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This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD).
We systematically searched PubMed/Medline, Embase and Web of Science databases from inception through March 22, 2021. This study was registered with PROSPERO (CRD42021243881). Any observational study was included that enrolled medication-naïve children and adolescents with ASD and compared objective (actigraphy and polysomnography) or subjective sleep parameters with typically developing (TD) counterparts. We extracted relevant data such as the study design and outcome measures. The methodological quality was assessed through the Newcastle-Ottawa Scale (NOS). A meta-analysis was carried out using the random-effects model by pooling effect sizes as Hedges’ g. To assess publication bias, Egger’s test and p-curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators.
Out of 4277 retrieved references, 16 studies were eligible with 981 ASD patients and 1220 TD individuals. The analysis of objective measures showed that medication-naïve ASD patients had significantly longer sleep latency (Hedges’ g 0.59; 95% confidence interval [95% CI] 0.26 to 0.92), reduced sleep efficiency (Hedges’ g −0.58; 95% CI −0.87 to −0.28), time in bed (Hedges’ g −0.64; 95% CI −1.02 to −0.26) and total sleep time (Hedges’ g −0.64; 95% CI −1.01 to −0.27). The analysis of subjective measures showed that they had more problems in daytime sleepiness (Hedges’ g 0.48; 95% CI 0.26 to 0.71), sleep latency (Hedges’ g 1.15; 95% CI 0.72 to 1.58), initiating and maintaining sleep (Hedges’ g 0.86; 95% CI 0.39 to 1.33) and sleep hyperhidrosis (Hedges’ g 0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25–8.75).
We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.
Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P) include adolescents and young adults, although most evidence has focused on adults. Negative symptoms are important prognostic indicators in psychosis. However, research focusing on children and adolescents is limited.
To provide meta-analytical evidence and a comprehensive review of the status and advances in the diagnosis, prognosis and treatment of negative symptoms in children and adolescents with EOP and at CHR-P.
PRISMA/MOOSE-compliant systematic review (PROSPERO: CRD42022360925) from inception to 18 August 2022, in any language, to identify individual studies conducted in EOP/CHR-P children and adolescents (mean age <18 years) providing findings on negative symptoms. Findings were systematically appraised. Random-effects meta-analyses were performed on the prevalence of negative symptoms, carrying out sensitivity analyses, heterogeneity analyses, publication bias assessment and quality assessment using the Newcastle–Ottawa Scale.
Of 3289 articles, 133 were included (n = 6776 EOP, mean age 15.3 years (s.d. = 1.6), males = 56.1%; n = 2138 CHR-P, mean age 16.1 years (s.d. = 1.0), males = 48.6%). There were negative symptoms in 60.8% (95% CI 46.4%–75.2%) of the children and adolescents with EOP and 79.6% (95% CI 66.3–92.9%) of those at CHR-P. Prevalence and severity of negative symptoms were associated with poor clinical, functional and intervention outcomes in both groups. Different interventions were piloted, with variable results requiring further replication.
Negative symptoms are common in children and adolescents at early stages of psychosis, particularly in those at CHR-P, and are associated with poor outcomes. Future intervention research is required so that evidence-based treatments will become available.
In this review, we introduce our recent applications of deep learning to solar and space weather data. We have successfully applied novel deep learning methods to the following applications: (1) generation of solar farside/backside magnetograms and global field extrapolation based on them, (2) generation of solar UV/EUV images from other UV/EUV images and magnetograms, (3) denoising solar magnetograms using supervised learning, (4) generation of UV/EUV images and magnetograms from Galileo sunspot drawings, (5) improvement of global IRI TEC maps using IGS TEC ones, (6) one-day forecasting of global TEC maps through image translation, (7) generation of high-resolution magnetograms from Ca II K images, (8) super-resolution of solar magnetograms, (9) flare classification by CNN and visual explanation by attribution methods, and (10) forecasting GOES solar X-ray profiles. We present major results and discuss them. We also present future plans for integrated space weather models based on deep learning.
Predictive values of multiple serum biomarkers for suicidal behaviours (SBs) have rarely been tested. This study sought to evaluate and develop a panel of multiple serum biomarkers for predicting SBs in outpatients receiving a 12-month pharmacotherapy programme for depressive disorders.
At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics including previous suicidal attempt and present suicidal severity were evaluated in 1094 patients with depressive disorders without a bipolar diagnosis. Of these, 884 were followed for increased suicidal severity and fatal/non-fatal suicide attempt outcomes over a 12-month treatment period. Individual and combined effects of serum biomarkers on these two prospective SBs were estimated using logistic regression analysis after adjustment for relevant covariates.
