Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents

Ota, Vanessa Kiyomi; Santoro, Marcos; Spíndola, Letícia; Pan, Pedro Mário; Simabucuro, Andressa; Xavier, Gabriela; Vieira-Fonseca, Tamiris; Zanardo, Évelin Aline; Santos, Felipe R. C. dos; Schäfer, Julia; Kulikowski, Leslie Domenici; Galante, Pedro A. F.; Asprino, Paula Fontes; Brietzke, Elisa; Grassi‐Oliveira, Rodrigo; Rohde, Luís Augusto; Miguel, Eurí­pedes Constantino; Gadelha, Ary; Mari, Jair J.; Bressan, Rodrigo Affonseca; Salum, Giovanni Abrahão; Belangero, Sintia

doi:10.1038/s41398-020-0772-3

Cited by 4 publications

(2 citation statements)

References 49 publications

(54 reference statements)

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“…NDUFA2 encodes a subunit of the hydrophobic protein fraction of Complex 1. The mRNA level of NDUFA2 was most significantly associated with schizophrenia ( 38 ) and the remission of psychiatric symptoms ( 39 ). NDUFB11 (ESSS protein), located in the short arm of the X-chromosome, is essential for the assembly and activity of Complex I. NDUFB11 may play a role in the mechanism underlying cognitive deficits in children and adolescents born preterm.…”

Section: Discussionmentioning

confidence: 99%

Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder

Gong

et al. 2023

Front. Neurol.

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BackgroundThe retrograde endocannabinoid (eCB) pathway is closely associated with the etiology of major depressive disorder (MDD) at both pathophysiological and genetic levels. This study aimed to investigate the potential role of genetic mutations in the eCB pathway and underlying mechanisms in Han Chinese patients with MDD.MethodsA total of 96 drug-naïve patients with first-episode MDD and 62 healthy controls (HCs) were recruited. Whole-exome sequencing was performed to identify the gene mutation profiles in patients with MDD. Results were filtered to focus on low-frequency variants and rare mutations (minor allele frequencies <0.05) related to depressive phenotypes. Enrichment analyses were performed for 146 selected genes to examine the pathways in which the most significant enrichment occurred. A protein–protein interaction (PPI) network analysis was performed to explore the biological functions of the eCB pathway. Finally, based on current literature, a preliminary analysis was conducted to explore the effect of genetic mutations on the function of this pathway.ResultsOur analysis identified 146 (15.02%) depression-related genetic mutations in patients with MDD when compared with HCs, and 37 of the mutations were enriched in the retrograde eCB signaling pathway. Seven hub genes in the eCB pathway were closely related to mitochondrial function, including Complex I genes (NDUFS4, NDUFV2, NDUFA2, NDUFA12, NDUFB11) and genes associated with protein (PARK7) and enzyme (DLD) function in the regulation of mitochondrial oxidative stress.ConclusionThese results indicate that genetic mutations in the retrograde eCB pathway represent potential etiological factors associated with the pathogenesis of MDD.

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Section: Discussionmentioning

confidence: 99%

Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder

Gong

et al. 2023

Front. Neurol.

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“…We will make inferences about which behavioral phenotypes are most predictive and evaluate their time-delayed impact upon mood at different time lags. Granger causality [30] is a quantitative framework for assessing the relationship between time series, and has been widely used in econometrics, neuroscience, and genomics to study the temporal causal relations among multiple economic events [30,31] directional interactions of neurobiological signals [32][33][34] and gene time-course expression levels [35][36][37], respectively. Given two time series and , the temporal structure of the data is used to assess whether the past values of , are predictive of future values of , beyond what the past of can predict alone; if is said to Granger cause .…”

Section: Data Analysis and Presentationmentioning

confidence: 99%

Use of Mobile Technology to Identify Behavioral Mechanisms Linked to Mental Health Outcomes in Kenya: Protocol for Development and Validation of a Predictive Model

Njoroge

Maina

Frank

et al. 2023

Preprint

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Objective: This study proposes to identify and validate weighted sensor stream signatures that predict near-term risk of a major depressive episode and future mood among healthcare workers in Kenya. Approach: The study will deploy a mobile app platform and use novel data science analytic approaches (Artificial Intelligence and Machine Learning) to identifying predictors of mental health disorders among 500 randomly sampled healthcare workers from five healthcare facilities in Nairobi, Kenya. Expectation: This study will lay the basis for creating agile and scalable systems for rapid diagnostics that could inform precise interventions for mitigating depression and ensure a healthy, resilient healthcare workforce to develop sustainable economic growth in Kenya, East Africa, and ultimately neighboring countries in sub-Saharan Africa. This protocol paper provides an opportunity to share the planned study implementation methods and approaches. Conclusion: A mobile technology platform that is scalable and can be used to understand and improve mental health outcomes is of critical importance.

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Inflammation and immune system pathways as biological signatures of adolescent depression—the IDEA-RiSCo study

Zonca,

Marizzoni,

Saleri

et al. 2024

Transl Psychiatry

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The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world’s adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14–16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p < 0.001), interferon signaling (z-score = 2.464, p < 0.001), interferon alpha/beta signaling (z-score = 3.873, p < 0.001), and complement signaling (z-score = 2, p = 0.002) were upregulated in adolescents with MDD compared with adolescents without MDD independently from their level of risk. The up-regulation of such inflammation-related pathways was observed in females but not in males. Inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling were identified as key indicators of adolescent depression, and this effect was present only in females.

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Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents

Cited by 4 publications

References 49 publications

Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder

Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder

Use of Mobile Technology to Identify Behavioral Mechanisms Linked to Mental Health Outcomes in Kenya: Protocol for Development and Validation of a Predictive Model

Inflammation and immune system pathways as biological signatures of adolescent depression—the IDEA-RiSCo study

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