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Biomedical subjects

Peter C Whybrow

Publications and source records attributed to Peter C Whybrow.

18 recordsLinked to original sources

Self-reported data from patients with bipolar disorder: frequency of brief depression.

OBJECTIVE: Patients with bipolar disorder often report depressive symptoms that do not meet the DSM-IV criteria for an episode. Using daily self-reported mood ratings, we studied how changing the length requirement to that typical of recurrent brief depression (2-4 days) would impact the number of depressed episodes. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software on a home computer (30,348 total days; mean 150 days). Episodes of depression and days of depression outside of episodes were determined. Symptom intensity (mild versus moderate or severe) was investigated within and outside of depressive episodes. RESULTS: Decreasing the minimum duration criterion for an episode of depression to 2 days increased the number of patients with a depressed episode two and a half times (52 to 131), and quadrupled both the number of depressed episodes per patient (0.62 to 2.88) and the number of depressed episodes for all patients (125 to 584). With a 2-day episode length, 34% of days of depression remained outside an episode. The ratio of days with severe symptoms within episodes remained consistent (about 25%) in spite of decreasing the episode length to 2 days. Considering only days with severe symptoms, about 25% remained outside of episodes even with a 2-day length. None of the results distinguished bipolar I from bipolar II disorder. LIMITATIONS: Self-reported data, computer access required, relatively short study length, no control group. CONCLUSION: Brief depressive episodes and single days of depression outside of episodes occur frequently in both bipolar I and bipolar II disorder. Moderate or severe symptoms occur during brief episodes at a ratio similar to that for episodes that meet the DSM-IV criteria.

Adult↗

Self-reported data from patients with bipolar disorder: impact on minimum episode length for hypomania.

OBJECTIVE: Some investigators have suggested decreasing the minimum hypomania episode length criterion from 4 days, as in the DSM-IV, to 2 days. Using daily self-reported mood ratings, we studied the impact of changing the length requirement on the number of hypomanic episodes in patients with bipolar disorder. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software (30,348 total days, mean 150 days). Episodes of hypomania and days of hypomania outside of episodes were determined. RESULTS: Decreasing the minimum duration criterion for an episode of hypomania from 4 to 2 days doubled the mean percent of days in a hypomanic episode for each patient (4% to 8%), doubled the number of patients with a hypomanic episode (44 to 96) and increased the number of hypomanic episodes for all patients about three-fold (129 to 404). With a minimum episode length of 4 days, bipolar I patients were more likely to report hypomania outside episodes than bipolar II patients (p=0.010), but with a length of 2 or 3 days there was no significant difference in the distribution of hypomania outside of episodes by diagnosis. With a 2-day length, about one-third (36%) of hypomania remained outside of an episode. LIMITATIONS: Self-reported data, computer access, relatively short length, fewer bipolar II than bipolar I patients. CONCLUSION: As the minimum length for an episode of hypomania decreases, there was a large increase in both the number of episodes and number of patients with episodes. One-day hypomania outside of episodes occurs frequently in both bipolar I and bipolar II disorder.

Adult↗

Memory improvement with treatment of hypothyroidism.

The consequences of inadequate thyroid hormone availability to the brain and treatment effects of levothyroxine on cognitive function are still poorly understood. This study prospectively assessed the effects of thyroid replacement therapy on cognitive function in patients suffering from biochemical evidenced, untreated hypothyroidism. Significant effects between the untreated hypothyroid group and control group were limited to verbal memory retrieval. When assessing the effects of 3-month treatment, results revealed that the treated hypothyroid group had significant increased verbal memory retrieval. Results suggest that specific memory retrieval deficits associated with hypothyroidism can resolve after replacement therapy with levothyroxine.

Adolescent↗

Temporal relation between sleep and mood in patients with bipolar disorder.