Increased suicidal severity and fatal/non-fatal suicide attempt during the 12-month pharmacotherapy were present in 155 (17.5%) and 38 (4.3%) participants, respectively. Combined cortisol, total cholesterol, and folate serum biomarkers predicted fatal/non-fatal suicide attempt, and these with interleukin-1 beta and homocysteine additionally predicted increased suicidal severity, with clear gradients robust to adjustment (p values < 0.001).
Application of multiple serum biomarkers could considerably improve the predictability of SBs during the outpatient treatment of depressive disorders, potentially highlighting the need for more frequent monitoring and risk appraisal.
The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis.
“Preferred Reporting Items for Systematic reviews and Meta-Analyses” and “Meta-analysis Of Observational Studies in Epidemiology”-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS).
Twenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges’ g = 1.410, 95% confidence interval (CI) 1.002–1.818]; negative psychotic symptoms (Hedges’ g = 0.683, 95% CI 0.371–0.995); depressive symptoms (Hedges’ g = 0.844, 95% CI 0.371–1.317); and functioning (Hedges’ g = 0.776, 95% CI 0.463–1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3–58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges’ g = 0.706, 95% CI 0.091–1.322) and functioning (Hedges’ g = 0.623, 95% CI 0.375–0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = −0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = −0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies.
Clinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.
Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies.
PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof.
Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1β, are associated with depression.
These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.
Individuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue.
“Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) and “Meta-analysis Of Observational Studies in Epidemiology” (MOOSE)–compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted.
Ninety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068–0.121) at 0.5 years, 0.140 (95% CI = 0.101–0.191) at 1 year and 0.165 (95% CI = 0.097–0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067–0.099) at 0.5 years, 0.138 (95% CI = 0.114–0.167) at 1 year, and 0.174 (95% CI = 0.156–0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3–21.0%) than in RCTs (3.4, 95% CI = 0.8–12.7%; p = 0.018).
There is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.
The role of childhood abuse and serum brain-derived neurotrophic factor (BDNF) levels in suicidal behaviour is controversial.
We aimed to investigate the individual and interactive effects of the childhood abuse and serum BDNF on suicidal behaviour before and after pharmacologic treatment in patients with depressive disorders.
At baseline, reported childhood emotional, physical and sexual abuse were ascertained and serum BDNF levels were measured in 1094 patients with depressive disorder, 884 of whom were followed during a 1-year period of stepwise pharmacotherapy. Suicidal behaviours evaluated at baseline were previous suicide attempt and baseline suicide severity, and suicidal behaviours evaluated at follow-up were increased suicide severity and fatal/non-fatal suicide attempt. Individual and interactive associations of any childhood abuse and serum BDNF levels with four types of suicidal behaviours were analysed using logistic regression models, after adjusting relevant covariates.
Individual associations of childhood abuse were significant only with previous suicide attempt, and no significant individual associations were found for serum BDNF with any suicide outcome. However, the presence of both childhood abuse and lower serum BDNF levels was associated with the highest prevalence/incidence of all four suicidal behaviours, with significant interactions for baseline suicide severity and fatal/non-fatal suicide attempt during follow-up.
Synergistic interactive effects of child abuse and serum BDNF levels on suicidal behaviours were found before and after pharmacologic treatment in patients with depressive disorders. Information combining childhood abuse and serum BDNF levels could improve predictions of suicidal behaviour in patients with depressive disorders.
Food insecurity has been shown to be associated with fast-food consumption. However, to date, studies on this specific topic are scarce. Therefore, the aim of the present study was to investigate the association between food insecurity and fast-food consumption in adolescents aged 12–15 years from sixty-eight countries (seven low-income, twenty-seven lower middle-income, twenty upper middle-income, fourteen high-income countries). Cross-sectional, school-based data from the Global School-based Student Health Survey were analysed. Data on past 30-d food insecurity (hunger) and fast-food consumption in the past 7 d were collected. Multivariable logistic regression and meta-analysis were conducted to assess associations. Models were adjusted for age, sex and BMI. There were 180 164 adolescents aged 12–15 years (mean age 13·8 (sd 1·0) years; 50·8 % boys) included in the analysis. Overall, severe food insecurity (i.e. hungry because there was not enough food in home most of the time or always) was associated with 1·17 (95 % CI 1·08, 1·26) times higher odds for fast-food consumption. The estimates pooled by country-income levels were significant in low-income countries (adjusted OR (aOR) = 1·30; 95 % CI 1·05, 1·60), lower middle-income countries (aOR = 1·15; 95 % CI 1·02, 1·29) and upper middle-income countries (aOR = 1·26; 95 % CI 1·07, 1·49), but not in high-income countries (aOR = 1·04; 95 % CI 0·88, 1·23). The mere co-occurrence of food insecurity and fast-food consumption is of public health importance. To tackle this issue, a strong governmental and societal approach is required to utilise effective methods as demonstrated in some high-income countries such as the implementation of food banks and the adoption of free school meals.
