Browsing by Author "Castro-Fornieles, Josefina"

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    Altered Temporal Dynamics of Resting-State Functional Magnetic Resonance Imaging in Adolescent-Onset First-Episode Psychosis
    (Oxford Univ. Press, 2023) Masias Bruns, Mireia; Ramírez Mahaluf, Juan Pablo; Valli, Isabel; Ortuno, Maria; Ilzarbe, Daniel; de la Serna, Elena; Navarro, Olga Puig; Crossley, Nicolás; Ballester, Miguel Angel Gonzalez; Baeza, Inmaculada; Piella, Gemma; Castro-Fornieles, Josefina; Sugranyes, Gisela
    Dynamic functional connectivity (dFC) alterations have been reported in patients with adult-onset and chronic psychosis. We sought to examine whether such abnormalities were also observed in patients with first episode, adolescent-onset psychosis (AOP), in order to rule out potential effects of chronicity and protracted antipsychotic treatment exposure. AOP has been suggested to have less diagnostic specificity compared to psychosis with onset in adulthood and occurs during a period of neurodevelopmental changes in brain functional connections. Study Design Seventy-nine patients with first episode, AOP (36 patients with schizophrenia-spectrum disorder, SSD; and 43 with affective psychotic disorder, AF) and 54 healthy controls (HC), aged 10 to 17 years were included. Participants underwent clinical and cognitive assessments and resting-state functional magnetic resonance imaging. Graph-based measures were used to analyze temporal trajectories of dFC, which were compared between patients with SSD, AF, and HC. Within patients, we also tested associations between dFC parameters and clinical variables. Study Results Patients with SSD temporally visited the different connectivity states in a less efficient way (reduced global efficiency), visiting fewer nodes (larger temporal modularity, and increased immobility), with a reduction in the metabolic expenditure (cost and leap size), relative to AF and HC (effect sizes: Cohen's D, ranging 0.54 to.91). In youth with AF, these parameters did not differ compared to HC. Connectivity measures were not associated with clinical severity, intelligence, cannabis use, or dose of antipsychotic medication. Conclusions dFC measures hold potential towards the development of brain-based biomarkers characterizing adolescent-onset SSD.
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    The genetic contribution to first psychotic episodes in children and adolescents of the child and adolescent first-episode psychosis study
    (2008) Patiño-Garcia, Ana| Santos Martín, José Luis; Paya, Beatríz; Parellada, Mara; Bombin, Igor; Sierrasesúmaga, Luisa; Castro-Fornieles, Josefina; Baeza, Immaculada; González-Pinto, Ana; Graell, Montserrat; Moreno, Dolores María; Rapado-Castro, Marta; Arango, Celso
    Psychotic disorders that begin during childhood and adolescence share many features of adult-onset psychotic disorders and can be diagnosed by using similar criteria, but there continues to be a strong need for data on differential diagnosis, comorbidity, neurobiological and genetic factors, treatment and prognosis (Kumra et al., 2002). The study of children and adolescents with psychosis is one way of determining a primarily genetic profile/contribution without the potential confounding effects of medication exposure and disease course in a population with a possibly greater genetic load. We report here the design and results of the genetic analyses of the child and adolescent first-episode psychosis study, CAFEPS, (Castro-Fornieles et al., 2007), which is a multicenter longitudinal follow-up study, designed to evaluate a wide range of variables in the early-onset first psychotic episode patients in Spain. DNA was available from 99 children and adolescents with a first psychotic episode [median age: 16 years (range: 11–17 years)], and 90 healthy controls from the child and adolescent first-episode psychosis study. Sixty-three patients had both parents available for transmission disequilibrium test (TDT) analysis. The study was approved by all the institutional review boards, parents/legal guardians gave written informed consent and patients agreed to participate. The polymorphisms analyzed were: Val158Met (COMT), C677T (MTHFR), Taq1A (DRD2), Ser9Gly (DRD3), -1438G>A, T102C and His452Tyr (HTR2A), Cys23Ser (HTR2C), 5-HTTLPR, and Stin2 VNTR polymorphisms (SLC6A4). Chi-square statistics were used to compare allele and genotype frequencies in patients versus controls. Statistical tests for case–control differences in haplotype frequencies were carried out by using the hapipf command of STATA 9.0 (Stata Corporation, College Station, Texas, USA). Additionally, P-values based on permutations were calculated using UNPHASED software (http://www.mrc-bsu.cam.ac.uk/personal/frank/). A TDT was carried out to assess the differential pattern of excess transmission of alleles from heterozygous parents to diseased children. Genotype frequencies did not substantially differ between cases and controls, except for the C677T polymorphism of the MTHFR gene, for which a statistically higher frequency of homozygous and polymorphic (TT) individuals was detected among patients (uncorrected P=0.039 in case–control and P=0.048 in combined case–control+TDT). The study of the HTR2A haplotype distribution for the case–control analysis showed an association with disease status (P=0.029 for -1438G>A-T102C-His452Tyr) that was not sustained in the TDT. Among the 63 case–parent trios, none of the alleles or haplotypes had a statistically increased probability of transmission. Overall, our results do not support a major role of HTR2A, HTR2C, SLC6A4, DRD2, DRD3, and COMT genes in the increased risk for developing early-onset psychosis, but suggest that folate homeostasis may play a modest role in neurodevelopmental psychiatric diseases. The meta-analyses published to date (Gilbody et al., 2007) report a moderate, but still significant association of the C677T polymorphism of the MTHR gene with several psychiatric disorders, varying among populations. In addition, the C677T polymorphism could be in linkage disequilibrium with other marker/s that might have an effect on the susceptibility to certain psychosis. Schizophrenia is considered as a neurodevelopmental disorder and, as such, the effect of DNA methylation (mediated by MTHFR) on its manifestation could be decisive (Singh et al., 2003; Rodenhiser and Mann, 2006). Alteration of the regulation of neurodevelopmental processes might be better detected in a sample such as the one presented herein than in an adult sample, in which multiple and complex mechanisms may interact and mask this gene effect.