•Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.•Approximately 1 in 3 individuals experienced fatigue 12 or more weeks following ...COVID-19 diagnosis.•Approximately 1 in 5 individuals exhibited cognitive impairment 12 or more weeks following COVID-19 diagnosis.•There was an elevation in proinflammatory markers and functional impairment in a subset of post-COVID individuals.
COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.
To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.
Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.
Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.
Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.
The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome.
The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.
A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.
PROSPERO (CRD42021256965).
•Mood disorders could have metabolic manifestations as part of the psychiatric syndrome.•Diet interventions present a unique and potentially useful treatment avenue for mood disorders.•Preliminary ...data suggest a potential role for ketogenic diet in the treatment of mood disorders.
Despite significant advances in pharmacological and non-pharmacological treatments, mood disorders remain a significant source of mental capital loss, with high rates of treatment resistance, requiring a coordinated effort in investigation and development of efficient, tolerable and accessible novel interventions. Ketogenic diet (KD) is a low-carb diet that substantially changes the energetic matrix of the body including the brain. It has been established as an effective anticonvulsant treatment, and more recently, the role of KD for mental disorders has been explored. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including but not limited to, glutamate/GABA transmission, monoamine levels, mitochondrial function and biogenesis, neurotrophism, oxidative stress, insulin dysfunction and inflammation. Preclinical studies, case reports and case series have demonstrated antidepressant and mood stabilizing effects of KD, however, to date, no clinical trials for depression or bipolar disorder have been conducted. Because of its potential pleiotropic benefits, KD should be considered as a promising intervention in research in mood disorder therapeutics, especially in treatment resistant presentations.
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.
Objective
Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). ...Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti‐inflammatory agents in the treatment of bipolar depression.
Methods
Completed and ongoing clinical trials of anti‐inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti‐inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone.
Results
Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti‐inflammatory drugs (n = 53), omega‐3 polyunsaturated fatty acids (n = 140), N‐acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti‐inflammatory agents on depressive symptoms was −0.40 (95% confidence interval −0.14 to −0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment‐emergent adverse events were reported.
Conclusions
Overall, a moderate antidepressant effect was observed for adjunctive anti‐inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.
Unipolar and bipolar disorders aggregate in families and have been associated with a reduced gray-matter volume in hippocampal and prefrontal cortex. Here we used structural MRI to clarify whether ...abnormalities in hippocampal subfield and prefrontal cortical morphology are associated with familial vulnerability (i.e., changes present both in patients and unaffected relatives compared to healthy individuals), resilience (i.e., changes differentiating unaffected relatives and patients), or sequalae of illness in a sample of monozygotic twins. We investigated regional differences in gray-matter volume extracted using FreeSurfer 6.0 between remitted affected twins (AT) with either unipolar or bipolar disorder (n = 67), unaffected discordant co-twins (UT, n = 39), and low-risk twins (LT, n = 31) with no personal or first-degree family history of affective disorders. The UT showed greater bilateral hippocampal volumes compared to AT. Between group differences in left hippocampal volume were driven by greater cornu ammonis 1-3 and 4, subiculum and subfield of dentate gyrus. For the right hippocampus, differences were driven by greater hippocampal tail and subiculum. There was a trend for UT having a larger left hippocampus than LT, but no significant differences in hippocampal volumes between AT and LT. Outside the hippocampus, AT showed a smaller volume of left dorsomedial prefrontal cortex compared to LT. Our results suggest that larger volume of specific hippocampal subfields may be associated with resilience in healthy relatives of patients with an affective illness. Moreover, a smaller volume of left dorsomedial prefrontal cortex may reflect a sequalae of illness.
Cognitive dysfunction is common in bipolar disorder (BD) but is not sufficiently addressed by current treatments. Cognitive remediation (CR) may improve cognitive function in schizophrenia but no ...randomised controlled trial has investigated this intervention in BD. The present study aimed to investigate the effects of CR on persistent cognitive dysfunction in BD.
Patients with BD in partial remission with cognitive complaints were randomised to 12 weeks group-based CR (n=23) or standard treatment (ST) (n=23). Outcomes were improved verbal memory (primary), sustained attention, executive and psychosocial function (secondary) and additional measures of cognitive and psychosocial function (tertiary). Participants were assessed at baseline and weeks 12 and 26.
Of the 46 randomised participants five dropped out and one was excluded after baseline. CR (n=18) had no effect on primary or secondary measures of cognitive or psychosocial function compared with ST (n=22). However, CR improved subjective sharpness at week 12, and quality of life and verbal fluency at week 26 follow-up (tertiary outcomes). Although the trial turned out to have suboptimal statistical power for the primary outcome analysis, calculation of the 95% confidence interval showed that it was highly unlikely that an increase in sample size would have rendered any beneficial effects of CR vs. ST on the verbal memory.
