Biogenetics plays an important role in the pathogenesis of depressive disorder in adolescents. Various genetic polymorphism studies have updated the understanding of adolescent depressive disorder. However, due to the influence of gene-environment interaction and age of puberty, the influence of gene polymorphisms on adolescent depressive disorder is complicated to clarify. Investigating and clarifying the relationship between gene polymorphisms and adolescent depressive disorder will promote the research on the pathogenesis of this disorder and provide a reference for the prevention and treatment of this disorder. This article reviews the genetic polymorphisms related to adolescent depressive disorder.
Humans ; Adolescent ; Depressive Disorder, Major/genetics* ; Polymorphism, Genetic ; Gene-Environment Interaction ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease

Objective: Due to genetic factors might increase the risk of depression, this study investigated the genetic risk factors of depression in Chinese Han population by analyzing the association between 13 candidate genes and depression. Methods: 439 depression patients and 464 healthy controls were included in this case-control study. Case group consisted of 158 males and 281 females, aged (29.84±14.91) years old, who were hospitalized in three departments of the affiliated Brain Hospital of Guangzhou Medical University including Affective Disorders Department, Adult Psychiatry Department and Geriatrics Department, from February 2020 to September 2021. The control group consisted of 196 males and 268 females, aged (30.65±12.63) years old. 20 loci of 13 candidate genes in all subjects were detected by MALDI-TOF mass spectrometry. Age difference was compared using the student's t-test, the distributions of gender and genotype were analyzed with Pearson's Chi-square test. The analyses of Hardy-Weinberg equilibrium, allele frequency and the genetic association of depression were conducted using the corresponding programs in PLINK software. Results: PLINK analysis showed that SCN2A rs17183814, ABCB1 rs1045642, CYP2C19*3 rs4986893 and NAT2*5A rs1799929 were associated with depression before Bonferroni correction (χ²=10.340, P=0.001; χ²=11.010, P=0.001; χ²=9.781, P=0.002; χ²=4.481, P=0.034). The frequencies of minor alleles of above loci in the control group were 12.07%, 43.64%, 2.59% and 3.88%, respectively. The frequencies of minor alleles of loci mentioned above in the case group were 17.43%, 35.99%, 5.47% and 6.04%, respectively. OR values were 1.538, 0.726, 2.178 and 1.592, respectively. After 1 000 000 permutation tests using Max(T) permutation procedure, the four loci were still statistically significant, the empirical P-value were 0.002, 0.001, 0.003 and 0.042, respectively. However, only three loci including SCN2A rs17183814, ABCB1 rs1045642 and CYP2C19 rs4986893 had statistical significance after Bonferroni correction, the adjusted P-value were 0.026, 0.018 and 0.035, respectively. Conclusion: SCN2A rs17183814, ABCB1 rs1045642 and CYP2C19*3 rs4986893 were associated with depression's susceptibility in Chinese Han population. The A allele of SCN2A rs17183814 and CYP2C19*3 rs4986893 were risk factors for depression, while the T allele of ABCB1 rs1045642 was a protective factor for depression.
ATP Binding Cassette Transporter, Subfamily B/genetics* ; Adolescent ; Adult ; Alleles ; Arylamine N-Acetyltransferase/genetics* ; Case-Control Studies ; Clopidogrel ; Cytochrome P-450 CYP2C19/genetics* ; Depressive Disorder, Major/genetics* ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; NAV1.2 Voltage-Gated Sodium Channel ; Polymorphism, Single Nucleotide ; Young Adult

OBJECTIVE: Genetics factors are likely to play a role in the risk, clinical presentation and treatment outcome in major depressive disorder (MDD). In this study, we investigated the role of three candidate genes for MDD; calcium voltage-gated channel subunit alpha1 C (CACNA1C), cholinergic receptor nicotinic alpha 7 subunit (CHRNA7), and mitogen-activated protein kinase 1 (MAPK1). METHODS: Two-hundred forty-two MDD patients and 326 healthy controls of Korean ancestry served as samples for the analyses. Thirty-nine single nucleotide polymorphisms (SNPs) within CACNA1C, CHRNA7, and MAPK1 genes were genotyped and subsequently tested for association with MDD (primary analysis) and other clinical features (symptoms’ severity, age of onset, history of suicide attempt, treatment outcome) (secondary analyses). Single SNPs, haplotypes and epistatic analyses were performed. RESULTS: Single SNPs were not associated with disease risk and clinical features. However, a combination of alleles (haplotype) within MAPK1 was found associated with MDD-status. Secondary analyses detected a possible involvement of CACNA1C haplotype in resistance to antidepressant treatment. CONCLUSION: These data suggest a role for MAPK1 and CACNA1C in MDD risk and treatment resistance, respectively. However, since many limitations characterize the analysis, the results must be considered with great caution and verified.
Age of Onset ; Alleles ; Calcium ; Depression ; Depressive Disorder, Major ; Genetics ; Haplotypes ; Humans ; Mitogen-Activated Protein Kinase 1 ; Neuronal Plasticity ; Polymorphism, Single Nucleotide ; Suicide ; Treatment Outcome

