The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in drug-free patients with DSM-III diagnoses of major depression, schizophrenia, or dementia. When compared to the controls and the other diagnostic groups, the patients with major depression showed significantly increased cerebrospinal fluid concentrations of CRF-like immunoreactivity; in 11 of the 23 depressed patients this immunoreactivity was greater than the highest value in the normal controls. These findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.

An apparent excess of sex chromosome aneuploidies (XXY, XXX, and possibly XYY) has been reported in populations of patients with schizophrenia by a number of authors. These reports have received little attention because transmission of psychosis is regarded as autosomal and not sex linked, and the detection of extra X chromosomes by Barr body estimation alone is not a reliable procedure. In this article, we review studies in which either complete karyotypes were determined for the whole sample or in which the presence of a Barr body in an individual was checked by full cytogenetic analysis. We also add two studies (of the former type) of our own--on a Swedish hospital cohort and a United States multiplex-schizophrenia family sample. These data, taken together, suggest that the sex chromosome aneuploidies, XXX and XXY, are increased in population of patients with schizophrenia, whereas too few subjects have been surveyed to determine whether an association also exists with XYY. Nevertheless, we conclude that this is consistent with a gene on the sex chromosomes having influence on the development of schizophrenia. A sex chromosome locus is compatible with an autosomal pattern of transmission if the gene is either pseudoautosomal (i.e., within the exchange region) or X-Y homologous (i.e., present in similar form in the nonrecombining regions of both X and Y chromosomes).

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