The concept of being at risk for psychosis has been introduced both for adults and children and adolescents, but fewer studies have been conducted in the latter population. The aim of this study is ...to systematically review the articles associated with clinical description, interventions, outcome and other areas in children and adolescents at risk for psychosis. We searched in MEDLINE/PubMed and PsycINFO databases for articles published up to 30/06/16. Reviewed articles were prospective studies; written in English; original articles with Clinical High Risk (CHR) for psychosis samples; and mean age of samples younger than 18 years. From 103 studies initially selected, 48 met inclusion criteria and were systematically reviewed. Studies show that CHR children and adolescents present several clinical characteristics at baseline, with most attenuated positive-symptom inclusion criteria observed, reporting mostly perceptual abnormalities and suspiciousness, and presenting comorbid conditions such as depressive and anxiety disorders. CHR children and adolescents show lower general intelligence and no structural brain changes compared with controls. Original articles reviewed show rates of conversion to psychosis between 17 and 20% at 1 year follow-up and between 7 and 21% at 2 years. While 36% of patients recovered from their CHR status at 6-year follow-up, 40% still met CHR criteria. Studies in children and adolescents with CHR were conducted with different methodologies, assessments tools and small samples. It is important to conduct studies on psychopharmacological and psychological treatment, as well as replication of the few studies found.
Cognitive impairment is an enduring and functionally relevant feature of early-onset schizophrenia (EOS). Cognitive remediation therapy (CRT) improves cognition and functional outcome in adults with ...schizophrenia, although data in adolescents with EOS remain scarce. The purpose of this study is to examine the efficacy of CRT in improving cognition and functional outcomes in a sample of symptomatically stable but cognitively disabled adolescents with EOS.
We performed a randomized, controlled trial of individually delivered CRT plus treatment-as-usual compared with treatment-as-usual (TAU). Fifty adolescents with EOS were randomly assigned to receive CRT (n = 25) or TAU (n = 25) and were included in an intention-to-treat analysis. Clinical symptoms and cognitive and functional performance were assessed before and after treatment in both groups and after 3 months in the CRT group. Cognitive domains were defined according to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus battery and averaged in a global cognitive composite score.
After CRT, significant improvements were found in verbal memory and executive functions, with medium-to-large effect sizes (ES). The derived cognitive composite score showed an improvement after the treatment, with a large ES. This change was reliable in more than two-thirds of the treated patients. Medium-sized ES were found for improvements after CRT in daily living and adaptive functioning, whereas large ES were observed for improvements in family burden. With the exception of functional gains, these changes were maintained after 3 months.
CRT appears to be a useful intervention strategy for adolescents with EOS. Cognitive improvements can be achieved through CRT, although further research is warranted to determine the durability of functional gains. Clinical trial registration information-Cognitive Remediation Therapy (CRT) in Adolescents With EOS; www.clinicaltrials.gov; NCT01701609.
•Onset of psychosis was linked to a lack of age-related improvement in theory of mind.•Reduced prefrontal connectivity preceded onset of psychosis in high risk youth.•High risk youth with lower ...prefrontal connectivity were at greatest risk of psychosis.
Theory of mind(ToM) impairment is a key feature of psychotic disorders and has been documented in individuals at clinical high-risk for psychosis (CHR), suggesting that it may predate illness onset. However, no study to date has examined brain functional correlates of ToM in individuals at CHR during adolescence. The “Reading-the-Mind-in-the-Eyes” test was used to measure ToM performance in 50 CHR youth, 15 of whom transitioned to psychosis (CHR-t) at follow-up (12 ± 6 months) and 36 healthy volunteers. Resting-state functional MRI was acquired to evaluate functional connectivity within the default mode network. Group by age interaction revealed an age-positive association in ToM performance in healthy volunteers, which was not present in adolescents at CHR-t. Intrinsic functional connectivity in the medial prefrontal cortex was reduced in adolescents at CHR-t relative to those who did not transition and to healthy volunteers. Survival analyses revealed that participants at CHR with lower medial prefrontal cortex connectivity were at greatest risk of developing psychosis at follow-up. We demonstrate that lack of age-related maturation of ToM and reduced medial prefrontal cortex connectivity both precede the onset of psychosis during adolescence. Medial prefrontal cortex connectivity holds potential as a brain-based marker for the early identification of transition to psychosis.
•Youth with early-onset psychosis displayed deficits in theory of mind performance.•They also showed reduced intrinsic connectivity in the medial prefrontal cortex.•Differences in theory of mind were ...partially mediated by prefrontal connectivity.•Both measures failed to show the age-positive associations observed in controls.•Onset of psychosis in adolescence may impact development of social cognition.
Psychotic disorders are characterized by theory of mind (ToM) impairment. Although ToM undergoes maturational changes throughout adolescence, there is a lack of studies examining ToM performance and its brain functional correlates in individuals with an early onset of psychosis (EOP; onset prior to age 18), and its relationship with age. Twenty-seven individuals with EOP were compared with 41 healthy volunteers using the “Reading-the-Mind-in-the-Eyes” Test, as a measure of ToM performance. A resting-state functional MRI scan was also acquired, in which the default mode network was used to identify areas relevant to ToM processing employing independent component analysis. Group effects revealed worse ToM performance and less intrinsic functional connectivity in the medial prefrontal cortex in EOP relative to healthy volunteers. Group by age interaction revealed age-positive associations in ToM task performance and in intrinsic connectivity in the medial prefrontal cortex in healthy volunteers, which were not present in EOP. Differences in ToM performance were partially mediated by intrinsic functional connectivity in the medial prefrontal cortex. Poorer ToM performance in EOP, coupled with less medial prefrontal cortex connectivity, could be associated with the impact of psychosis during a critical period of development of the social brain, limiting normative age-related maturation.
