Genomic Association Analysis Of The Melanocortin System In Patients With Depressive Disorders

Objective(s):To investigate the correlation between the characteristics of anhedonia,appetite changes,and BMI values in patients with depressive disorders and the polymorphic loci of melanocortin systemic factor POMC,CART,Ag RP,NPY,MC3 R,MC4R,PCSK1,PCSK2 candidate genes.Methods:1093 depressive disorder patients who met the ICD-10 diagnostic criteria for depressive disorder at the Second Affiliated Hospital of Kunming Medical University from January 2016 to November 2022 were selected,and general demographic information of depressive disorder patients was collected using a self-administered available information form,and a psychiatrist with the title of attending physician or above conducted a structured interview to assess the patients’ anhedonia according to the ICD-10 diagnostic criteria 5 ml of peripheral venous blood was drawn at enrollment for 1093 study subjects,divided,numbered and preserved in deep freeze,and a broad genome association study(GWAS)was conducted using microarray SNP typing technology.1018 samples were finally tested through quality control and genotype data filling 8304713 SNPs were screened for all single nucleotide polymorphisms(SNPs)in the POMC,CART,Ag RP,NPY,MC3 R,MC4R,PCSK1,and PCSK2 genes of the melanocortin system to investigate the depressive disorders of anhedonia further.The results show that the three clinical phenotypes of depression,appetite changes,and BMI are correlated with candidate genes of the melanocortin system.Results: 1.Of the 1093 patients with depressive disorder enrolled in this study,340(31.11%)were male,and 753(69.89%)were female.The age of onset was as young as 11 years old and as old as 84 years old,with a mean age of 33.25±17.50 years.The mean total HAMD score of the enrolled patients was 27.20±8.765,including 6.41±2.961 for the anxiety/somatization factor,0.74±0.946 for the weight factor,5.25±3.448 for the cognitive impairment factor,0.66±0.835 for the day-night variation factor,5.94±2.182 for the blocking element,4.01±2.351 points,and despair factor 4.37±1.974 points.The mean total HAMA score was 18.23±7.526,the somatization anxiety factor 6.54±4.818,and the psychogenic anxiety factor11.70±3.992.2.Of the 1093 patients with depressive disorders enrolled in this study,931(85.18%)had anhedonia,and 162(14.82%)had no anhedonia features.Of the 585 cases with suicidal ideation,all 536 had the anhedonia trait(91.62%);the total HAMD score and all factor scores were more significant in patients with anhedonia than in those without it,and the total score,anxiety/somatization,cognitive impairment,day-night variation,blocking and despair factor scores were statistically different between the two groups.There were 651 cases(59.56%)of decreased appetite,398 cases(36.41%)of regular need,30 patients(2.74%)of alternating reduced and increased appetite,and 14 points(1.29%)of increased appetite.The BMI was normal in 666 cases(60.93%),overweight in 189 cases(17.29%),lean in 168cases(15.37%),and obese in 30 patients(6.41%).4.The melanocortin system candidate genes POMC,CART,Ag RP,NPY,MC3 R,MC4R,PCSK1,and PCSK2 polymorphic loci were tested for compliance with the Hardy-Weinberg equilibrium law.One hundred and fourteen SNP loci for the above candidate genes were correlated with anhedonia traits in patients with depressive disorders(P<0.05),with patients with depressive disorders who had the CART rs281126(A)allele variant likely to be at higher risk for anhedonia traits;159 SNP loci were correlated with changes in appetite in patients with depressive disorders(P<0.05),with SNP loci rs2206452,rs2424074,rs1015776,rs2424066,rs1361510,rs1417559,rs1417560 of the PCSK2 gene reached a more significant level(P<5.0x10-5)and all were possible risk factors for appetite changes in patients with depressive disorders(OR= 2.754,2.652,2.603,2.52,2.478);114 SNP loci for candidate genes were also found to be correlated with BMI values in patients with depressive disorders(P<0.05).Conclusion(s):1.A higher proportion of patients with depressive disorders had an anhedonia profile,were more depressed,and had a more pronounced loss of appetite,with most patients having a standard baseline BMI.2.Polymorphic loci POMC,CART,Ag RP,NPY,MC3 R,MC4R,PCSK1,and PCSK2 candidate genes in the melanocortin system correlate with the anhedonia,appetite changes,and BMI characteristics of patients with depressive disorders.3.Allelic variants at polymorphic loci in selected genes in the melanocortin system may be associated with a higher risk of the anhedonia trait,a higher risk profile for appetite changes,and changes in BMI.Those are risk factors for developing this clinical trait in patients with depressive disorders.