| 1 | Genes Brain Behav. 2006 Mar 5: 150-7 |
|---|---|
| PMID | 16507006 |
| Title | Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia. |
| Abstract | We hypothesize that circadian dysfunction could underlie, at least partially, the liability for bipolar 1 disorder (BD1). Our hypothesis motivated tests for the association between the polymorphisms of genes that mediate circadian function and liability for BD1. The US Caucasian patients with BD1 (DSM-IV criteria) and available parents were recruited from Pittsburgh and surrounding areas (n = 138 cases, 196 parents) and also selected from the NIMH Genetics Collaborative Initiative (n = 96 cases, 192 parents). We assayed 44 informative single-nucleotide polymorphisms (SNPs) from eight circadian genes in the BD1 samples. A population-based sample, specifically cord blood samples from local live births, served as community-based controls (n = 180). It was used as a contrast for genotype and haplotype distributions with those of patients. US patients with schizophrenia/schizoaffective disorder (SZ/SZA, n = 331) and available parents from Pittsburgh (n = 344) were assayed for a smaller set of SNPs based on the results from the BD1 samples. Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples. The associations were detected using family-based and case-control analyses, albeit with different SNPs. Associations with TIMELESS and PERIOD3 were also detected in the Pittsburgh SZ/SZA group. Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Psychiatry Clin. Neurosci. 2007 Feb 61: 3-19 |
| PMID | 17239033 |
| Title | Molecular genetics of bipolar disorder and depression. |
| Abstract | In this review, all papers relevant to the molecular genetics of bipolar disorder published from 2004 to the present (mid 2006) are reviewed, and major results on depression are summarized. Several candidate genes for schizophrenia may also be associated with bipolar disorder: G72, DISC1, NRG1, RGS4, NCAM1, DAO, GRM3, GRM4, GRIN2B, MLC1, SYNGR1, and SLC12A6. Of these, association with G72 may be most robust. However, G72 haplotypes and polymorphisms associated with bipolar disorder are not consistent with each other. The positional candidate approach showed an association between bipolar disorder and TRPM2 (21q22.3), GPR50 (Xq28), Citron (12q24), CHMP1.5 (18p11.2), GCHI (14q22-24), MLC1 (22q13), GABRA5 (15q11-q13), BCR (22q11), CUX2, FLJ32356 (12q23-q24), and NAPG (18p11). Studies that focused on mood disorder comorbid with somatic symptoms, suggested roles for the mitochondrial DNA (mtDNA) 3644 mutation and the POLG mutation. From gene expression analysis, PDLIM5, somatostatin, and the mtDNA 3243 mutation were found to be related to bipolar disorder. Whereas most previous positive findings were not supported by subsequent studies, DRD1 and IMPA2 have been implicated in follow-up studies. Several candidate genes in the circadian rhythm pathway, BmaL1, TIMELESS, and PERIOD3, are reported to be associated with bipolar disorder. Linkage studies show many new linkage loci. In depression, the previously reported positive finding of a gene-environmental interaction between HTTLPR (insertion/deletion polymorphism in the promoter of a serotonin transporter) and stress was not replicated. Although the role of the TPH2 mutation in depression had drawn attention previously, this has not been replicated either. Pharmacogenetic studies show a relationship between antidepressant response and HTR2A or FKBP5. New technologies for comprehensive genomic analysis have already been applied. HTTLPR and BDNF promoter polymorphisms are now found to be more complex than previously thought, and previous papers on these polymorphisms should be treated with caution. Finally, this report addresses some possible causes for the lack of replication in this field. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | 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 |
| 4 | Isr J Psychiatry Relat Sci 2010 -1 47: 27-35 |
| PMID | 20686197 |
| Title | Circadian rhythms and clock genes in psychotic disorders. |
| Abstract | Numerous lines of evidence suggest that a disordered circadian system contributes to the etiology and symptomatology of major psychiatric disorders. Sleep disturbances, particularly rapid eye movement (REM) sleep, have been observed in bipolar affective disorder (BPD) and schizophrenia. Therapies aimed at altering the timing and duration of sleep and realigning circadian rhythms, including sleep scheduling, wake extension, light therapy and drug therapies that alter sleep and circadian rhythms appear beneficial for affective disorders. Interventional studies aiming to correct sleep and circadian disturbances in schizophrenia are scarce, although exogenous melatonin has been shown to improve both sleep structure and psychotic symptoms. The study of molecular clock mechanisms in psychiatric disorders is also gaining interest. Genetics studies have found associations with CLOCK, PERIOD1, PERIOD3, and TIMELESS in schizophrenia. Most research on BPD has focused on polymorphisms of CLOCK, but the lithium target GSK-3 may also be significant. New research examining the role of circadian rhythms and clock genes in major mental illness is likely to produce rapid advances in circadian-based therapeutics. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Chronobiol. Int. 2013 May 30: 443-59 |
| PMID | 23286280 |
| Title | Dopamine D2 receptor as a cellular component controlling nocturnal hyperactivities in Drosophila melanogaster. |
