To the authors knowledge, there has been no study verifying the epigenetic changes following antidepressant treatment in children despite many promising results on this subject coming from adult studies [80]. Although mounting evidence implicates the potential of BDNF to be used as a biomarker in depression, the studies on BDNF peripheral level in the population of children and adolescents with depression are scarce and inconclusive. All 12 studies analyzed the association between BDNF Val66Met genotype/gene plasticity index and depressive symptoms. https://doi.org/10.1016/j.psychres.2014.11.018, Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Zhang H, Pavuluri MN (2010) Brain-derived neurotrophic factor gene and protein expression in pediatric and adult depressed subjects. Numerous findings suggest that circulating miRNA levels could be used as promising biomarkers of depression state or antidepressant treatment response in adult patients [124, 125]. Polymorphisms of the 5-hydroxytryptamine (serotonin) transporter gene-linked polymorphic region (5-HTTLPR) have been widely demonstrated to be a risk factor for depression following adverse life experiences. Only three studies investigated the gene polymorphism and the risk of depression in young adults at an age range of 2025 years. Biol Psychiatry 68(2):209212. Increased serum lipids are often associated with obesity, which has been associated with depressive symptoms in the pediatric population [99]. Nilsson K. W., Sjberg R. L., Leppert J., Oreland L., Damberg M. (2009). Hormone changes can contribute to depression. A recent report suggested that TPH2 gene expression in the dorsal raphe nuclei of depressed suicidal patients is upregulated [14]. A summary of major findings is included in Table 1. (2007). Deregulated gene expression and specific functional genetic polymorphisms have been demonstrated to be risk factors of depression or to be associated with the severity of depressive symptoms (Dunn et al., 2011). A meta-analysis has demonstrated that the 5-HTTLPR long-allele carriers had higher probability of response than patients with short-allele homozygotes of 5-HTTLPR with heterogeneity effect (Serretti et al., 2007). A total of 47 studies on early adolescence and three studies on young adults were included in the current review. What role does genetic risk play in shaping the developmental https://doi.org/10.1016/j.neubiorev.2019.04.010, Fuchikami M, Morinobu S, Segawa M, Okamoto Y, Yamawaki S, Ozaki N et al (2011) DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression. Brent D., Melhem N., Ferrell R., Emslie G., Wagner K. D., Ryan N., et al.. (2010). Bai M., Zhu X., Zhang Y., Zhang S., Zhang L., Xue L., et al.. (2012). Studies performed on the adult population have proposed plenty of putative biomarkers that might prove helpful in diagnosing and treating depression, whereas research on biomarkers in child and adolescent depression has been far more limited. The .gov means its official. and transmitted securely. The short version of the serotonin-related gene 5HTTLPR Dopamine-related genes The Y chromosome The BRCA-1 and BRCA-2 genes. government site. https://doi.org/10.1016/j.pnpbp.2010.03.003, Parekh A, Smeeth D, Milner Y, Thure S (2017) The role of lipid biomarkers in major depression. In this study, the age range of 1019 years was defined as adolescence while an age range of 2025 years was defined as young adult for analysis. Results showed that the Met allele of BDNF Val66Met significantly moderates the relationship between life stress and depression (p = 0.03; Hosang et al., 2014). https://doi.org/10.1037/a0018875, Katrenkov B, Vavkov M, Waczulkov I, Oravec S, Garaiova I, Nagyov Z et al (2020) Lipid profile, lipoprotein subfractions, and fluidity of membranes in children and adolescents with depressive disorder: effect of omega-3 fatty acids in a double-blind randomized controlled study. Some studies investigated the threeway interaction model of BDNF Val66Met polymorphism, the serotonin transporter linked promoter region (5-HTTLPR) polymorphism, and childhood adversity in predicting the development of depression. For instance, Sasaki et al. Only one study investigated the association of BDNF Val66Met genotypes with cognitive dysfunction. The