Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study

Ehud Mekori-Domachevsky, Yael Guri, James Yi, Omri Weisman, Monica E. Calkins, Sunny X. Tang, Raz Gross, Donna M. McDonald-McGinn, Beverly S. Emanuel, Elaine H. Zackai, Gil Zalsman, Abraham Weizman, Ruben C. Gur, Raquel E. Gur, Doron Gothelf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


About one third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop schizophrenia. Notably, a full-blown psychotic disorder is usually preceded by subthreshold symptoms. Therefore, it is important to identify early signs of psychosis in this population, a task that is complicated by the intellectual disabilities typically seen in 22q11.2DS. We aimed to identify subthreshold psychotic symptoms that distinguish 22q11.2DS from other neurodevelopmental disorders. The study included two independent cohorts from Tel Aviv and Philadelphia. 22q11.2DS (N = 171) and typically developing (TD; N = 832) individuals were enrolled at both sites and further compared to two groups with intellectual disabilities: Williams syndrome (WS; N = 21) in the Tel Aviv cohort and idiopathic developmental disabilities (IDD; N = 129) in the Philadelphia cohort. Participants and their primary caregivers were interviewed with the Structured Interview for Prodromal Symptoms (SIPS) and psychopathologies were assessed using standardized tools; general cognitive abilities were assessed with the Computerized Neurocognitive Battery. Negative/disorganized subthreshold syndrome was significantly more common in the 22q11.2DS group than in the WS (OR = 3.90, 95% CI = 1.34–11.34) or IDD (OR = 5.05, 95% CI = 3.01–10.08) groups. The 22q11.2DS group had higher scores than the two intellectual disabilities groups on several SIPS negative items, including avolition and decreased expression of emotion. Overall, there were few significant correlations between level of cognitive deficits and severity of negative symptoms in 22q11.2DS and only in the Tel Aviv cohort. Our findings suggest that 22q11.2DS individuals at the age of risk for developing psychosis should be closely monitored for negative symptoms.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalSchizophrenia Research
StatePublished - Oct 2017


FundersFunder number
Dowshen Program for Neuroscience
National Institutes of HealthRC2 MH089983
Foundation for the National Institutes of Health
National Institute of Mental HealthU01MH101722, RC2MH089924, K08MH079364
United States-Israel Binational Science Foundation2011378


    • Computerized Neurocognitive Battery (CNB)
    • Negative symptoms
    • Structured Interview for Prodromal Symptoms (SIPS)
    • Velocardiofacial syndrome
    • Williams syndrome


    Dive into the research topics of 'Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study'. Together they form a unique fingerprint.

    Cite this