Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: A longitudinal study

Abstract

The 22q11.2 deletion syndrome (22q11.2DS) is associated with very high rates of schizophrenialike psychosis and cognitive deficits. Here we report the results of the first longitudinal study assessing brain development in individuals with 22q11.2DS. Twenty-nine children with 22q11.2DS and 29 age and gender matched controls were first assessed during childhood or early adolescence; Nineteen subjects with 22q11.2DS and 18 controls underwent follow-up during late adolescenceearly adulthood. The 22q11.2DS subjects showed greater longitudinal increase in cranial and cerebellar white matter, superior temporal gyrus, and caudate nucleus volumes. They also had a more robust decrease in amygdala volume. Verbal IQ (VIQ) scores of the 22q11.2DS group that developed psychotic disorders declined significantly between assessments. Decline in VIQ in 22q11.2DS was associated with more robust reduction of left cortical grey matter volume. No volumetric differences were detected between psychotic and nonpsychotic subjects with 22q11.2DS. Brain maturation associated with verbal cognitive development in 22q11.2DS varies from that observed in healthy controls. Further longitudinal studies are likely to elucidate brain developmental trajectories in 22q11.2DS and their association to psychotic disorders and cognitive deficits in this population.

Increased corpus callosum volume in children with chromosome 22q11.2 deletion syndrome is associated with neurocognitive deficits and genetic polymorphisms

“…This could be due to a plateau in the compensatory drive or a decrease in myelination/fiber size with age. One longitudinal study reported an increase in cranial white matter in children with 22q11DS over time, 15 but there were no CC measurements in this study or others, 38 and thus the trajectory of CC development in 22q11DS remains unknown.…”

Schizophrenia and 22q11.2 deletion syndrome

“…As noted, no differences were observed in brain volumes between the 7 psychotic and 12 nonpsychotic patients with 22qDS studied prospectively with MRI scans and compared with normal controls [21]. There was also no evidence of the accelerated decrease in cortical gray matter volume commonly reported in other samples at high risk for schizophrenia.…”

“…There was also no evidence of the accelerated decrease in cortical gray matter volume commonly reported in other samples at high risk for schizophrenia. The decrease in volume (pruning) of the superior temporal gyrus gray matter usually seen in normal adolescent development was not observed in 22qDS, possibly due to delayed maturation [21]. The significance of the results from this cohort study is limited by the small sample size, possible ascertainment bias of patients referred for a psychiatric study, factors selected for investigation, and the young age of nonpsychotic patients at follow-up.…”

“…Structural brain abnormalities in 22qDS-schizophrenia appear to be similar to those found in general population samples of schizophrenia, although only two studies to date have compared small samples of individuals with 22qDS with and without schizophrenia [20,21]. Findings include smaller overall brain volume [20], midline defects such as cavum septum pellucidum [22], and white matter hyper-intensities on MRI [20,22].…”

“…As in general schizophrenia populations, some evidence suggests that increased ventricular and sulcal cerebrospinal fluid and decreased temporal gray matter volumes are associated with schizophrenia in 22qDS [20,23]. A young sample showed no differences in brain volumes between 7 psychotic and 12 nonpsychotic patients with 22qDS; however, the latter (mean age 18 years) remain at risk for developing schizophrenia [21]. Qualitative MRI findings for 68 adults with 22qDS revealed evidence of neuronal migration abnormalities in 2 (8%) of 26 patients with schizophrenia-polymicrogyria in one and right cerebellar disorganization in the other-whereas none was found in 42 nonpsychotic individuals [24].…”