Prodromal positive psychotic symptoms and anxiety are two strong risk factors for schizophrenia in 22q11.2 deletion syndrome (22q11DS). The analysis of large-scale brain network dynamics during rest is promising to investigate aberrant brain function and identify potentially more reliable biomarkers. We retrieved and examined dynamics of large-scale functional brain networks using innovation-driven co-activation

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Low hippocampal volume is a consistent finding in schizophrenia and across the psychosis spectrum. However, there is a lack of studies investigating longitudinal hippocampal development and its relationship with psychotic symptoms. The 22q11.2 deletion syndrome (22q11DS) has proven to be a remarkable model for the prospective study of individuals at high risk of schizophrenia to unravel the pathophysiological processes predating the onset of psychosis. Repeated cerebral MRIs were acquired from 140 patients with 22q11DS (53 experiencing moderate-to-severe psychotic symptoms) and 135 healthy controls aged from 6 to 35 years and with up to 5 time points per participant. Hippocampal subfield analysis was conducted using FreeSurfer-v.6 and FIRST-FSL. Then, whole hippocampal and subfield volumes were compared across the groups. Relative to controls, patients with 22q11DS showed a remarkably lower volume of all subfields except for CA2/3. No divergent trajectories in hippocampal development were found. When comparing patients with 22q11DS exhibiting psychotic symptoms to those without psychosis, we detected a volume decrease during late adolescence, starting in CA1 and spreading to other subfields. Our findings suggested that hippocampal volume is consistently smaller in patients with 22q11DS. Moreover, we have demonstrated that patients with 22q11DS and psychotic symptoms undergo a further decrease in volume during adolescence, a vulnerable period for the emergence of psychosis. Interestingly, CA2/3, despite being affected in patients with psychotic symptoms, was the only area not reduced in patients with 22q11DS relative to controls, thus suggesting that its atrophy exclusively correlates with the presence of positive psychotic symptoms. 25 32 hippocampal volume has been found in patients across the 33 psychosis spectrum [3, 10, 11], comprising first-episode 34 psychosis patients (FEP) [12, 13] and subjects at high/ 35 ultrahigh (UHR) risk for psychosis [14, 15]. However, a 36 meta-analysis has recently shown that there was no evi-37 dence for a significant reduction in the whole hippocampal Q3 38 volume in patients at clinical high risk for psychosis [16], 39 suggesting that only subtler changes might be detectable 40 early in disease progression. Indeed, a dose-response rela-41 tionship depending on the stage of the disease has been 42 found in individuals at UHR for psychosis [10].