Short-term group-based CR did not seem to improve overall cognitive or psychosocial function in individuals with BD in full or partial remission. The present findings suggest that that longer-term, more intensive and individualised CR may be necessary to improve cognition in BD.
ClinicalTrials.gov NCT01457235.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Relatives of patients with bipolar disorder (BD) often experience emotional burden with stress and depressive symptoms that again increase the likelihood of destabilization and relapses in the ...patient. The effects of group-based psychoeducation have not been investigated in large-scale real-world settings. We are currently conducting a large-scale real-world randomized controlled parallel group trial (RCT) to test whether group-based psychoeducation for 200 relatives to patients with BD improves mood instability and other critical outcomes in relatives and the corresponding patients with BD.
The trial is designed as a two-arm, parallel-group randomized trial with a balanced randomization 1:1 to either group-based psychoeducation or a waiting list for approximately 4 months and subsequent group-based psychoeducation. The primary outcome measure is mood instability calculated based on daily smartphone-based mood self-assessments. Other relevant outcomes are measured, including patients' reported outcomes, assessing self-assessed burden, self-efficacy, and knowledge about BD.
This protocol describes our currently ongoing randomized controlled trial (RCT) that aims at investigating group-based psychoeducation as an intervention for relatives of individuals diagnosed with bipolar disorder (BD). The study is the first large-scale real-world RCT to focus on a relatively short intervention of psychoeducation (6 sessions of 2 h each) in a large group of relatives (approximately 30 participants per group). With this focus, we wish to test an intervention that is feasible to implement in real-life psychiatric settings with limited budgets and time. It is also the first study to use mood instability in relatives as the primary outcome measure and to investigate whether mood instability and other affective symptoms in patients and relatives covary. It could be considered as limitations, that the trial is not blinded and does not include long-term follow-up.
ClinicalTrials.gov NCT06176001. Registered on 2023-12-19. The study is approved by the data agency (P-2021-809). The project was allowed to be initiated without permission from the Scientific Ethical Committees for the Capital Region, because it according to section 1, paragraph 4 of the Committee Act was not defined as a health scientific intervention study (case number 21063013).
Abstract Cognitive dysfunction is prevalent in bipolar disorder (BD). However, the evidence regarding the association between subjective cognitive complaints, objective cognitive performance and ...psychosocial function is sparse and inconsistent. Seventy seven patients with bipolar disorder who presented cognitive complaints underwent assessment of objective and subjective cognitive function and psychosocial functioning as part of their participation in two clinical trials. We investigated the association between global and domain-specific objective and subjective cognitive function and between global cognitive function and psychosocial function. We also identified clinical variables that predicted objective and subjective cognitive function and psychosocial functioning. There was a correlation between global subjective and objective measures of cognitive dysfunction but not within the individual cognitive domains. However, the correlation was weak, suggesting that cognitive complaints are not an assay of cognition per se. Self-rated psychosocial difficulties were associated with subjective (but not objective) cognitive impairment and both subjective cognitive and psychosocial difficulties were predicted by depressive symptoms. Our findings indicate that adequate assessment of cognition in the clinical treatment of BD and in drug trials targeting cognition requires implementation of not only subjective measures but also of objective neuropsychological tests.
Background:
Persistent cognitive impairment is frequent across bipolar disorder (BD) and major depressive disorder (MDD), highlighting an urgent need for pro-cognitive treatments.
Aim:
This study ...investigated effects of erythropoietin (EPO) on cognitive impairment and dorsal prefrontal cortex (dPFC) activity in affective disorders.
Methods:
In this randomized, double-blinded, placebo-controlled trial, cognitively impaired patients with remitted BD or MDD received 1 weekly recombinant human EPO (40,000 IU/mL) or saline infusion for a 12-week period. Assessments were conducted at baseline, after 2 weeks of treatment (week 3), immediately after treatment (week 13) and at 6-months follow-up. Participants underwent functional MRI during performance on a n-back working memory (WM) task at baseline and week 3, and for a subgroup 6 weeks post-treatment (week 18). The primary outcome was a cognitive composite score at week 13, whereas secondary outcomes comprised sustained attention and functioning. WM-related dPFC activity was a tertiary outcome.
Results:
Data were analysed for 101 of the 103 included patients (EPO, n = 58; saline, n = 43). There were no effects of EPO over saline on any cognitive or functional outcomes or on WM-related dPFC activity.
Conclusions:
The absence of treatment-related changes in cognition and neural activity was unexpected and contrasts with multiple previous preclinical and clinical studies. It is possible that the lack of effects resulted from a recent change in the manufacturing process for EPO. Nevertheless, the findings support the validity of dPFC target engagement as a biomarker model for pro-cognitive effects, according to which treatments that do not improve cognition should not modulate dPFC activity.
Trial registrations:
EudraCT no.: 2016–004023-24; ClinicalTrials.gov identifier: NCT03315897.
PDF