China ; Depressive Disorder, Major ; genetics ; Humans ; Polymorphism, Single Nucleotide ; Sirtuin 1 ; genetics

OBJECTIVETo explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment.

METHODSTwo hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis.

RESULTSNo significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment.

CONCLUSIONThe SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

Adolescent ; Adult ; Antidepressive Agents ; therapeutic use ; Child Abuse ; psychology ; Depressive Disorder, Major ; drug therapy ; genetics ; psychology ; Diagnostic and Statistical Manual of Mental Disorders ; Female ; Gene Frequency ; Genotype ; Humans ; Interleukin-1beta ; genetics ; Logistic Models ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Polymorphism, Single Nucleotide ; Young Adult

OBJECTIVETo analyze the potential association between the EHD3 gene and the cognitive function of patients with major depressive disorder (MDD).

METHODSA total of 47 MDD patients and 40 healthy controls were enrolled in this study. After their cognitive functions were analyzed, the scores of the MDD patients were used as the quantitative traits; by using the quantitative trait module in the UNPHASED software, we analyzed the potential association of the cognitive traits with the EHD3 gene.

RESULTSThe cognitive scores (WAIS-RC and WMS-R) of MDD patients were significantly lower than those of controls (P<0.05). The rs3769621 allele and genotype of EHD3 gene were significantly associated with the raw score and scaled score of WAIS-RC (Χ(2)=10.561, P=0.001; Χ(2)=7.922, P=0.019; Χ(2)=12.627, P=0.00038; Χ(2)=11.775, P=0.0027)and WMS-R (Χ(2)=8.762, P=0.003; Χ(2)=17.399, P=0.00016; Χ(2)=10.356, P=0.001; Χ(2)=14.958, P=0.00056). Such associations remained statistically significant after Bonferroni correction.

CONCLUSIONThe EHD3 gene may be associated with the endophenotype of cognitive function in MDD patients.

Adolescent ; Adult ; Carrier Proteins ; genetics ; Case-Control Studies ; Cognition ; Depressive Disorder, Major ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Young Adult

OBJECTIVETo assess the influence of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene on response to antidepressant treatment.

METHODSTwo hundred and eight one Chinese Han patients have received single antidepressant drugs for at least 6 weeks, among whom 275 were followed up for 8 weeks. Hamilton depression scale 17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effects. Single nucleotide polymorphisms (SNPs) of the MTHFR gene were determined using gene chips. Associations of single loci and haplotypes with response to treatment were analyzed using an Unphased 3.0.13 software.

RESULTSNo significant differences in gender, age, year of education, family history, episode times, and antidepressant agents were found between responders and non-responders (all P U+003E 0.05), while the baseline scores of HAMD-17 was significantly different(t=2.891, P=0.004). There was also no significant difference between age, years of education, family history, baseline scores of HAMD-17 and antidepressant agents between remitters and non-remitters (both P U+003E 0.05), while proportion of male patients was significantly higher in non-remission group than remission group (t=2.381, P=0.018), and episode times in non-remission group was significantly higher (t=-1.983, P=0.049). Single locus association analysis has found no significant association between SNPs rs1801131 and rs1801133 in the MTHFR gene with antidepressant response (P U+003E 0.05). On the other hand, haplotype A-C of MTHFR gene (rs1801131 and rs1801133) was significantly associated with antidepressant response in total group (U+03C7 2=11.39, P=0.0007), male subgroup (U+03C7 2=8.767, P=0.003) and serotonin noradrenaline reuptake inhibitors (SNRIs) subgroup (U+03C7 2=10.51, P=0.001).

CONCLUSIONParticular haplotype of MTHFR gene may be related with antidepressant effect, in which the haplotype (rs1801131, rs1801133) A-C type may be associated with better antidepressant efficacy, particularly in males and patients receiving SNRIs drugs.

