Cross-sectional associations between adaptive functioning and social cognitive and neurocognitive functions in adolescents with first-episode, early-onset schizophrenia spectrum disorders.

BACKGROUND: Few studies have explored associations between adaptive functioning and cognition in adolescents with early-onset schizophrenia spectrum disorders (EOS). METHODS: Adaptive functioning, cognition, positive, negative, and general symptoms were characterized in adolescents with EOS and healthy controls. A modified scale of negative, respectively, general symptoms was used. Bivariate analyses identified correlates of adaptive functioning to be included in multivariate analysis. RESULTS: Adolescents with EOS showed significant impairments of social- and neurocognitive functions (-0.86 < Cohen´s ds < -0.58) and adaptive functioning (Cohen´s d = -2.23). Visual memory, verbal working memory, processing speed, reaction time, social cognition, and modified negative and general symptoms correlated significantly with adaptive functioning. The multiple regression analysis revealed only verbal working memory as uniquely associated with adaptive functioning (explaining 22.7 % of its variance). Verbal working memory also associated significantly with adaptive functioning in the context of the nonsignificant modified negative and the significant modified general symptoms dimension. CONCLUSIONS: Adolescents with first-episode EOS had large impairments in adaptive functioning and moderate to large cognitive deficits. Verbal working memory was an important associate to concurrent adaptive functioning and may be a treatment target for trials to improve cognitive and adaptive functioning in adolescents with EOS.

Brief Report: Clusters and Trajectories Across the Autism and/or ADHD Spectrum.

Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) frequently co-occur and show high genetic correlation. With the introduction of DSM-5, there is a new concept of an ASD and/or ADHD spectrum (ASD/ADHD). This study aimed to identify predictors of severity and need of healthcare within this spectrum. 39 families with multiple individuals affected by ASD/ADHD were recruited from a psychiatric clinic. Diagnoses, functional and demographic characteristics were retrieved from journals while hospital admissions were identified in the Danish health register. An estimated fraction of 31% ASD/ADHD patients had never been hospitalized and 35% remained undiagnosed despite hospitalization. Cluster analysis identified trajectories that discriminate age of diagnosis, educational attainment to degree of severity, need of hospitalization and genetic risk.

Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia.

OBJECTIVE: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. METHODS: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval (CI) = -0.57 to -0.17, P < 0.001], driven by negative (SMD = -0.25, 95% CI = -0.44-0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = -0.42, 95% CI = -0.77, -0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = -0.71, 95% CI = -1.21, -0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = -0.43, 95% CI = -0.77, -0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04-2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation. CONCLUSIONS: For schizophrenia patients on stable antipsychotic treatment, adjunctive antidepressants are effective for total and particularly negative symptom reduction. However, effects are small-to-medium, differ across antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.

Overlapping and disease specific trait, response, and reflection impulsivity in adolescents with first-episode schizophrenia spectrum disorders or attention-deficit/hyperactivity disorder.

BACKGROUND: Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are developmental disorders with shared clinical characteristics such as cognitive impairments and impulsivity. Impulsivity is a core feature of ADHD and an important factor in aggression, violence, and substance use in schizophrenia. Based on the hypothesis that schizophrenia and ADHD represent a continuum of neurodevelopmental impairments, the aim was to identify overlapping and disease specific forms of impulsivity. METHODS: Adolescents between 12 and 17 years of age were assessed with the Schedule for Affective Disorders and Schizophrenia for School-aged Children - Present and Lifetime Version. Subjects with early-onset, first-episode schizophrenia spectrum disorders (EOS) (N = 29) or ADHD (N = 29) and healthy controls (N = 45) were compared on two performance measures (Information Sampling Task, Stop Signal Task) and a subjective personality trait measure of impulsivity (Barratt Impulsiveness Scale, Version 11 (BIS-11)). RESULTS: Significantly increased reflection impulsivity was observed in ADHD but not in the EOS group. No significant response inhibition deficits (stop signal reaction time) were found in the two clinical groups. The ADHD and the EOS group showed significantly increased motor, attentional, and non-planning subtraits of impulsivity. CONCLUSIONS: Impaired pre-decisional information gathering appeared to be specific for ADHD while the information gathering was not significantly reduced in subjects with EOS. Neither the ADHD nor EOS group showed impaired response inhibition but shared increased personality subtraits of attentional, non-planning, and motor impulsivity although the latter was significantly more pronounced in ADHD. These increased subtraits of impulsivity may reflect diagnostic non-specific neurodevelopmental impairments in ADHD and EOS in adolescence.

