Table 2.
Summary of studies to date that use a longitudinal framework to examine relationships between neuroimaging metrics and psychotic symptoms in 22q11DS. The majority of studies also studied a control sample; however, this table presents comparisons within the 22q11.2 Microdeletion Syndrome (22q11DS) sample because this review focuses on psychosis risk within this group. N=Number; T1=time point 1; T2=time point 2; T3=time point 3; T4=time point 4; 22q11DS-psychosis+=22q11DS individuals with a psychotic disorder diagnosis; 22q11DS-psychosis-=22q11DS individuals who do not have a psychotic disorder diagnosis; 22q11DS-psychosis-spectrum+=22q11DS individuals that had subthreshold and/or psychotic level positive symptoms; 22q11DS-psychosis-spectrum-=22q11DS individuals who did not have clinically significant positive symptoms; CSF=cerebrospinal fluid; ROI=region of interest; SIPS=Structured Interview for Prodromal Syndromes; *Berhanu et. al. 2016 was a study of 22q11DS participants who had four time points but T1 and T4 were the focus of the study.
| Author and year | Total N 22q11DS | Neuroimaging predictors examined | Analysis conducted | Results | |
|---|---|---|---|---|---|
| N 22q11DS-psychosis+ at T1 | N 22q11DS-psychosis+ at final follow-up | ||||
| Age Information (e.g., range, mean ± SD) | |||||
| Number of time points Approximate length of time between each time point | |||||
| Gothelf et al. 2007 (16) | Total N 22q11DS=19 | Semi-automated segmentation: cortical lobes (frontal, parietal, temporal, occipital), cerebellum, ventricular CSF (143) Manually delineated ROIs: caudate, amygdala, hippocampus, superior temporal gyrus (144–146) | Analysis: Repeated measures analysis of variance Between-subjects factor: Group; Within-subjects factor: brain volumes at T1 and T2 | No significant differences in developmental trajectories between 22q11DS-psychosis+ vs. 22q11DS-psychosis- | |
| N 22q11DS-psychosis+ at T1=0 | N 22q11DS-psychosis+ at T2=7 | ||||
| Age range: 5–20 years Mean age (±SD) 12.3±4.0 years | |||||
| 2 time points Mean 4.9 (± 0.7) years between time points | |||||
| Kates et al., 2011 (52) | Total N 22q11DS=72 | Semi-automated segmentation (147–150) Manually delineated ROIs: frontal lobe subregions, amygdala, hippocampus, superior temporal gyrus, cerebellum, ventricles (145,146,151–155) | Analysis: Poisson zero-inflated regression Predictors: ((T2 volume-T1 volume) * 100) / (T1 volume * interval between scans in years) for each segmentation or ROI Outcome: Total SIPS positive symptom score at T2 | Greater decreases in superior temporal gyrus volume (T1-T2) predicted higher positive symptom scores at T2 | |
| N 22q11DS-psychosis+ at T1=0 | N 22q11DS-psychosis+ at T2=0 | ||||
| Age range: 9–15; Mean age (±SD): 11.9 (±2.1) years | |||||
| 2 time points ~3 years between time points | |||||
| Kunwar et al., 2012 (156) | Total N 22q11DS=58 | Gyrification index of frontal, temporal, parietal, and occipital lobar ROIs | Analysis: Poisson zero-inflated regression Predictors: T2 gyrification index-T1 gyrification index for each ROI Outcome: Total SIPS positive symptom score at T2 | Greater decreases in occipital gyrification index (T2-T1) predicted higher positive symptom scores at T2 | |
| N 22q11DS-psychosis+ at T1=0 | N 22q11DS-psychosis+ at T2=0 | ||||
| Age range: 9–15 years Mean age: 14.9±2.5 years | |||||
| 2 time points ~3 years between time points | |||||
| Berhanu et al., 2016 (157) | Total N 22q11DS=73 | Cortical volume-to-amygdala ratios for 68 ROIs from Desikan atlas (158) | Analysis: Poisson zero-inflated regression Predictors: Cortical volume-amygdala ratios at T1; Outcome: Total SIPS positive symptom score at T4 | Lower anterior cingulate to amygdala volume ratios at T1 predicted higher levels of positive symptoms at T4 Higher occipital to amygdala volume ratios and parietal to amygdala volume ratios at T1 baseline predicted higher positive symptom scores at T4 | |
| N 22q11DS-psychosis+ at T1=0 | N 22q11DS-psychosis+ at T4=Not reported. | ||||
| Age range: 9–15 years Mean age (±SD) 12.1 ± 2.2 years | |||||
| 2 time points* ~12 years between time points examined | |||||
| Ramanathan et al., 2017 (54) | Total N 22q11DS=72 | Cortical thickness and surface area for 5 lobes: frontal, parietal, temporal, occipital and cingulate. Followed up with examination of individual brain regions in any lobe that showed a differential trajectory in 22q11DS vs. controls. | Analysis: Mixed model regressions Model 1: Age*Group (22q11DS-psychosis-spectrum+ vs. 22q11DS-psychosis-spectrum-) Model 2: Age*Group (22q11Ds-psychosis+ vs. 22q11DS-UHR+ vs. 22q11DS-psychosis-spectrum) Model 3: Age*Total SIPS positive symptom score at T3 Outcomes: neuroimaging ROIs | Model 1: Accelerated decreases in superior frontal cortical thickness in 22q11DS-psychosis-spectrum+ vs. 22q11DS-psychosis-spectrum- Model 2: Accelerated decreases in frontal cortical thickness in 22q11DS-psychosis+ vs. others Model 3: steeper linear trajectories in occipital and parietal cortical thickness are associated with higher positive symptoms at T3 | |
| N 22q11DS-psychosis+ at T1=0 | N 22q11DS-psychosis+ at T3=6 | ||||
| Age range: 9–18 years Mean age: 11.8 years | |||||
| 2–3 time points ~3 years between each time point | |||||
| Mancini et al., 2019 (57) | Total N 22q11DS=107 | whole hippocampal volume; hippocampal subfields | Analysis: Mixed model regression Predictors: Age*Group (22q11DS-psychosis-spectrum+ vs. 22q11DS-psychosis-spectrum-) Outcomes: hippocampal ROIs | Group effect: reduced bilateral whole hippocampal volume, reduced bilateral subregions: CA2/CA3, CA4, dentate gyrus, Group x age effect: Steeper decrease in left whole hippocampus in 22q11DS-psychosis-spectrum+ Effect driven by sub-regions: CA2/CA3, CA4, and dentate gyrus | |
| N 22q11DS-psychosis+ at T1=not reported. | N 22q11DS-psychosis+ any time point=20 | ||||
| Age range: 6–35 years Mean age (±SD): 13.5 ± 6.4 years | |||||
| 1–5 time points Mean 3.8 (± 1.07) years between each time point | |||||
| Mancini et al., 2020 (58) | Total N 22q11DS=120 | whole thalamus volume, thalamic sub-regions | Analysis: Mixed model regression Predictors: Age*Group (22q11DS-hallucinations+ vs. 22q11DS-hallucinations-) Outcome: thalamic ROIs | Group effect: reduced bilateral medial geniculate nuclei in 22q11DS-hallucinations+ vs. 22q11DS-hallucinations- Group x age effect: Steeper decrease in medial geniculate nuclei 22q11DS- hallucinations+ | |
| N 22q11DS-psychosis+ at T1=not reported. | N 22q11DS-psychosis+ any time point=20 | ||||
| Age range: 8–35 years Mean age (±SD): 17.7 ± 6.0 years | |||||
| 1–4 time points ~3 years between each time point | |||||