Adult ; Alleles ; Antidepressive Agents ; therapeutic use ; Depressive Disorder, Major ; drug therapy ; genetics ; Female ; Haplotypes ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Serotonin Uptake Inhibitors ; therapeutic use ; Sex Factors ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate whether the genetic polymorphism, upstream variable number of tandem repeats (uVNTR), in the monoamine oxidase A (MAOA) gene, is associated with major depressive disorder (MDD) in adolescents and to test whether there is gene-environment interaction between MAOA-uVNTR polymorphism and stressful life events (SLEs).

METHODSA total of 394 Chinese Han subjects, including 187 adolescent patients with MDD and 207 normal students as a control group, were included in the study. Genotyping was performed by SNaP-shot assay. SLEs in the previous 12 months were evaluated. The groups were compared in terms of the frequency distributions of MAOA-uVNTR genotypes and alleles using statistical software. The binary logistic regression model of gene-environment interaction was established to analyze the association of the gene-environment interaction between MAOA-u VNTR genotypes and SLEs with adolescent MDD.

RESULTSThe distribution profiles of MAOA-u VNTR genotypes and alleles were not related to the onset of MDD, severity of depression, comorbid anxiety and suicidal ideation/behavior/attempt in adolescents. The gene-environment interaction between MAOA-u VNTR genotypes and SLEs was not associated with MDD in male or female adolescents.

CONCLUSIONSIt is not proven that MAOA-u VNTR polymorphism is associated with adolescent MDD. There is also no gene-environment interaction between MAOA-u VNTR polymorphism and SLEs that is associated with adolescent MDD.

Adolescent ; Depressive Disorder, Major ; genetics ; Female ; Gene-Environment Interaction ; Genotype ; Humans ; Life Change Events ; Logistic Models ; Male ; Minisatellite Repeats ; Monoamine Oxidase ; genetics ; Polymorphism, Genetic

Major depression disorder is an increasing heavy burden in modem society, but its pathological mechanism is still vague. Recent evidence indicated that two pore potassium channel, TREK1, is one of the important drug targets of antidepressants. The structural and functional research progress of TREK1 potassium channel were reviewed with an emphasis on its roles in anti-depression, neuronal protection, and neuronal plasticity. The complicated interactions between TREK1 potassium channel and monoamine transmitters-receptors were also reviewed and future directions to explore the underline mechanism were also discussed.
Animals ; Antidepressive Agents ; pharmacology ; Depressive Disorder, Major ; genetics ; metabolism ; physiopathology ; Drug Delivery Systems ; Gene Knockout Techniques ; Humans ; Neuronal Plasticity ; Polymorphism, Genetic ; Potassium Channels, Tandem Pore Domain ; genetics ; metabolism ; physiology ; Receptors, Serotonin ; metabolism ; Receptors, Serotonin, 5-HT4 ; Serotonin ; pharmacology

OBJECTIVETo explore the genetic association between protein tyrosine phosphatase receptor type R (PTPRR) gene polymorphism and major depressive disorder (MDD) and its endophenotype.

METHODSA total of 517 unrelated MDD patients and 455 unrelated healthy subjects were recruited in this study to detect 11 single nucleotide polymorphisms (SNPs) in the PTPRR locus. They all were of the Chinese Han origin. Genotyping of SNPs was performed by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) -based genotyping approach. The UNPHASED program was applied to analyze the genotyping data.

RESULTSOf the 11 selected SNPs, no significant allelic and genotypic association was found between MDD patients and the normal controls (corrected P > 0.05). However, analysis of haplotypes showed that the three SNPs haplotype rs1398599 (C) -rs2175711 (A) - rs4489789 (T) (P = 0.0023, OR = 1.334, 95% CI = 1.104-1.612) and four SNPs haplotype rs11178391 (C) -rs1398599 (C) -rs2175711 (A)-rs4489789(T) (P = 0.0063, OR = 1.281, 95% CI = 1.059-1.549) were associated with increased risk of MDD. Quantitative trait analysis revealed that rs2203231 in the PTPRR locus had strong allelic and genotypic association with the raw score of long-term memory (P = 0.0038 for allelic association, P = 0.0024 for genotypic association), the scaled score of long-term memory (P = 0.0057 for allelic association, P = 0.0038 for genotypic association), the raw score of short-term memory (P = 0.0027 for allelic association, P = 0.0015 for genotypic association), and the scaled score of short-term memory (P = 0.0035 for allelic association, P = 0.002 for genotypic association) in MDD patients.

CONCLUSIONThe polymorphism of PTPRR gene rs2203231 may be associated with the impairment of long-term and short-term memories in MDD patients.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Depressive Disorder, Major ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptor-Like Protein Tyrosine Phosphatases, Class 7 ; genetics ; Young Adult