The NMDA receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine’s antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg/kg i.v.) was administered to eleven depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total ≤ 10) within 230 minutes of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 minutes. Mean areas under the curve (AUC) for Glx/W (p = 0.025) and GABA/W (p = 0.005) increased and correlated (r = 0.796; p=0.018). Clinical improvement correlated with 90-minute norketamine concentration (df=6, r=−0.78, p=0.023), but no other measures. Rapid increases in Glx and GABA in MDD following ketamine administration support the postulated antidepressant role of glutamate and for the first time raises the question of GABA’s role in the antidepressant action of ketamine. These data support the hypothesis1 that ketamine administration may cause an initial increase in glutamate that potentially activates mammalian target of rapamycin (mTOR) pathway via AMPA receptors, since ketamine blocks NMDA receptors. The role of the contemporaneous surge in GABA remains to be determined.2

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Little quantitative information is available on the effects of age on peripheral autonomic function. We studied the effect of age on the heart rate (HR) responses to deep breathing and the Valsalva maneuver in 122 and 155 subjects, respectively, aged 10 to 83 years. The quantitative sudomotor axon reflex test (QSART) was determined in 114 subjects in the same age group. The HR responses were not different between the sexes, but a consistently significant regression with age was demonstrated in response to deep breathing and the Valsalva ratio. The QSART responses were significantly larger in male subjects and were generally lower in older subjects of both sexes but a significant negative regression with age was found only in female subjects. Cardiac vagal function is impaired with age, but postganglionic sympathetic function is little affected by age, suggesting selectivity of effects of aging on autonomic function.

Limb dependency activates the venoarteriolar reflex (VAR), resulting in reflex vasoconstriction (RV). Since others have reported the VAR to fail in diabetic neuropathy, we examined the reliability of this test in detecting sympathetic failure in diabetic and other neuropathies. We studied 40 controls, 49 diabetic subjects, and 29 patients with other neuropathies. The mean RV was greater in controls than in diabetics or other neuropathies, but there were marked overlaps among groups. We conclude that the VAR, while impaired in the neuropathies, is of little value as a clinical test and is a poorer test of autonomic function than the quantitative sudomotor axon reflex test or heart rate responses to deep breathing or the Valsalva maneuver.