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Exposure to natural daylight benefits human well-being, alertness, circadian rhythms and sleep. Many workplaces have limited or no access to daylight. Thus, we implemented a light-panel (“Virtual Sky“), which reproduced nature-adapted light scenarios. In a laboratory office environment, three lighting scenarios were presented during the day: two lighting conditions with nature-adapted spectral light distributions, one with static and one with dynamic clouds, and a standard office lighting condition. We compared the impact of the three lighting scenarios on subjective and objective measures of alertness, cognitive performance, wellbeing, visual comfort, contrast sensitivity, and cortisol levels in 18 healthy young male volunteers in a within-participant cross-over study design. We found no evidence that an 8-h lighting scenario with static or dynamic clouds during the waking day (9am-5pm) was associated with any significant effect on objective and/or subjective alertness, cognitive performance and morning cortisol concentrations compared to standard workplace lighting. However, the dynamic light scenario was accompanied with lower levels of perceived tensionafter completing cognitive tasks and less effort to concentrate compared to the static lighting scenarios. Our findings suggest that apart from smaller effects on tension and concentration effort, nature-adapted lighting conditions did not improve daytime alertness and cognitive performance in healthy well-rested young participants, as compared to standard office lighting.

Exposure to natural daylight benefits human well-being, alertness, circadian rhythms and sleep. Many workplaces have limited or no access to daylight. Thus, we implemented a light-panel (\"Virtual Sky\"), which reproduced nature-adapted light scenarios. In a laboratory office environment, three lighting scenarios were presented during the day: two lighting conditions with nature-adapted spectral light distributions, one with static and one with dynamic clouds, and a standard office lighting condition. We compared the impact of the three lighting scenarios on subjective and objective measures of alertness, cognitive performance, wellbeing, visual comfort, contrast sensitivity, and cortisol levels in 18 healthy young male volunteers in a within-participant cross-over study design. We found no evidence that an 8-h lighting scenario with static or dynamic clouds during the waking day (9am-5pm) was associated with any significant effect on objective and/or subjective alertness, cognitive performance and morning cortisol concentrations compared to standard workplace lighting. However, the dynamic light scenario was accompanied with lower levels of perceived tensionafter completing cognitive tasks and less effort to concentrate compared to the static lighting scenarios. Our findings suggest that apart from smaller effects on tension and concentration effort, nature-adapted lighting conditions did not improve daytime alertness and cognitive performance in healthy well-rested young participants, as compared to standard office lighting.

Study Objectives: We aimed to examine the association between self-rated and clinician-rated sleep disturbances and C-reactive protein (CRP), an objective marker of inflammation, in pediatric depression. Methods: Two hundred fifty-six children and adolescents (15.2 ± 1.6 y, 72.3% female) with moderate to severe symptoms of depression participated in the study. Sleep disturbances were assessed by self-reports (Insomnia Severity Index) and clinician ratings (Kiddie-Schedule for Affective Disorder and Schizophrenia), inflammation by plasma CRP levels. Results: Higher levels of CRP correlated positively with clinician-rated middle insomnia and hypersomnia. After adjusting for control variables (body mass index, tobacco, alcohol, stress, age, sex, antidepressants, sleep medication, depression severity), regression models confirmed the significant association of clinician-rated hypersomnia and middle insomnia symptoms with elevated CRP levels. In the adjusted regression models, other clinician-rated manifestations of sleep disturbance (eg, initial insomnia) and insomnia self-ratings were not significantly associated with CRP. Body mass index correlated positively with CRP, but body mass index had no mediating effect on the associations between sleep disturbances and CRP. We did not find an association between depression severity, assessed by the Children’s Depression Rating Scale-Revised, and CRP. Conclusions: Results of the present study indicate a significant association of hypersomnia and middle insomnia symptoms with CRP in pediatric depression, not linked to alterations in the body mass index. Citation: Strumberger MA, Häberling I, Emery S, et al. Sleep disturbance, but not depression severity, is associated with inflammation in children and adolescents. J Clin Sleep Med . 2023;19(10):1775–1784.

