Do clinical characteristics predict the cognitive course in early-onset schizophrenia-spectrum disorders?

BACKGROUND: Being in a period with extensive brain maturation, adolescents with early-onset schizophrenia-spectrum disorders (EOS) provide unique neurodevelopmental data that may contribute to a better understanding of schizophrenia at all ages. Cognitive dysfunction is a central feature of schizophrenia and is more pronounced in EOS than in later onset illness. However, there is limited research on both the long-term course of global cognition in EOS, and how cognition over time is influenced by clinical characteristics during the early illness period. METHODS: Thirty-one EOS patients and 73 controls (age 12-18) were assessed on clinical variables at baseline (PANSS, duration of untreated psychosis [DUP], hospitalizations, suicide attempts, and remission). Neuropsychological assessments with the MATRICS Consensus Cognitive Battery (MCCB) were conducted at baseline and after both 1 and 2 years, and composite scores of total performances were calculated. The analyses were performed with a linear mixed model. RESULTS: The present study found that global cognition followed a stable course over the first years of the disease in EOS, though at a significantly lower level in EOS compared with the controls. We did not detect a relationship between DUP, remission, positive/negative symptoms, and hospitalizations on one hand, and long-term cognition on the other hand, but PANSS-general and suicide attempt history at baseline were identified as risk factors of longitudinal cognitive function. CONCLUSIONS: Though at different levels, the EOS group and the controls had a similar cognitive course over 2 years. Some baseline characteristics (psychotic symptoms, DUP, remission, and hospitalization) had no influence on cognition within the first 2 years of illness. In contrast, general symptoms and a history of suicide attempts at baseline were more potent risk factors of the cognitive course than the psychotic-specific symptoms, and should, therefore, be subject to specific attention in the evaluation and treatment of patients with early-onset psychosis.

The development, validation, and feasibility of the Experienced Coercion Scale.

Existing scales for experienced coercion have limitations. We developed and validated a short self-report form for experienced coercion for use across care settings, care phases, and care measures. In Stage 1, we developed an item pool, based on the literature, patient accounts, interviews, and expert feedback. Stages 2 and 3 consisted of 2 cross-sectional studies, with patients from acute and nonacute inpatient wards, outpatient care, and supported housing. In Stage 2, patients (N = 212) responded to the Coercion Ladder and the experienced coercion items from Stage 1. We selected 20 items for Stage 3 based on item performance in typically coercive versus voluntary care settings, each items' relation to the Coercion Ladder score, and with regard to the component structure from principal component analysis (PCA). In Stage 3, we collected and examined item responses and clinical and coercion data from a new sample of patients (N = 219). We selected 15 items based on factor loadings to form part of the final Experienced Coercion Scale (ECS). The internal consistency was high and score distribution approached the normal curve. ECS sum scores correlated strongly with scores on the Coercion Ladder. In a regression analysis, demographic variables, diagnosis, duration of treatment, and care setting did not predict ECS scores, while legal status and continuing involuntary medication significantly predicted scores. In this initial study, the ECS scores showed promising psychometric properties, suggesting it can be used across care settings and is suitable for research and service evaluation. (PsycINFO Database Record

Impaired Verbal Learning Is Associated with Larger Caudate Volumes in Early Onset Schizophrenia Spectrum Disorders.

BACKGROUND: Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB) in early onset schizophrenia spectrum disorders (EOS). To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS. METHODS: Twenty-four patients with EOS and 33 healthy controls (HC) were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables. RESULTS: The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034). There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship. CONCLUSION: Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups.

Relative stability of neurocognitive deficits in early onset schizophrenia spectrum patients.

