We read with interest Dr. Anderson’s letter and appreciated his hypothesis. He prospected that by giving melatonin along with venesections we could have possibly enhanced our patient’s response. It is fascinating to hypothesize a link between melatonin and microglial quinolinic acid, which is recently advocated to be part of a glutamatergic hypothesis of bipolar disorder . Despite the lack of data involving melatonin or quinolinic acid in hemochromatosis, it is possible that the mechanisms proposed by Anderson did determine decreased iron chelation by melatonin, hence increased serum iron levels. One case series of melatonin secretion pattern in hemochromatosis had shown a reduction of the night peak of melatonin secretion in three patients out of nine , but none of these patients had psychiatric symptoms. A hypothesis of altered kynurenine metabolism in bipolar depression has been advanced as early as 1967 , while melatonin was hypothesized to have a role in bipolar disorder since the early 1980s . However, a link between the two has not been proposed heretofore in bipolar disorder. We did not measure melatonin in this patient specifically, as melatonin assays are not routinely available in our hospital, but we should underline that sleep disorder promptly responded to venesection, while other bipolar depression symptoms responded later. Hence, we are unable to speculate as to whether pharmacological melatonin supplementation could have accelerated the course of improvement. It appears from animal studies that for melatonin to lower brain iron, supraphysiological concentrations are needed ; since our patient’s sleep disorder resolved without added melatonin, we may suppose that he had sufficient natural resources to overcome any temporary melatonin deficit. Furthermore, there is no standard for melatonin supplementation in affective disorders; Dr. Anderson feels that it would have been useful in our case, since melatonergic mechanisms are involved in both sleep and mood disorders; however, improvement in sleep quality often, but not always, triggers improvement in mood. Pure melatonergic drugs were shown to improve sleep, while for depressive mood disorders, evidence has been obtained only for combined melatonergic MT1–MT2 agonists/serotonin 5-HT2C antagonists . Hence, we are unable at this stage to formulate valid melatonergic hypotheses for mood disorders. There is genetic evidence that the kynurenic acid pathway is disturbed in major psychoses ; we are currently conducting a study of xanthurenic acid in patients with psychoses and the patient described in our case report is part of this study. The research line indicated by Dr. Anderson is interesting and worth pursuing.