Reduced thickness of the cingulate cortex in adolescents at ultra-high risk for psychosis

Introduction Identification of individuals at ultra-high risk for psychosis (UHR) has the potential to help prevent or delay the onset of disease [1]. Structural MRI studies have revealed that UHR are characterized by cortical thickness (CTH) reductions in temporal, frontal and cingulate cortices in both cross-sectional and longitudinal comparisons [2,3]. However, studies so far have focused on adult samples, with few exceptions [4]. Aim To provide evidence regarding how onset of prodromal symptoms during adolescence impacts on changes in CTH, and how CTH relates with clinical features. Methods Multicentre cross-sectional case-control study, including adolescents aged 10-17 years, recruited from child and adolescent mental health services of two independent Hospitals in Barcelona. UHR individuals were identified using the Structured Interview for Prodromal Syndromes criteria with some modifications. Healthy controls (HC) were recruited from the same geographical area. Exclusion criteria for all participants comprised personal history of psychotic symptoms, IQ High-resolution magnetic resonance structural images were acquired on a 3Tesla and 1.5Tesla scanners. An inter-site compatibility study (conducted with healthy controls) revealed high inter-site correlation coefficients (r>.6) for CTH measures. Images were pre-processed employing automated procedures implemented in FreeSurfer 5.3.0, cortical parcellation employed the Desikan-Killiany brain atlas. Analyses: First, mean global and lobar (frontal, parietal, temporal, occipital, insula and cingulate) CTH measurements were computed. Then, within lobes showing group effects, CTH was measured for each parcellation. Between-group analyses were conducted with the general linear model in SPSS 22.0, including gender, age, total intracranial volume and site as covariates. Finally, pearson correlations were performed to test associations between CTH measures and symptom severity (Scale of Prodromal Symptoms). Significance was set at p Results 122 subjects were included (77 UHR vs. 45 HC, mean ages: 15.1(SD=1.8) vs. 15.8(SD=1.5), t=1.9, p=0.055; gender (%female): 61.0% vs 69.9%, χ2=0.76, p=0.38). There were no significant differences in case-control proportion between centres: χ2=1.3, p=0.25. No significant differences in global CTH in UHR (2.57mm, SD=0.10) relative to HC (2.59mm, SD=0.14) were found. Between-group analyses showed a significantly lower CTH in the right cingulate in UHR compared to HC (F=12.2, pFDR=0.01). Within the right cingulate, CTH in the posterior cingulate (F=11.5, pFDR=0.004), isthmus cingulate (F=8.2, pFDR=0.01) and caudal anterior cingulate (F=5.4, pFDR=0.03) was smaller in UHR compared to HC. Pearson correlation showed a significant inverse association between symptom severity and CTH in right posterior cingulate (p=0.01) and isthmus cingulate (p=0.04) uncorrected. Discussion UHR showed significant cortical thinning in several regions of the right cingulate, which correlated with symptom severity. These findings add support to the notion that structural alterations in the cingulate cortex may be present in children and adolescents prior to onset of psychosis and may be associated with attenuated psychotic symptoms. Longitudinal follow-up of this sample will inform on which of these cross-sectional changes are related to transition.