Association study between bipolar disorder and candidate genes involved in dopamineserotonin metabolism and GABAergic neurotransmission

GABAergic dysfunction in mood disorders

“…This reaction is sensitive to tricyclic antidepressants and electroconvulsive shock therapy (ECST), but not to anxiolytic or major GABA plasma levels kin 40% of depressed, manic, and euthymic mood disorder patients 98,[116][117][118][119][120] 2 in depressed patients 132 GABA enzyme activities kplatelet GABA-T and plasma GAD activities in unipolar and bipolar patients 127,128 Post-mortem studies kGAD activity 130 and mGABA A receptors 141 in the brain of depressed patients k GABA cortical levels with m depression severity in mood disorder patients 151 kexpression of GAD 65 and GAD 67 in prefrontal cortex 148 [141][142][143][144][145][146] Neuroimaging studies kGABA A receptors in the sensory motor cortex of mood disorder patients with akinetic catatonia 152 kGABA occipital cortex levels in depressed patients 153 Neuroendocrine studies (GH response to baclofen ) k in depressed patients 163,164 m in manic patients 161 2 in depressed patients, 162,165,166 Genetic studies Bipolar disorder: association with GABA A receptor a5 (GABRA5) 178 and a3 subunits (GABRA3) 180 possible linkage of GABRA5 and GABA A receptor b1 subunit (GABRB1) loci 181 no association with GABRA1, 179,181,186,188 70,71 Reduced GABA levels in rat nucleus accumbens, brain stem, and cortex have been reported after a session of forced swimming test. 72 Also, muscimol, a GABA agonist, reduced the immobility,...…”

“…A linkage study examining two large families segregating bipolar disorder could not exclude linkage of GABRA5 and GABA A receptor b1 subunit (GABRB1) loci in one of the families, although negative results were reported in the other study. 181 However, several studies reported negative findings for GABA A receptor subunits in bipolar (GABRA1,2,3,4,5,6, GABRB1,3, GABRG2) 177,[181][182][183][184][185][186][187][188][189] and unipolar disorders (GABRA3, GABRA5). 178,179 Although some support for association between GABRA1, GABRA3, and GABRA5 and mood disorders have been reported, the findings from the genetic studies taken together remain conflicting and preliminary.…”

Excess of allele1 for α3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study

“…A total of 555 subjects were recruited, including 185 BPAD patients, each matched with two controls (n = 370) for sex and ethnogeographical origin (see Table 2). To our knowledge, only three association studies have examined the role of GABRA3 in BPAD, and didn't report significant findings [30][31][32] (Table 3). Three other genes have been investigated in the same region: FMR1 implicated in the fragile X syndrome in Xq27.3 33 reported negative findings, G6PD in Xq28 34-37 reported positive results in two different populations.…”

“…Our results are not in line with some previous association studies testing the same GABRA3 (CA) n repeat polymorphism. [30][31][32] However, samples used in previous studies didn't have a sufficient statistical power for detecting association, if we consider a minor or moderate effect of genetic variant at this polymorphism. Furthermore, our present investigation supports DNA studies that have reported positive association findings for G6PD enzyme deficiency (Xq28) in BPAD patients in two populations.…”

Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and disorganization symptomatology in major psychoses

“…19 Up to now both linkage and association studies failed to detect any association of DRD2 with mood disorders. [20][21][22][23][24][25][26][27][28] A small positive association was reported in a Spanish sample 29 but it failed to be replicated and a positive association was also found by Arinami et al, 19 but only when consider-ing mood disorder subjects with mood incongruent psychotic features. Traditionally the definition of the phenotype has been based on categorical diagnoses which do not guarantee biological homogeneity and have been considered reductive of the amount of information available from the whole symptomatologic presentation of patients.…”