Developmental changes in multivariate neuroanatomical patterns that predict risk for psychosis in 22q11.2 deletion syndrome

Abstract

The primary objective of the current prospective study was to examine developmental patterns of voxel-by-voxel gray and white matter volumes (GMV, WMV, respectively) that would predict psychosis in adolescents with 22q11.2 deletion syndrome (22q11.2DS), the most common known genetic risk factor for schizophrenia. We performed a longitudinal voxel-based morphometry analysis using structural T1 MRI scans from 19 individuals with 22q11.2DS and 18 typically developing individuals. In 22q11.2DS, univariate analysis showed that greater reduction in left dorsal prefrontal cortical (dPFC) GMV over time predicted greater psychotic symptoms at Time2. This dPFC region also showed significantly reduced volumes in 22q11.2DS compared to typically developing individuals at Time1 and 2, greater reduction over time in 22q11.2DS COMTMet compared to COMTVal, and greater reduction in those with greater decline in verbal IQ over time. Leave- one-out multivariate pattern analysis (MVPA) on the other hand, showed that patterns of GM and WM morphometric changes over time in regions including but not limited to the dPFC predicted risk for psychotic symptoms (94.7-100% accuracy) significantly better than using univariate analysis (63.1%). Additional predictive brain regions included medial PFC and dorsal cingulum. This longitudinal prospective study shows novel evidence of morphometric spatial patterns predicting the development of psychotic symptoms in 22q11.2DS, and further elucidates the abnormal maturational processes in 22q11.2DS. The use of neuroimaging using MVPA may hold promise to predict outcome in a variety of neuropsychiatric disorders.

The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety

“…Another recent report on brain morphology in adolescents with 22q11.2DS described increased grey matter volume in the hippocampal complex, which did not predict any outcome variables. 31 Rather, declining grey matter volume in the prefrontal cortex, which is another vulnerable cortical region in 22q11.2DS, predicted increased psychosis risk. 66 Generally, our findings are consistent with those of structural brain image analyses in individuals with 22q11.2DS.…”

“…To date, multiple groups have identified predictive neuroanatomical markers of schizophrenia-related symptomology in individuals with 22q11.2DS, such as reduced hippocampal volume [27][28][29] and declining prefrontal grey matter. 30,31 Thus, the characterization of hippocampal morphology associated with elevated risk of schizophrenia development calls for more in-depth investigation.…”

Identifying 22q11.2 Deletion Syndrome and Psychosis Using Resting-State Connectivity Patterns

“…However, only longitudinal studies will determine if such dysconnectivity can predict clinical outcome in patients. Good prediction rates have been obtained for instance with structural neuroimaging in patients with a prodromal syndrome (Mourao-Miranda et al 2012;Koutsouleris et al 2009Koutsouleris et al , 2010Borgwardt et al 2013) and in 22q11DS (Gothelf et al 2011). However, evidence is still lacking for other neuroimaging features.…”

Resting-state networks in adolescents with 22q11.2 deletion syndrome: Associations with prodromal symptoms and executive functions

“…Cognitive delay, as well as increased prevalence of attention deficits, mood and anxiety disorders, is characteristic of this population (De Smedt et al, 2007a;Green et al, 2009). Concern relating to psychological health in these adolescents is matched by the neuroscientists' efforts to identify the neural markers associated with early schizotypal trait expression in 22q11DS (Schaer et al, 2009a;Gothelf et al, 2011). Indeed, in this deletion syndrome where 25-30% are thought to evolve into formal schizophrenia spectrum disorders by adulthood (Murphy et al, 1999), neurodevelopment during adolescence may provide key insights to understanding the unfolding of psychotic symptoms.…”