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Identifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20–25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS.
We used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level.
The regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness.
The findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.
Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure.
We compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; −18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data.
FA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline.
Within 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.
Cannabis use is associated with psychosis and a range of subclinical psychiatric symptoms. The strength of this association depends on dosage and age at first use. The current study investigates whether level of cannabis exposure and starting age are associated with specific profiles of subclinical symptoms.
We collected cross-sectional data from a young adult population sample by administering an online version of the Community Assessment of Psychic Experiences (CAPE). Cannabis exposure was quantified as the amount of Euros spent on cannabis per week and the age of initial cannabis use. The primary outcome measure was the odds ratio (OR) to belong to the highest 10% of scores on the total CAPE and the positive-, negative- and depressive symptom dimensions.
In 17 698 adolescents (mean age 21.6, s.d.=4.2 years), cannabis use at age 12 years or younger was strongly associated with a top 10% score on psychotic experiences [OR 3.1, 95% confidence interval (CI) 2.1–4.3] and to a lesser degree with negative symptoms (OR 1.7, 95% CI 1.1–2.5). The OR of heavy users (>€25/week) for negative symptoms was 3.4 (95% CI 2.9–4.1), for psychotic experiences 3.0 (95% CI 2.4–3.6), and for depressive symptoms 2.8 (95% CI 2.3–3.3).
Early start of cannabis use is strongly associated with subclinical psychotic symptoms and to a lesser degree with negative symptoms, while smoking high amounts of cannabis is associated with increased levels of all three symptom dimensions: psychotic, negative and depressive. These results support the hypothesis that the impact of cannabis use is age specific.
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