Early Life Developmental Deviances and Prediction of Psychosis in 22q11.2 Syndrome

Background: The chromosomal region 22q11.2 is particularly vulnerable to aberrant rearrangements, generating deletions or duplications, and producing a set of developmental anomalies. The 22q11 deletion syndrome (22q11.2DS) occurs at a frequency of around 1 in every 2,000-4,000 live births, making it the most common known interstitial deletion in humans.

This syndrome is one of the most common genetic causes of neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) or autism spectrum disorders (ASD). It has also become one of the better known risk factors for developing psychotic symptoms. It has been estimated that the risk of developing schizophrenia for an individual with 22q11DS approaches 20 times the risk in the general population.

Objectives: The objective of this analysis was to evaluate the predictive value of the presence of developmental alterations in early childhood (retrospective assessment at age 4) on the risk of psychosis in late childhood and adolescence (current assessment).

Methods: 55 individuals with 22q11.2DS were recruited consecutively from the outpatient unit "Genetics and Mental Health Program" in the Child and Adolescent Psychiatry Service of the University Hospital Gregorio Marañón, Madrid.

We collected data on sociodemographic characteristics, retrospective neurodevelopment and social functioning in early childhood (by means of the social communication questionnaire, SCQ), and current psychotic symptoms and diagnosis (by means of diagnostic interviews, K-SADS or SCID, according to the age of participants, and the clinical scales PANSS and SIPS).

The objective of this analysis was to evaluate the predictive value of the presence of developmental alterations in early childhood (retrospective assessment at age 4) on the risk of psychosis in late childhood and adolescence (current assessment).

Results: The presence of aberrant neurodevelopmental processes in early childhood, measured by the SCQ, was associated with an increased risk of psychosis in late childhood and adolescence, Odds Ratio=1.16, Cohen’s D=1.08, p<0.001.

Conclusions: To the best of our knowledge, this is the first report describing an excess risk of psychosis in a sample of patients with 22q11.2DS with abnormal neurodevelopmental indicators during early childhood. These data support the importance of the so-called "personalized medicine" to develop strategies to get early detection and early intervention in specific populations such as subjects with 22q11.2DS.