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

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

OBJECTIVETo investigate the association between single nucleotide polymorphisms (SNPs) in cyclic adenosine monophosphate response element-binding protein(CREB1) gene and major depressive disorder (MDD).

METHODSWe recruited 105 parent-offspring trios of Chinese descent, extracted whole blood genomic DNA, and genotyped the SNPs in rs10932201 and rs6740584 loci. Single-marker transmission disequilibrium test (TDT), pairwise SNP linkage disequilibrium(LD) and haplotype-based TDT were performed.

RESULTSNo significant association with MDD was observed for SNPs rs10932201 and rs6740584 (P=0.1004 and P=0.4986). However, there was strong positive association between the rs10932201-rs6740584 haplotype and MDD (P=0.00003241), and both haplotypes of A-C and A-T were significantly associated with MDD (P=0.020 and P=0.00022).

CONCLUSIONThe rs10932201-rs6740584 haplotype of the CREB1 gene may play an important role in the pathogenesis of MDD.

Cyclic AMP Response Element-Binding Protein ; genetics ; Depressive Disorder, Major ; genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Male ; Polymorphism, Single Nucleotide ; genetics

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

OBJECTIVETo understand the environmental risk factors on attempted suicide in patients with major depression, and to study the interaction between factors as single nucleotide polymorphism(SNP) of TPH2 gene rs7305115 associated to attempted suicide in major depression.

METHODSPaired case-control study on 215 suicide attempters with major depression (92 male, 123 female) and molecular biological techniques were used to study the relation between TPH2 gene rs7305115 SNP,interrelated environmental factors and the rate of attempted suicide. Controls were paired with cases according to the same gender, similar age (no more than 3 years) and from the same district.

RESULTSThere were remarkably significant differences in gene types and gene frequency between case and control groups (P < 0.001). Data from multivariate conditional logistic regression model analysis showed that hopelessness, negative life-events and family history of suicide were relationship of attempted suicide in patients with major depression with OR values as 0.33 (95% CI: 0.22-0.99), 7.68 (95% CI: 5.79-13.74), 6.64 (95% CI: 2.48-11.04), 2.98 (95% CI: 1.17-5.04) respectively. There was no first level interaction between any of the two risk factors.

CONCLUSIONResults from the study supported the idea that hopelessness, negative life-events and family history of suicide were risk factors of attempted suicide in major deprbssion while TPH2 gene rs7305115 A/A might be the protective factor.

Case-Control Studies ; China ; epidemiology ; Depressive Disorder, Major ; genetics ; psychology ; Humans ; Odds Ratio ; Polymorphism, Single Nucleotide ; Risk Factors ; Suicide, Attempted ; psychology ; statistics & numerical data ; Tryptophan Hydroxylase ; genetics

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

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

OBJECTIVETo explore the association between monoamine oxidase A (MAOA) variable number tandem repeat (VNTR) polymorphism and major depression in Chinese Han population.

METHODSPolymerase chain reaction was used to genotype MAOA VNTR polymorphism. A total of 512 major depression patients and 566 normal controls were recruited in our study. These patients were also assessed using the 14-item Hamilton anxiety scale. RESULTS The allele frequency of MAOA VNTR was not significantly different between the male/female major depression patients and the normal controls. Compared with the normal controls, MAOA VNTR genotype was significantly more frequent in female major depression patients (P=0.002), but not in male patients (P=0.17). MAOA VNTR-L carrier was also associated with "fear" symptom in female patients (P=0.0056).

CONCLUSIONMAOA gene is associated with the major depression in Chinese Han population, especially among female patients.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; Depressive Disorder, Major ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Minisatellite Repeats ; genetics ; Monoamine Oxidase ; genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; genetics ; Young Adult

BACKGROUNDRecent studies have suggested that susceptibility to major depressive disorder (MDD) might be related to the serotonin 1A receptor (5-HTR1A) C (-1019) G polymorphism. In this study, we aimed to assess the association between 5-HTR1A C (-1019) G polymorphism and MDD in the Northern Han ethnic group of China.

METHODSThe C (-1019) G of 5-HTR1A was detected with polymerase chain reaction (PCR) in 400 patients with MDD and 400 unrelated age- and sex-matched healthy control subjects. Association between the C (-1019) G and MDD was statistically analyzed.

RESULTSThere was a statistically significant difference between MDD patients and controls in both the genotype distribution (Chi(2) = 10.913, df = 2, P = 0.004) and the allele frequency (Chi(2) = 10.379, df = 1, P = 0.001), and a significant difference in the genotype distribution and the allele frequency was found both in the female subjects (Genotype distribution: Chi(2) = 15.406, df = 2, P = 0.000; allele frequency: Chi(2) = 15.552, df = 1, P = 0.000) and the late-onset subjects (Genotype distribution: Chi(2) = 7.771, df = 2, P = 0.021; allele frequency: Chi(2) = 8.007, df = 1, P = 0.005) in the two groups.

CONCLUSIONThese results suggest that 5-HTR1A C (-1019) G polymorphism is probably associated with MDD and it is likely to be the susceptible gene locus for the female and late-onset MDD.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Depressive Disorder, Major ; ethnology ; genetics ; pathology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptor, Serotonin, 5-HT1A ; genetics

OBJECTIVETo study the association between the epidermal growth factor (EGF) gene and intelligence in patients with major depression.

METHODSIntelligence measurement using Wechsler Adult Intelligence Scale (WAIS) was performed on 120 unrelated patients with major depression and 46 control subjects. Blood was collected from all subjects for extraction of genomic DNA. Four single nucleotide polymorphisms (SNPs) in the EGF gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI- TOF-MS).

RESULTSMean scores of both score lang and score task, two subtests in WAIS, differed significantly between major depression patients and controls (P<0.0001). Quantitative trait analysis showed that the genotype of rs2250724 was closely associated with score lang and score task in major depression patients. The associations were still significant after 10 000 permutations.

CONCLUSIONSAlthough preliminary, our results provide evidence for association between the EGF gene and intelligence in patients with major depression. Genetic variation in the EGF gene may increase the susceptibility of major depression.

Adult ; Case-Control Studies ; Depressive Disorder, Major ; genetics ; Epidermal Growth Factor ; genetics ; Female ; Humans ; Intelligence ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization