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Biomedical subjects

Daniel F Kripke

Publications and source records attributed to Daniel F Kripke.

At least 19 recordsLinked to original sources
PubMed2006

Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder.

Bipolar affective disorder (BPAD) is suspected to arise in part from malfunctions of the circadian system, a system that enables adaptation to a daily and seasonally cycling environment. Genetic variations altering functions of genes involved with the input to the circadian clock, in the molecular feedback loops constituting the circadian oscillatory mechanism itself, or in the regulatory output systems could influence BPAD as a result. Several human circadian system genes have been identified and localized recently, and a comparison with linkage hotspots for BPAD has revealed some correspondences. We have assessed evidence for linkage and association involving polymorphisms in 10 circadian clock genes (ARNTL, CLOCK, CRY2, CSNK1epsilon, DBP, GSK3beta, NPAS2, PER1, PER2, and PER3) to BPAD. Linkage analysis in 52 affected families showed suggestive evidence for linkage to CSNK1epsilon. This finding was not substantiated in the association study. Fifty-two SNPs in 10 clock genes were genotyped in 185 parent proband triads. Single SNP TDT analyses showed no evidence for association to BPAD. However, more powerful haplotype analyses suggest two candidates deserving further studies. Haplotypes in ARNTL and PER3 were found to be significantly associated with BPAD via single-gene permutation tests (PG = 0.025 and 0.008, respectively). The most suggestive haplotypes in PER3 showed a Bonferroni-corrected P-value of PGC = 0.07. These two genes have previously been implicated in circadian rhythm sleep disorders and affective disorders. With correction for the number of genes considered and tests conducted, these data do not provide statistically significant evidence for association. However, the trends for ARNTL and PER3 are suggestive of their involvement in bipolar disorder and warrant further study in a larger sample.

ARNTL Transcription Factors↗
PubMed2005

Daily illumination exposure and melatonin: influence of ophthalmic dysfunction and sleep duration.

BACKGROUND: Ocular pathology lessens light's efficacy to maintain optimal circadian entrainment. We examined whether ophthalmic dysfunction explains unique variance in melatonin excretion of older adults over and above the variance explained by daily illumination, medical, and sociodemographic factors. We also examined whether ophthalmic dysfunction influences relationships between ambient illumination and melatonin. METHODS: Thirty older adults (mean age = 69 years; Blacks = 42% and Whites = 58%) of both genders participated in the study. Demographic and health data were collected at baseline. Participants underwent eye exams at SUNY Downstate Medical Center, wore an actigraph to monitor illumination and sleep, and collected urine specimens to estimate aMT6s concentrations. RESULTS: Hierarchical regression analysis showed that illumination factors explained 29% of the variance in aMT6s mesor. The proportion of variance explained by ophthalmic factors, sleep duration, and race was 10%, 2%, and 2%, respectively. Illumination factors explained 19% of the variance in aMT6s acrophase. The proportion of variance explained by ophthalmic factors, sleep duration, and race was 11%; 17%; and 2%, respectively. Controlling for sleep duration and race reduced the correlations between illumination and melatonin, whereas controlling for ophthalmic factors did not. CONCLUSION: Ophthalmic exams showed that elevated intraocular pressure and large cup-to-disk ratios were independently associated with earlier melatonin timing. Lower illumination exposure also had independent associations with earlier melatonin timing. Conceivably, ophthalmic and illumination factors might have an additive effect on the timing of melatonin excretion, which in turn might predispose individuals to experience early morning awakenings.

Journal Article↗
PubMed2005

Bright light treatment of depression for older adults [ISRCTN55452501].

