A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice

<p>Abstract</p> <p>Background</p> <p>Many genes control circadian period in mice. Prior studies suggested a quantitative trait locus (QTL) on proximal mouse chromosome 12 for interstrain differences in circadian period. Since the B6.D2N<it>Ahr</it>^<it>d</it>/J strain has DBA/2 alleles for a portion of proximal chromosome 12 introgressed onto its C57BL/6J background, we hypothesized that these mice would have a shorter circadian period than C57BL/6J mice.</p> <p>Methods</p> <p>We compared circadian phenotypes of B6.D2N<it>Ahr</it>^<it>d</it>/J and C57BL/6 mice: period of general locomotor activity in constant dark and rest/activity pattern in alternating light and dark. We genotyped the B6.D2N<it>Ahr</it>^<it>d</it>/J mice to characterize the size of the genomic insert. To aid in identifying candidate quantitative trait genes we queried databases about the resident SNPs, whole brain gene expression in C57BL/6J versus DBA/2J mice, and circadian patterns of gene expression.</p> <p>Results</p> <p>The B6.D2N<it>Ahr</it>^<it>d</it>/J inbred mice have a shorter circadian period of locomotor activity than the C57BL/6J strain. Furthermore, the genomic insert is associated with another phenotype: the mean phase of activity minimum in the dark part of a light-dark lighting cycle. It was one hour later than in the background strain. The B6.D2N<it>Ahr</it>^<it>d</it>/J mice have a DBA/2J genomic insert spanning 35.4 to 41.0 megabase pairs on Chromosome 12. The insert contains 15 genes and 12 predicted genes. In this region <it>Ahr </it>(arylhydrocarbon receptor) and <it>Zfp277 </it>(zinc finger protein 277) both contain non-synonymous SNPs. <it>Zfp277 </it>also showed differential expression in whole brain and was cis-regulated. Three genes and one predicted gene showed a circadian pattern of expression in liver, including <it>Zfp277</it>.</p> <p>Conclusion</p> <p>We not only fine-mapped the QTL for circadian period on chromosome 12 but found a new QTL there as well: an association with the timing of the nocturnal activity-minimum. Candidate quantitative trait genes in this QTL are zinc finger protein 277 and arylhydrocarbon receptor. Arylhydrocarbon receptor is structurally related to <it>Bmal1</it>, a canonical clock gene.</p

Intermittent long-wavelength red light increases the period of daily locomotor activity in mice

BACKGROUND: We observed that a dim, red light-emitting diode (LED) triggered by activity increased the circadian periods of lab mice compared to constant darkness. It is known that the circadian period of rats increases when vigorous wheel-running triggers full-spectrum lighting; however, spectral sensitivity of photoreceptors in mice suggests little or no response to red light. Thus, we decided to test the following hypotheses: dim red light illumination triggered by activity (LEDfb) increases the circadian period of mice compared to constant dark (DD); covering the LED prevents the effect on period; and DBA2/J mice have a different response to LEDfb than C57BL6/J mice. METHODS: The irradiance spectra of the LEDs were determined by spectrophotometer. Locomotor activity of C57BL/6J and DBA/2J mice was monitored by passive-infrared sensors and circadian period was calculated from the last 10 days under each light condition. For constant dark (DD), LEDs were switched off. For LED feedback (LEDfb), the red LED came on when the mouse was active and switched off seconds after activity stopped. For taped LED the red LED was switched on but covered with black tape. Single and multifactorial ANOVAs and post-hoc t-tests were done. RESULTS: The circadian period of mice was longer under LEDfb than under DD. Blocking the light eliminated the effect. There was no difference in period change in response to LEDfb between C57BL/6 and DBA/2 mice. CONCLUSION: An increase in mouse circadian period due to dim far-red light (1 lux at 652 nm) exposure was unexpected. Since blocking the light stopped the response, sound from the sensor's electronics was not the impetus of the response. The results suggest that red light as background illumination should be avoided, and indicator diodes on passive infrared motion sensors should be switched off

Quality of sleep in patients with schizophrenia is associated with quality of life and coping

BACKGROUND: While sleep disturbance is widespread in schizophrenia it is less clear whether sleep disturbance is uniquely related to impaired coping and perceived quality of life. METHODS: We simultaneously assessed sleep quality, symptoms, and coping in 29 persons with schizophrenia or schizoaffective disorder in a post acute phase of illness. Assessment instruments included the Pittsburgh Sleep Quality Index; the Positive and Negative Symptom Scale; the Heinrichs Quality of Life Scale; and the Ways of Coping Scale. Multiple regressions were performed predicting quality of life and coping from sleep quality controlling for age and symptom severity. On a subset of seven subjects non-dominant wrist actigraphy was used as an objective check of their self-reported poor sleep. RESULTS: Analyses revealed that poor sleep quality predicted low quality of life (r = -0.493; p = .022) and reduced preference for employing positive reappraisal when facing a stressor (r = -0.0594; p = 0.0012). Actigraphy confirmed poor sleep quality in a subset of subjects. They had shorter sleep duration (p < .0005), shorter average sleep episodes (p < .005) and more episodes of long awakening (p < 0.05) than community norms. CONCLUSION: The results are consistent with the hypotheses that poor sleep may play a unique role in sustaining poor quality of life and impaired coping in patients with schizophrenia. These associations may hold for community controls as well

A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice-0

<p><b>Copyright information:</b></p><p>Taken from "A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice"</p><p>http://www.jcircadianrhythms.com/content/5/1/7</p><p>Journal of Circadian Rhythms 2007;5():7-7.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2174920.</p><p></p>ays is plotted beneath the previous pair of days. Activity is indicated by the height of the narrow histograms each 10 min wide

A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice-3

<p><b>Copyright information:</b></p><p>Taken from "A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice"</p><p>http://www.jcircadianrhythms.com/content/5/1/7</p><p>Journal of Circadian Rhythms 2007;5():7-7.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2174920.</p><p></p

A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice-4

<p><b>Copyright information:</b></p><p>Taken from "A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice"</p><p>http://www.jcircadianrhythms.com/content/5/1/7</p><p>Journal of Circadian Rhythms 2007;5():7-7.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2174920.</p><p></p>ays is plotted beneath the previous pair of days. Activity is indicated by the height of the narrow histograms each 10 min wide

A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice-2

<p><b>Copyright information:</b></p><p>Taken from "A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice"</p><p>http://www.jcircadianrhythms.com/content/5/1/7</p><p>Journal of Circadian Rhythms 2007;5():7-7.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2174920.</p><p></p>he activity profiles for the last eight days under LD 12:12. The gray arrow shows the placement of the siesta. The dark line indicates the mean, the shaded areas are SEM

A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice-5

<p><b>Copyright information:</b></p><p>Taken from "A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice"</p><p>http://www.jcircadianrhythms.com/content/5/1/7</p><p>Journal of Circadian Rhythms 2007;5():7-7.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2174920.</p><p></p

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

ImportanceLess than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant.ObjectiveTo determine the relative effectiveness and safety of 3 common alternate treatments for MDD.Design, setting, and participantsFrom December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks.InterventionsSwitch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase).Main outcomes and measuresThe primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects.ResultsAmong 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain.Conclusions and relevanceAmong a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach.Trial registrationclinicaltrials.gov Identifier: NCT01421342