Summary
In a representative sample of 392 first hospital admissions for schizophrenia from a population of 1.5 million we assessed the “true” age of onset by a semistandardized interview “IRAOS”. We demonstrated that the mean age at onset of the disease is 3–4 years higher in females than in males, with the lifetime risk being exactly equal. In males, the rates of onset show a steep increase — starting from school age and reaching their maximum value in the age group 15–24 years — followed by a steady decrease. Females reach the first peak with a clear delay between 20 and 29 years. After the decrease, a second smaller peak is observed consistently in females within the age group 45–49 years and over. After having excluded competing explanations, we hypothesized that the effect of oestradiol on the dopaminergic system enhances the vulnerability threshold, which is lowered again during the menopause. Alternatively, we assumed that testosterone reduces the vulnerability threshold and thus furthers the earlier onset of the disease in males. We tested the hypotheses in three animal models by examining the effect of gonadal hormones on haloperidol-induced catalepsy and on apomorphine-induced stereotypies in both neonatal and adult rats. No clear influence by testosterone was shown. Oestradiol caused a significant reduction of both dopamine-agonist and dopamine-antagonist induced behaviour. The effects were stronger in neonatal rats. Since oestradiol caused the dopamine (DA) receptor affinity for sulpiride to be reduced by a factor of 2.8, we assumed that the behavioural changes due to oestradiol were accounted for by a down-regulation of DA receptor sensitivity. The higher age at onset and the second peak of onsets after menopause in females may therefore be due to a functional effect and possibly also to an additional structural effect of oestrogens already exerted on the development of the brain.
Article PDF
Avoid common mistakes on your manuscript.
References
Bédard P, Langelier P, Villeneuve A (1977) Oestrogens and extrapyramidal system. Lancet II:1367–1368
Bleuler M (1943) Die spätschizophrenen Krankheitsbilder. Fortschr Neurol Psychiatr 15:259
Bleuler M (1972) Die schizophrenen Geistesstörungen im Lichte langjähriger Kranken- und Familiengeschichten. Thieme, Stuttgart
Chang SS, Renshaw DC (1986) Psychosis and pregnancy. Compr Ther 12:36–41
DiPaolo T, Falardeau P (1985) Modulation of brain and pituitary dopamine receptors by estrogens and prolactin. Prog Neuropsychopharmacol Biol Psychiatry 9:473–480
Fields JZ, Gordon JH (1982) Estrogen inhibits the dopaminergic supersinsitivity induced by neuroleptics. Life Sci 30:229–234
Häfner H (1987) Epidemiology of schizophrenia. In: Häfner H, Gattaz WF, Janzarik W (eds) Search for the causes of schizophrenia. Springer, Berlin Heidelberg New York, pp 47–74
Häfner H, Riecher A, Maurer K, Löffler, Munk-Jorgensen P, Strömgren E (1989) How does gender influence age at first hospitalization for schizophrenia? A transnational case register study. Psychol Med 19:903–918
Häfner H, Behrens S, De Vry J, Gattaz WF, Löffler W, Maurer K, Riecher-Rössler A (1991) Warum erkranken Frauen später an Schizophrenie? Nervenheilkunde (in press)
Häfner H, Maurer K, Löffler W, Riecher-Rössler A (1991a) Schizophrenie und Lebensalter. Nervenarzt (in press)
Harris MJ, Jeste DV (1988) Late-onset schizophrenia: an overview. Schizophr Bull 14:39–55
Huber G, Gross G, Schüttler R (1979) Schizophrenie. Verlaufund sozial-psychiatrische Langzeituntersuchungen an den 1945 bis 1959 in Bonn hospitalisierten schizophrenen Kranken. Monographie aus dem Gesamtgebiet der Psychiatrie. Springer, Berlin Heidelberg New York
Hruska RE (1986) Elevation of striatal dopamine receptors by estrogen: dose and time studies. J Neurochem 47:1908–1915
Kendell RE, Chalmers JC, Platz C (1987) Epidemiology of puerperal psychoses. Br J Psychiatry 150:662–673
Labrie F, Beaulieu M, Caron M, Raymond V (1978) The adenohypophyseal dopamine receptors, specificity and modulation of its activity by estradiol. In: Robin C and Harter M (eds) Proc Int Symp on Prolactin, Elsevier, Amsterdam, pp 121–136
Raymond V, Beaulieu M, Labrie F, Boissier JR (1978) Potent antidopaminergic activity of estradiol at the pituitary level of prolactin release. Science 200:1173–1175
Seeman MV, Lang M (1990) The role of estrogens in schizophrenia gender differences. Schizophr Bull 16:185–194
Sovner R, DiMascio A (1978) Extrapyramidal syndromes and other neurological side effects of psychotropic drugs. In: Lipton MA (eds) Psychopharmacology: a generation of progress. Raven Press, New York, pp 1021–1032
Villeneuve A, Cazejust T, Coté M (1980) Estrogens in tardive dyskinesia in male psychiatric patients. Neuropsychobiology 6:145–151
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Häfner, H., Behrens, S., De Vry, J. et al. Oestradiol enhances the vulnerability threshold for schizophrenia in women by an early effect on dopaminergic neurotransmission. Eur Arch Psychiatry Clin Nuerosci 241, 65–68 (1991). https://doi.org/10.1007/BF02193758
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02193758