BACKGROUND: The incidence of insomnia and depression in the elder population is significant. It is hoped that use of light treatment for this group could provide safe, economic, and effective rapid recovery. METHODS: In this home-based trial we treated depressed elderly subjects with bright white (8,500 Lux) and dim red (<10 Lux) light for one hour a day at three different times (morning, mid-wake and evening). A placebo response washout was used for the first week. Wake treatment was conducted prior to the initiation of treatment, to explore antidepressant response and the interaction with light treatment. Urine and saliva samples were collected during a 24-hour period both before and after treatment and assayed for aMT6s and melatonin respectively to observe any change in circadian timing. Subjects wore a wrist monitor to record light exposure and wrist activity. Daily log sheets and weekly mood (GDS) and physical symptom (SAFTEE) scales were administered. Each subject was given a SCID interview and each completed a mood questionnaire (SIGH-SAD-SR) before and after treatment. Also, Hamilton Depression Rating (SIGH-SAD version) interviews were conducted by a researcher who was blind to the treatment condition. A control group of healthy, age-matched, volunteers was studied for one day to obtain baseline data for comparison of actigraphy and hormone levels. RESULTS: Eighty-one volunteers, between 60 and 79 years old, completed the study. Both treatment and placebo groups experienced mood improvement. Average GDS scores improved 5 points, the Hamilton Depression Rating Scale (HDRS) 17 scores (extracted from the self-rated SIGH-SAD-SR) improved 6 points. There were no significant treatment effects or time-by-treatment interactions. No significant adverse reactions were observed in either treatment group. The assays of urine and saliva showed no significant differences between the treatment and placebo groups. The healthy control group was active earlier and slept earlier but received less light than the depressed group at baseline. CONCLUSION: Antidepressant response to bright light treatment in this age group was not statistically superior to placebo. Both treatment and placebo groups experienced a clinically significant overall improvement of 16%.

Age Factors↗
PubMed2005

Bright green light treatment of depression for older adults [ISRCTN69400161].

BACKGROUND: Bright white light has been successfully used for the treatment of depression. There is interest in identifying which spectral colors of light are the most efficient in the treatment of depression. It is theorized that green light could decrease the intensity duration of exposure needed. Late Wake Treatment (LWT), sleep deprivation for the last half of one night, is associated with rapid mood improvement which has been sustained by light treatment. Because spectral responsiveness may differ by age, we examined whether green light would provide efficient antidepressant treatment in an elder age group. METHODS: We contrasted one hour of bright green light (1,200 Lux) and one hour of dim red light placebo (<10 Lux) in a randomized treatment trial with depressed elders. Participants were observed in their homes with mood scales, wrist actigraphy and light monitoring. On the day prior to beginning treatment, the participants self-administered LWT. RESULTS: The protocol was completed by 33 subjects who were 59 to 80 years old. Mood improved on average 23% for all subjects, but there were no significant statistical differences between treatment and placebo groups. There were negligible adverse reactions to the bright green light, which was well tolerated. CONCLUSION: Bright green light was not shown to have an antidepressant effect in the age group of this study, but a larger trial with brighter green light might be of value.

Adult↗
PubMed2005

Circadian phase-shifting effects of a laboratory environment: a clinical trial with bright and dim light.

BACKGROUND: Our aims were to examine the influence of different bright light schedules on mood, sleep, and circadian organization in older adults (n = 60, ages 60-79 years) with insomnia and/or depression, contrasting with responses of young, healthy controls (n = 30, ages 20-40 years). METHODS: Volunteers were assessed for one week in their home environments. Urine was collected over two 24-hour periods to establish baseline acrophase of 6-sulphatoxymelatonin (aMT6s) excretion. Immediately following home recording, volunteers spent five nights and four days in the laboratory. Sleep periods were fixed at eight hours in darkness, consistent with the volunteers' usual sleep periods. Volunteers were randomly assigned to one of three light treatments (four hours per day) within the wake period: (A) two hours of 3,000 lux at 1-3 hours and 13-15 hours after arising; (B) four hours of 3,000 lux at 6-10 hours after arising; (C) four hours of dim placebo light at 6-10 hours after arising. Lighting was 50 lux during the remainder of wakefulness. The resulting aMT6s acrophase was determined during the final 30 hours in the laboratory. RESULTS: Neither mood nor total melatonin excretion differed significantly by treatment. For the three light treatments, significant and similar phase-response plots were found, indicating that the shift in aMT6s acrophase was dependent upon the circadian time of treatment. The changes in circadian timing were not significantly correlated to changes in sleep or mood. CONCLUSION: The trial failed to demonstrate photoperiodic effects. The results suggest that even low levels of illumination and/or fixed timing of behavior had significant phase-shifting effects.

