0000000000125224
AUTHOR
Joachim Hallmayer
Evidence against linkage of schizophrenia to chromosome 5q11-q13 markers in systematically ascertained families.
Ten pedigrees systematically ascertained in Germany were tested for linkage to chromosome 5q11-q13. In order to replicate the previous report by Sherrington et al (1988), families with a bipolar family member were omitted from the lod score calculations, all diagnoses were based upon Research Diagnostic Criteria, and four different models of the affection status were calculated, including the model for which Sherrington et al calculated the highest lod scores. None of the families investigated showed a positive lod score. Using multipoint linkage analyses, we were able to exclude the region for which a positive linkage has been reported.
Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study.
Objective This study investigated whether the distinction between schizoaffective disorder and affective disorders with mood-incongruent psychotic features as described in DSM-III-R is reflected by aggregation of schizophrenia in the families of probands with the former disorder and aggregation of affective disorders mainly among the relatives of probands with the latter type of disorders. Method The probands were 118 inpatients with definite lifetime diagnoses of DSM-III-R schizoaffective disorder or a major mood disorder with incongruent psychotic features according to structured clinical interviews. Diagnostic information on 475 of the probands' first-degree relatives was gathered throug…
The impact of gender and age at onset on the familial aggregation of schizophrenia.
Some recent family studies have shown that the familial risk for schizophrenia is higher in female than in male schizophrenics. It is debated whether the risks for the other disorders, such as schizotypal personality disorder or affective disorders in families of schizophrenics are similarly influenced by the proband's gender. Also, the reason for the effect of proband's gender on the recurrence risk for schizophrenia has not been clarified. This family study (159 probands, 589 first degree relatives) confirms that schizophrenia, but also schizophrenia spectrum disorders were more frequent in families of female compared with male schizophrenics. Neither age at onset in probands nor the inte…
Persönlichkeitsfaktoren als Risiko- und Krankheitsindikatoren der unipolaren Depression
Pramorbiden Personlichkeitszugen wird in vielen Modellvorstellungen zur Atiologie affektiver Storungen eine zentrale Rolle zugewiesen. Die klassischen Bezugspunkte sind die psychoanalytische Theorie (Abraham 1925) und die Konstitutionstypologie (Kretschmer 1921); diese Ansatze sind in den vergangenen Jahrzehnten in vielfaltiger Weise fortentwickelt worden (vgl. die Ubersichtsarbeiten von Akiskal et al. 1983; von Zerssen 1982; Tolle 1987). Bestimmten Personlichkeitszugen bzw. Personlichkeitstypen wird dabei entweder die Rolle eines a) Risikofaktors, der uber ein theoriespezifisches pathogenetisches Bindeglied mit dem Auftreten der Erkrankung in Verbindung gebracht wird, oder b) die Rolle ein…
Morbid Risks in Relatives of Affective, Schizoaffective, and Schizophrenic Patients — Results of a Family Study
Affective disorders have been the major focus of recent family studies; the results of many family studies agree as regards the increased morbid risks for family members of patients with affective disorders and the distinction between unipolar and bipolar affective disorders. However, in spite of the large number of family studies that have been done there are still some unsettled problems, such as the association of delusional unipolar depression and bipolar depression (Weissman et al. 1986), the relationship of anxiety disorders and depressive disorders in families (Leckman et al. 1983), and the modeling of the association between depression and alcoholism in families (Merikangas et al. 1…
The impact of the endogenous subtype on the familial aggregation of unipolar depression.
The endogenous/non-endogenous distinction of unipolar major depression is widely accepted, as is the family study approach to the validation of diagnostic distinctions. Rates of affective disorders were examined in 689 first-degree relatives of 184 patients with unipolar major depression and were compared with 312 first-degree relatives of 80 healthy controls. Only unipolar depression and alcoholism were more common in families of depressed probands compared with families of healthy controls. As a variety of diagnostic definitions of endogenous depression have been proposed, probands and relatives were diagnosed in a polydiagnostic manner. None of the five diagnostic definitions of endogeno…
Gegenwärtiger Stand der Kopplungsuntersuchungen bei Schizophrenie
Fur schizophrene Erkrankungen besteht ein deutlich erhohtes genetisches Risiko, belegt durch Familien-, Zwillings- und Adoptionsstudien [1]. Die Konkordanzrate bei eineiigen Zwillingen betragt etwa 50%, ein im Vergleich zu zweieiigen Zwillingen etwa 3fach erhohtes Erkrankungsrisiko [1]. Ein einfacher Mendelscher Erbgang mit einem einzigen verantwortlichen Genort ist jedoch nicht nachweisbar. Schizophrene Erkrankungen gehoren wie zum Beispiel auch Diabetes, Bluthochdruck, Krebserkrankungen, zu den komplexen genetischen Erkrankungen mit polygener, bzw. multifaktorieller Vererbung.
Untersuchungen zur Kopplung zwischen Schizophrenie und der pseudoautosomalen Region
Fur die Suche nach Genorten fur genetisch determinierte Erkrankungen mit Hilfe von Kopplungsanalysen werden zwei Strategien angewandt: 1. das systematische Absuchen des Genoms auf Kopplung von Genort mit Marker mit Hilfe von DNA-Markern (RFLP, Short Tandem Repeats) in regelmasigen Abstanden, 2. die Verwendung von DNA-Markern zur Kopplungsanalyse in Kandidatengenregionen, fur die ein Zusammenhang mit der Erkrankung angenommen wird, bei psychiatrischen Erkrankungen, z. B. Genorte fur Enzyme, Rezeptoren, Transporter fur Neurotransmitter.
Potential linkage for schizophrenia on chromosome 22q12-q13: a replication study.
In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al. [1994: Am J Med Genet 54:36–43], we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Zmax = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a non-parametric method, sib pair analysis, a P value of 0.068 correspon…
Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis
The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6…
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in …
Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study.
Background: It is widely acknowledged that the genetic diatheses for schizophrenia and affective disorders are independent. However, there are increasing doubts about this classic view, and empirical evidence for a dichotomy of these two prototypes of functional psychoses is limited. A controlled family study of consecutive admissions was conducted to determine whether familial risks for schizophrenic (SCZ) and affective disorders were independent or overlapping. Methods: Index probands met Research Diagnostic Criteria for SCZ (n=146), schizoaffective (SA [n=115]), bipolar (BP [n=80]), or unipolar major depressive (UP [n=184])disorder. Comparison probands met Research Diagnostic Criteria fo…
Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an an…