dopamine D2 receptor Polymorphism (DRD2 TaqIA) interacts with maternal parenting in predicting early adolescent depressive symptoms: evidence of differential susceptibility and age differences, http://www.who.int/mediacentre/factsheets/fs369/en/, http://www.who.int/topics/adolescent_health/en/, http://www.emro.who.int/media/news/mental-health-day2012.html, Adolescents depressive symptoms are not modified by 5-HTTLPR, Short alleles were associated with higher affective problems scores, The s/l vs. l/l genotype showed greater reduction in depression symptoms, 5-HTTLPR interacted with unfavorable environment in relation to depressive symptoms, Positive G E effects on depression were found, Short allele confers susceptibility to stress for females with depression, Cannabis use increases the risk of depression only in the presence of 5-HTTLPR short allele genotype, 5-HTTLPR short allele modify the risk of a new depressive episode associated with elevated morning salivary cortisol, Short alleles confers vulnerability to depressive symptoms in girls, Episode of depression was increased in those with the s allele, LL genotype of 5-HTTLPR displayed significantly higher rates of depressive disorders and more depressive symptoms, Females carrying the short 5-HTTLPR allele tend to develop depressive symptoms, Interaction between 5-HTTLPR polymorphism and childhood adversities did not predict depression score, G E interaction of 5-HTTLPR and maltreatment on depression symptoms, Structural abnormalities in the left hippocampus may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness, Among girls, but not boys, each copy of the s allele of the 5-HTTLPR was related to increased depressive symptoms, The carriers of the BDNF Met and 5-HTTLPR s allele are susceptible to depressive symptoms, Youth with SS genotype of 5-HTTLPR experienced greatest increases in depressive symptoms when exposed to elevations in materal symptoms, Stress affect adolescents likelihood of experiencing depressed symptoms when they have a low serotonin TE (A/Gmodified5-HTTLPR) genotype, Girls with homozygous for short 5-HTTLPR allele showed stronger association between depressive and bulimic symptoms the long allele, 5-HTTLPR confers susceptibility to depression via stress reactivity, 5-HTTLPR sl genotype is a risk of depressive symptom in adolescent male, A GxE interaction effect of 5HTTLPR ss allele was found among girls, not boys, A significant genotype-environmental risk interaction for 5HTTLPR in the risk of depression in girls only, Adolescents depressive symptoms are not modified by BDNF, Depressive symptoms and depression were more common among carriers of either the Val/Val or Met genotypes, Depression score was not significantly predicted by interaction between BDNF Val66Met polymorphism and childhood adversities, BDNF met allele moderate the relation between exercise and depressive symptoms, Val/Val genotype correlated with higher levels of depression symptoms, Val/Val genotype was associated with more depressive symptoms, Possession of BDNF Met allele was statistically linked with a resilient phenotype of major depression disorder, Adolescents depressive symptoms are not modified by COMT, DRD2*304/178 and DRD4*379/379 genotype are associated with a level of depressive symptoms, DRD4 polymorphism is linked to comorbid marijuana use and depression, OXTR influences the development of depressive symptoms, S-allele predicts relative increases in probability of depression among boys with low security, Chronic family stress at age 15 predicted higher depression scores at 20 among those females with one or two S alleles. Involvement of Genetic and Environmental Factors in the Onset of Biol Psychiatry 39(4):267277. Prog Neuropsychopharmacol Biol Psychiatry 29(7):11031112. Available studies show that hypermethylation of the NR3C1 gene [38,39,40,41] and decreased peripheral NR3C1 mRNA expression [42] could be considered markers of increased susceptibility to early-onset depression. For example, Hetrick et al. Brain biology and chemistry. Gene-environment interaction analysis of serotonin system markers with adolescent depression. A systematic review of original studies on gene expression or genetic polymorphisms in adolescents with depression