Psychiatric Disorders in VCFS Throughout Development Doron Gothelf

Psychiatric Disorders in VCFS Throughout Development Doron Gothelf, Tamar Green, Bronwyn Glaser, Martin Debbane, Stephan Eliez Schneider Children’s Medical Center of Israel Tel Aviv University Department of Psychiatry, University of Geneva School of Medicine, Switzerland

Common Psychiatric Disorders in VCFS • • • schizophrenia ADHD Anxiety disorders Depressive disorders Autism spectrum disorders Antshel et al 2006; Feinstein et al 2002; Gothelf et al 2004; Murphy et al 1999; Vorstman et al 2006

High Variability in Reported Rates of Psychiatric Disorders in VCFS • • • Schizophrenia Bipolar affective disorders Major depression Specific phobias ADHD Autism spectrum disorders 0% – 38% 0% - 52% 4% - 20% 4% - 61% 0% - 48% 14% - 45%

Possible Explanations for the Variability in the Reported Rates • Small sample size • Variability in samples’ age: – Children and adolescents – Adults – Mixed samples • Variability in psychiatric assessment tools • Cultural biases

Study Aim • To assess the rate of psychiatric disorders in VCFS from childhood to adulthood by pulling two large samples

Subjects Total n Age (years) Males : Females Tel Aviv Geneva 172 86 86 15. 9 ± 9. 1 15. 7 ± 9. 7 16. 0± 8. 5 (5 – 54) 90 : 82 53 : 33 37 : 49 P NS 0. 01

Assessment • Cognitive testing – Wechsler Intelligence test • Psychiatric assessment – SCID – K-SADS (Tel Aviv sample) – DICA-R (Geneva sample)

Differences in the Rate of Psychiatric Disorder between Samples Tel Aviv Geneva Any DSM Disorder OCD 81% 65% 24% 7% ADHD 43% 25% Dysthimia 16% 7%

Age Stratification • • Children Adolescents Young adults Adults 5 – 12 years 12 – 18 years 18 – 24 years above 24 years

Distribution of Psychiatric Disorders at Different Age Groups

Psychotic Disorders

Mood Disorders

Disruptive disorders

Anxiety Disorders

IQ Scores * * *

Correlation between Age and Cognitive Scores VIQ -0. 39 <0. 0001 PIQ -0. 27 0. 001 Information -0. 33 <0. 0001 Block design -0. 19 0. 02 Vocabulary -0. 27 0. 002 Object assembly -0. 17 0. 08 Arithmetics -0. 30 <0. 0001 -0. 21 0. 01 comprehension -0. 32 <0. 0001 Picture completion Digit coding -0. 27 0. 001 Similarities -0. 46 <0. 0001 Picture arrangement -0. 25 0. 004 Digit Span -0. 25 0. 009

Correlation Between Decrease in VIQ Scores and Severity of Psychotic Symptoms: Stanford Longitudinal Data Gothelf et al 2005

Parent of Origin and risk for Psychosis • 11 of 12 subjects with a psychotic disorder had a maternal origin of the deletion

Conclusions • The psychiatric phenotype of individuals with VCFS vary with age. • ADHD rates are high in childhood and are relatively low in adulthood. • There is a high stable rate of anxiety disorders (40%-50%) in all age groups. • Psychotic disorders are rare during childhood and adolescence and significantly increase above the age of 18 years. • There is a peak in the rate of depressive disorders (44%) between age 18 to 24 years.

Conclusions • Young adulthood (18 to 24 years) is especially vulnerable period for youngsters with VCFS due to: – Genetic factors (e. g. decreased dosage of COMT gene) – Difficulties in coping with the challenges of becoming independent adults (e. g. , leaving home, finding a vocation, intimate relations). • Psychiatric assessment and early intervention is recommended for: – ADHD and anxiety symptoms- childhood – Depression and psychosis- young adulthood

The Behavioral Neurogenetics Center § Ronnie Weinberger § Tamar Green, M. D. § Omer Zarchi § Liron Saporta § Merav Burg § Yael Inbar § Maayan Abraham § Lital Steingart, M. D. § Olga Goraly, M. D § Elena Michaelovsky, Ph. D § Miri Carmel , Ph. D § Amos Frisch , Ph. D § Prof. Abraham Weizman, M. D. § Grant Support March of Dimes NARSAD Young Investigator Award Israel Psychobiology Institute Stolz Foundation