However, reports of a significant reduction in psychotic activity after a hearing aid has been fitted indicate that deafness is, at least in part, a predisposing factor for the development of symptoms, even though it is difficult to explain such a complex disorder on the basis of a simple sensory deficit.42 Gender and hormonal status Practically all studies of late-onset schizophrenia
and late paraphrenia, Inhibitors,research,lifescience,medical or more particularly PHC, report a large excess of affected women. Reported female/male ratios range from 6:143 to 45:244; in one PHC group, Bénazet found a 1:7 female/male ratio.45 Seeman and Lang proposed that the higher level of estrogen before the menopause might result in the delayed onset of symptoms in women.46 Pearlson et al reported an increased Natural Product Library density of D2 receptors in lateonset schizophrenia,39 although a recent attempt to replicate this finding has failed.47 Estrogens seem to modulate the sensitivity of D2 receptors in brain and, according to some authors, estrogens could have
a ncuroleptic-like effect.48 Moreover, estrogens Inhibitors,research,lifescience,medical can reduce the dopamine concentration in the striatum,49 thereby modulating the sensitivity and the number of dopamine receptors.50-52 Estrogens could thus act as a protective factor, delaying the onset of the psychotic syndrome in women. The menopause could represent a high-risk period in vulnerable women in terms of loss of estrogen. An alternative hypothesis Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical is that, rather than the existence of a delaying factor detected in all female patients, some vulnerability factors may be involved
in a subgroup of patients, with a particular range of age at onset. For example, in a recent genetic analysis, we observed a significant excess of one D2 receptor gene haplotype in schizophrenic patients, specifically in a subsample of patients with a disease onset occurring after 20 years of age.53 Another hypothesis is that significant vulnerability genes are differentially expressed among generations, with a milder form and late onset (such as PHC) in older generations, Inhibitors,research,lifescience,medical and a more severe disorder with younger age at onset (such as schizophrenia) in younger generations. Unstable mutations (Figure 1) can shed light on such mechanisms.54 If such mutations are involved, and if the PHC phenotype from is the milder form of the schizophrenia spectrum disorder, we should observe a decreased risk in ascendants (this is the Sherman paradox), and an increased risk in descendants. This can be analyzed on the basis of our 30 families with PHC. Figure 1. Expanded trinucleotide repeats, or unstable DNA, are the biological basis of the clinical phenomenon of genetic anticipation in different neurodegenerative disorders, and could be involved in schizophrenia. Usually, the CAG (triplet) repeat is repeated … Family history Family, adoption, and twin studies suggest that there are genetic factors in the risk for schizophrenia.