The Mental Implications of Sex Chromosome Aberrations

Abstract

I have chosen as the subject for my Blake Marsh Lecture the influence of sex chromosome aberrations on intelligence, mental health and social adjustment. This subject provides a fascinating example of how a branch of research, beginning in the field of mental retardation, arrived at discoveries which proved to be of significance to quite other fields of psychiatry. Ten years ago we learned that sex-chromatin-positive males, that is, males with additional X chromosomes, at least in some cell lines, were more often encountered among the intellectually retarded than among the average population of males. Shortly after this we learned that the same was true of women with double Barr bodies, that is, women with more than the usual two X chromosomes, at least in some cell lines. Today we have facts showing that an abnormal sex chromosome complement may have an unfavourable effect on mental health, and this in several different ways; thus we know that it may contribute to the development of functional psychoses, and may even influence such a complex variable of behaviour as our ability to adapt ourselves to the laws of the community. Myself, I am convinced that study of aberrations in the sex chromosomes will prove to have a radical effect on large sections of psychiatric thinking.

Klinefelter's syndrome (XXY) as a genetic model for psychotic disorders

“…Much attention has previously been given to the association of the XXY karyotype with psychiatric disorders, particularly affective psychoses and schizophrenia [e.g., Rohde, 1963;Kvale and Fishman, 1965;Hambert, 1966;Nielsen, 1969;Nielsen et al, 1969Nielsen et al, , 1980Forsmann, 1970;Rosen et al, 1970;Sorensen and Nielsen, 1977;Roy, 1981;reviewed in DeLisi et al, 1994] Of the 11 subjects with Klinefelter's syndrome in the present study, 1 was diagnosed with chronic schizoaffective disorder, and 3 others had a predominant affective disorder with psychotic features. None of the controls had any evidence of psychosis, although four of them had a major affective disorder.…”

Two New Cases of XYY Chromosome Complement: And a Review of the Literature

“…The (Case 1) patient had been convicted of rape at the age of 14 and therefore shows a similarity to the 20 cases of sexual crimes among XYY men described in the literature (16,18,21,37). Although he was of normal intelligence, he did not progress well in school (44), and the patient in Case 2 had no better than borderline intelligence similar to the retardates (6,7,19,33) and retarded criminals (5,7,12,23,41). Other similarities include the preoccupation with fire (11,21,23) and the normal anatomy and physiology except for tallness.…”

“…There were a number of case reports that pointed out the incidence of sexual crimes (20 cases), especially against minors, (16,18,(21)(22)(23) and of arson, (six cases -11, 19, 21, 23). Of those cases described in detail there are at least 11 with a diagnosis of schizophrenia or "chronic functional psychosis" (1, 2, 9, 11, 12,29), with an additional four cases of very severe schizoid personality (7,12,21). In addition, some of the 47 patients found in maximum security hospitals were probably schizophrenic, although the psychiatric description or diagnosis was not included in many of the case reports.…”

“…On the one hand, approximately 1:500-1:900 live male newborns have this complement (3,9,24,39) but very few seem to come to clinical attention; on the other hand, surveys of institutions for the retarded (6,18), the mentally ill (2,12,16,22), the criminally insane (5,9,18,28,30) and the aggressive offender (11,21,23,26,38) have all shown a higher incidence of the XYY complement than would be expected in the general population. Some investigators (4,15) have tried to explain these individuals, in mental institutions and prisons, on the basis of their being tall and therefore more likely to be considered as dangerous by judges and psychiatrists.…”

De cognitieve en neurale basis van sociaal disfunctioneren bij mannen met het Klinefelter-syndroom

“…Een studie gebaseerd op de analyse van ziekenhuisopnames heeft laten zien dat XXY-mannen driemaal zo vaak worden opgenomen, voornamelijk naar aanleiding van psychotische stoornissen (Forssman, 1970). Meer recent heeft een analyse van ziekenhuisopnames en -ontslagdiagnoses laten zien dat mensen met het XXY-patroon een verhoogd relatief risico hebben (ten aanzien van mensen uit de algemene populatie) om opgenomen te worden met een psychose, waarbij de hazard ratio 4.97 was (Bojesen et al, 2006).…”