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SUMMARY Psychiatric patients suffering from endogenous depression and a control group without endogenous depression were given oral loads of L-tryptophan and urinary excretion determined of the tryptophan metabolites on the pyrrolase pathway: kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid. Female endogenously depressed subjects excreted significantly more kynurenine and 3-hydroxykynurenine but not the subsequent metabolite 3-hydroxyanthranilic acid than did female control subjects. Variability of excretion of kynurenine and 3-hydroxykynurenine at different times by the same subject was much greater in the endogenously depressed than in the control group. There was no consistent temporal relationship between excretion of metabolites and severity of the depressive illness. The possible significance of the findings in relation to defective tryptophan metabolism in the brain in endogenous depression is commented upon.The considerable efficacy of physical treatments in patients with affective illnesses has encouraged research into the implied physical abnormalities present. A relatively specific indication of the presence of a biochemical disturbance is provided by the therapeutic effectiveness of monoamine oxidase inhibitor (MAOI) and tricyclic antidepressants, which influence monoamine metabolism. The extent to which amines derived from tryptophan, such as 5-hydroxytryptamine (5HT), and those derived from tyrosine, such as the catecholamines, play a part in the regulation of mood has been the subject of much controversy and has been discussed by Schildkraut (1965) and by Brodie and Reid (1968).There is considerable evidence that tryptophan metabolism is disturbed in affective illnesses. Thus the therapeutic activity of MAOI compounds was found by Coppen, Shaw, Herzberg, and Maggs (1967) to be enhanced by oral tryptophan, suggesting that depression may be associated with insufficient cerebral 5HT. In addition, depressed subjects responding to iproniazid were found by Pare and Sandler (1959) and Van Praag and Leijnse (1963), but not by Burgermeister, Dick, Garrone, Guggesberg, and Tissot (1963), to have lower initial levels of 5-hydroxy-indolylacetic acid (5HIAA), which reflects overall 5HT metabolism, than those who did not respond to the drug. Also depressed subjects were found by Ashcroft, Crawford, Eccleston, Sharman, MacDougall, Stanton, and Binns (1966) 698 to have a low content of 5HIAA in the cerebrospinal fluid, which is a measure of brain 5HT metabolism. Low hind-brain 5HT has been reported in depressive suicides by Shaw, Camps, and Eccleston (1967). This was not confirmed by Boume, Bunney, Colbum, Davis, Davis, Shaw, and Coppen (1968), although 5HIAA was found to be low.5HT is formed in vivo from tryptophan by a minor pathway. A quantitatively much more important route of tryptophan metabolism through kynurenine starts with oxidation by liver tryptophan pyrrolase.Increased synthesis of this enzyme was shown by Knox and Auerbach (1955) to result from increased secretion of adrenocortical ho...

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The MRI T1 proton relaxation values were assessedin 14 patients with bipolar affective disorder and 10 with a unipolar disorder and a matched normal control group. The T1values in the frontal white matter of patients significantlyexceeded those of the controls. This difference was accounted for by an increase in T1 values in the frontal white matter of unipolarpatients:the valuesfor bipolarpatientsalonedid not differ from those for controls. These preliminary findings support a hypothesis of frontal lobe dysfunction mediating pathologicalchangesin mood. (Braftos & Sagedal, 1960; Haug, 1962; Nagy, 1963) (Jacoby & Levy, 1980; Pearlson & Veroff, 1981; Dolan et a!, 1985 Dolan et a!, , 1986. Using a CT index of brain tissue density (Hounsfield units), patients suffering affective disorders were found to differ from both controls and patients with dementia (Jacoby et a!, 1983). Magnetic resonance imaging (MRI) represents a further technological advance in the study of brain structure. It is sensitive to pathological changes (Bydder eta!, 1984)and has the potential to examine physiochemical changes. The proton relaxation parameters, T1 and T2, are sensitive to patho physiological change, particularly shifts in water distribution. As yet, this potential of MRI has been little used in the study of so-called functional psychoses. However, in one study of patients with bipolar affective disorder an increase in T1 values in frontal and temporal white matter, which normal ised following lithium therapy, was reported (Rangel Guerra et a!, 1983). The present study was under taken to explore further the relationship between regional brain T1 values of patients with affective disorders by comparison with an age-and sex matched control group. MethodPatients were selected from the acute in-patient population of a teaching hospital, the Royal Free Hospital, and a large mental hospital, Friern Barnet Psychiatric Hospital. A further sample was recruited from patients undergoing evaluation for psychosurgery at the Geoffrey Knight Unit for Affective Disorders. All patients fulfilled Research Diagnostic Criteria (RDC) for current major depressive disorder (Spitzer et al, 1978). Exclusion criteria included a history of significantpast or concurrent medicalillness or of alcohol abuse. Normal control subjects, matched with the patients for age and sex, wererecruited from hospital staff and from the general public by advertisement. None of the controls had a past or present history of significant physical illness, alcohol abuse, or a family history of psychiatric disorder. All patients and controls gave written informed consent.Iwenty-four patients (12 men, 12women) and 13control subjects (6 men, 7 women) were included in the study. Fourteen patients had a bipolar illness (8 men, 6 women) while the remainder had a unipolar disorder. Three of the bipolar and four of the unipolar women were menopausal.Sixpatients wererecruited fromtheGeoffrey Knight Unit for Affective Disorders.A detailedpsychiatrichistoryobtained by interviewwas supplem...