To investigate the impacts of depression screening, diagnosis and treatment on major adverse cardiac events (MACEs) in acute coronary syndrome (ACS).
Prospective cohort study including a nested 24-week randomised clinical trial for treating depression was performed with 5–12 years after the index ACS. A total of 1152 patients recently hospitalised with ACS were recruited from 2006 to 2012, and were divided by depression screening and diagnosis at baseline and 24-week treatment allocation into five groups: 651 screening negative (N), 55 screening positive but no depressive disorder (S), 149 depressive disorder randomised to escitalopram (E), 151 depressive disorder randomised to placebo (P) and 146 depressive disorder receiving medical treatment only (M).
Cumulative MACE incidences over a median 8.4-year follow-up period were 29.6% in N, 43.6% in S, 40.9% in E, 53.6% in P and 59.6% in M. Compared to N, screening positive was associated with higher incidence of MACE [adjusted hazards ratio 2.15 (95% confidence interval 1.63–2.83)]. No differences were found between screening positive with and without a formal depressive disorder diagnosis. Of those screening positive, E was associated with a lower incidence of MACE than P and M. M had the worst outcomes even compared to P, despite significantly milder depressive symptoms at baseline.
Routine depression screening in patients with recent ACS and subsequent appropriate treatment of depression could improve long-term cardiac outcomes.
Depressive symptoms are common in bereaved caregivers; however, there have been few prospective studies using a structured interview. This study investigated the prevalence and preloss predictors of major depressive disorder (MDD) in bereaved caregivers of patients in a palliative care unit.
This prospective cohort study collected caregiver sociodemographic and psychological data before the death of a palliative care unit patient, including MDD, care-burden, coping style, and hopeful attitude. Postloss MDD was assessed 6 and 13 months after death, and a multivariate logistic regression analysis was conducted to identify its predictors.
Of 305 caregivers contacted, 92 participated in this study. The prevalence of preloss MDD was 21.8%; the prevalences of postloss MDD were 34.8% and 24.7% at 6 and 13 months, respectively. Preloss MDD predicted postloss MDD at 6 months (odds ratio [OR] = 5.38, 95% confidence interval [CI95%] = 1.29, 22.43); preloss nonhopeful attitude and unemployment status of caregivers predicted postloss MDD at 13 months (OR = 8.77, CI95% = 1.87, 41.13 and OR = 7.10, CI95% = 1.28, 39.36, respectively).
Significance of results
Approximately 35% of caregivers suffered from MDD at 6 months postloss, but the prevalence of MDD decreased to about 25% at 13 months. Preloss MDD significantly predicted postloss MDD at 6 months, whereas hopeful attitude and unemployment at baseline were significantly associated with postloss MDD at 13 months.
We trace Sn nanoparticles (NPs) produced from SnO2 nanotubes (NTs) during lithiation initialized by high energy e-beam irradiation. The growth dynamics of Sn NPs is visualized in liquid electrolytes by graphene liquid cell transmission electron microscopy. The observation reveals that Sn NPs grow on the surface of SnO2 NTs via coalescence and the final shape of agglomerated NPs is governed by surface energy of the Sn NPs and the interfacial energy between Sn NPs and SnO2 NTs. Our result will likely benefit more rational material design of the ideal interface for facile ion insertion.
Although late-life anxiety occurs frequently and is associated with higher morbidity, few longitudinal studies have been concerned with the evaluation thereof. We investigated the prevalence, incidence, and persistence of anxiety and related factors over a two-year period in community-dwelling Korean elderly individuals.
A total of 1,204 Korean elderly individuals were evaluated at baseline, and 909 were followed up two years later. The community version of the Geriatric Mental State Schedule was used to estimate anxiety at both baseline and follow-up interviews. We defined “prevalence” as the rate of anxiety symptoms (for both anxiety cases and sub-threshold anxiety) at baseline; “incidence” as the rate of anxiety symptoms at follow-up in those without baseline anxiety symptoms; and “persistence” as the rate of anxiety symptoms at follow-up in those with baseline anxiety symptoms. Associations between various covariates and anxiety status were examined using multivariate logistic regression models.
