Premorbid adjustment and schizophrenia in individuals with 22q11.2 deletion syndrome

The literature on idiopathic schizophrenia has consistently reported that poor premorbid functioning precedes onset of psychosis. Individuals with 22q11.2 deletion syndrome (22q11.2DS) are at heightened risk of developing schizophrenia. The present study examined the relationship between adult-onset schizophrenia and social and academic functioning across childhood and early adolescent development in 22q11.2DS.

Premorbid adjustment in social and academic domains during childhood (ages 5-11 years) and early adolescence (ages 12-15 years) of 103 adults with 22q11.2DS was assessed using the Premorbid Adjustment Scale (PAS). Linear mixed-models were used to compare PAS scores between the 43 subjects who later developed schizophrenia and the 60 subjects who did not.

Social functioning and academic functioning deteriorated from childhood to early adolescence among those who later developed schizophrenia compared to stable functioning, on average, in those who did not later develop a psychotic disorder. Those who developed schizophrenia had significantly higher PAS scores (indicating poorer functioning) in social (β=0.118, 95% CI: 0.046-0.189) and academic (β=0.072, 95% CI: 0.015-0.129) domains between childhood and early adolescence, independent of the presence of intellectual disability. The two groups had similar PAS scores during childhood.

Consistent with the literature on idiopathic schizophrenia, deterioration in social and academic functioning between childhood and early adolescence preceded onset of schizophrenia in this cohort of 22q11.2DS patients, regardless of functioning at baseline. These findings suggest that monitoring for changes in functioning, in addition to emergence of typical symptoms, may help to prevent delays in diagnosis and treatment of major psychotic illness in 22q11.2DS.