance, a neurocognitive endophenotype, are associated with a functional variant in PER3 gene. |
| Abstract | Performance alterations in executive function have been studied as potential endophenotypes for several neuropsychiatric diseases. Planning is an important component of executive function and has been shown to be affected in diseases such as attention deficit hyperactivity disorder, schizophrenia, obsessive-compulsive disorder and Parkinson's disease. Several genes related to dopaminergic systems, such as COMT, have been explored as candidates for influencing planning performance. The circadian clock gene PERIOD3 (PER3) has been shown to be associated with several complex behaviors in humans and could be involved in different signaling mechanisms. In this study, we evaluated the possible association between a functional polymorphism in the PER3 gene (PER3-VNTR, rs57875989) and performance in a commonly used test of planning (Tower of London, TOL) in 229 healthy subjects from Bogotá, Colombia. PER3-VNTR genotyping was carried out with conventional PCR and all participants completed the TOL test using the computerized Psychology Experiment Building Language (PEBL) battery. A linear regression model was used for the analysis of association with the SNPStats program. We found that 4/4 genotype carriers showed a better performance and made fewer moves, in comparison to 4/5 and 5/5 genotype carriers (p?=?0.003). These results appear to be independent from effects of this polymorphism on self-reported average hours of sleep during work days in our sample. This is the first evidence of an association between PER3-VNTR and planning performance in a sample of healthy subjects and our results are consistent from previous findings for alterations in other cognitive domains. Future studies examining additional genes could lead to the identification of novel molecular underpinnings of planning in healthy subjects and in patients with neuropsychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Psychoneuroendocrinology 2016 Feb 64: 108-16 |
| PMID | 26630391 |
| Title | Diurnal neurobiological alterations after exposure to clozapine in first-episode schizophrenia patients. |
| Abstract | Irregular circadian rhythm and some of its most characteristic symptoms are frequently observed in patients with schizophrenia. However, changes in the expression of clock genes or neuropeptides that are related to the regulation of circadian rhythm may influence the susceptibility to recurrence after antipsychotic treatment in schizophrenia, but this possibility has not been investigated. Blood samples were collected from 15 healthy male controls and 13 male schizophrenia patients at 4h intervals for 24h before and after treatment with clozapine for 8 weeks. The outcome measures included the relative expression of clock gene mRNA PERIOD1 (PER1), PERIOD2 (PER2), PERIOD3 (PER3) and the levels of plasma cortisol, orexin, and insulin. Compared with healthy controls, schizophrenia patients presented disruptions in diurnal rhythms of the expression of PER1, PER3, and NPAS2 and the release of orexin, accompanied by a delayed phase in the expression of PER2, decreases in PER3 and NPAS2 expression, and an increase in cortisol levels at baseline. Several of these disruptions (i.e., in PER1 and PER3 expression) persisted after 8 weeks of clozapine treatment, similar to the decreases in the 24-h expression of PER3 and NPAS2. Clozapine treatment for 8 weeks significantly decreased the 24-h levels of PER2 and increased the 24-h levels of insulin. These persistent neurobiological changes that occur after 8 weeks of clozapine treatment may contribute to the vulnerability to recurrence and efficacy of long-term maintenance treatment in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |