Reduction of GH response to the GABA-B agonist baclofen in patients with major depression

GABAergic dysfunction in mood disorders

“…158,159 Baclofen, a GABA B receptor agonist, stimulates GH secretion in healthy individuals, [160][161][162] and is considered to be an in vivo index of human hypothalamic GABA B receptor function. The GH response to baclofen has been found to be significantly lower in depressed patients 163,164 and significantly higher in manic patients than healthy subjects. 161 However, the findings suggesting abnormal regulation of GABA B receptors in mood disorder patients through the GH response are controversial, as other studies reported negative findings in depressed patients.…”

“…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 preliminary study of baclofen‐induced growth hormone release in generalised social phobia

“…Because of these limitations our results should be viewed as preliminary and our conclusions tentative. Although contradictory reports exist, two studies have reported a significant reduction of GH responses to baclofen in patients with major depression compared with matched normal controls (Marchesi et al, 1991;O'Flynn and Dinan, 1993), suggesting that downregulated GABA B receptor function is associated with depression. However, none of our patients suffered from a current or lifetime history of major depression and therefore this would not explain our results.…”

“…Thus, plasma GH levels after oral administration of baclofen should provide an index of hypothalamic GABA activity. This test has been extensively used to study GABA B receptor and GABA system function in many psychopathologies including schizophrenia (Monteleone et al, 1988), major depression (Monteleone et al, 1990;Marchesi et al, 1991;O'Flynn and Dinan, 1993;Davis et al, 1997) and mania (Shiah et al, 1999).…”

The GABAB receptor as a target for antidepressant drug action

“…Thus, GABA levels in the cerebral cortex, plasma and CSF are lower than normal in depressed patients, as is the number of GABA neurons in layer II of the orbitofrontal cortex (Petty, 1995;Rajkowska et al, 1999;Sanacora et al, 2000;Krystal et al, 2002). A GABAB receptor involvement is suggested by the findings of some (Marchesi et al, 1991;O'Flynn and Dinan, 1993;Lucey et al, 1994), but not others (Davis et al, 1997), that the growth hormone response to baclofen is blunted in depressed individuals as compared with controls, suggesting altered GABAB receptor responsiveness in these patients. Also, an efficacy study with baclofen indicates that this GABAB receptor agonist worsens BJP S Ghose et al…”