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Objective：Recent studies suggested that the neurotrophic effects might be a major therapeutic mechanism of antidepressants. However, these effects have not been confirmed yet in depressed patients. We investigated whether mirtazapine treatment has the neurotrophic effects in depressed patient by using 1^H-MRS and explored the relationship between these effects and clinical improvements and neuropsychological functions. Methods Fourteen female, right-handed patients with major depressive disorder and 12 healthy controls participated in the study. Before the treatment with mirtazapine, we measured severity of illness, neuropsychological functions, and the levels of NAA, Cho and Cr in both hippocampi using 1^H-MRS in the depressed subjects. After the treatment with mirtazapine for 6 weeks, we repeated the measures of the pretreatment condition in the depressed subjects. We also measured variables of severity of illness and hippocampal metabolites with 1^H-MRS in the control group. Results：There were no significant differences in NAA/Cr, Cho/Cr, and Cho/NAA between the depressed subjects and the control group. However, after the treatment with mirtazapine, there were significant improvements in severity of illness, immediate memory, and delayed memory. The posttreatment ratio of the total hippocampal Cho/Cr was significantly lowered than the ratio of the pretreatment Cho/Cr. However, the percent changes of the hippocampal Cho/Cr from the pretreatment Cho/Cr ratio were not correlated with the changes of severity of illness or neuropsychological functions from the pretreatment condition. Conclusions：These findings indicate that mirtazapine may reduce the level of choline metabolites by stabilizing the effect on the cholinergic neurons, reducing turnover or metabolism of neuronal membranes, or modulating the neuroendocrine systems in the depressed patients. However, this effect is not necessarily related to clinical improvements. Further studies on the therapeutic action of mirtazapine are needed.
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