Genetic disorders presenting as ?schizophrenia?. Karl bonhoeffer's early view of the psychoses in the light of medical genetics

Abstract

There is overwhelming empirical evidence for the influence of genetic factors in the etiology of schizophrenic psychoses. An appreciable and still increasing number of exogenous factors have been known for decades that are capable of inducing psychoses that present as "schizophrenia" or are more or less similar to it. In this article, genetic disorders--chromosomal abnormalities and Mendelian diseases--are summarized that may be associated with such psychoses. These disorders frequently but not necessarily exhibit additional physical symptoms. Although the majority of schizophrenic psychoses can so far not be explained by exogenous factors or well-defined genetic disorders, the proportion of these etiologies among all cases may be higher than presumed so far, because they evade detection. Data from the literature are discussed in the light of Karl Bonhoeffer's early concept of exogenous reaction types and modern medical genetics.

Chromosomal Aberrations and Schizophrenia

“…The focus in the current paper, however, is restricted to autosomal abnormality associations, which have been less discussed than the sex chromosomal anomalies. The present review updates and extends the references catalogued in the Propping (1983) and DeLisi & Lovett (1990) articles, and critically reviews the evidence for reported associations of autosomal abnormalities and psychiatric illness. The relevance of these associations for genetic linkage studies was estimated with standardised criteria for specificity, diagnosis, family history, and overall weight of evidence.…”

“…References to autosomal abnormalities in Schmid & Nielsen (1981), Propping (1983), and DeLisi & Lovett (1990) served as a starting point. As an update of these studies, a Medline search was done for the years 1966-1990 by using the search strategy: "Schizophrenia" or "Mental disorders", and "Chromosomal abnormalities" or "Chromosomal aberrations".…”

“…Chromosomal abnormalities may involve either the sex chromosomes (X and Y) or the autosomes (chromosomes 1-22). Propping (1983) tabulated three chromosomal abnormalities associated with possible schizophrenia-like psychoses: XXY, XXX, and 18q-or ring 18. More recently, in the context of their own cytogenetic survey of 46 men with schizophrenia, DeLisi & Lovett (1990) summarised 15 X chromosome studies and four reports of autosomal abnormalities associated with psychoses.…”

The unstable trinucleotide repeat story of major psychosis

“…Although it is unclear whether the psychiatric symptoms are secondary to the neurodegeneration, or a result of increased environmental loading, or whether there is genetic linkage between these disorders, it seems appropriate that such cases should be considered as phenocopies of major psychosis [Propping, 1983]. Some studies have, however, investigated whether expansion mutations may occur in psychosis patients, who may be non-penetrant for the neurodegenerative disorder, or whether there may be linkage disequilibrium with other, uncharacterized mutations/ polymorphisms at these genes.…”

Psychiatric genetics — Does diagnosis matter?

“…On the other hand, many less complex and more uncommon conditions can lead to behavioural phenotypes presenting, for instance, as schizophrenia. 1 The large case-control samples available also permit tests of shared predisposition to disorders traditionally considered to be distinct diagnostic entities. 2,3 These studies show considerable overlap in polygenic susceptibility, with reported correlations between liabilities for major psychiatric disorders in the range of 0.3 to 0.7.…”