Thinking within the spectrum: schizophrenic thought disorder in six Danish pedigrees.

Formal thought disorder (FTD), a major symptom of schizophrenia, is known to aggregate in families. Our aim was to examine the specificity of FTD in the schizophrenia spectrum disorders and the hypothesized linear aggregation of FTD within pedigrees. Six individuals with a diagnosis of schizophrenia were identified in the Copenhagen High-Risk study and each pedigree was centered on one of the six original schizophrenic probands' nuclear families. The 329 pedigree members in the study were considered at risk for schizophrenia spectrum disorders because most were genetically related to the originating schizophrenic probands. The participants were administered the Copenhagen Interview of Functional Illness to determine diagnoses and the Thought Disorder Index (TDI) was used to assess FTD. Individuals with a schizophrenia diagnosis had higher global levels of FTD, exhibited more severe types of FTD, and had a qualitatively different type of FTD than did participants with other diagnoses or no mental illness. Individuals with Cluster A diagnoses exhibited more FTD and FTD similar in quality to participants with schizophrenia. These results support the construct of a spectrum of schizophrenia conditions. There was a generally high level of FTD in the pedigrees, in part due to assortative mating in this sample. However, there was no apparent pattern of linear aggregation of FTD within the families.

Linkage of eye movement dysfunction to chromosome 6p in schizophrenia: additional evidence.

Establishing the genetics of physiological traits associated with schizophrenia may be an important first step in building a neurobiological bridge between the disease phenotype and its genetic underpinnings. One of the best known of the traits associated with schizophrenia is a disorder of smooth pursuit eye tracking (ETD), which is present in 50-80% of schizophrenia patients. ETD is more than three times more prevalent in the families of a schizophrenia patient than is schizophrenia itself. Arolt et al. [1999] estimated LOD scores for ETD of 2.85 for D6S282 and 3.70 for D6S271, two markers on 6p21.1, as well as obtaining an indication of possible linkage for schizophrenia. Our sample comprised two large families in Denmark. Markers in the region that was implicated by the study of Arolt et al. [1996, 1999] were analyzed as part of a genome scan using the "latent trait (L.T.) model" for the co-transmission of schizophrenia and ETD that we had previously fitted to segregation analysis data from Norway. We obtained a LOD score of 2.05 for D6S1017, a marker within 3 cM of the positive markers obtained by Arolt et al. [1996, 1999]. We regard our results as independent evidence supporting the findings of Arolt et al. [1996, 1999] and also as support for the L.T. model as a way of combining the traits ETD and schizophrenia.