Journal Article↗
PubMed2005

Suicides in the midnight sun--a study of seasonality in suicides in West Greenland.

Greenland is the most extreme of human habitats in regard to annual changes in natural light. From being very low, the rate of suicides in Greenland has increased during the past few decades to be among the highest in the world. Several studies have shown seasonality in suicides with spring or summer peaks, but this has not been previously shown in Greenland. Official data from 1968 to 1995 from West Greenland were pooled. A significant seasonality in the 833 suicides was found using Rayleigh's test, a peak in June and a trough in the winter. Suicides increased during the period, and reached high rates in most age groups, up to 577 per 100,000 person-years in men aged 15-24 years in 1990, and up to 147 per 100,000 person-years in women aged 15-24 years in 1995. Violent methods of suicide were used by 93%. Depression has been reported uncommonly. High alcohol intake and extended periods of light in the summer may contribute to impulsive-aggressive summer suicides.

Adolescent↗
PubMed2005

Examination of the clock gene Cryptochrome 1 in bipolar disorder: mutational analysis and absence of evidence for linkage or association.

Bipolar disorder is associated with malfunctions of the circadian system, which regulates individual circadian rhythms and which enables the adaptation to a daily 24-h cycle and seasonal change. One of the human circadian clock genes, cryptochrome 1 (Cry1) (located on 12q23-q24.1) was analyzed because of its close correspondence to a linkage hotspot for bipolar disorder. We found no evidence for linkage of 52 bipolar families to two Cry1 flanking microsatellites under several parametric and non-parametric models. In order to employ association for a more sensitive test, 25 affected subjects selected from families with positive LOD scores were screened for mutations by sequencing 9.5% of the Cry1 gene. A total of 16 single nucleotide polymorphisms (SNPs) and a 3 base pair insertion were identified. However, no mutations with probable functional impact were found. These novel SNPs and data on allele frequency and linkage disequilibrium structure will be useful for future association analyses. Nine SNPs have been analyzed in a set of 159 parent proband triads. Linkage disequilibrium analyses using single SNPs and haplotypes showed no association to bipolar disease.Additional, more powerful, studies involving Cry1 and other circadian clock genes need to be tested before an association of circadian abnormalities with bipolar disorder can be excluded.

Base Sequence↗
PubMed2004

Ethnicity, sleep, mood, and illumination in postmenopausal women.

BACKGROUND: This study examined how ethnic differences in sleep and depression were related to environmental illumination and circadian rhythms. METHODS: In an ancillary study to the Women's Health Initiative, 459 postmenopausal women were recorded for one week in their homes, using wrist monitors. Sleep and illumination experience were estimated. Depression was self-rated with a brief adjective check list. Affective diagnoses were made using the SCID interview. Sleep disordered breathing was monitored with home pulse oximetry. RESULTS: Hispanic and African-American women slept less than European-American women, according to both objective recordings and their own sleep logs. Non-European-American women had more blood oxygen desaturations during sleep, which accounted for 26% of sleep duration variance associated with ethnicity. Hispanic women were much more depressed. Hispanic, African-American and Native-American women experienced less daily illumination. Less daily illumination experience was associated with poorer global functioning, longer but more disturbed sleep, and more depression. CONCLUSIONS: Curtailed sleep and poor mood were related to ethnicity. Sleep disordered breathing was a factor in the curtailed sleep of minority women. Less illumination was experienced by non-European-American women, but illumination accounted for little of the contrasts between ethnic groups in sleep and mood. Social factors may be involved.

