Changes of sphingolipid metabolism were suggested to contribute to the patho-etiology of major depression (MD) and bipolar disorder (BD). In a pilot study we assessed if lipid allostasis manifested ...in pathological plasma concentrations of bioactive lipids i.e. endocannabinoids, sphingolipids, ceramides, and lysophosphatidic acids.
Targeted and untargeted lipidomic analyses were performed according to GLP guidelines in 67 patients with unipolar or bipolar disorders (20–67 years, 36 male, 31 female) and 405 healthy controls (18–79 years, 142 m, 263 f), who were matched according to gender, age and body mass index. Multivariate analyses were used to identify major components, which accounted for the variance between groups and were able to predict group membership.
Differences between MD and BP patients versus controls mainly originated from ceramides and their hexosyl-metabolites (C16Cer, C18Cer, C20Cer, C22Cer, C24Cer and C24:1Cer; C24:1GluCer, C24LacCer), which were strongly increased, particularly in male patients. Ceramide levels were neither associated with the current episode, nor with the therapeutic improvement of the Montgomery Åsberg Depression Rating Scale (MARDS). However, long-chain ceramides were linearly associated with age, stronger in patients than controls, and with high plasma levels of diacyl- and triacylglycerols. Patients receiving antidepressants had higher ceramide levels than patients not taking these drugs. There was no such association with lithium or antipsychotics except for olanzapine.
Our data suggest that high plasma ceramides in patients with major depression and bipolar disorder are indicative of a high metabolic burden, likely aggravated by certain medications.
•Plasma levels of ceramides are strongly increased in patients with major depression and bipolar disorder.•Plasma ceramides are associated with gender, age and metabolic comorbidities but not with the current episode.•Plasma ceramides are particularly high in patients receiving antidepressants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In 2 meta-analyses on gender differences in depression in nationally representative samples, we advance previous work by including studies of depression diagnoses and symptoms to (a) estimate the ...magnitude of the gender difference in depression across a wide array of nations and ages; (b) use a developmental perspective to elucidate patterns of gender differences across the life span; and (c) incorporate additional theory-driven moderators (e.g., gender equity). For major depression diagnoses and depression symptoms, respectively, we meta-analyzed data from 65 and 95 articles and their corresponding national data sets, representing data from 1,716,195 and 1,922,064 people in over 90 different nations. Overall, odds ratio (OR) = 1.95, 95% confidence interval (CI) 1.88, 2.03, and d = 0.27 0.26, 0.29. Age was the strongest predictor of effect size. The gender difference for diagnoses emerged earlier than previously thought, with OR = 2.37 at age 12. For both meta-analyses, the gender difference peaked in adolescence (OR = 3.02 for ages 13-15, and d = 0.47 for age 16) but then declined and remained stable in adulthood. Cross-national analyses indicated that larger gender differences were found in nations with greater gender equity, for major depression, but not depression symptoms. The gender difference in depression represents a health disparity, especially in adolescence, yet the magnitude of the difference indicates that depression in men should not be overlooked.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
We are facing an unprecedented time during the COVID-19 pandemic. Measures have been taken to reduce the spread of the virus, including school closures and widespread lockdowns. Physical isolation ...combined with economic instability, fear of infection, and uncertainty for the future has had a profound impact on global mental health. For adolescents, the effects of this stress may be heightened due to important developmental characteristics. Canadian adolescents (n = 1,054; Mage = 16.68, SD = 0.78) completed online surveys and responded to questions on stress surrounding the COVID-19 crisis, feelings of loneliness and depression, as well as time spent with family, virtually with friends, doing schoolwork, using social media, and engaging in physical activity. Results showed that adolescents are very concerned about the COVID-19 crisis and are particularly worried about schooling and peer relationships. COVID-19 stress was related to more loneliness and more depression, especially for adolescents who spend more time on social media. Beyond COVID-19 stress, more time connecting to friends virtually during the pandemic was related to greater depression, but family time and schoolwork was related to less depression. For adolescents with depressive symptoms, it may be important to monitor the supportiveness of online relationships. Results show promising avenues to stave off loneliness, as time with family, time connecting to friends, as well as physical activity were related to lower loneliness, beyond COVID-19 stress. These results shed light on the implications of the COVID-19 pandemic for adolescents and document possible pathways to ameliorate negative effects.
