Dopamine DRD2 and DRD3 Polymorphisms Involvement in Nicotine Dependence in Patients with Treatment-Resistant Mental Disorders

Abstract

Patients affected by mental disorders smoke more than the general population. The reasons behind this habit are genetic, environmental, etc. This study aims to investigate the correlations between some polymorphisms and the smoking habits and nicotine dependence in patients with psychiatric disorders. We recruited 88 patients with treatment-resistant mental disorders, including 35 with major depressive disorder, 43 with bipolar spectrum disorder, and 10 with schizophrenia spectrum disorder. We carried out a clinical and psychometric assessment on current smoking habits, years of smoking, number of daily cigarettes, and level of nicotine addiction. The patients performed a peripheral blood sample for DNA analyses of different polymorphisms. We searched for correlations between the measures of nicotine addiction and analysed genotypes. The expression of the T allele of the DRD2 rs1800497 and DRD3 rs6280 polymorphisms significantly correlated with a lower level of nicotine dependence and lower use of cigarettes. We did not find significant correlations between nicotine dependence and OPRM1 rs1799971, COMT rs4680 and rs4633 polymorphisms, CYP2A6 rs1801272 and rs28399433, or 5-HTTLPR genotype. Concluding, DRD2 rs1800497 and DRD3 rs6280 polymorphisms are involved in nicotine dependence and cigarette smoking habits in patients with treatment-resistant mental disorders

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

“…CFTR (CF transmembrane conductance regulator) [380], ABCA2 [381], HK2 [382], NGFR (nerve growth factor receptor) [383], TF (transferrin) [384], GLUL (glutamate-ammonia ligase) [324], ADAMTS4 [385], BIN1 [386], HSPA2 [387], LMNA (lamin A/C) [388], HSD11B1 [389], HTRA1 [390], APLP1 [391], MT3 [392], ADORA1 [393], DYSF (dysferlin) [394], SLC24A4 [395], RHOB (ras homolog family member B) [396], NINJ2 [397], LRP2 [398], LIPC (lipase C, hepatic type) [399], DHCR7 [400], SCD (stearoyl-CoA desaturase) [401], F11 [402], PFKL (phosphofructokinase, liver type) [403], ALDH1A1 [404], SPON1 [405] and CTNNA3 [406] are significantly associated with the Alzheimer’s Disease. CCR4 [407], CCR2 [408], CD48 [409], CD28 [410], CCL3 [411], CTLA4 [412], C6 [413], MICB (MHC class I polypeptide-related sequence B) [414], DRD3 [415], HGF (hepatocyte growth factor) [416], DIO3 [417], TTR (transthyretin) [418], GRHL3 [419], VEGFA (vascular endothelial growth factor A) [420], ADM (adrenomedullin) [421], CHI3L1 [422], SOX3 [423], MAG (myelin associated glycoprotein) [424], CNP (2’,3’-cyclic nucleotide 3’ phosphodiesterase) [425], SREBF1 [426], OLIG2 [427], ATF3 [428], NGFR (nerve growth factor receptor) [429], TF (transferrin) [430], GLUL (glutamate-ammonia ligase) [324]. MOG (myelin oligodendrocyte glycoprotein) [431], ERBB3 [432], NHLH2 [433], GADD45B [434], PADI2 [435], ADORA1 [436], NINJ2 [437], WNT7A [438], DAO (D-amino acid oxidase) [439], PRODH (proline dehydrogenase 1) [440] and HCRTR1 [441] could regulate the development of psychiatric disorders.…”

Tobacco Smoking as an EDC in Aging

“…We selected the 96 target SNPs, based on the SNPs of tobacco smoking-responsive genes, of which expression levels were altered by tobacco smoking in our previous microarray study [15], i.e., ACTG1, DEFA4, VAV3, FCGR3A, etc., as well as the SNPs related to metabolism, e.g., CYP2A6, CYP1B1, CYP2E1, and NQO1, addiction [38], e.g., CHRNA5/A3/B4, 5-HTTLPR, and DRD2 [39], risks for lung cancer, e.g., CYP1A1, GSTP1, and MPO1 [39,40], DNA repair, e.g., ERCC1, MGMT, XRCC1, etc. [41], and epigenetic modulation, e.g., HDAC1 and MTHFR [33], of tobacco smoking (supplement Table 1).…”

Lateral Septal Circuits Govern Schizophrenia-Like Effects of Ketamine on Social Behavior

“…However, schizophrenia treatment tends to focus on the so-called positive symptoms which are often salient but less debilitating than negative and cognitive symptoms. Many currently approved drugs primarily target dopamine D 2 and 5-HT 2A receptors [10,11], which influence positive symptoms but are also associated with motor and cognitive side effects. Despite the urgent need, developing effective treatments for the negative symptoms of schizophrenia and other neurodevelopmental disorders remains a challenge given the complexity of the neural circuits governing affective and social behavior.…”