Black or African American↗
PubMed2004

Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure.

PURPOSE: To compare the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure (IOP) in patients with ocular hypertension or early glaucomatous changes. DESIGN: Prospective, open-label, experimental study with crossover design. METHODS: Eighteen patients with ocular hypertension or early glaucomatous changes (aged 41 to 79 years) each received topical treatments with timolol (0.5% Timoptic-XE), latanoprost (0.005% Xalatan), and no IOP-lowering medication, for at least 4 weeks. Timolol was given once in the morning upon awakening and latanoprost once in the evening at bedtime. At the end of each treatment period, the patient was housed in a sleep laboratory for 24 hours and IOP was measured every 2 hours using a pneumatonometer. Measurements were taken sitting and supine during the 16-hour diurnal/wake period and only supine during the 8-hour nocturnal/sleep period. Mean diurnal and nocturnal IOP levels were compared among the treatments with timolol, latanoprost, and no medication. RESULTS: In the diurnal period, the mean IOP under the timolol or the latanoprost treatment was significantly less than the mean IOP under no medication in both the sitting and the supine positions. There was no statistical difference between the timolol and latanoprost treatments. In the nocturnal period, supine IOP with timolol treatment was not different from the supine IOP with no medication but was significantly higher than supine IOP with the latanoprost treatment. CONCLUSION: Although both once-daily timolol and latanoprost were effective in lowering IOP during the diurnal period, only latanoprost reduced IOP during the nocturnal period.

Adult↗
PubMed2004

Long sleep and mortality: rationale for sleep restriction.

Epidemiologic studies have consistently shown that sleeping >8 h per night is associated with increased mortality. Indeed, the most recent American Cancer Society data of 1.1 million respondents showed that sleeping longer than 7.5 h was associated with approximately 5% of the total mortality of the sample. The excess mortality was found even after controlling for 32 potentially confounding risk factors. Although epidemiologic data cannot prove that long sleep duration causes mortality, there is sufficient evidence to warrant future testing of the hypothesis that mild sleep restriction would decrease mortality in long sleepers. Sleep restriction might resemble dietary restriction as a potential aid to survival. Sleep restriction has several potential benefits besides possible enhanced survival. Acute sleep restriction can have dramatic antidepressant effects. Also, chronic sleep restriction is perhaps the most effective treatment for primary insomnia. Conversely, spending excessive time in bed can elicit daytime lethargy and exacerbate sleep fragmentation, resulting in a vicious cycle of further time in bed and further sleep fragmentation. Sleep restriction may be most beneficial for older adults, who tend to spend excessive time in bed and have more sleep fragmentation compared with young adults.

Aging↗
PubMed2004

Naps and circadian rhythms in postmenopausal women.

BACKGROUND: Napping patterns and relationships among naps, circadian rhythms, and nocturnal sleep were evaluated in postmenopausal women. Naps and nocturnal sleep were compared between depressed women and healthy volunteers. METHODS: The study included 436 postmenopausal women between the ages of 50 and 81 years. Psychiatric interviews were conducted using the Structured Clinical Interview for DSM-IV Axis I Disorders. Each participant wore a wrist-activity monitor and kept a daily sleep log at home for 1 week. The major urinary melatonin metabolite (6-sulfatoxymelatonin [aMT6s]) was measured for two 24-hour periods at home. RESULTS: There was no significant difference in naps and nocturnal sleep patterns between depressed participants (n = 30) and those with no history of mental disorder (n = 222). Three peaks occurred in the timing of napping: approximately 1 hour before bedtime, 8 to 9 hours after wake-up time, and 2 hours after waking, in descending order of magnitude. Significant inverse correlations were observed between evening nap duration and both wake-up time and aMT6s acrophase. The onset time of aMT6s excretion was advanced by 32 minutes in evening nappers. CONCLUSIONS: Evening napping, a characteristic of these postmenopausal women, may be related to an advance of circadian rhythms in this age group. Relationships between evening napping and earlier wake-up time may be a common manifestation of advanced circadian rhythms or may be a homeostatic effect.