Pediatric major depressive disorder (MDD) represents a leading cause of disability worldwide in children and adolescents, while its underlying pathophysiology remains largely elusive. The endocannabinoid system (ECS) and the hypothalamus-pituitary-adrenal (HPA) axis are considered intertwined regulatory systems crucially implicated in the pathophysiology of depressive disorders. This study explores the cross-sectional and longitudinal association between the ECS, specifically anandamide (AEA), and the HPA axis with its main effector cortisol and MDD status and severity in children and adolescents. Utilizing data from the omega-3-pMDD trial, a phase III Randomized Clinical Trial assessing the efficacy and safety of omega-3 fatty acid supplementation in pediatric MDD, we examined hair AEA and cortisol concentrations in 110 children and adolescents aged 8-17 years, with MDD. Associations between MDD, symptom severity and hair AEA and cortisol concentrations were explored across four measurement time points (baseline, week 6, 24 and 36). Additionally, 127 healthy children and adolescents were examined once to enable cross-sectional comparisons between MDD cases and healthy controls. Baseline comparisons for the 237 children and adolescents showed lower cortisol and AEA levels in hair of children and adolescents with MDD compared to healthy controls. Longitudinal multi-level analysis over all time-points further corroborated negative longitudinal associations between hair cortisol and depressive symptoms in children and adolescents with MDD. Taken together, reduced baseline AEA and cortisol levels emerge as robust biomarker in depressed youth, while the negative longitudinal association between hair cortisol and depression symptoms might provide useful for therapy monitoring purposes. These results hold implications for early detection, diagnosis, and therapeutic response prediction in pediatric MDD.

Executive functions (EF) consolidate during adolescence and are impaired in various emerging psychiatric disorders, such as pediatric Major Depressive Disorder (pMDD) and Borderline Personality Disorder. Previous studies point to a marked heterogeneity of deficits in EF in pMDD. We examined the hypothesis that deficits in EF in adolescents with pMDD might be related to comorbid Borderline Personality features (BPF). We examined a sample of 144 adolescents (15.86 ± 1.32) diagnosed with pMDD. Parents rated their child's EF in everyday life with the Behavior Rating Inventory of Executive Function (BRIEF) and BPF with the Impulsivity and Emotion Dysregulation Scale (IED-27). The adolescents completed equivalent self-rating measures. Self- and parent-ratings of the BRIEF scores were compared with paired t-Tests. Correlation and parallel mediation analyses, ICC, and multiple regression analyses were used to assess symptom overlap, parent-child agreement, and the influence of depression severity. Over the whole sample, none of the self- or parent-rated BRIEF scales reached a mean score above T > 65, which would indicate clinically impaired functioning. Adolescents tended to report higher impairment in EF than their parents. Depression severity was the strongest predictor for BPF scores, with predicting parent-rated BPF and predicting self-rated BPF. Furthermore, the Behavioral Regulation Index, which includes EF closely related to behavioral control, significantly mediated the relationship between depression severity and IED-27 factors and but not On average, adolescents with depression show only subtle deficits in executive functioning. However, increased EF deficits are associated with the occurrence of comorbid borderline personality features, contributing to a more severe overall psychopathology. Therefore, training of executive functioning might have a positive effect on psychosocial functioning in severely depressed adolescents, as it might also improve comorbid BPF. www.ClinicalTrials.gov, identifier NCT03167307.

