Platelet GABA-transaminase in affective illness

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,...…”

“…104,115,[124][125][126] Additional evidence in support of a GABA deficit in mood disorder patients are the findings of lower platelet GABA-T and plasma GAD activities reported in unipolar and bipolar patients. 127,128 Furthermore, dysphoria and mood disturbances were reported in euthymic bipolar and normal individuals after intravenous GABA administration. 129 Interestingly, higher plasma GABA levels have been reported to correlate with clinical response to electroconvulsive therapy (ECT) in depressed patients 130 and to valproate in manic patients, 131 possibly suggesting that the affective patients with least abnormal GABA levels may have superior response.…”

Variants within the GABA transaminase (ABAT) gene region are associated with somatosensory evoked EEG potentials in families at high risk for affective disorders

“…Luscher et al 2011; Sanacora & Saricicek, 2011). Berrettini et al (1980) proposed platelet ABAT expression as a vulnerability marker for affective illness and furthermore suggested the importance of genetic factors in its regulation. Moreover, a role of ABAT for affective disorders as well as somatosensory processing is also suggested by the fact that ABAT inhibitors such as valproate or vigabatrin show effectiveness as mood stabilizers (Gajwani et al 2005) as well as antinociceptive (Enna & McCarson, 2006) and anxiolytic compounds (e.g.…”

Gaba and Depression

“…Four of the six studies that measured CSF GABA in depressed patients found it to be significantly lower, with the two negative studies employing either a different aliquot of CSF (Post et al, 1980) or ambiguous diagnostic criteria (Zimmer et al, 1980). Generally CSF GABA levels are decreased to between 55% and 92% of control values.…”

“…However, the GABA synthesized enzyme, GAD in plasma, has been shown to be lower in symptomatic patients with both unipolar and bipolar depression (Kaiya, Namba, Yoshida, & Nakamura, 1982). Similarly, activity of the GABA-metabolizing enzyme GABAT in platelets was found to be low in euthymic bipolar patients off medications (Berrettini, Umberkoman-Writa, Nurnberger, Vogel, Gershon, & Post, 1980). Except for these two studies, other examinations of peripheral GABA utilized levels of plasma GABA (pGABA) itself.…”