Abstract Background It is unclear whether cognitive impairment is prevalent in the remitted state of unipolar disorder. Aim To evaluate whether cognitive function is impaired in the remitted state in ...patients with unipolar depression compared with healthy control individuals, and to investigate the association to prior course of illness, i.e. the number, duration and severity of prior depressive episodes. Method Systematic search on existing on-line databases and hand-search of original published papers. Results A total of 11 studies fulfilled the selection criteria and were included in the review, including a total of 500 patients remitted from unipolar depression and 471 healthy control individuals. In nine of the eleven studies performance on neuropsychological tests was found to be decreased in patients compared to healthy control individuals in at least one of the tests. Methodological drawbacks were prevalent including non-stringent definition of remission and non-correction for multiple testing. Only few studies investigated the association between cognition and prior course of illness and the results were divergent. Limitations Stringent criteria were used in the assessment of eligibility of studies. The studies were first and foremost selected according to the criteria for remission used. Conclusion Cognitive dysfunction seems to be present in individuals suffering from unipolar disorder in the remitted state. We recommend that future studies should focus on disentangling the state and trait characteristics of cognitive dysfunction in unipolar disorder and further clarify the associations with clinical phenotype, course of illness and subsyndromal psychopathology. Furthermore, there is a need to identify the cognitive difficulties in individuals suffering from unipolar disorder in relation to psychosocial function, quality of life and risk of recurrence and to assess the effect of treatment intervention on cognitive function.
Summary The pathophysiology of depression has been associated to dysregulation of the hypothalamic–pituitary–adrenal axis and the use of salivary cortisol measures is increasingly being incorporated ...into research. The aim of the present study was to investigate whether salivary cortisol differs for patients with depression and control persons. We did a systematic review with sequential meta-analysis and meta-regression according to the PRISMA Statement based on comprehensive database searches for studies of depressed patients compared to control persons in whom salivary cortisol was measured. Twenty case–control studies, including 1354 patients with depression and 1052 control persons were identified. In a random-effects meta-analysis salivary cortisol was increased for depressed patients as compared to control persons on average 2.58 nmol/l (95% C.I.: 0.95–4.21) p = 0.002 in the morning and on average 0.27 nmol/l (95% C.I.: 0.03–0.51) p = 0.03 in the evening. In a fixed-effects model the mean difference was 0.58 nmol/l (95% C.I.). Study sequential cumulative meta-analyses suggested random error for the finding of this rather small difference between groups. The reference intervals for morning salivary cortisol in depressed patients (0–29 nmol/l) and control persons (1–23 nmol/l) showed substantial overlap suggesting lack of discriminative capacity. These results should be interpreted with caution as the heterogeneity for the morning analysis was large and a funnel plot, suggested presence of bias. Further, in meta-regression analyses higher intra-assay coefficients of variation in cortisol kits ( p = 0.07) and mean age ( p = 0.08) were associated with a higher mean difference of morning salivary cortisol between depressed and controls, while gender and depression severity were not. Based on the available studies there is not firm evidence for a difference of salivary cortisol in depressed patients and control persons and salivary cortisol is unable to discriminate between persons with and without depression.
Background: Patients with unipolar depressive disorder may present with cognitive deficits in the remitted state, and the aim of the present study was to investigate whether cognitive deficits within ...specific cognitive domains are present. Method: Via the Danish registers (Civil Person Register, Danish Psychiatric Register) we identified individuals between 40 and 80 years of age with a diagnosis of unipolar disorder at their first discharge from a psychiatric hospital, and a gender- and age-matched control group. Particular emphasis was placed on assuring that patients were in a remitted state. Cognitive function was assessed with a broad range of neuropsychological tests. Results: A total of 88 patients and 50 controls were included in the study. In multiple linear regression analyses with simultaneous adjustment for age, gender, education level, premorbid IQ, and residual depressive symptoms, a diagnosis of unipolar disorder predicted lower performance on the Trail Making Test, the Symbol Digit Modalities Test, and on the Stroop test. Conclusion: Cognitive deficits are present in patients with unipolar disorder in the remitted state. The deficits seem to reside more within the cognitive domain of attention than within other domains, and may be characterized by impairment of processing speed and cognitive flexibility.
Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas ...hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC). Also, we explored if the cortisol response of those patients interacted with robust markers of oxidative stress. Thirty inpatients with MDD and 23 outpatients with ED were recruited. Plasma cortisol and ACTH were sampled during a DEX-CRH test. The main outcome measure, area under the curve (AUC) for cortisol and ACTH, was compa-red between MDD vs. ED participants and a historical HC group. Secondary markers of oxidative stress urinary 8-oxodG and 8-oxoGuo; quality of sleep and psychometrics were obtained. Cortisol concentrations were higher in MDD and ED participants compared to HC, and no differences in AUC cortisol and ACTH were found between ED vs. MDD. Compared to ED, MDD participants had higher stress symptom severity and a lower sense of well-being. No differences in oxidative stress markers or quality of sleep between the groups were found. The result indicates that the patients with ED, like patients with MDD, are non-suppressors in DEX-CRH test and not hypocortisolemic as suggested.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Background Abnormalities in psychomotor activity are a central and essential feature of affective disorder. Studies measuring differences in psychomotor activity between unipolar and bipolar ...disorder show divergent results and none have used a combined heart rate and movement monitor for measuring activity during free-living conditions. Objective To compare objectively measured psychomotor activity in patients with unipolar and bipolar disorder in a remitted or mild/moderate depressive state. Further, both groups were compared to a healthy control group. Methods A cross-sectional study of outpatients suffering from unipolar (n = 20) and bipolar (n = 18) disorder and healthy controls (n = 31), aged 18–60 years. For three consecutive days a combined acceleration (m/s2 ) and heart rate (beats per minute) monitoring was used in conjunction with a step test to estimate activity energy expenditure (J/min/kg) as measures of psychomotor activity and physical fitness. Results Overall score on Hamilton-17 items ranged between 0 and 22. Patients had higher sleeping heart rate (p < 0.001), lower fitness (p = 0.02), lower acceleration (p = 0.004), and lower activity energy expenditure (p = 0.004) compared to controls. Comparing unipolar and bipolar patients and adjusting for differences in Hamilton-17 revealed lower acceleration (p = 0.01) and activity energy expenditure in bipolar patients (p = 0.02); the difference was most prominent in the morning. Conclusions Electronic monitoring of psychomotor activity may be a promising additional tool in the distinction between unipolar and bipolar affective disorder when patients present in a remitted or depressive state.
Background
Visible light, predominantly in the blue range, affects mood and circadian rhythm partly by activation of the melanopsin-containing intrinsically photosensitive retinal ganglion cells ...(ipRGCs). The light-induced responses of these ganglion cells can be evaluated by pupillometry. The study aimed to assess the blue light induced pupil constriction in patients with bipolar disorder (BD).
Methods
We investigated the pupillary responses to blue light by chromatic pupillometry in 31 patients with newly diagnosed bipolar disorder, 22 of their unaffected relatives and 35 healthy controls. Mood state was evaluated by interview-based ratings of depressive symptoms (Hamilton Depression Rating Scale) and (hypo-)manic symptoms (Young Mania Rating Scale).
Results
The ipRGC-mediated pupillary responses did not differ across the three groups, but subgroup analyses showed that patients in remission had reduced ipRGC-mediated responses compared with controls (9%,
p
= 0.04). Longer illness duration was associated with more pronounced ipRGC-responses (7% increase/10-year illness duration,
p
= 0.02).
Conclusions
The ipRGC-mediated pupil response to blue light was reduced in euthymic patients compared with controls and increased with longer disease duration. Longitudinal studies are needed to corroborate these potential associations with illness state and/or progression.
Abstract
Introduction
A substantial proportion of patients with bipolar disorder experience daily subsyndromal mood swings, and the term “mood instability” reflecting the variability in mood seems ...associated with poor prognostic factors, including impaired functioning, and increased risk of hospitalization and relapse.
During the last decade, we have developed and tested a smartphone-based system for monitoring bipolar disorder. The present SmartBipolar randomized controlled trial (RCT) aims to investigate whether (1) daily smartphone-based outpatient monitoring and treatment
including
clinical feedback versus (2) daily smartphone-based monitoring
without
clinical feedback or (3) daily smartphone-based mood monitoring
only
improves mood instability and other clinically relevant patient-related outcomes in patients with bipolar disorder.
Methods and analysis
The SmartBipolar trial is a pragmatic randomized controlled parallel-group trial. Patients with bipolar disorder are invited to participate as part of their specialized outpatient treatment for patients with bipolar disorder in Mental Health Services in the Capital Region of Denmark. The included patients will be randomized to (1) daily smartphone-based monitoring and treatment
including
a clinical feedback loop (intervention group) or (2) daily smartphone-based monitoring
without
a clinical feedback loop (control group) or (3) daily smartphone-based mood monitoring only (control group). All patients receive specialized outpatient treatment for bipolar disorder in the Mental Health Services in the Capital Region of Denmark. The trial started in March 2021 and has currently included 150 patients. The outcomes are (1) mood instability (primary), (2) quality of life, self-rated depressive symptoms, self-rated manic symptoms, perceived stress, satisfaction with care, cumulated number and duration of psychiatric hospitalizations, and medication (secondary), and (3) smartphone-based measures per month of stress, anxiety, irritability, activity, and sleep as well as the percentage of days with presence of mixed mood, days with adherence to medication and adherence to smartphone-based self-monitoring. A total of 201 patients with bipolar disorder will be included in the SmartBipolar trial.