Summary Objective To characterize Helicobacter pylori isolates from western Argentina using virulence markers and antimicrobial susceptibility patterns in order to assess the association between ...virulent genotypes, antimicrobial resistance, and disease. DNA fingerprinting was also evaluated for the segregation of virulent or resistant strain clusters. Methods Genotyping of 299 H. pylori isolates was performed by PCR using specific primers for the cagA, vacA and iceA genes. Random amplification of polymorphic DNA (RAPD)-PCR and rep-PCR genetic clustering were assessed using five random primers and BOXA1R and ERIC primers, respectively. Resistance to clarithromycin (Cla) and metronidazole (Mtz) was assessed by the agar dilution method. Results It was observed that 40.8% of the genotypes were cagA -positive; 66.9% were vacA s1m1 genotype and the iceA1 allele was found in 40.8%. A significant correlation ( p = 0.0000) was observed between cagA positivity and vacA s1m1 / iceA1 genotypes. Triple virulent genotypes were statistically associated with peptic ulcer (PU) ( p = 0.0001) and Cla resistance ( p = 0.0000). RAPD fingerprints obtained with AO2 primers identified clusters that were strongly associated with PU, virulence markers, and resistance to Cla and Mtz. Conclusions The H. pylori isolates that harbored two or three virulence markers were more resistant to Cla and Mtz. Combined analysis of virulent genotypes and resistance patterns may permit identification of high-risk patients to prevent PU later in life or to avoid antimicrobial treatment failure.
Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors ...sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.
Structural T
-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).
No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.
The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
Previous studies have shown high rates of comorbid disorders in children and adolescents with autism spectrum disorder, but failed to compare them with general population and few of them have ...identified predictors of comorbidity. This study compared the rates of psychiatric disorders in 50 children and adolescents with autism spectrum disorder, 24 of their siblings, 32 controls from general population and 22 of their siblings. Children and adolescent with autism spectrum disorder and their siblings had higher rates of attention deficit and hyperactivity disorder compared to controls. Lower socioeconomic status and intelligence quotient were the main risk factors. The contribution of socioeconomic status and intelligence quotient to increase the risk of developing comorbidity in autism spectrum disorder and psychopathology in their siblings deserves further study.
To compare clinical and functional variables among 3 groups of children and adolescents: subjects at clinical high risk for psychosis (CHR-P) who also have obsessive-compulsive symptoms (OCS), CHR-P ...patients without OCS, and healthy controls (HC).
A total of 128 CHR-P patients and 98 HC between the ages of 10 and 17 years were recruited as part of a multicenter prospective longitudinal study conducted in Spain between January 1, 2011, and December 31, 2018, with diagnoses made for CHR-P using the Scale of Prodromal Symptoms (SOPS). Two groups were obtained based on Leyton Obsessional Inventory-Child Version (LOI-CV) scores: 64 CHR-P patients with OCS (OCS+) and 64 CHR-P patients without OCS (OCS-). Clinical variables were analyzed with a generalized linear model.
Overall, 128 CHR-P patients, 64 (50%) with OCS (mean ± SD age = 15.5 ± 1.4 years, 34.4% male), 64 CHR-P patients without OCS (mean ± SD age = 15.1 ± 1.9 years, 34.4% male), and 98 HC (mean ± SD age = 15.5 ± 1.5 years, 42.9% male), of whom 19 (19.5%) had OCS, were included. Generalized linear model analysis revealed significant differences between the groups. The OCS+ group showed more severe prodromal symptoms (
= .007), worse functioning at baseline (
= .044) and during the previous year (
= .004), and more dysmorphophobic symptoms (
< .001) compared to the OCS- group. OCS+ patients were also more frequently treated with antidepressants (
= .004) than were OCS- patients.
In our sample, among children and adolescents with CHR-P, the prevalence of OCS was high (50%). OCS+ subjects had a more severe clinical and functional profile than OCS- subjects. Early detection and treatment of these symptoms can lead to better outcomes for these patients.
Progression to psychosis has been associated with increased cortical thinning in the frontal, temporal and parietal lobes in individuals at clinical high risk for the disorder (CHR-P). The timing and ...spatial extent of these changes are thought to be influenced by age. However, most evidence so far stems from adult samples. Longitudinal studies are essential to understanding the neuroanatomical changes associated to transition to psychosis during adolescence, and their relationship with age. We conducted a longitudinal, multisite study including adolescents at CHR-P and healthy controls (HC), aged 10–17 years. Structural images were acquired at baseline and at 18-month follow-up. Images were processed with the longitudinal pipeline in FreeSurfer. We used a longitudinal two-stage model to compute the regional cortical thickness (CT) change, and analyze between-group differences controlling for age, sex and scan, and corrected for multiple comparisons. Linear regression was used to study the effect of age at baseline. A total of 103 individuals (49 CHR-P and 54 HC) were included in the analysis. During follow-up, the 13 CHR-P participants who transitioned to psychosis exhibited greater CT decrease over time in the right parietal cortex compared to those who did not transition to psychosis and to HC. Age at baseline correlated with longitudinal changes in CT, with younger individuals showing greater cortical thinning in this region. The emergence of psychosis during early adolescence may have an impact on typical neuromaturational processes. This study provides new insights on the cortical changes taking place prior to illness onset.
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