BACKGROUND: Early recognition of the prodromal symptoms of bipolar disorder, combined with a patient action plan, may help to prevent relapses. Sleep disturbances are frequent warning signs of both mania and depression. This study used cross correlation analysis to characterize the relationship between mood, sleep and bedrest in longitudinal data. METHODS: Self-reported mood, sleep and bedrest (mean 169 +/- 59 days of data per patient) from 59 outpatients with bipolar disorder receiving standard treatment were analyzed. The cross correlation function was used to determine the latency between the changes in sleep and/or bedrest and mood for time shifts of between -7 and 7 days. RESULTS: For sleep and/or bedrest, a significant inverse correlation was found with the change in mood, most commonly with a time latency of one day. Sleep plus bedrest had the strongest relationship with a change in mood, with a significant correlation in 24 of 59 patients (41%) for the night before or night of a mood change. The patients with a significant cross-correlation between mood and sleep plus bedrest reported about two thirds of all large sleep changes of >3 h and three fourths of all large mood changes (>20 on 100-unit scale). Patients with a significant cross correlation were more likely to take benzodiazepines. CONCLUSION: In most patients with a significant cross correlation between sleep and/or bedrest and mood, the mood change occurred on the day following the change in sleep and/or bedrest. Sleep changes from a previous pattern, especially those of more than 3 h, may indicate that a large mood change is imminent.

Adult↗

Approximate entropy of self-reported mood prior to episodes in bipolar disorder.

BACKGROUND: Approximate entropy (ApEn) measures regularity in time series data, while traditional linear statistics measure variability. Using self-reported mood data from patients with bipolar disorder, this preliminary study addressed whether ApEn could distinguish (i) the 60 days prior to the start of a manic or depressed episode from the 60 days prior to a month of euthymia, and (ii) the 60 days prior to a manic episode from the 60 days prior to a depressed episode. METHODS: Self-reported mood data from 49 outpatients with bipolar disorder receiving standard treatment were analysed. The data contained 27 episodes (12 manic and 15 depressed), and 43 periods of 1 month of euthymia. For the 60 days prior to episode or euthymia, the ApEn, linear statistics and the correlation between linear and non-linear measures were calculated. RESULTS: ApEn was significantly greater in the 60 days prior to a manic or depressive episode than the 60 days prior to a month of euthymia. The onset of an episode was associated with greater irregularity in mood. Variability was also significantly larger and correlated with ApEn. ApEn was significantly greater in the 60 days prior to a manic episode than in the 60 days prior to a depressed episode, whereas measures of variability were not significantly different. Mood in the 60 days prior to mania was more irregular than prior to depression. CONCLUSIONS: Non-linear measures may complement traditional linear measures in the analysis of longitudinal data in bipolar disorder. A larger study is indicated.

Adult↗

Does the use of an automated tool for self-reporting mood by patients with bipolar disorder bias the collected data?

CONTEXT: Automating data collection from patients can improve data quality, enhance compliance, and decrease costs in longitudinal studies. About half of all households in industrialized countries now have a home computer. OBJECTIVE: While we previously validated the ChronoRecord software for self-reporting mood on a home computer with patients who have bipolar disorder, this study further investigates whether this technology created a bias in the collected data. METHODS: During the validation study, 80 of 96 (83%) patients returned 8662 days of data (mean, 114.7 +/- 32.3 SD days). The patients' demographics were compared with those of similar longitudinal studies in which patients used paper-based data collection tools. In addition, because demographic characteristics may influence attitudes toward technology, observer-rated scores on the Hamilton Depression Rating Scale and Young Mania Rating Scale were used to group patients by severity of illness, and the self-reported mood ratings were analyzed for evidence of bias from the patients' gender, ethnicity, diagnosis, age, disability status, or years of education. Analysis was performed using the 2-way analysis of variance and general linear model. RESULTS: The patients' demographic characteristics were very similar to those of patients with bipolar disorder who participated in comparable longitudinal studies using paper-based tools. After grouping the patients by severity of illness, none of the demographic variables had a significant effect on the patients' self-reported mood using the automated tool. CONCLUSION: The use of a computer does not seem to bias sample data. As with studies using paper-based self-reporting, results from studies of patients using ChronoRecord software on a home computer to report mood can be generalized.

