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.
Highlights
Cognitive impairment, including working memory deficits, is increasingly recognized as a core feature of psychosis and plays a crucial role in the overall disability[1,2]
Characteristics of the sample The overall number of deletion carriers included in the present study was 98 (30 without any medication, 38 treated with SSRIs, of which 23 endorsing psychotic symptoms, and 30 psychotics not treated with SSRIs) with 264 visits and an average of 2.78 visits for each subject
Differences in IQ developmental trajectories Differences in developmental trajectories of cognitive and brain measures were computed across groups and subgroups to explore the potential effect of SSRIs on development
Summary
Cognitive impairment, including working memory deficits, is increasingly recognized as a core feature of psychosis and plays a crucial role in the overall disability[1,2]. One of the factors most likely contributing to such lack of studies in humans is the extreme difficulty in identifying individuals at risk for psychosis in the general population before the onset of the first psychotic symptoms, intervene, and follow them up over time. A low IQ before the onset of adolescence predates the emergence of psychotic symptoms and cognitive decline— especially in the domain of verbal IQ—is higher in individuals who develop a psychotic disorder[14]. These findings are mirrored by abnormal brain development of cortical and subcortical structures. Many studies indicated that psychosis in 22q11DS is associated with lower volume of frontal and temporal areas[16,17] and subcortical structures as hippocampus, thalamus, and amygdala[18,19,20]
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