Using the lod score method of Morton (1955) for determining linkage, these data indicated that close linkage is unlikely for affective disorder and HLA alleles, haptoglobin, Rh factor, or ABO blood groups.
The results of such studies lead to the conclusion that the association of ABO and HLA subtypes with affective disorders and schizophrenia is extremely variable, although there may be an association between HLA A9 and paranoid schizophrenia.
Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51).
This converging cross-species evidence implicates ADCY7 in the modulation of mood regulatory neural mechanisms and, possibly, risk for and pathophysiology of depression, together supporting a continuous dimensional approach to major depressive disorder and other affective disorders.
The distribution of the A2aAR genotypes and alleles did not differ significantly comparing the two groups, suggesting that it is unlikely that the A2aAR 1976C>T polymorphism plays a major role in the development of mood disorders.
Further, several genome scans for mood disorders, both unipolar and bipolar, have indicated linkage to the chromosomal regions of 5q23-q33.3, 8p12-p11.2, 4p16, and 10q24-q26, the location of the adrenergic receptors alpha1B (ADRA1B), beta3 (ADRB3), alpha2C (ADRA2C), alpha2A (ADRA2A), and beta1 (ADRB1).
Further, several genome scans for mood disorders, both unipolar and bipolar, have indicated linkage to the chromosomal regions of 5q23-q33.3, 8p12-p11.2, 4p16, and 10q24-q26, the location of the adrenergic receptors alpha1B (ADRA1B), beta3 (ADRB3), alpha2C (ADRA2C), alpha2A (ADRA2A), and beta1 (ADRB1).
Further, several genome scans for mood disorders, both unipolar and bipolar, have indicated linkage to the chromosomal regions of 5q23-q33.3, 8p12-p11.2, 4p16, and 10q24-q26, the location of the adrenergic receptors alpha1B (ADRA1B), beta3 (ADRB3), alpha2C (ADRA2C), alpha2A (ADRA2A), and beta1 (ADRB1).
Further, several genome scans for mood disorders, both unipolar and bipolar, have indicated linkage to the chromosomal regions of 5q23-q33.3, 8p12-p11.2, 4p16, and 10q24-q26, the location of the adrenergic receptors alpha1B (ADRA1B), beta3 (ADRB3), alpha2C (ADRA2C), alpha2A (ADRA2A), and beta1 (ADRB1).
A recently identified functional polymorphism in the beta(1)-adrenergic receptor (G1165C) leading to the amino acid variation Gly389Arg was associated with an enhanced coupling to the stimulatory G(s)-protein and increased adenylyl cyclase activation, disturbances which are often observed in affective disorders.
AKT-glycogen synthase kinase 3beta (GSK3beta) signaling is a target of lithium and has been implicated in the pathogenesis of mood disorders and schizophrenia.
We therefore wanted to examine whether the reported BD genetic variants in CACNA1C, ANK3, MYO5B, TSPAN8 and ZNF804A loci are associated with ADHD or with scores on the Mood Disorder Questionnaire (MDQ), a commonly used screening instrument for bipolar spectrum disorders.
Carriers of the minor BDNF and ANK3 alleles showed nonsignificant trends toward protective association in controls relative to mood disorder patients (P = 0.047).
We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.
Polymorphisms in the CLOCK, BMAL1, Per3 and TIMELESS genes have been associated with susceptibility to mood disorder, and single nucleotide polymorphisms and haplotypes in several circadian genes have been observed among those displaying certain circadian phenotypes, including worse mood in the evening, insomnia in mania and early, middle or late insomnia in depression.
Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder.
Deficient beta-arrestin-2-CRF(1) receptor interactions could contribute to the pathophysiology of affective disorders by inducing excessive CRF(1) receptor signaling.