Adolescent↗

Mood changes related to antidepressants: a longitudinal study of patients with bipolar disorder in a naturalistic setting.

This prospective, longitudinal study investigated the frequency and pattern of mood changes between outpatients receiving usual care for bipolar disorder who were either taking or not taking antidepressants. Eighty patients with bipolar disorder self-reported mood and psychiatric medications daily for 3 months using a computerized system (ChronoRecord) and returned 8662 days of data. Of the total group of 80 patients, 47 took antidepressants; 33 did not. Patients taking antidepressants reported depression twice as frequently (29% of days vs. 13.8% of days). In both groups, two-thirds of all mood changes over a 1-, 2- and 3-day period were small, between -5 and 5 on a 100-point scale. No statistically significant difference was found in the frequency of large mood changes (>10 on a 100-point scale) or in switches between depression and mania (0.7% if not taking antidepressants vs. 0.9% if taking), independent of diagnosis of bipolar I or II. Eighty-nine percent of patients taking antidepressants were also taking mood stabilizers. In this naturalistic setting, no significant difference between the rate of switches to mania or rapid cycling was found between those taking and not taking antidepressants, regardless of diagnosis. The primary difference in pattern between the groups was the time spent in depressed or normal mood, with minor daily mood variations.

Adult↗

Sex-specific self-reported mood changes by patients with bipolar disorder.

INTRODUCTION: While the prevalence of bipolar disorder I is similar between men and women, the clinical course may differ. This study investigated if there are differences in the clinical presentation of bipolar disorder between the sexes. METHODS: Mood patterns were documented using ChronoRecord software for self-reporting. Patients entered mood, medications, sleep, life events and menstrual data daily acquired over the period of three months. 8662 Days of data were received from 80 patients: 3483 days from 35 men and 5179 days from 45 women. RESULTS: The distribution of the time spent in mood categories differed between men and women (P<0.001). Men were depressed 17.0% of the time, euthymic 74.0% of the time and manic 5.6% of the time. Women were depressed 28.3% of the time, euthymic 64.2% of the time and manic 7.5% of the time. Over 80% of all reported symptoms for both sexes were mild. Women exhibited large mood fluctuations (greater than 10 in either direction on a 100-unit scale) more frequently than men. Most of the reproductive aged women (55%) reported significant mood changes across the menstrual cycle. CONCLUSIONS: The clinical course of bipolar disorder differed between the sexes. Women reported depression and large fluctuations in mood more frequently than men. Women also experienced mood changes across the menstrual cycle.

Activities of Daily Living↗

Rapid antidepressant response after nocturnal TRH administration in patients with bipolar type I and bipolar type II major depression.

BACKGROUND: Thyrotropin-releasing hormone (TRH) is a tripeptide that produces endocrine and behavioral effects in animals and humans. Some studies have shown transient antidepressant activity after morning administration of TRH. We hypothesized that nocturnal administration of TRH, when the circadian sensitivity of the TRH receptor is at its peak, may result in a more robust antidepressant effect. METHODS: Twenty patients with bipolar (BP) type I or BP type II major depressive episode (MDE) were given nocturnal intravenous TRH 500 microg (n = 10) or saline (n = 10) at midnight in a randomized, double-blind fashion. Antidepressant activity was assessed using the Hamilton Depression Rating (HAM-D), Young Mania Rating (YMR), and Profile of Mood (POMS) scales over a 48-hour period. Thyrotropin (TSH), total T4, and free T3 concentrations were measured before and after TRH administration. Data were analyzed using chi test, Fisher exact test, and repeated-measures ANOVA. RESULTS: Sixty percent of the TRH group and 10% of the saline group showed a > or =50% reduction in baseline total HAM-D score within 24 hours (P = 0.03). HAM-D ratings fell by an average of 52% after TRH administration versus 12% after saline administration (P = 0.038). There was a modest increase in YMR scores after TRH compared with saline (P < 0.032). No manic or hypomanic episodes were observed. Antidepressant effects of TRH lasted up to 48 hours. There was no correlation between DeltaTSH, DeltaT4, or DeltaT3 measures after TRH (or saline) administration and the change in HAM-D scores. CONCLUSIONS: Nocturnal TRH administration may produce a rapid antidepressant effect in some patients with BP I and BP II MDE.