Nous nous trouvons, avec la pandémie de COVID-19, dans une situation sans précédent. Des mesures ont été prises pour réduire la propagation du virus, notamment des fermetures d'établissements scolaires et des confinements à grande échelle. L'isolement physique, combiné à l'instabilité économique, à la crainte de l'infection et à l'incertitude quant à l'avenir, a eu de profondes répercussions sur la santé mentale globale. Chez les adolescents, les effets de ce stress peuvent être exacerbés en raison des caractéristiques importantes du développement. Des adolescents canadiens (n = 1 054; Mage = 16,68, écart-type = 0,78) ont répondu à un sondage en ligne comportant des questions sur le stress dû à la crise de la COVID-19, le sentiment de solitude et de dépression, ainsi que le temps passé avec la famille ou les amis (virtuellement), ainsi que le temps consacré aux devoirs, aux médias sociaux et à l'activité physique. Les résultats ont démontré que les adolescents sont très préoccupés par la crise de la COVID-19, et qu'ils sont particulièrement inquiets par rapport à leurs études et aux relations avec leurs pairs. Le stress dû à la COVID-19 était lié à une plus grande solitude et à la hausse des cas de dépression, en particulier chez les adolescents qui passent plus de temps sur les médias sociaux. Outre le stress dû à la COVID-19, le fait de passer plus de temps en contact virtuel avec ses amis durant la pandémie était lié à une hausse des cas de dépression, tandis que le temps passé en famille ou consacré aux devoirs était lié à une incidence moindre de la dépression. Dans le cas des adolescents souffrant de symptômes de dépression, il pourrait être important de surveiller le niveau de soutien fourni par les relations en ligne. Les résultats laissent entrevoir des pistes prometteuses pour prévenir la solitude. Notamment, le temps en famille, le temps consacré aux contacts avec les amis, ainsi que l'activité physique étaient liés à une diminution de la solitude dans le contexte du stress lié à la COVID-19. Ces résultats permettent de mieux comprendre les répercussions de la pandémie de COVID-19 sur les adolescents et font état de possibles voies d'intervention pour atténuer les conséquences négatives.
Public Significance Statement
Adolescents are concerned about the COVID-19 crisis and their pandemic stress is related to heightened depression and loneliness. However, time with family, time connecting virtually to friends, as well as physical activity were related to less loneliness during the initial COVID-19 crisis. On the contrary, although more time on social media and virtually connecting to friends was related to more reported depression, time engaging with family was related to less reported depression.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK, VSZLJ
Schizophrenia and major depression are associated with alterations in peripheral inflammatory markers, and anti-inflammatory therapy has been proposed as a promising add-on approach in the ...pharmacologic treatment of both disorders. Second-generation atypical antipsychotics are currently first-line drugs in the treatment of schizophrenia and are also used as augmentation strategies in treatment-resistant major depression. Furthermore, these drugs have been reported to exhibit distinct metabolic side effects and to influence inflammatory processes.
In this study, we used ex vivo stimulation of primary human peripheral blood mononuclear cells (PBMC) from healthy blood donors with atypical antipsychotics olanzapine or aripiprazole to examine effects on cytokine production independent from metabolic side effects and disease status.
Both olanzapine and aripiprazole stimulation decreased mRNA levels of IL-1β, IL-6, and TNF-α and resulted in diminished protein concentrations of IL-6 and TNF-α in conditioned medium of stimulated PBMC. A multiplex approach revealed additional downregulation of IL-2; MIP-1β and IP-10 secretion. Similarly, olanzapine and aripiprazole stimulation of the human monocytic cell line THP-1 resulted in a significant decrease in expression and secretion of IL-1β and TNF-α. Our results suggest that atypical antipsychotics directly influence immune cell function and thereby highlight the importance to factor in potential side effects of drugs routinely used in treatment of schizophrenia and major depression on inflammatory processes when considering anti-inflammatory drug therapy as an additional treatment option.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Major depression (MD) is a highly heterogeneous diagnostic category. Diverse symptoms such as sad mood, anhedonia, and fatigue are routinely added to an unweighted sum-score, and cutoffs are used to ...distinguish between depressed participants and healthy controls. Researchers then investigate outcome variables like MD risk factors, biomarkers, and treatment response in such samples. These practices presuppose that (1) depression is a discrete condition, and that (2) symptoms are interchangeable indicators of this latent disorder. Here I review these two assumptions, elucidate their historical roots, show how deeply engrained they are in psychological and psychiatric research, and document that they contrast with evidence. Depression is not a consistent syndrome with clearly demarcated boundaries, and depression symptoms are not interchangeable indicators of an underlying disorder. Current research practices lump individuals with very different problems into one category, which has contributed to the remarkably slow progress in key research domains such as the development of efficacious antidepressants or the identification of biomarkers for depression. The recently proposed network framework offers an alternative to the problematic assumptions. MD is not understood as a distinct condition, but as heterogeneous symptom cluster that substantially overlaps with other syndromes such as anxiety disorders. MD is not framed as an underlying disease with a number of equivalent indicators, but as a network of symptoms that have direct causal influence on each other: insomnia can cause fatigue which then triggers concentration and psychomotor problems. This approach offers new opportunities for constructing an empirically based classification system and has broad implications for future research.