Aged↗
PubMed2004

Menopause: neuroendocrine changes and hormone replacement therapy.

OBJECTIVE: We evaluated the effects of hormone replacement therapy (HRT) alone and in combination with a selective serotonin reuptake inhibitor on mood, cognition, and neuroendocrine parameters in peri- and postmenopausal women. METHODS: We measured neuroendocrine variations in peri- and postmenopausal depressed patients (DP) and postmenopausal normal control (NC) women (45 to 72 years old) before and after treatment with HRT alone and HRT combined with antidepressant medication. All subjects were without significant medical illness and off psychoactive or other medication that would interfere with neuroendocrine measures. RESULTS: Menopausal DP women reported greater severity of hot flashes, were less likely to be "morning" types, and had relatively good neuropsychological function compared with NC. DP and NC had comparable levels of reproductive hormones, with the exception of elevated prolactin levels, which increased, as did thyroid-stimulating hormone levels, in response to estradiol treatment. DP had poor sleep quality as measured both by subjective ratings and objective polysomnographic measures compared with NC. In DP estradiol did not enhance the effect of antidepressant alone on mood ratings. CONCLUSION: These findings may differ from other reports in the literature as a function of diagnoses of major depressive episode, randomized controlled trials, or dose and preparation of HRT. Further work is needed on the differential effect of treatment regimens in these disturbances that are evident primarily in baseline neuroendocrine function.

Affect↗
PubMed2003

Measurement of illumination exposure in postpartum women.

BACKGROUND: Low levels of light exposure at critical times are thought to cause seasonal affective disorder. Investigators, in studies demonstrating the usefulness of bright light therapy, also have implicated light's role in non-seasonal depression. The precise cause of postpartum depression has not been delineated, but it seemed possible that new mothers would spend reduced time in daylight. The goal of this study was to examine the levels of illumination experienced by postpartum mothers and to discover any relationship between light exposure and mood levels experienced during the postpartum period. METHODS: Fifteen postpartum women, who did not have any baseline indication of depression, wore a wrist device (Actillume) for 72 hours to measure their exposure to light. At the end of the recording period, they completed a self-reported measure of mood. The mean light exposure of these postpartum women (expressed as the 24-hour average logarithm of illumination in lux) was compared with that of a representative sample of women of comparable age, residence, and seasonal months of recording. Mood levels were then rank-ordered and tested for correlation with light exposure levels. RESULTS: There was no significant difference between the amount of light [log10lux] experienced by postpartum (1.01 SD 0.236) and control women (1.06 SD 0.285). Mood was not correlated with illumination in the postpartum sample. CONCLUSIONS: Postpartum women in San Diego did not receive reduced light, nor was low mood related to low illumination.

Adult↗
PubMed2003

Melatonin excretion with affect disorders over age 60.

Numerous studies have reported low melatonin secretion in depression, but other studies have suggested no deficit or an increase. Alterations of circadian phase or duration of melatonin secretion have also been described. Since melatonin secretion decreases as we age, it seemed interesting to examine melatonin and depression in an aging sample. Volunteers who complained of mood or sleep problems were recruited for studies in which fractional urine specimens were collected for 24 h, both at home and in the laboratory. The major metabolite, 6-sulfatoxymelatonin (aMT6s), was determined by radioimmunoassay. Of 72 volunteers aged 60-78 years, seven had current major depression and 55% had a lifetime history of an affective disorder. A 55-fold range of home aMT6s excretion rates was observed. A lifetime history of any affective disorder was significantly associated with greater log(10)[mesor] aMT6s excretion in home collections and laboratory collections, but current affective disorders were neither significantly related to melatonin excretion nor to aMT6s acrophase timing, onset, offset or duration. These results are only weakly consistent with a photoperiodic hypothesis of depression.

Aged↗