UNLABELLED: In contrast to the findings of progressive structural brain changes in adolescence, longitudinal studies of patients with early onset schizophrenia spectrum disorders (EOS) indicate that neurocognitive deficits are relatively stable over the first years. The aim of this study is to assess neurocognitive functions longitudinally in patients with EOS compared to healthy controls (HC) using the MATRICS Cognitive Consensus Battery (MCCB). METHODS: Twenty patients with EOS and 41 HC were tested with the MCCB at baseline (T1) and after one (T2) and two years (T3). The mean age for the EOS group was 15.6 (SD=1.8) years, while the mean duration of illness was 1.7 (SD=1.4) years at T1. RESULTS: The EOS group's neurocognitive performances indicate a stable deficit on most measures. Both the EOS and HC groups showed improved neurocognitive functioning over time on all measures except for the verbal learning domain. There was an interaction between the EOS and HC groups' performance over time on the Trail Making Test A (TMA), a subtest on the processing speed domain. CONCLUSION: The longitudinal neurocognitive performances measured by the MCCB confirm previous findings of stable deficits in patients with EOS. It is premature to conclude whether the increases in neurocognitive performance reflect developmental processes in adolescence or may be explained by learning effects, or both. As opposed to the other tests in this domain, a stagnation in processing speed as measured by the TMA suggests that the TMA is a particularly sensitive measure of neurodevelopmental deviance in EOS.

Age-related cortical thickness differences in adolescents with early-onset schizophrenia compared with healthy adolescents.

The aim of the present study was to investigate the influence of age on cerebral cortical thickness in adolescents with early-onset schizophrenia (EOS) (n=22, aged 12-18 years), as compared to an age-matched healthy control group (n=32). All participants were scanned with magnetic resonance imaging. Whereas in the healthy control group there was a negative association between increasing age and cortical thickness measures in widespread brain regions, including frontal and parietal cortices, the patient group showed no significant effects of age when the groups were studied separately. There was a trend towards an age-by-group effect in the left supramarginal gyrus and the right pre- and postcentral gyri. The between-group statistical analysis indicated similar cortical thickness in the patients as in the healthy controls. There were no significant effects of medication on cortical thickness, nor was there any significant sex-by-group interaction. The results suggest that patients with EOS have a deficiency of the expected cortical thinning to occur during adolescence development. The findings are discussed in context of neurobiological processes known to be involved in brain maturation, including synaptic reorganization, pruning and myelination.

Executive function in early- and adult onset schizophrenia.

BACKGROUND: The goal of this study was to investigate differences in executive functioning between patients with early-onset and adult-onset schizophrenia spectrum psychoses at the time of first treatment. METHODS: Neuropsychological tests covering executive functioning domains were performed for 20 adolescents with early-onset schizophrenia (EOS) close to first treatment and 90 first episode patients with adult onset schizophrenia (AOS) in addition to 66 adolescent- and 127 adult age and gender matched healthy controls. RESULTS: Both EOS and AOS patients had significantly poorer executive performance than their age- and gender matched healthy counterparts. Both healthy adolescent controls and EOS patients had poorer executive performance than their adult counterparts. However, there were no differences in executive functioning between EOS and AOS patients after controlling for the levels of their age matched healthy control groups. Substituting EOS/AOS status with other age-at-onset thresholds had no effect. CONCLUSIONS: We find the same relative levels of executive dysfunction in EOS- and AOS groups at the time of first treatment. This does not necessarily contradict previous findings of more severe dysfunction in EOS patients over time, but indicates an interaction between the disorder and the maturational processes that only can be investigated through longitudinal studies.

Comprehensive segmentation of subcortical brain volumes in early onset schizophrenia reveals limited structural abnormalities.

Structural brain abnormalities are well documented in adult schizophrenia, but there are few studies of brain structures in early onset schizophrenia (EOS) and findings are inconsistent. Most previous EOS studies have been limited to global morphometric measures, such as whole gray matter (GM) or cerebrospinal fluid (CSF), or to single brain structures. The purpose of this study was to compare specific volumes and hemispheric lateralization in a large number of subcortical brain structures, between EOS patients and a healthy control group. High-resolution structural magnetic resonance images (MRI) and automatic brain volume segmentation were performed on 18 EOS patients and 33 healthy controls (11-18 years). A total of 29 brain structures were studied. The patients showed marked bilateral enlargements of the lateral ventricles and of the fourth ventricle, and bilateral enlargement of the caudate nuclei compared to the controls. For all other subcortical brain structures, there were no significant differences between the EOS group and the healthy control group, contrary to findings from the majority of morphometric studies of childhood or adult onset schizophrenia.

