Splitting schizophrenia: periodic catatonia-susceptibility locus on chromosome 15q15.
The nature of subtypes in schizophrenia and the meaning of heterogeneity in schizophrenia have been considered a principal controversy in psychiatric research. We addressed these issues in periodic catatonia, a clinical entity derived from Leonhard's classification of schizophrenias, in a genomewide linkage scan. Periodic catatonia is characterized by qualitative psychomotor disturbances during acute psychotic outbursts and by long-term outcome. On the basis of our previous findings of a lifetime morbidity risk of 26.9% of periodic catatonia in first-degree relatives, we conducted a genome scan in 12 multiplex pedigrees with 135 individuals, using 356 markers with an average spacing of 11 cM. In nonparametric multipoint linkage analyses (by GENEHUNTER-PLUS), significant evidence for linkage was obtained on chromosome 15q15 (P = 2.6 x 10(-5); nonparametric LOD score [LOD*] 3.57). A further locus on chromosome 22q13 with suggestive evidence for linkage (P = 1.8 x 10(-3); LOD* 1.85) was detected, which indicated genetic heterogeneity. Parametric linkage analysis under an autosomal dominant model (affecteds-only analysis) provided independent confirmation of nonparametric linkage results, with maximum LOD scores 2.75 (recombination fraction [theta].04; two-point analysis) and 2.89 (theta =.029; four-point analysis), at the chromosome 15q candidate region. Splitting the complex group of schizophrenias on the basis of clinical observation and genetic analysis, we identified periodic catatonia as a valid nosological entity. Our findings provide evidence that periodic catatonia is associated with a major disease locus, which maps to chromosome 15q15.
Stöber
G
G
1Department of Psychiatry and Psychotherapy, University of Würzburg, 97080 Würzburg, Germany. nerk105@rzkli.uni-wuerzburg.de
Saar
K
K
Rüschendorf
F
F
Meyer
J
J
Nürnberg
G
G
Jatzke
S
S
Franzek
E
E
Reis
A
A
Lesch
K P
KP
Wienker
T F
TF
Beckmann
H
H
D002389:Catatonia / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003198:Computer Simulation; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D010375:Pedigree; D010507:Periodicity; D012559:Schizophrenia / Q000235:genetics*; D018709:Statistics, Nonparametric