Ethics and dissemination
The SmartBipolar trial is funded by the Capital Region of Denmark and the Independent Research Fund Denmark. Ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248) as well as data permission (journal number: P-2019–809). The results will be published in peer-reviewed academic journals, presented at scientific meetings, and disseminated to patients’ organizations and media outlets.
Trial registration
Trial registration number: NCT04230421. Date March 1, 2021. Version 1.
Background
Abnormalities in cerebrospinal fluid (CSF)-amyloid-beta (Aβ)42, CSF-Aβ40, CSF-Aβ38, CSF-soluble amyloid precursor proteins α and β, CSF-total-tau, CSF-phosphorylated-tau, CSF-neurofilament ...light protein (NF-L), CSF-neurogranin, plasma-Aβ42, plasma-Aβ40, plasma-total-tau, plasma-NF-L and, serum-S100B during affective episodes may reflect brain changes that could impact cognitive function in patients with bipolar disorder (BD). The study aimed to investigate the association between these biomarkers indicative of Alzheimer’s disease and those reflecting neurodegeneration alongside their impact on cognitive function in patients with BD and healthy control individuals (HC). The primary hypothesis was that GL and VL would increase with increasing levels of CSF-Aβ42 based on data from T0 and T3 in BD and HC jointly.
Methods
In a prospective, longitudinal case–control study euthymic patients with BD (N = 85) and HC (N = 44) were evaluated with clinical assessment and neuropsychological testing at baseline (T0) and during euthymia after a year (T3). Patients’ affective states were recorded weekly as euthymic, subthreshold level, major depression, or (hypo)mania. If an episode occurred during follow-up, the patient was also assessed in post-episode euthymia. Cognitive performance was measured as a global cognitive score (GL) for four cognitive domains including verbal learning and memory (VL).
Results
Estimated in a linear mixed model GL increased with 0.001 for each increase of 1 pg/ml of CSF-Aβ42 (97.5%, CI 0.00043–0.0018, adjusted-p = 0.0005) while VL increased by 0.00089 (97.5%, CI 0.00015–0.0018, adjusted-p = 0.045) in BD and HC jointly. The association was weak, however stronger in patients with BD compared to HC. Associations between other biomarkers including CSF-neurogranin, and cognitive domains were overall weak, and none remained significant after adjustment for multiple testing.
Limitations
Modest sample size. A complete data set regarding both CSF-AB-42 and cognitive test scores was obtained from merely 61 patients with BD and 38 HC individuals.
Conclusion
CSF-Aβ42 may be associated with cognitive dysfunction in patients with BD and HC individuals. The association appeared to be stronger in BD but with overlapping confidence intervals. Hence it remains uncertain whether the association is a general phenomenon or driven by BD.
The transition phase from inpatient to outpatient care for patients suffering from Major Depressive Disorder represents a vulnerable period associated with a risk of depression worsening and suicide. ...Our group has recently found that the sleep-wake cycle in discharged depressive patients became irregular and exhibited a drift towards later hours, associated with worsening of depression. In contrast, an advancement of sleep phase has earlier been shown to have an antidepressant effect. Thus, methods to prevent drift of the sleep-wake cycle may be promising interventions to prevent or reduce worsening of depression after discharge.
In this trial, we apply a new treatment intervention, named Circadian Reinforcement Therapy (CRT), to patients discharged from inpatient psychiatric wards. CRT consists of a specialized psychoeducation on the use of regular time signals (zeitgebers): daylight exposure, exercise, meals, and social contact. The aim is to supply stronger and correctly timed zeitgebers to the circadian system to prevent sleep drift and worsening of depression. The CRT is used in combination with an electronic self-monitoring system, the Monsenso Daybuilder System (MDB). By use of the MDB system, all patients self-monitor their sleep, depression level, and activity (from a Fitbit bracelet) daily. Participants can inspect all their data graphically on the MDB interface and will have clinician contact. The aim is to motivate patients to keep a stable sleep-wake cycle. In all, 130 patients referred to an outpatient service will be included. Depression rating is blinded. Patients will be randomized 1:1 to a Standard group or a CRT group. The intervention period is 4 weeks covering the transition phase from inpatient to outpatient care. The primary outcome is score change in interviewer rated levels of depression on the Hamilton Depression Rating Scale. A subset of patients will be assessed with salivary Dim Light Melatonin Onset (DLMO) as a validator of circadian timing. The trial was initiated in 2016 and will end in 2020.
If the described intervention is beneficial it could be incorporated into usual care algorithms for depressed patients to facilitate a better and safer transition to outpatient treatment.
Posted prospectively at ClinicalTrials.gov at February 10, 2016 with identifier NCT02679768 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