Objectives: Patients affected by major depression (MDD) are at high risk of suicide. The metabolism of tryptophan (Trp) along the serotonin (5-HT) and kynurenine (Kyn) pathways was found ...dysfunctional in MDD and in suicide. However, a clear biological framework linking dysfunctions in Trp metabolism via 5-HT and Kyn, cortisol, and the activities of tryptophan and indoleamino 2,3-dioxygenase (TDO, IDO) enzymes has not been yet clarified in MDD with or without suicidal behaviours.
Methods: We analysed peripheral markers of Trp via 5-HT and Kyn pathways, Kyn/Trp ratio as a measure of TDO/IDO activities, cortisol, and psychopathology in 73 non-suicidal and 56 suicidal MDD patients, and in 40 healthy controls.
Results: Plasma Trp levels were lower and the ratio Kyn/Trp higher in suicidal MDD than in non-suicidal MDD patients and controls. Trp levels and the ratio Kyn/Trp correlated with suicidal ideation, and cortisol with the Kyn/Trp ratio. Finally, Trp levels discriminated controls from non-suicidal and suicidal MDD patients, and also non-suicidal from suicidal MDD patients.
Conclusions: Reduced availability of Trp for 5-HT synthesis and increased activation of the Kyn pathway and cortisol correlate with depression and suicide. Low plasma Trp levels may be a biomarker of MDD and suicide in MDD.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Despite the importance for understanding mechanisms of change, little is known about the order of change in daily life emotions, cognitions, and behaviors during treatment of depression. This study ...examined the within-person temporal order of emotional, cognitive, and behavioral improvements using ecological momentary assessment data.
Thirty-two individuals with diagnosed depression completed ecological momentary assessment questions on emotions (sad mood, happy mood), behaviors (social interaction, number of activities), and cognitive variables (worrying, negative self-thoughts) 5 times a day during a 4-month period in which they underwent psychotherapy for depression. Nonparametric change-point analyses were used to determine the timing of gains (i.e., improvements in the mean of each variable) for each individual. We then established whether the first (i.e., earliest) gains in emotions preceded, followed, or occurred in the same week as cognitive and behavioral gains for each individual.
Contrary to our hypotheses, first gains in behaviors did not precede first emotional gains (3 times, 8%) more often than they followed them (26 times, 70%). Cognitive gains often occurred in the same week as first emotional gains (43 times, 58%) and less often preceded (13 times, 18%) or followed emotional gains (18 times, 24%).
The first improvements in behaviors did not tend to precede the first improvements in emotions likely because fewer behavioral gains were found. The finding that cognitive variables tend to improve around the same time as sad mood may explain why many studies failed to find that cognitive change predicts later change in depressive symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Background
The Covid-19 pandemic is affecting the entire world population. During the first spread, most governments have implemented quarantine and strict social distancing procedures. Similar ...measures during recent pandemics resulted in an increase in post-traumatic stress, anxiety and depression symptoms. The development of novel interventions to mitigate the mental health burden are of utmost importance.
Objective
In this rapid review, we aimed to provide a systematic overview of the literature with regard to associations between physical activity (PA) and depression and anxiety during the COVID-19 pandemic.
