This preliminary communication reports that the mothers of 104 schizophrenic patients had: (1) a significantly higher incidence of thyroid disease than a carefully matched control group; (2) significantly more abortions, still-births and greater infant mortality. The findings and possible relevance of thyroid disease to schizophrenia are discussed. Three prospective studies currently in progress are outlined.

Depressed patients (unipolar) were given one of the following combinations in an attempt to test aspects of the ‘amine hypothesis’ and to find a preferential therapy: (1) clomipramine; (2) clomipramine and tryptophan; (3) desipramine and clomipramine, and (4) desipramine and tryptophan. Treatment (2) should have given optimal potentiation of 5-HT neurones and (3) and (4) should have acted similarly on both serotoninergic and adrenergic pathways. In no group was there any evidence of accelerated recovery, indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis.

The study of tryptophan metabolism using compartmental analysis suggested differences between males and females, and between control subjects and patients with affective illness, patients treated with tricyclic drugs, and those established on lithium therapy. The total mass of tryptophan in the body may be reduced in people prone to affective disorder, and in depressed patients (ill and well) turnover of tryptophan seemed to be reduced. The reduction of concentration of tryptophan in compartment S2 in affective illness could affect protein synthesis.

In this study we have compared certain personality variables in alcoholic individuals, depressed subjects and in controls.

Folate (RBC, serum, CSF) and B12 (serum and CSF) and 5-HIAA and HVA (CSF) concentrations were measured in patients with senile dementia. Those with RBC folate < 130 ng/ml. were given folate/B12 in a double-blind crossover trial. (1) Amine metabolites and folate were unrelated. (2) CSF folate levels rose significantly but slowly on ward diet only independently of the period of intensive replacement. (3) There was no clinical improvement over the 24 weeks of observation but in view of the biochemical findings the period of study may have been too short.

A proportion of individuals suffering from schizophrenia show either physical or psychological signs of gonadal underfunction or incomplete sexual maturation (Hoskins, 1943; Hoskins and Pincus, 1949; Bleuler, 1954; Sands, 1957; Reiss, 1958; cf. Shader and Grinspoon, 1967). Rey and Coppen (1959) reported significantly lower, that is more feminine, androgyny scores (Tanner, 1962) in schizophrenic patients, although reduced scores were also found to a lesser extent in depressive and neurotic patients. Sex chromosome anomalies were not found in those patients with abnormally low androgyny scores (Cowie, Coppen and Norman, 1960), and it is possible that the abnormal physique is caused by some hormonal malfunction during development which also may be associated with a predisposition to psychiatric illness.

Pollin et al. (12) found that in a series of 11 monozygotic twins (MZ) discordant for schizophrenia all of the index twins weighed less at birth, 8 of the index twins were second- born and 7 out of the 11 mothers had varying thyroid pathology ‘of clinical significance’. The following report is probably the first giving details of investigations into a pair of MZ twins who were given thyroid extract during the neonatal period because of failure to make normal progress.