E. De la Serna

Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses

BACKGROUND The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders. Method Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls. RESULTS EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405). CONCLUSIONS Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

Intrinsic functional connectivity of fronto-temporal networks in early onset psychosis at 2 years after the first episode

Introduction Intrinsic functional connectivity (iFC) of resting-state networks has been reported to be altered in schizophrenia, especially in fronto-temporal networks [1]. Our team have recently observed reduced connectivity in the right middle/inferior frontal gyrus (rIFG) within a network functionally related to language, in adolescents suffering a first episode of psychosis in comparison to healthy controls (HC) [2]. The aim of this study is to test whether these changes persist two year after clinical onset and to examine whether there are any structural correlates. Methods A case-control cross-sectional study was performed evaluating iFC and grey matter structure in adolescents two-years-after their first psychotic episode compared to HC, in sample with a partial overlap (33%) with regards to our previous report. Twenty-nine adolescents with Early Onset Psychosis (EOP) participated in this two-year follow-up assessment and were compared cross-sectionally to 36 HC. After excluding 3 cases due to excess movement, final sample (n=62) did not present significant differences in age (EOP=17.6 ± 0.3 years; HC= 18.3 ± 0.3 years) or sex (EOP=58% female; HC=50% female). Diagnoses were: schizophrenia (8), schizoaffective disorder (5), bipolar disorder (4), major depression (2) and psychosis not-otherwise specified (7). A DARTEL algorithm was applied to the segmented T1-structural volumes to generate a sample-specific template. Functional resting-state images were pre-processed using SPM12 and co-registered to this template. Three components obtained with independent component analysis (toolbox GIFT) corresponding to the salience, language and DMN were identified from visual inspection. Whole brain analysis t-tests were covaried by sex and age using an inclusive grey-matter mask. No differences were observed in total intracraneal, grey matter or white matter volumes amongst groups. Voxel Based Morphometry (VBM) analysis was covaried for age, sex and total intracranial volume. Secondarily, we performed a region of interest (ROI) analysis using the marsbar toolbox: data of iFC and grey matter volume was extracted, using a 10-mm-radius sphere centred at MNIx,y,z [42, 39, -3] [2] (rIFG) and performed a group comparison in Stata13. Results There were no differences between groups in iFC in either of the resting state networks. The ROI analysis corresponding to the rIFG in the language network revealed an effect of group, consisting of reduced iFC in EOP participants relative to HC, survived when controlled by age and sex (p = 0.026). There were no group-effects in grey matter volumes for this region of interest. It was found an inverse correlation between grey matter and iFC at rIFG, only significant in HC group (p = 0.02). Discussion Our results support persistence of reduced iFC in the language network in adolescents with EOP, 2 years after the first episode, in a mostly independent sample with regards our baseline study [2]. This provides further support to the notion that abnormal fronto-temporal connectivity may characterize EOP at different stages of the disease. Nevertheless, this finding needs to be interpreted taking into account that the present results correspond to ROI analyses and that the current study design does not allow to examine longitudinal change. Further research should focus on assessing longitudinal differences in resting-state networks in EOP.

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.

EPA-0863 - Progression of changes in brain structure and executive functions in children and adolescents with first-episode psychosis

Background Previous studies have reported progressive brain changes and cognitive deficits in early-onset psychosis (EOP). Little is known on the relationship between longitudinal changes in brain structure and neurocognition. Methods Naturalistic 5-year prospective study comparing frontal gray matter (GM) volume and executive functions in adolescents with a first episode of EOP and a sample of healthy controls at baseline, 2-year and 5-year follow-up. Results Thirty-six patients (age at baseline 15.8 ±.7, 66.6% male) and 34 controls (15.4±1.4, 55.9% male) comprised the study sample. Both patients and controls presented with frontal GM loss during the first five years of follow-up. During the first two years, patients presented with significantly greater GM loss than controls in the left (F=9.642, p=0.003) and right frontal lobe (F=7.585, p=0.008), with no significant differences between year 2 and 5. Patients with EOP performed significantly worse in executive tasks than controls in all visits. During the first two years of follow-up, controls, but not patients, presented with a significant improvement in executive functioning (F=7.523, p=0.009), with similar evolution of cognitive functioning between years 2 and 5 in both groups (F=0.908, p=0.346). Changes in frontal GM volume and executive functioning were not significantly correlated within the entire follow-up period. Conclusion Over the first two years of illness, patients with EOP show greater frontal GM loss and less improvement in executive functions than expected. This could be a critical period for the development of deficits in EOP, in which more intensive interventions would be warranted.

P.7.a.005 Antipsychotic metabolic effects in bipolar youth: comparison with other psychotic and non-psychotic diagnoses

• There is increased prevalence of metabolic conditions, which are known cardiovascular risk factors, among patients with mental disorders (1, 2). • Second-generation antipsychotics (SGAs) increase metabolic risk both in pediatric and in adult patients with schizophrenia and bipolar disorder (1, 3) • SGAs are used in children and adolescents to treat a variety of conditions, including pediatric bipolar disorder (4) but comparative effects in youth with different diagnoses remain underreported.