Splitting schizophrenia: periodic catatonia-susceptibility locus on chromosome 15q15

Am J Hum Genet. 2000 Nov;67(5):1201-7. doi: 10.1016/S0002-9297(07)62950-4. Epub 2000 Sep 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catatonia / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15 / genetics*
  • Chromosomes, Human, Pair 22 / genetics
  • Computer Simulation
  • Female
  • Genes, Dominant / genetics
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Linkage Disequilibrium
  • Lod Score
  • Male
  • Microsatellite Repeats / genetics
  • Models, Genetic
  • Pedigree
  • Periodicity*
  • Schizophrenia / genetics*
  • Statistics, Nonparametric