The prevalence, incidence, and persistence of anxiety symptoms were 38.1%, 29.3%, and 41.1%, respectively. Prevalent anxiety symptoms were associated independently with female, rented housing, more stressful life event and medical illness, physical inactivity, depression, insomnia, and lower cognitive function. Incident anxiety symptoms were predicted by older age, female gender, depression, and insomnia; persistent anxiety symptoms were predicted by older age, more medical illness, and baseline depression.
Since depression was associated with prevalent, incident, and persistent anxiety symptoms, effective detection and management thereof is important in older adults to reduce anxiety. Furthermore, preventive collaborative care should be considered, particularly for older, female, insomniac patients.
To determine the influence of caregiver personality and other factors on the burden of family caregivers of terminally ill cancer patients.
We investigated a wide range of factors related to the patient–family caregiver dyad in a palliative care setting using a cross-sectional design. Caregiver burden was assessed using the seven-item short version of the Zarit Burden Interview (ZBI–7). Caregiver personality was assessed using the 10-item short version of the Big Five Inventory (BFI–10), which measures the following five personality dimensions: extroversion, agreeableness, conscientiousness, neuroticism, and openness. Patient- and caregiver-related sociodemographic and psychological factors were included in the analysis because of their potential association with caregiver burden. Clinical patient data were obtained from medical charts or by using other measures. Multivariate linear regression analysis was performed to identify the independent factors associated with caregiver burden.
We analyzed 227 patient–family caregiver dyads. The multivariate analysis revealed that caregiver extroversion was protective against caregiver burden, whereas depressive symptoms in caregivers were related to increased burden. Neuroticism was positively correlated with caregiver burden, but this relationship was nonsignificant following adjustment for depressive symptoms. Patient-related factors were not significantly associated with caregiver burden.
Significance of Results:
Evaluating caregiver personality traits could facilitate identification of individuals at greater risk of high burden. Furthermore, depression screening and treatment programs for caregivers in palliative care settings are required to decrease caregiver burden.
This study aimed to assess the prevalence, incidence, and persistence of suicidal ideation (SI), and to investigate the psychosocial factors associated with these.
A total of 1,204 community dwelling elderly adults aged 65 years or older were evaluated at baseline, 909 (75%) of whom were followed two years later. The presence of SI was identified using the questions from the community version of the Geriatric Mental State (GMS) diagnostic schedule (GMS B3) at both baseline and follow-up interviews. Baseline measures included demographic status, years of education, rural/urban residence, accommodation, past and current occupation, monthly income, marital status, stressful life events, social support deficits, number of physical illnesses, severity of pain, physical activity, disability, depressive symptoms, anxiety, insomnia, cognitive function, alcohol consumption, and smoking.
Baseline SI prevalence, follow-up incidence (SI rate at follow-up of 805 elderly subjects who did not have SI at baseline), and persistence (SI rate at follow-up of 104 elderly subjects who had SI at baseline) were 11.5%, 9.6%, and 36.5%, respectively. Baseline SI was independently associated with no current employment, lower monthly income, stressful life events, more severe pain, presence of disability, depressive symptoms, and smoking. Incident SI was independently predicted by baseline unmarried status, social support deficit, severe pain, presence of depressive symptoms, and smoking. Persistent SI was independently predicted by baseline stressful life events and depressive symptoms.
Depressive symptoms were independently associated with prevalent, incident, and persistent SI, but other predictors varied according to incidence and persistence outcomes.
The role of folate, vitamin B12 and homocysteine levels in
depression is not clear.
To investigate cross-sectional and prospective associations between
folate, B12 and homocysteine levels and late-life
A total of 732 Korean people aged 65 years or over were evaluated at
baseline. Of the 631 persons who were not depressed, 521 (83%) were
followed over a period of 2–3 years and incident depression was
ascertained with the Geriatric Mental State schedule. Serum folate, serum
vitamin B12 and plasma homocysteine levels were assayed at
both baseline and follow-up.
Lower levels of folate and vitamin B12 and higher homocysteine
levels at baseline were associated with a higher risk of incident
depression at follow-up. Incident depression was associated with a
decline in vitamin B12 and an increase in homocysteine levels
over the follow-up period.
Lower folate, lower vitamin B12 and raised homocysteine levels
may be risk factors for late-life depression.