In adults, anxious depression has been identified as a more severe form of major depressive disorder (MDD), associated with higher depression severity, more suicidal ideation and worse treatment outcome. Research in pediatric depression, however, has been sparse. 126 children and adolescents aged 8–18 years with a primary diagnosis of MDD were categorized into a MDD-only group and an anxious depression group based on clinically elevated scores on the Beck Anxiety Inventory. One-third of the sample was classified as having anxious depression with females being overrepresented in the anxious depressed compared to the MDD-only group. 42.2% of the anxious depressed youth met diagnostic criteria for a comorbid anxiety disorder. Anxious depressed youth were more likely to suffer recurrent depressive episodes, showed higher depression severity and a unique pattern of depressive symptoms characterized by more severe sleep problems, more somatic complaints, more severely depressed mood and more frequent suicidal ideations. Scores on a suicidal ideation scale were increased even when controlling for overall depression severity. However, when comparing depressed patients with and without comorbid anxiety disorders, no differences in depression severity, symptom patterns or suicidal ideations were observed. The results indicate that high anxiety levels in depressed youth are clinically relevant, and given the increase in suicidal ideation, anxiety symptoms during depressive episodes should routinely be screened in clinical practice even in the absence of a fully formed comorbid anxiety disorder.

Depression has been associated with subclinical hypothyroidism and altered hypothalamic-pituitary-thyroid axis functioning. Adequate iodine nutrition is essential for healthy thyroid functioning. We therefore determined associations of iodine and thyroid status with paediatric major depressive disorder (pMDD) among Swiss adolescents and explored whether associations are sex-specific and mediated by stress. We conducted a matched case–control study in 95 adolescents with diagnosed pMDD and 95 healthy controls. We assessed depression severity using the Children’s Depression Rating Scale-Revised and stress using the perceived stress scale (PSS) and measuring hair cortisol levels. We determined iodine status by measuring urinary iodine concentrations (UIC) and thyroid status by thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in serum. Median (IQR) UIC did not differ between cases (121 (87, 174) µg/l) and controls (114 (66, 183) μg/l, P = 0·3). Median TSH and FT4 were lower in cases than controls (TSH: 1·36 (0·91, 2·00) mlU/l v. 1·50 (1·18, 2·06) mlU/l, P = 0·039; FT4: 14·7 (12·9, 16·9) pmol/l v. 15·7 (14·3, 17·2) pmol/l, P = 0·004). The prevalence of hypothyroxinaemia (normal TSH; low FT4) was higher among female cases than controls (21 % v. 4%, P = 0·006). PSS scores were higher while hair cortisol was lower in cases than controls (PSS: 25 (20, 28) v. 11 (7, 15), P < 0·001; cortisol: 2·50 (1·34, 3·57) pg/mg v. 3·23 (1·79, 4·43) pg/mg, P = 0·044). After adjusting for confounders, the associations of TSH and hair cortisol with pMDD were no longer significant. Furthermore, TSH and FT4 were not associated with PSS scores and hair cortisol levels. Summarising, iodine nutrition was adequate for adolescents with and without pMDD. However, FT4 concentrations were lower in those with pMDD, and 1 in 5 female adolescents with pMDD were hypothyroxinaemic.

Purpose Depression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status. Methods This is a matched case–control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13–17 years. We assessed depression severity using the Children’s Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire. Results SF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) μg/L) and controls (32.5 (22.6, 48.3) μg/L, p  = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p  < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p  = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p  = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p  = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls ( p  = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls. Conclusion Cases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been described as positively associated with cognitive functioning. Current meta-analyses have identified eicosapentaenoic acid (EPA) as potentially more effective than docosahexaenoic acid (DHA). An especially vulnerable subgroup that might benefit from these beneficial effects are depressed youths. In this study, we examined associations between red blood cell (RBC) DHA and EPA levels and depression severity and verbal memory performance in a sample of 107 moderately (n = 63) and severely (n = 44) depressed youths. The findings showed that youths with high RBC EPA levels had steeper learning curves compared to those with moderate or low RBC EPA levels (Pillai’s Trace = 0.195, p = 0.027, ηp2 = 0.097). No associations between RBC DHA levels or depression severity and verbal memory performance were observed. Our results further confirm previous findings indicating a more important role of EPA compared to DHA in relation to cognitive functioning. Future research should further investigate the differential role of EPA and DHA concerning cognitive functioning in depressed youths. Evidence supporting beneficial supplementation effects could potentially establish a recommendation for a natural and easily accessible intervention for cognitive improvement or remission.