Visual backward-masking performance in a longitudinal study of early onset schizophrenia.

The aim of the present study was to examine the effect of visual backward-masking (VBM) in patients with early onset schizophrenia (EOS, n=28) compared to healthy controls (n=80) at baseline and at one- and two-year follow-ups. Seventeen patients and 40 controls performed a VBM task at all three sessions, which included five different interstimuli intervals (ISI) at 16.5, 33.5, 49.5, 116 and 166ms, and an additional no-masking control task. Patients with EOS revealed no impairment of VBM performance at baseline and at the two follow-ups compared to healthy controls at one- and two-year follow-ups. However, the patients demonstrated a deficit of simple early visual processing. Both groups showed effects of development over a period of 24 months for the shortest ISIs.

Executive function tests in early-onset psychosis: which one to choose?

People with schizophrenia exhibit executive functioning deficits, an area well investigated in the adult onset schizophrenia (AOS) group, but far less so in early-onset schizophrenia (EOS). Since EOS in general seems to exhibit poorer cognitive functions and is clinically more compromised than AOS, choice of efficient and sensitive assessment measures is not necessarily the same within the two groups. The MATRICS Consensus Cognitive Battery was developed for adults when studying treatment effects and uses Mazes (Neuropsychological Assessment Battery [NAB]) to assess executive functioning. We tested 31 adolescents with schizophrenia spectrum disorders and 66 healthy controls in order to examine how Mazes compares to two other commonly used tests to measure executive functioning, D-KEFS Color Word Interference Test (Stroop) and the Wisconsin Card Sorting Test (WCST). Significant discriminating power was found for all three measures. Patients performed 0.8-1.5 SD below controls with Stroop as the most sensitive measure, followed by Mazes and WCST. Mazes was selected by the MATRICS to assess treatment effects in AOS and is shown to be able. We find the instrument also able to separate adolescent patients from controls and thus, it appears a sensible choice in clinical settings. If a more elaborated neuropsychological evaluation of the executive functioning domain is needed, Stroop should be considered a complementary test.

Prefrontal hyperactivation during a working memory task in early-onset schizophrenia spectrum disorders: an fMRI study.

Working memory (WM) dysfunction is increasingly recognized as a core feature of schizophrenia, but few studies have investigated prefrontal activation during WM tasks in early-onset schizophrenia spectrum disorder (EOS). Our aim was to explore prefrontal activation during a WM-task in EOS patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Fifteen patients with EOS and 15 matched healthy controls performed a 0-back and a 2-back task while fMRI data were acquired. Results indicated that even though performance between patients and controls was comparable on both tasks, there was a hyperactivation in patients' ventrolateral prefrontal cortex (VLPFC) during the 2-back task compared to healthy controls. This pattern of activation suggests that, in patients with EOS, the VLPFC compensated in order to match performance of the controls. The activations in the EOS group may reflect the use of a compensatory, cognitive strategy while solving WM-tasks.

Neuropsychological profile in early-onset schizophrenia-spectrum disorders: measured with the MATRICS battery.

OBJECTIVE: Neurocognitive impairments have been documented in adolescents with early-onset schizophrenia (EOS). There is still inconsistency regarding an average profile, which could be due to the fact that each study uses different tests. The purpose of this study was to examine whether the "Measurement and Treatment Research to Improve Cognition in Schizophrenia" (MATRICS) battery is useful in detecting differences between the patient group and the healthy controls, and to describe the neuropsychological pattern in the EOS group. METHOD: Neuropsychological functioning was examined in 31 adolescents with schizophrenia spectrum disorders and 67 healthy controls, using the MATRICS battery. RESULTS: There were significant differences between the patients and the controls on every domain except for social cognition. Patients showed a generalized neurocognitive deficit of 0.8-1.8 SDs compared with controls, with verbal learning, working memory, and visual learning being the most affected areas. CONCLUSIONS: The MATRICS battery is sensitive in detecting differences between patients and controls in the adolescent population. However, we question the use of Mayer-Salovey-Caruso Emotional Intelligence Test in this age group. Results document a significant generalized deficit in adolescents with EOS.