Anticipation in schizophrenia: Biology or bias?

Abstract

Anticipation is a genetic phenomenon wherein age of disease onset decreases and/ or severity increases in successive generations. Anticipation has been demonstrated for several neuropsychiatric disorders with expanding trinucleotide repeats recently identified as the underlying molecular mechanism. We report here the results of an analysis of anticipation performed with multiplex families segregating schizophre-nia. Thirty-three families were identified through the NIMH Genetics Initiative that met the following criteria: had at least two affected members in successive generations and were not bilineal. Affectation diagnoses included schizophrenia, schizoaffective disorder depressed , and psychosis NOS. Additional analyses included the Cluster A personality disorders. Three indices of age of onset were used. Disease severity was measured by several different indices. Four sampling schemes as suggested by McInnis et al. were tested, as well as additional analysis using pairs ascertained through the parental generation. Anticipation was demonstrated for age of onset, regardless of the index or sampling scheme used (P<0.05). Anticipation was not supported for disease severity. Analyses that took into account drug use and diminished fecundity did not affect the results. While the data strongly support intergenerational differences in disease onset consistent with anticipation, they must be viewed cautiously given unavoidable biases attending these analyses.

Study of anticipation in Chinese families with schizophrenia

“…In our sample of 38 Chinese schizophrenic families, preliminary analysis showed that the mean AAO in the offspring generation was significantly lower than that in the parental generation ( P < 0.001). This finding is in agreement with those of previous studies 5–13 . There was a medium difference in AAO of 11 years in previous reports, 15 and in the present study the difference is 8.8 years.…”

“…In families with schizophrenia, reduced penetrance and variable expansion are commonly found. Recent studies demonstrate that the clinical phenomenon of anticipation is present in the inheritance of schizophrenic disorders 5–13 . These findings may implicate genes with expanding trinucleotide repeat sequences in the genetic etiology of schizophrenia.…”

“…These findings may implicate genes with expanding trinucleotide repeat sequences in the genetic etiology of schizophrenia. Previous studies of anticipation in schizophrenia were done in the West and in Japan 5–13 . Therefore, we investigated anticipation in Chinese schizophrenic families.…”

Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?

“…[9][10][11][12] Additionally, intergenerational lengthening of the hSKCa3 CAG repeat may contribute to the phenomenon of 'anticipation' (increase in severity and decrease in age of onset in successive generations) that has been described for these disorders. 27 In order to help clarify the complex genetic basis of these neuropsychiatric diseases, we have embarked on case-control studies as a first test of the candidate role for hSKCa3. We have used two Caucasian populations which have previously been used in published studies.…”

Anticipation in Japanese families with schizophrenia

“…Several researchers who have minimized ascertainment biases and overcome methodological problems such as cohort effect and bilineality, have demonstrated a decrease in AO and an increase in severity in lower generations of schizophrenia patients, (Bassett and Honer 1994;Stöber et al 1995;Thibaut et al 1995;Gorwood et al 1996;Johnson et al 1997). On the other hand, doubts have been cast on data which showed anticipation in schizophrenia (Asherson et al 1994;Yaw et al 1996) and other familial disorders (Heiman et al 1996;Fraser 1997).…”