| Abstract | Dysfunctional regulation of brain dopamine (DA) functions has been found in patients with drug addiction and various neurological disorders that frequently accompany disturbance in sleep behavior. In this study, the roles of the dopaminergic nervous system on the regulation of daily locomotor activity rhythm were investigated in Drosophila melanogaster. Reduced synaptic DA release by expressing tetanus toxin gradually attenuated peak activity levels by altering activity patterns, particularly under constant darkness. Besides, flies with a mutant dopamine transporter fumin (fmn), in which the synaptic DA levels were elevated, displayed increased activities in both daytime and nighttime, but did more so at nighttime, suggesting that DA function is involved in regulation of fruit fly's nocturnal locomotor activities. Furthermore, flies treated with bromocriptine, an agonist of Drosophila dopamine D2 receptor (dD2R), exhibited nocturnal locomotor hyperactivity in a dose-dependent manner and this effect was inhibited in dD2R knockdown flies. When mutant flies null for period (per), TIMELESS (tim), dClock (dClk), or cycle (cyc) were treated with bromocriptine, only cycle-null flies (cyc(01)) did not show induced nocturnal hyperactivities, suggesting that cyc might play a role in bromocriptine-induced nocturnal hyperactivities. Elevation of experimental temperature also increased nocturnal activities at the expense of daytime activities. The heat-induced increase in nocturnal activities gradually returned to basal levels at continuously elevated temperature. Inhibition of DA synthesis did not suppress heat-induced early development of nocturnal hyperactivity but prevented gradual decrement of initially elevated nocturnal activities, suggesting that DA impinges on certain adaptive roles in response to changes in environmental temperature. These results overall suggest that controlling dopaminergic transmission is important for daily locomotor behavior and bromocriptine-induced nocturnal hyperactivity which is mediated through dD2R receptor and CYC functions. In parallel to these results, excessive activation of dopaminergic neurotransmission, the primary cause of schizophrenia, is associated with abnormally elevated nocturnal locomotor activities through D2-type receptor in Drosophila. The results suggest that fruit flies are an excellent model system to provide some answers to previously unexplainable observations regarding the compromised dopaminergic nervous system and the related therapeutic agents. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Compr Psychiatry 2013 Jan 54: 74-82 |
| PMID | 22794944 |
| Title | "By the foolish Paynter Bayer"--characteristics of the psychopathology of expression in a previously unknown work of the early 18th century by a very probably schizophrenic heraldic painter and his identification. |
| Abstract | Whether schizophrenia existed before the 19th century is an important issue within the history of psychiatry. Written records or other documents that could identify this psychopathology are extremely rare and must therefore be subjected to meticulous historical and psychopathologic analysis. A previously unknown heraldic sheet, with accompanying text, was subjected to historical, heraldic, and psychopathologic analysis. The contemporary inscription "by the mad paynter Bayer" was found on the back of the painting. The phenomenologic analysis emphasized the phenomenology of Jaspers for the formal criteria of a psychosis. Many of the characteristics as seen typical psychopathologic of presumably schizophrenic psychoses by some authors can be found in the formal features of the work. Moreover, a precise historic and heraldic investigation (blazon) allowed us to assign this previously anonymous work to an artist of the period around 1720 to 1740, Abraham Beurer, and to find his contemporary portrait. This is one of the earliest works that can be unambiguously assigned to the psychopathology of expression (art brut). The formal features of schizophrenia appear to be remarkably typical, TIMELESS, and stable, although the objective features are strictly historical. The work provides further evidence that there were individual cases of schizophrenia even before the 18th century. The external designation as "mad" provides important additional support for this view. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Compr Psychiatry 2013 Jan 54: 74-82 |
| PMID | 22794944 |
| Title | "By the foolish Paynter Bayer"--characteristics of the psychopathology of expression in a previously unknown work of the early 18th century by a very probably schizophrenic heraldic painter and his identification. |
| Abstract | Whether schizophrenia existed before the 19th century is an important issue within the history of psychiatry. Written records or other documents that could identify this psychopathology are extremely rare and must therefore be subjected to meticulous historical and psychopathologic analysis. A previously unknown heraldic sheet, with accompanying text, was subjected to historical, heraldic, and psychopathologic analysis. The contemporary inscription "by the mad paynter Bayer" was found on the back of the painting. The phenomenologic analysis emphasized the phenomenology of Jaspers for the formal criteria of a psychosis. Many of the characteristics as seen typical psychopathologic of presumably schizophrenic psychoses by some authors can be found in the formal features of the work. Moreover, a precise historic and heraldic investigation (blazon) allowed us to assign this previously anonymous work to an artist of the period around 1720 to 1740, Abraham Beurer, and to find his contemporary portrait. This is one of the earliest works that can be unambiguously assigned to the psychopathology of expression (art brut). The formal features of schizophrenia appear to be remarkably typical, TIMELESS, and stable, although the objective features are strictly historical. The work provides further evidence that there were individual cases of schizophrenia even before the 18th century. The external designation as "mad" provides important additional support for this view. |
| SCZ Keywords | schizophrenia, schizophrenic |