Early development in schizophrenia: Relationship with trinucleotide repeats

In recent years, trinucleotide repeat expansion has been suggested as an explanation for the unusual features of schizophrenia genetics. Three studies have confirmed the association between schizophrenia and excess of trinucleotide repeats, but negative results have also been reported. This inconsistency might be due to aetiological heterogeneity and different sampling methods. Furthermore, the relationship between the number of CAG repeats and the clinical picture is equivocal. Cardno et al. found no significant relationship between the length of the trinucleotide repeats and clinical features. They conclude that the current clinical subtypes may not be genetically valid. Schizophrenia is a lifelong condition and the clinical picture changes with time; therefore, examination of the longitudinal course might be more relevant. In the present study, we investigated the relationship between the number of (CAG)_n repeats and early developmental factors. Twenty-two unrelated patients (12 male and 10 female) with a DSM-IV diagnosis of schizophrenia and a living relative have participated in our study so far. The age range of patients was from 24 to 45 years. Early development was assessed by a structured interview with the mother. Trinucleotide repeats were measured by the RED method. In this relatively young sample, about 40% of the patients had larger than (CAG)₆₀ repeats. We found a small but significant difference in the speech and motor development between patients with normal and large CAG repeats. Although the results should be regarded as preliminary, they suggest that the developmental model may be useful for research into the genetics of schizophrenia.