Risk of impaired cognition after prenatal exposure to psychotropic drugs.

OBJECTIVE: Prenatal exposure to psychotropic drugs may affect the trajectories of brain development. In a register study, we investigated whether such exposure is associated with long-term impaired cognitive abilities. METHOD: Individuals born in Denmark in 1995-2008 were included. As proxies for cognitive impairment, requiring special needs education, attending special needs school, diagnoses of neurological/mental disorder, missed final examinations, and low school grade average were used. We accounted for maternal confounders. RESULTS: We identified 868 159 individuals of whom 13 983 (1.6%) were prenatally exposed. The adjusted odds ratio (OR) was 0.97[0.92-1.02] for requiring special needs education, 1.28[1.14-1.43] for attending special needs school, 1.32[1.20-1.46] for a neurological/mental disorder diagnosis, 1.37[1.22-1.54] for missing the final examinations, and 1.13[0.82-1.55] for obtaining a low school grade average. Exposure to psycholeptics (primarily antipsychotics and sedatives) was correlated with significantly increased risk for four outcomes. The highest was the risk of missing the primary school examinations (OR: 1.51[1.29-1.76]). The overall highest risk concerned the presence of a neurological/mental disorder after prenatal exposure to psychoanaleptics (primarily antidepressants) (OR: 1.86[1.24-2.78). CONCLUSION: Prenatal exposure to psychotropic drugs affects proxy outcomes of cognitive disabilities at school age. Exposure to psycholeptics carries the largest risk. The role of psychoanaleptics is currently unclear.

Mismatch negativity and P3a amplitude in young adolescents with first-episode psychosis: a comparison with ADHD.

BACKGROUND: Deficient mismatch negativity (MMN) has been proposed as a candidate biomarker in schizophrenia and may therefore be potentially useful in early identification and intervention in early onset psychosis. In this study we explored whether deficits in the automatic orienting and reorienting responses, measured as MMN and P3a amplitude, are present in young adolescents with first-episode psychosis (FEP) and whether findings are specific to psychosis compared to young adolescents with attention deficit hyperactivity disorder (ADHD). METHOD: MMN and P3a amplitude were assessed in young adolescents (age 12-17 years) with either FEP (N = 27) or ADHD (N = 28) and age- and gender-matched healthy controls (N = 43). The MMN paradigm consisted of a four-tone auditory oddball task with deviant stimuli based on frequency, duration and their combination. RESULTS: Significantly less MMN was found in patients with psychosis compared to healthy controls in response to frequency and duration deviants. MMN amplitudes in the group of patients with ADHD were not significantly different from patients with psychosis or healthy controls. No significant group differences were found on P3a amplitude. CONCLUSION: Young adolescents with FEP showed impaired MMN compared to healthy controls while intermediate and overlapping levels of MMN were observed in adolescents with ADHD. The findings suggest that young FEP patients already exhibit pre-attentive deficits that are characteristic of schizophrenia albeit expressed on a continuum shared with other neuropsychiatric disorders.

Methylphenidate misuse in adult patients and the impact of therapeutic use.

