Early-onset Schizophrenia Spectrum Disorders Research Articles

Same same but different: Neuroanatomic and connectomic profiles of early-onset schizophrenia and autism spectrum disorder

BackgroundEarly-onset schizophrenia (EOS) and autism spectrum disorder (ASD) are two mental disorders with abnormal neurodevelopment and overlapping clinical symptoms. However, few prospective multi-center imaging studies explored their pathophysiological differences and similarities comprehensively. MethodsWe utilized a large cohort of functional magnetic resonance imaging data with standardized scanning protocols from 594 participants (276 participants with high-functioning ASD, 187 participants with EOS, and 131 normal controls (NCs)) recruited at five centers. A comprehensive evaluation of anatomical and connectomic features, including cortical thickness, subcortical nuclei volume, functional connectivity, functional gradients, and network efficiency, was conducted, culminating in the construction of imaging-based neuro-profiles for individuals with EOS and ASD. ResultsThe derived neuro-profiles revealed that EOS is characterized by more pronounced reductions in cortical thickness and subcortical nuclei volumes. In contrast, ASD exhibited more pronounced abnormalities in connectomic attributes. The decreased network functional connectivity and compressed functional gradients in ASD are likely to contribute to reduced network efficiency. Classifiers based on imaging profiles successfully distinguished individuals with EOS, ASD, and NCs with commendable performance in leave-site-out cross-validation (area under the operating characteristic curve (AUC) for ASD vs. NC: 0.769, AUC for ASD vs. EOS: 0.792, AUC for EOS vs. NC: 0.854). ConclusionThe neuro-profiles revealed that EOS and ASD exhibit overlapping as well as unique imaging characteristics; however, EOS exhibits greater structural variation, while ASD presents with more subtle connectomic abnormalities. These findings offer valuable insights into the distinct neurobiological mechanisms of EOS and ASD and enhance the prospect of early diagnosis through objective imaging-based biomarkers.

The association between plasma thyroxine levels and neurocognitive impairment in early-onset schizophrenia and other psychosis spectrum disorders

Background/aimLimited studies have delved into the association between thyroid hormones and neurocognition in schizophrenia. We aimed to evaluate the relationship between thyroid hormone levels and neurocognitive functions in patients with schizophrenia and other psychosis spectrum disorders (SSD). MethodA total of 135 patients with early-onset SSD were included in the study. The participants underwent a cognitive assessment. Blood samples were collected to measure serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Subgroup analyses were conducted based on the severity of the psychosis. FindingsThe results revealed a significant association between fT4 levels and various cognitive domains, including processing speed, verbal fluency, working memory, verbal learning, verbal memory, and visual memory. However, serum TSH and fT3 levels exhibited no significant association with neurocognitive impairment in adjusted linear regression models. Specifically, the correlation between fT4 levels and global cognition was more pronounced in patients with higher scores. ConclusionsSerum fT4 levels were associated with the performance across various cognitive domains in cases of early-onset psychotic disorders. This correlation was accentuated among patients with higher illness severity. Future studies could focus on the effects of specific pathways that can affect the course and progression of psychosis.

Ribosomal DNA Abundance in the Patient's Genome as a Feasible Marker in Differential Diagnostics of Autism and Childhood-Onset Schizophrenia.

Introduction: Differential diagnostics of early-onset schizophrenia and autism spectrum disorders (ASD) are a problem of child psychiatry. The prognosis and relevant treatment are to a large degree determined by the correctness of diagnosis. We found earlier that leucocyte DNA of adult schizophrenia patients contained significantly larger copy numbers of ribosomal repeats (rDNA) coding for rRNA, than DNA of mentally healthy controls. Aim: To compare the contents of ribosomal repeats in the leucocyte DNA of children with schizophrenia, children with ASD, and healthy age-matched controls to estimate the possibility of using this genetic trait in the differential diagnostics of the two types of disorders. Patients and methods: Blood samples of patients with infantile autism (A—F84.0 according to ICD-10, N = 75) and with childhood-onset schizophrenia (SZ—F20.8 according to ICD-10, N = 43) were obtained from the Child Psychiatry Department of the Mental Health Research Center. The healthy control blood samples (HC, N = 86) were taken from the Research Centre for Medical Genetics collection. The recruitment of cases was based on the clinical psychopathologic approach. DNA was extracted from blood leukocytes with organic solvents. Nonradioactive quantitative hybridization technique was applied for determining the abundance of ribosomal repeats in the genomes. Statistical processing was performed using StatPlus, Statgraphics and MedCalc. Findings: DNA derived from SZ cases contained 565 ± 163 rDNA copies, which is significantly (p < 10−6) higher than the rDNA content in ASD cases (405 ± 109 copies) and controls (403 ± 86 copies). The HC and A groups did not differ by rDNA copy number (p > 0.4). The genetic trait “rDNA copy number in patient’s genome” can potentially be applied as an additional marker in differential diagnostics of childhood-onset schizophrenia and autism spectrum disorders.

