Electrolytes and Depressive Illness

Interest in water and electrolyte metabolism in mental illness is not new, nor is it confined to depressive illness. In fact schizophrenic patients have been intensively studied and there have been, for example, reports of phasic variations in sodium excretion in the acute episodes of periodic catatonia (Gjessing, I953) and of delayed diuretic response to a water load taken by mouth in chronic schizophrenic subjects (Pfister, I937). The first studies in depressives derived from the old observation that the urinary output tended to be low in depressive and high in manic illness (Allers, I914). The obvious explanation, that manic patients are often thirsty and drink more, was not thought to be the complete explanation in every case and, as we shall see, there is justification for this view. The first thorough attempt to correlate variations in metabolism, including the excretion of water and sodium, with variations in mental illness was made by Gjessing (1932, I953) in his famous studies of periodic catatonia. This is a rare condition in w'hich attacks of stupor or excitement occur at regular and predictable intervals. Gjessing's patients were given a fixed intake of food and fluids for many months, so that a detailed balance study was made during several cycles of illness. Most depressive patients, however, either have only one attack of illness or have their attacks at long and quite irregular intervals. A very few patients suffer from rapid alternations of mood, a short period of elation and overactivity being followed by a similar period of depression and retardation, with perhaps a day or more of normal mood at some stage of the cycle. Such patients can obviously be studied in Gjessing's wayalways provided that they will cooperate with the investigator. Only a handful of studies have been reported, but they are worth considering in some detail for the light they may throw on the possible metabolic accompaniments of the commoner and more prolonged depressive illnesses. The most intensive study is that reported by Klein and Nunn (I945). Their patient, a man aged 67, had suffered from chronic depression for 14 years from the age of 5 I. Later his illness took the form of regular weekly cycles consisting of five days of depression and retardation and two days of elation and overactivity. Various autonomic changes accompanied the changes in mood: thus his pulse was slower and his blood pressure lower during the depressed phases. For a period of several months he was given a constant mixed diet, with a constant fluid intake, and 12-hourly urine collections were made. When biochemical investigations were in progress he was kept in bed. The findings of interest in the present context may be summarized as follows. During the depressive phases the patient retained sodium and water, which was excreted again during the manic phase. The daily volume of urine averaged 780 ml. in the depressive and i,670 ml. in the manic phases, and the urinary excretion of sodium and chloride was increased by 6o to 70% during mania. Potassium excretion was unrelated to mood change and the same was true of other urinary constituents (calcium, ammonia, phosphate and nitrogen). Daily blood samples were taken throughout three consecutive cycles but no variations in hlimatocrit or hemoglobin concentration were seen. The change in weight was in the direction expected-a gain of o.9 to I.3 kg. during depression which was promptly lost again during mania. More detailed study of the rate of urine flow during the changeover from depression to mania showed that an abrupt increase in urine flow actually preceded the mood change. The second of the two cases reported by Crammer (1959) was very similar. The patient was a 49-year-old man with a regular six to seven day cycle for at least five years. Two days were spent in stupor and four in manic overactivity. On a constant intake of food and fluids this patient also showed retention of water and sodium and gain in weight during his depressed phase-about 225 mEq. of sodium and I.75 kg. in weight. Polyuria and excretion of sodium followed during the overactive phase. Hamodilution during the stuporous period was indicated by appropriate fluctuations in packed cell volume. In this patient also there were no regular variations in the serum concentration or urinary excretion of potassium. Crammer observed that the magnitude of the weight gain varied directly with the amount of sodium in the diet. Thus the gain was only about 700 g. on a diet containing I5 mEq. of sodium a day, while fluid restriction (to 500 ml. a day) practically abolished the weight changes. It should be mentioned that none of these manouvres had any effect on either the timing or the intensity of the mood change. Moreover the time relationship between mood and fluid retention was reversed after several months of treatment with coright.