OBJECTIVE: Methylphenidate (MPH) prescription rates for adults increase, but the extent of a parallel rise in toxic exposures and their causes and distribution between different MPH trade names are unexplored. METHOD: We retrospectively analyzed adult MPH exposures reported to the Danish Poison Information Centre from January 2006 to July 2012 and the association with MPH sales and the number of patients prescribed MPH. RESULTS: Of the 394 exposures (57% males, median age 27 years) reported, MPH status was available in 249 of whom 65.5% were prescribed MPH. Exposure was in 54% motivated by suicidal attempt and in 40% by recreational use (based on 375 cases). Exposure was dominated by one trade name and exposure incidence correlated significantly with sales ( p = 0.001) and prevalence of MPH-treated patients ( p = 0.0008). CONCLUSIONS: The increase in MPH exposures parallels the prescription rates (particularly Ritalin(®)/Ritalin(®) Uno). Most exposures were intentional and motivated by suicide attempts or recreational use.

Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders: protocol for a network meta-analysis of randomised trials.

INTRODUCTION: Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative effectiveness studies in children and adolescents are limited in number and size, and only a few meta-analyses based on conventional methodologies have been conducted. METHODS AND ANALYSES: We will conduct a network meta-analysis of all randomised controlled trials (RCTs) that evaluate antipsychotic therapies for EOS to determine which compounds are efficacious, and to determine the relative efficacy and safety of these treatments when compared in a network meta-analysis. Unlike a contrast-based (standard) meta-analysis approach, an arm-based network meta-analysis enables statistical inference from combining both direct and indirect comparisons within an empirical Bayes framework. We will acquire eligible studies through a systematic search of MEDLINE, the Cochrane Central Registry of Controlled Trials, Clinicaltrials.gov and Centre for Reviews and Dissemination databases. Eligible studies should randomly allocate children and adolescents presenting with schizophrenia or a related non-affective psychotic condition to an intervention group or to a control group. Two reviewers will-independently and in duplicate-screen titles and abstracts, complete full text reviews to determine eligibility, and subsequently perform data abstraction and assess risk of bias of eligible trials. We will conduct meta-analyses to establish the effect of all reported therapies on patient-relevant efficacy and safety outcomes when possible. ETHICS AND DISSEMINATION: No formal ethical procedures regarding informed consent are required as no primary data collection is undertaken. The review will help facilitate evidence-based management, identify key areas for future research, and provide a framework for conducting large systematic reviews combining direct and indirect comparisons. The study will be disseminated by peer-reviewed publication and conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013006676.

Structural brain abnormalities in early onset first-episode psychosis.

BACKGROUND: Brain morphometry in children and adolescents with first-episode psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We compared high-resolution 3D T1-weighted magnetic resonance images of the brain in 29 patients (schizophrenia, schizotypal disorder, delusional disorder or other non-organic psychosis), aged 10-18 to those of 29 matched controls, using optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white matter abnormalities, but expected (regional) gray matter reductions were not observed. Post hoc analyses revealed that schizophrenia patients (n = 15) had significantly larger lateral ventricles as compared to controls. Duration and dose of antipsychotics correlated negatively with global gray matter volume in minimally medicated patients (n = 18). CONCLUSION: Findings of white matter changes and enlarged lateral ventricles already at illness onset in young schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes in the pathogenesis of these disorders. Gray matter volume changes, however, appear not to be a key feature in early onset first-episode psychosis.

Epidemiology of anorexia nervosa and bulimia nervosa in Bornholm County, Denmark, 1970-1989.

In a retrospective study of anorexia nervosa and bulimia nervosa, potential cases were traced, studied, and diagnosed according to ICD-10. Forty-two cases were found in Bornholm County, comprising the island of Bornholm in Denmark, in a population of 47,000 from 1970 to 1989. Less than half of these cases (n = 16) were registered in Danish psychiatric case registers, and 35% (n = 14) could be found only by search in primary care. The incidence rates were stable during most of the study period, but a significant increase occurred during the last 5 years. The prevalence rates, determined by counting the number of cases in the population year by year, also increased during the late part of the study period. In 1989 the incidence rate of the high-risk group of females 10 to 24 years of age was 136 per 100,000 for anorexia nervosa and 45 per 100,000 for bulimia nervosa, and the prevalence rate was 222 per 100,000 for anorexia nervosa and 89 per 100,000 for bulimia nervosa.