Adult↗

Bone mineral density during maintenance treatment with supraphysiological doses of levothyroxine in affective disorders: a longitudinal study.

BACKGROUND: This prospective study was designed to determine whether patients with prophylaxis-resistant affective disorders, receiving adjunctive maintenance therapy with supraphysiological doses of levothyroxine (L-T4), show evidence of accelerated bone loss compared to the reference population database. METHODS: In 21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and femur (femoral neck, trochanter, and Ward's triangle) was measured by dual energy X-ray absorptiometry (DXA). BMD measurement was performed first after patients had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T4 (mean dose=411 mcg/d) for an average of 16.4 months and again after 33.6 months of L-T4 (mean dose=416 mcg/d) therapy. RESULTS: There was no statistically significant difference between the actual percentage decline in bone mineral density and the expected percentage decline in any of the measured bone regions. In a stepwise linear regression analysis, age was identified as a predictor of percentage change in BMD. After controlling for age, the only other variable that showed a consistent trend was the dose of L-T4, with higher doses being positively correlated with the percentage decline of BMD. LIMITATIONS: Relatively small sample size, no bone density assessment prior to treatment with L-T4, no patient control group with mood disorders who did not receive L-T4 treatment, and bone density follow-up intervals were variable. CONCLUSIONS: This study did not demonstrate evidence that long-term treatment of affectively ill patients with supraphysiological doses of L-T4 significantly accelerates loss of bone mineral density compared to the age-matched reference population. However, the decline of BMD in one individual patient underscores that caution is indicated and that regular assessment of BMD during longer-term supraphysiological thyroid hormone treatment is needed.

Absorptiometry, Photon↗

Using technology to improve longitudinal studies: self-reporting with ChronoRecord in bipolar disorder.

OBJECTIVES: Longitudinal studies are an optimal approach to investigating the highly variable course and outcome associated with bipolar disorder, but are expensive and often have missing data. This study validates patient self-reported mood ratings using a home computer-based system (ChronoRecord) with clinician mood ratings on the Hamilton Depression Rating scale (HAMD) and Young Mania Rating scale (YMRS), and investigates the patient acceptance of the technology. METHODS: After brief training, outpatients with bipolar disorder were given the software version of an established paper based self-reporting form (ChronoSheet) to install on a home computer. Every day for 3 months, patients entered mood, medications, sleep, life events, and menstrual data. Weight was entered weekly. RESULTS: Eighty of 96 (83%) patients returned 8662 days of data. The mean days of data returned was 114.7 +/- 32.3 SD The mean percentage of days missing for mood data was 6.1% +/- 9.3 SD, equivalent to missing 7.3 day of the 114.7 days. Self-reported ratings were strongly correlated with clinician HAMD ratings (-0.683, p < 0.001). CONCLUSIONS: This study demonstrates concurrent validity between ChronoRecord and HAMD. Patients with bipolar disorder showed high acceptance of a computer-based system for self-reporting of daily data. Automation of data collection can reduce missing data and eliminate errors associated with data entry. This technology also enables on-going feedback for both patient and researcher during a long-term study.

Adult↗

Thyroid hypofunction in patients with rapid-cycling bipolar disorder after lithium challenge.