Data Source
We searched major databases (PubMed, EMBASE, SPORTDiscus, and Web of Science) and preprint servers (MedRxiv, SportRxiv, ResearchGate, and Google Scholar), for relevant papers up to 25/07/2020.
Study Eligibility Criteria
We included observational studies with cross-sectional and longitudinal designs. To qualify for inclusion in the review, studies must have tested the association of PA with depression or anxiety, using linear or logistic regressions. Depression and anxiety must have been assessed using validated rating scales.
Study Appraisal and Synthesis Methods
Effect sizes were represented by fully adjusted standardized betas and odds ratios (OR) alongside 95% confidence intervals (CI). In case standardized effects could not be obtained, unstandardized effects were presented and indicated.
Results
We identified a total of 21 observational studies (4 longitudinal, 1 cross-sectional with retrospective analysis, and 16 cross-sectional), including information of 42,293 (age 6–70 years, median female = 68%) participants from five continents. The early evidence suggests that people who performed PA on a regular basis with higher volume and frequency and kept the PA routines stable, showed less symptoms of depression and anxiety. For instance, those reporting a higher total time spent in moderate to vigorous PA had 12–32% lower chances of presenting depressive symptoms and 15–34% of presenting anxiety.
Conclusion
Performing PA during Covid-19 is associated with less depression and anxiety. To maintain PA routines during Covid-19, specific volitional and motivational skills might be paramount to overcome Covid-19 specific barriers. Particularly, web-based technologies could be an accessible way to increase motivation and volition for PA and maintain daily PA routines.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Depressive symptomatology is manifested in greater first-person singular pronoun use (i.e., I-talk), but when and for whom this effect is most apparent, and the extent to which it is specific to ...depression or part of a broader association between negative emotionality and I-talk, remains unclear. Using pooled data from N = 4,754 participants from 6 labs across 2 countries, we examined, in a preregistered analysis, how the depression-I-talk effect varied by (a) first-person singular pronoun type (i.e., subjective, objective, and possessive), (b) the communication context in which language was generated (i.e., personal, momentary thought, identity-related, and impersonal), and (c) gender. Overall, there was a small but reliable positive correlation between depression and I-talk (r = .10, 95% CI .07, .13). The effect was present for all first-person singular pronouns except the possessive type, in all communication contexts except the impersonal one, and for both females and males with little evidence of gender differences. Importantly, a similar pattern of results emerged for negative emotionality. Further, the depression-I-talk effect was substantially reduced when controlled for negative emotionality but this was not the case when the negative emotionality-I-talk effect was controlled for depression. These results suggest that the robust empirical link between depression and I-talk largely reflects a broader association between negative emotionality and I-talk. Self-referential language using first-person singular pronouns may therefore be better construed as a linguistic marker of general distress proneness or negative emotionality rather than as a specific marker of depression.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the ...lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within the context of these clusters.
We analyzed 77,519 participants and 6,266,189 single-nucleotide polymorphisms (SNPs) of the UK Biobank database. Childhood trauma burden was assessed using the Childhood Trauma Screener (CTS). For each cluster, Plink 2.0 was used to calculate SNP × CTS interaction effects on the participants' cluster membership probabilities. We especially focused on the effects of 31 candidate genes and associated SNPs selected from previous G × E studies for childhood maltreatment's association with depression.
At SNP-level, only the high-multimorbidity Cluster 6 revealed a genome-wide significant SNP rs145772219. At gene-level, MPST and PRH2 were genome-wide significant for the low-multimorbidity Clusters 1 and 3, respectively. Regarding candidate SNPs for G × E interactions, individual SNP results could be replicated for specific clusters. The candidate genes CREB1, DBH, and MTHFR (Cluster 5) as well as TPH1 (Cluster 6) survived multiple testing correction.
CTS is a short retrospective self-reported measurement. Clusters could be influenced by genetics of individual disorders.
The first G × E GWAS for MDD-related multimorbidity trajectories successfully replicated findings from previous G × E studies related to depression, and revealed risk clusters for the contribution of childhood trauma.
•First G × E GWAS with childhood trauma for MDD-related multimorbidity trajectories.•Most G × E findings for high MDD-multimorbidity Clusters 5–6.•Significant correlation between cluster probability and CTS (high vs low risk clusters).•stronger genetic findings in the clusters with higher childhood trauma burden.•Differential effects of candidate genes in different comorbidity clusters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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