A longitudinal examination of the psychoeducational, neurocognitive, and psychiatric functioning in children with 22q11.2 deletion syndrome
Highlights
► Children with 22q11DS and controls underwent two neurocognitive and psychiatric evaluations 3.5 years apart. ► Significant cognitive deficits and higher incidence of psychiatric manifestations seen in 22q11DS children relative to controls at both T1 and T2. ► Slowed growth in attention, increased psychiatric symptoms and prodromal signs, and decreased GAF over time noted in 22q11DS children. ► T1 predictors of psychopathology at T2 included full-scale IQ and social-behavioral problems.
Introduction
Chromosome 22q11.2 Deletion Syndrome (22q11DS), also known as Velocardiofacial syndrome (VCFS) or DiGeorge Syndrome, is the most common microdeletion syndrome in humans with an incidence of 1:2000 to 1:4000 (Devriendt et al., 1998, Shprintzen, 2000b, Shprintzen, 2008, Wilson et al., 1994). In addition to multiple medical problems, individuals with 22q11DS experience a wide range of neurocognitive impairments and a high rate of major psychiatric disorders (Robin and Shprintzen, 2005, Shprintzen, 2000a).
Intellectual functioning in children with 22q11DS varies from the borderline to mild intellectual disability range, along with deficits in sustained attention, executive function, and visual spatial functioning, with some reported similarities to a non-verbal learning disability (De Smedt et al., 2007, Jacobson et al., 2010, Lewandowski et al., 2007, Moss et al., 1999, Schoch et al., 2012, Swillen et al., 1997, Woodin et al., 2001). Common psychiatric disorders in childhood include Attention-Deficit/Hyperactivity Disorder (ADHD) and anxiety disorders such as Specific Phobias and Obsessive-Compulsive Disorder (OCD; Antshel et al., 2007). In particular, children with 22q11DS evidence a poor repertoire of social skills and high rates of internalizing symptoms (Kiley-Brabeck and Sobin, 2006, Shashi et al., 2011). In a prior study, we found that about 60% of children with 22q11DS met criteria for at least one psychiatric diagnosis, with the most frequent diagnoses including ADHD and various anxiety disorders (Lewandowski et al., 2007, Young et al., 2011). In later adolescence or early adulthood, upwards of 25% develop major psychiatric illnesses such as Schizophrenia, Bipolar illness, and Major Depression (Baker and Skuse, 2005, Murphy et al., 1999, Papolos et al., 1996, Pulver et al., 1994, Usiskin et al., 1999).
In one of the first longitudinal studies of individuals with 22q11DS, Gothelf et al. (2005) reported significant declines in verbal IQ and expressive language scores across two time points separated by approximately five years. Similar findings were identified in subsequent longitudinal examinations by Gothelf and colleagues with an association between changes in various cortical structures, verbal deterioration, and the appearance of severe psychopathology being highlighted (Gothelf et al., 2007, Green et al., 2009). Abnormal developmental trajectories of cortical thickness, with cortical loss during adolescence, has been documented both cross-sectionally and longitudinally, which may affect neurocognitive and psychiatric functioning over time (Schaer et al., 2009). Most recently, Kates and colleagues documented a relationship between changes in brain structure and the emergence of prodromal schizophrenia symptoms at two time points over a three year time period (Kates et al., 2011a, Kates et al., 2011b). Although the developmental trajectories of most brain structures were similar to their matched controls, volumetric decreases in temporal lobe gray matter and verbal IQ were especially related to positive prodromal psychotic symptoms in their preadolescent sample of children with 22q11DS. Green et al. (2009) noted the need for ongoing prospective longitudinal studies to continue to examine the nature of these changes. Since most of the above studies included children with 22q11DS that were older or included both children and adults and/or examined change over time mainly as related to schizophrenia symptoms, little is known about the longitudinal changes in neurocognition and other psychiatric diagnoses in early adolescence.
The primary purpose of the current study was to examine the longitudinal psychoeducational, neurocognitive, and psychiatric functioning of a well characterized group of children and young adolescents with 22q11DS. We had previously reported children with 22q11DS as having an IQ in the borderline range, with deficits in executive function, attention and verbal memory (Lewandowski et al., 2007, Shashi et al., 2009). Our first research objective in this study was to provide a more comprehensive description of the psychoeducational, neurocognitive and psychiatric findings of our sample at T1, and also provide the newest findings of our sample's performance 3.5 years later (T2). A second research question examined change over time for the 22q11DS group in comparison to age and gender matched healthy controls across the psychoeducational, neurocognitive, and psychiatric domains. Finally, a third research question examined specific T1 variables as potential predictors of the emergence of targeted psychopathology at T2, approximately 3.5 years post study entry.
Section snippets
Participants
Forty-two children with 22q11DS, ages 7.0–15.67 years (M = 10.05, SD = 2.49), were recruited either at Duke University Medical Center (DUMC) or Wake Forest Baptist Medical Center. All subjects with 22q11DS had a molecularly confirmed deletion of the 22q11.2 region. Twenty-nine healthy control participants were recruited by advertisement in local pediatric practices, schools, and the research study website at DUMC. Control participants ranged in age from 7.92 to 14.33 years (M = 10.13, SD = 1.74) and
Initial evaluation at time 1 (T1)
Data were collected from 71 participants at T1, of which 42 were diagnosed with 22q11DS and 29 were healthy controls. Initial neuropsychological results on a subset of these individuals have been previously reported elsewhere (Lewandowski et al., 2007). All 71 participants are part of a cohort of over 160 children with 22q11DS and control subjects who are part of a longitudinal study to ascertain the trajectory of neuropsychology in children with 22q11DS. In the current study, we report on T1
Discussion
The primary objective of this study was to examine the longitudinal psychoeducational, neurocognitive and psychiatric outcomes in children and adolescents with 22q11DS at T1 and T2, with a specific focus on change over time. In addition, we were interested in capturing predictors of emergent psychopathology within our 22q11DS sample. This study is one of the largest, and the first to present a comprehensive longitudinal multifaceted assessment of cognition, behavior, and psychiatric findings
Acknowledgements
This research was supported by funding from the National Institute of Mental Health (grant number R01MH78015-04) awarded to Vandana Shashi, M.D.
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