BACKGROUND: There is debate whether patients with rapid-cycling bipolar disorder (BD) are predisposed to thyroid axis abnormalities and whether this may contribute to development of rapid mood shifts. Using lithium carbonate as a challenge to the hypothalamic-pituitary-thyroid (HPT) system, we determined whether patients with rapid-cycling BD are sensitive to the "antithyroid" properties of lithium. METHODS: We studied the response to thyrotropin-releasing hormone (TRH) of HPT system hormones in 20 medication-free patients with rapid-cycling BD and compared these measurements with those of 20 healthy age- and gender-matched control subjects. The same measurements were repeated after both groups had received lithium carbonate for 4 weeks in sufficient doses to maintain blood levels between.7-1.2 mEq/L. RESULTS: At baseline, the results of thyroid function tests, including the TRH challenge test, did not differ between patients and control subjects. After treatment with lithium, serum concentrations of thyroxine significantly decreased, whereas basal thyrotropin (TSH) and DeltaTSH(max) significantly increased in both patients and control subjects; however, patients had significantly higher DeltaTSH(max) after TRH stimulation. More patients than control subjects developed laboratory evidence consistent with grade III hypothyroidism after lithium treatment. CONCLUSIONS: Rapid-cycling BD is associated with a latent hypofunction of the HPT system. This dysfunction becomes manifest with short-term lithium challenge.

Adult↗

Menstrual cycle related mood changes in women with bipolar disorder.

OBJECTIVES: A relationship between affective symptoms and menstrual cycle in women with bipolar disorder (BPD) has been suggested. This study investigates the influence of the menstrual cycle on mood in women with BPD who are taking medication, but not selected for menstrual abnormalities. METHODS: Data from women with BPD (n = 17) consecutively enrolled into a ChronoRecord validation study were included in the current analysis. All women received medication for BPD, in addition, 35% received oral contraceptives (OC). Participants entered mood, menstrual data, psychiatric medications, and life events daily for a 3-month period using a computerized version (ChronoRecord) of an established paper based form for self-reporting (ChronoSheet). RESULTS: The majority of women treated for BPD (65%) reported significant mood changes across the menstrual cycle. Long menstrual cycle was present in 59% of subjects, including those taking OC. CONCLUSIONS: Women with BPD taking medication report a high rate of long menstrual cycles, and significant mood changes in relation to menstrual cycle phase.

Adult↗

Effects of supraphysiological doses of L-thyroxine on cognitive function in healthy individuals.

Cognitive disturbance is commonly associated with disorders of the thyroid gland, particularly hypothyroidism, and usually subsides following thyroid hormone replacement therapy. In contrast, the effects of thyroid hormones on cognitive functions in healthy individuals have rarely been studied. The goal of this open-label study was to investigate the short-term effects (duration of administration 45 days on average) of supraphysiological doses of L-thyroxine (L-T(4)) on cognitive performance in young, euthyroid, healthy subjects. Eleven subjects performed a comprehensive neuropsychological test battery, once without and once during administration of supraphysiological doses of L-T(4). There were no significant differences in any of the cognitive test results between the two test sessions. The results of this study do not support our working hypothesis that thyroid hormone can change cognitive performance in young, euthyroid, healthy individuals.

Adult↗

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and continuation treatment of major depressive disorder.

These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). This first part of the guidelines covers disease definition, classification, epidemiology and course of unipolar depressive disorders, as well as the management of the acute and continuation-phase treatment. These guidelines are primarily concerned with the biological treatment (including antidepressants, other psychopharmacological and hormonal medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Adolescent↗

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions.

These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of the complete spectrum of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). The first part of these WFSBP guidelines on unipolar depressive disorders covered the acute and continuation treatment of major depressive disorder (Bauer et al 2002). This second part of the guidelines covers the management of the maintenance-phase treatment of major depressive disorder, as well as the treatment of chronic and subthreshold depressive disorders (dysthymic disorder, double depression, minor depressive disorder and recurrent brief depression). These guidelines are primarily concerned with the biological treatment (including antidepressants, lithium, other psychopharmacological and hormonal medications, and electroconvulsive therapy) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Adolescent↗