title: [A chapter in systematic schizophrenia research--the search for causal explanations for sex differences in age of onset].
abstract: With the aim of detecting causal processes contributing to the onset of schizophrenic symptoms a systematic search strategy was worked out. One of the few epidemiological findings on schizophrenia consistently diverging from expected values, the sex difference in age at first admission, was taken as a basis and replicated on data from the Danish and the Mannheim case registers by controlling for selection and diagnostic artefacts. Danish psychiatrists turned out to have underdiagnosed schizophrenia to a considerable extent at least in 1976, the year from which the analysed case-register data dated. After the exclusion of alternative explanations, the time when symptoms appeared for the first time and the first acute episode occurred was determined for a representative sample of 267 first-admitted cases with a diagnosis of non-affective functional disorder by using the IRAOS interview designed for this purpose. At any of the definitions of first onset applied the mean age of females was significantly higher than that of males, the difference ranging from 3.2 to 4.1 years. The distribution of onsets across the female life cycle showed a clearly delayed increase at young age and a second, lower peak of onsets at the age of 45-54, whereas the cumulative incidence up to the age of 60 years was equal for males and females. On assessing the plausibility of psychosocial versus biological explanations it was hypothesized that due to the effect of estrogens the vulnerability threshold for schizophrenia is raised in females until the menopause. Animal experiments and postmortem analysis showed that chronic estrogen applications significantly shortened dopamine-induced behaviour and reduced D2 receptor sensitivity in the brain. The applicability of this pathophysiological mechanism on human schizophrenia was tested on acutely schizophrenic females with normal menstrual cycles. A significant negative correlation was found between measures of symptomatology and plasma estrogen levels. Apparently, the manifestation of schizophrenic symptoms is influenced by a sufficiently sensitive D2 receptor system in the brain, blocked by neuroleptics and modulated by estrogens.
authors.affiliation: Zentralinstitut für Seelische Gesundheit, Mannheim.
authors.forename: H
authors.initials: H
authors.lastname: Häfner
authors.forename: W
authors.initials: W
authors.lastname: an der Heiden
authors.forename: M
authors.initials: M
authors.lastname: Hambrecht
authors.forename: A
authors.initials: A
authors.lastname: Riecher-Rössler
authors.forename: K
authors.initials: K
authors.lastname: Maurer
authors.forename: W
authors.initials: W
authors.lastname: Löffler
authors.forename: B
authors.initials: B
authors.lastname: Fätkenheuer
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D012565:Schizophrenic Psychology; D012737:Sex Factors
vernacular_title: Ein Kapitel systematischer Schizophrenieforschung-Die Suche nach kausalen Erklärungen für den Geschlechtsunterschied im Ersterkrankungsalter.