Another marker for different types of depression

Lerer and Macciardi (2002) mention predictors of response to various mood-stabilizing agents, including demographic and clinical characteristics, personality features, biological markers and psychophysiological features. These workers conclude that the above predictors of response are not robust enough to be clinically relevant and thus have not been helpful in the emerging field of pharmacogenetics. One predic-tor not mentioned by these authors is the variable response to the exogenous opioid, psychotropic analgesic nitrous oxide (PAN) in depressive patients The first indication of this differential response to nitrous oxide was described by Zádor (1928) using anaesthetic concentrations of nitrous oxide. He observed that endogenous depressions were often resistant to the effects of the gas, whereas reactive depressions responded positively. These findings stimulated our work. A pilot study of 24 cases of depression was under-taken in which the effects of non-anaesthetic concentrations of nitrous oxide were investigated, such that the patient was fully conscious, coherent and cooperative throughout the administration (Gillman, 1984). Nitrous oxide was titrated until the symptoms of the depression were lifted or not affected. In recal-citrant cases, a maximum of 9 l of nitrous oxide mixed with oxygen was given. In all cases, the nitrous oxide was given for approx. 20 min, but never longer than 30 min. At all times a minimum of 30 % oxygen was administered with the nitrous oxide. Of the 24 patients studied, 20 responded positively and 4 were recalci-trant. After the trial it was found that the responders had been diagnosed as reactive and/or neurotic depression , whereas the non-responders had been diagnosed as endogenous depression. Since this work was completed in the early 1980s and psychiatric nosology was not as exact as it is today, it is possible that some of the responders may well have been suffering from endo-reactive depression (or unipolar depressive disorder). At the time, it was suggested that there was underactivity of the endogenous opioid system in depression (Gillman, 1984), which could explain the positive therapeutic actions of PAN (Gillman and Lichtigfeld, 1994; Lichtigfeld and Gillman, 1985). More recently the hypothesis in which depression can arise from underactivity of the opioid system has been supported by other investigations. For instance post-mortem examination has revealed increases in m-opioid receptor density, but not in affinity, in the brains of suicide victims (Gross-Isseroff et al., 1990). And the prolactin response to exogenous opioids in depression strongly suggests opioid sub-sensitivity. However, this decrease of …