Long-term effects of early treatment with SSRIs on cognition and brain development in individuals with 22q11.2 deletion syndrome

Abstract

Cognitive deficits in individuals at risk of psychosis represent a significant challenge for research, as current strategies for symptomatic treatment are often ineffective. Recent studies showed that atypical cognitive development predicts the occurrence of psychotic symptoms. Additionally, abnormal brain development is known to predate clinical manifestations of psychosis. Therefore, critical developmental stages may be the best period for early interventions expected to prevent cognitive decline and protect brain maturation. However, it is challenging to identify and treat individuals at risk of psychosis in the general population before the onset of the first psychotic symptoms. 22q11.2 deletion syndrome (22q11DS), the neurogenetic disorder with the highest genetic risk for schizophrenia, provides the opportunity to prospectively study the development of subjects at risk for psychosis. In this retrospective cohort study, we aimed to establish if early treatment with SSRIs in children and adolescents with 22q11DS was associated with long-term effects on cognition and brain development. We included 98 participants with a confirmed diagnosis of 22q11DS followed up 2–4 times (age range: 10–32). Thirty subjects without psychiatric disorders never received psychotropic medications, thirty had psychotic symptoms but were not treated with SSRIs, and 38 received SSRIs treatment. An increase in IQ scores characterized the developmental trajectories of participants receiving treatment with SSRIs, even those with psychotic symptoms. The thickness of frontal regions and hippocampal volume were also relatively increased. The magnitude of the outcomes was inversely correlated to the age at the onset of the treatment. We provide preliminary evidence that early long-term treatment with SSRIs may attenuate the cognitive decline associated with psychosis in 22q11DS and developmental brain abnormalities.

Altered developmental trajectories of verbal learning skills in 22q11.2DS: associations with hippocampal development and psychosis

“…We analyzed the volume of the whole hippocampus and of the following seven hippocampal subfields: tail, subiculum, granulate cells of the molecular layer of the dentate gyrus (GC-ML-DG), molecular layer, CA1, CA2/3, and CA4 (Iglesias et al, 2015). Quality control procedures of the segmentation were performed as in Mancini et al (2019Mancini et al ( , 2021.…”

Effects of risperidone on psychotic symptoms and cognitive functions in 22q11.2 deletion syndrome: Results from a clinical trial

“…Another important limitation is that we could not control for the effect of concomitant psychotropic medication, taken by 5/13 participants (2/6 and 3/7 in the treated and placebo groups, respectively). As SSRIs and MPH significantly improve cognitive functions in 22q11DS (18,22), concurrent treatment likely had an effect on our findings. The presence of multiple treatments that could interfere with the outcome measures stresses the need for larger datasets and alternative study designs.…”

“…Yet currently, one major challenge is to develop early neuroprotective interventions to prevent the cerebral and cognitive deteriorations which predate psychosis ( 17 ). A recent study has highlighted the promising neuroprotective effect of selective serotonin reuptake inhibitors (SSRI) treatment in children and adolescents with 22q11DS ( 18 ). Participants treated with SSRIs showed improved IQ scores and increased cortical thickness in the frontal lobe and the hippocampus, which were more pronounced as treatment started early, suggesting the potential benefit to intervene during the critical developmental window of adolescence.…”

Contribution of schizophrenia polygenic burden to longitudinal phenotypic variance in 22q11.2 deletion syndrome

“…For the purposes of this study, we analysed full-scale intelligence quotient (FSIQ), and the subscales of verbal IQ (VIQ) and performance IQ (PIQ). While different versions of the test (version III or IV) were used between participants over the years to fit the longitudinal design as described in previous studies [ 45 , 46 ], the same version was kept for each participant across visits. The type of test was used as a covariate in analyses with IQ measurements.…”