was conducted. J Affect Disord 265:325332. https://doi.org/10.1007/s10519-009-9285-9, Benjet C, Thompson RJ, Gotlib IH (2010) 5-HTTLPR moderates the effect of relational peer victimization on depressive symptoms in adolescent girls. revealed no association between 5-HTTLPR polymorphism and treatment outcomes [22], such a correlation was found in the meta-analysis performed by Porcelli et al. Genetics of childhood and adolescent depression: insights into Bethesda, MD 20894, Web Policies The hypothesis derives from the research on animals indicating that downregulation of the OTX gene in a reward circuit is critical in developing depressive-like behaviors in a mouse model of early-life stress [119]. Outcomes of studies on the relationship between BDNF and dopaminergic pathway and depression in adolescents. revealed significantly decreased folic acid level in the group of children and adolescents with the first episode of depression [90]. (2010). Transcription factor AP-2 beta genotype and psychosocial adversity in relation to adolescent depressive symptomatology. Accessed 26 Mar 2021, Fava M (2003) Diagnosis and definition of treatment-resistant depression. https://doi.org/10.1007/s10578-021-01246-y, DOI: https://doi.org/10.1007/s10578-021-01246-y. Regarding the youth population Spindola et al. It has been suggested that serum cholesterol may directly influence brain lipids and the fluidity of the cell membrane, with secondary effects on serotonergic neurotransmission. Approximately half of the depressed adults display stress-induced hyperactivity of the HPA-axis with impaired negative feedback regulation [26]. A meta-analysis performed by Ribeiro et al. For instance, a study performed by Hankin et al. The results indicated that a history of steeply increasing triglycerides levels at an early age was associated with depression onset later in life. Cutuli J. J., Raby K. L., Cicchetti D., Englund M. M., Egeland B. 5-HTT (5-HTTLPR polymorphism) is the most frequently examined gene (26 articles) followed by Brain-derived neurotropic factor (BNDF; 12 articles). https://doi.org/10.1007/s11302-016-9551-2, Ciuculete DM, Voisin S, Kular L, Welihinda N, Jonsson J, Jagodic M et al (2020) Longitudinal DNA methylation changes at MET may alter HGF/c-MET signalling in adolescents at risk for depression. The study performed by Brent et al. For instance, a study performed by Chen et al. Neuropsychiatr Dis Treat 13:12451262. BDNF was the second most frequently studied gene in adolescents. https://doi.org/10.1089/cap.2006.0144, Rotberg B, Kronenberg S, Carmel M, Frisch A, Brent D, Zalsman G et al (2013) Additive effects of 5-HTTLPR (serotonin transporter) and tryptophan hydroxylase 2 G-703T gene polymorphisms on the clinical response to citalopram among children and adolescents with depression and anxiety disorders. Reduced peripheral brain-derived neurotrophic factor mRNA levels are normalized by antidepressant treatment, Interacting effect of BDNF Val66Met polymorphism and stressful life events on adolescent depression, The interacting effect of the BDNF Val66Met polymorphism and stressful life events on adolescent depression is not an artifact of gene-environment correlation: evidence from a longitudinal twin study, Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET) and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children. https://doi.org/10.1093/cercor/bhx086, Zhao M, Chen L, Yang J, Han D, Fang D, Qiu X, Yang X, Qiao Z, Ma J, Wang L, Jiang S, Song X, Zhou J, Zhang J, Chen M, Qi D, Yang Y, Pan H (2018) BDNF Val66Met polymorphism, life stress and depression: a meta-analysis of gene-environment interaction. Similarly, Brent et al. J Clin Psychiatry 77(5):668671. Another hypothesis explaining the pathogenesis of depression is associated with possible maladaptive inflammation processes occurring in the central nervous system due to chronic psychological or physical stress (Fig. The https:// ensures that you are connecting to the Although some research confirmed the combined influence of these factors on early-life depression, the results were differential, and the relation was not confirmed in a representative, population-based study of adolescents [74,75,76].
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