Objectives-Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, diYculties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. Methods-In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. Results-Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. Conclusions-Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement. (J Neurol Neurosurg Psychiatry 2000;69:228-232)

The establishment of a classification of affective disorders commanding wide agreement among clinical practitioners and investigators is one of the most pressing needs of contemporary psychiatry. This group of conditions has, in recent decades, displaced schizophrenia from the centre of the clinical stage. However, despite its prominence and importance in clinical practice, the territory remains inadequately charted. There is evidence to indicate that the uncertainty about the most clear and convenient lines of demarcation within this clinical territory makes a large contribution to the unreliability of psychiatric diagnosis. Thus, in a recent enquiry (Sandifer, Pettus and Quade, 1965) into the reliability of diagnoses made in 91 first admissions to a mental hospital by ten experienced psychiatrists, it was shown that the resolution of disagreement in the areas of “psychoneurosis—affective disorder” and “psychoneurosis—personality disorder” would have raised the overall reliability of diagnosis in this enquiry from 57 per cent. to 83 per cent.

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