The pathogenesis of schizophrenia is hypothesized to involve abnormal neurodevelopment (1
). A subtype of schizophrenia has been identified that has a relatively homogeneous genetic etiology associated with a microdeletion on chromosome 22q11.2 (3
). The genetic syndrome associated with this deletion, 22q11 deletion syndrome (22qDS), has a variable physical and neurobehavioral phenotype that includes schizophrenia (3
). High rates of congenital dysmorphic features (5
), developmental structural brain abnormalities (7
), and cognitive dysfunction (8
) in 22qDS are consistent with this subtype of schizophrenia, representing an especially neurodevelopmental form of the illness (2
). The genetic risk for schizophrenia is related to the deletion, which usually occurs as a spontaneous (de novo) mutation and in the absence of a family history of psychotic illness (9
). Individuals with 22qDS represent a particularly high-risk group (9
): 25% or more are estimated to develop schizophrenia (4
). The only groups at higher risk are individuals with two parents with schizophrenia or monozygotic co-twins of individuals with schizophrenia. A 22qDS subtype of schizophrenia may be present in up to one in 50 patients with schizophrenia (11
). Higher rates of 22qDS may be present in subsets of schizophrenia with childhood onset or dual diagnosis schizophrenia and mental retardation (9
). Individuals with 22qDS would therefore represent a relatively prevalent (≥1/4000 of the general population ) and identifiable (3
) high-risk group for schizophrenia, well suited for studies of predictive features.
For a 22qDS subtype of schizophrenia to be accepted as a useful model for schizophrenia in general, researchers must be assured that the schizophrenia phenotype is similar to that in other forms of schizophrenia. Clinicians may also wonder if there are specific features of the schizophrenia phenotype that could be used to help identify patients with a 22qDS subtype of the illness (22qDS-schizophrenia). For example, there is some evidence that impulsivity may be a component of the adult neurobehavioral phenotype of 22qDS (5
), but it is unclear if there are differences in core schizophrenic symptoms in 22qDS-schizophrenia. There are few studies detailing the clinical phenotype in adults with 22qDS-schizophrenia, however. Sample sizes have been small, particularly if one considers individuals without mental retardation (six or fewer subjects) (4
). Differences in ascertainment between these small samples and inclusion of subjects with mental retardation may explain why different studies have proposed age at onset to be younger (5
) and older (4
) in 22qDS-schizophrenia than in schizophrenia without 22qDS.
We investigated the largest group of subjects with 22qDS-schizophrenia yet reported to our knowledge (N= 24). Our goal was to determine the similarities and differences of the schizophrenia phenotype from other, more typical groups of patients with schizophrenia. We studied a subgroup of individuals with 22qDS-schizophrenia who did not have mental retardation to eliminate potential confounders due to mental retardation and make our study group more comparable to subjects with schizophrenia usually studied. We hypothesized that age at onset and core signs and symptoms of 22qDS-schizophrenia would be similar to those of patients with schizophrenia without 22qDS. We further hypothesized that the 22qDS-schizophrenia group would have greater severity of the excitement symptom grouping, which includes an item on impulse control.