Disembodied Language in Early-Onset Schizophrenia.

A recent view on schizophrenia phenomenology underlines the impaired relations between the mind and the body. An aberrant feeling of ipseity may be the real source of suffering of the patients from psychosis and impacts general symptomatology. The disturbed connection between thinking processes and environmental stimuli may lead to language disembodiment. In the study, we aimed to experimentally test the presence of disembodied language and investigate its association with symptoms of psychosis in adolescents diagnosed with early-onset schizophrenia spectrum disorders. Assessment of language embodiment was conducted using the Zabór Verbal Task (ZVT) with concurrent linguistic and clinical assessment using the Thought, Language, and Communication Scale (TLCS) and Positive and Negative Symptoms Scale (PANSS). The study group of patients (n = 31) aged 11–18 years, with the diagnosis of schizophrenia spectrum according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and the International Classification of Diseases (ICD-10) criteria, was compared with a sex- and age-matched healthy control sample (n = 31). Patients with psychosis made more errors in ZVT than healthy controls (p = 0.01) and this parameter did not improve after 6–8 weeks of standard treatment (p = 0.55). A higher number of errors in ZVT were associated with the presence of auditory hallucinations (odds ratio [OR] 1.14; 95% CI 1.02–1.26). ZVT errors coincided with perception disorders, alternatively to the TLCS scores where we observed association with abnormal beliefs. The results of these preliminary studies indicate the value of the phenomenological approach in the diagnosis of schizophrenia spectrum and suggest a potential involvement of language disembodiment in symptomatology.

Neurocognitive and social cognitive impairments in remission and symptomatic states of early-onset schizophrenia spectrum disorders.

Previous studies demonstrated neurocognitive impairments in early-onset schizophrenia (EOS) and other psychotic spectrum disorders (PSD). This study aimed to compare remitted and symptomatic cases in terms of neurocognition and theory of mind (ToM). 50 healthy controls (HC) and 106 patients diagnosed schizophrenia in remission (EOS-R, n = 38), symptomatic schizophrenia (EOS-S, n = 34), and other PSD (n = 34) were included in our study. The Positive and Negative Symptom Scale, Columbia-Suicide Severity Rating Scale, Reactive and Proactive Aggression Questionnaire were used to evaluate psychopathology. A cognitive battery was conducted to measure verbal learning/memory, visual learning/memory, executive functions (EF), inhibition, processing speed (PS), verbal fluency skills. Reading Mind in Eyes Test (RMET) and Faux-Pas tests were implemented to assess ToM. Principal Component Analysis was used to identify cognitive domain scores. Patient groups had poorer performance in cognitive domains than the HC group. The cognitive impairment and psychopathology levels of EOS-R and the PSD groups were comparable for all cognitive domains. The EOS-S group also had poorer scores in Rey verbal learning score (d = 0.87), RMET (d = 0.72), verbal fluency (d = 0.66), PS/EF (d = 0.82) and visual learning/memory (d = 0.83) test scores than the PSD group. Only RMET (d = 0.72) and executive function/processing speed domain (d = 0.63) were significantly impaired in the EOS-S group than the EOS-R group Cognitive impairments seen in remitted psychotic disorders were on the same continuum. Impaired EF/PS and ToM skills could be a cognitive marker for symptomatic illness in youth.

Identifying clinical and psychological correlates of persistent negative symptoms in early-onset psychotic disorders.

Persistent negative symptoms (PNS) contribute to impairment in psychosis. The characteristics of PNS seen in youth remained under-investigated. We aimed to demonstrate clinical, treatment-related, and psychosocial characteristics of PNS in early-onset schizophrenia-spectrum disorders (EOSD). 132 patients with EOSD were assessed with Positive and Negative Symptom Scale, Brief Negative Symptom Scale, Calgary Depression Scale for Schizophrenia, and Simpson-Angus Scale. Parenting skills and resilience were evaluated using Parental Attitude Research Instrument and Child and Youth Resilience Measure-12. Longer duration of untreated psychosis (DUP) and prodromal phase were found in primary and secondary PNS groups, compared to the non-PNS group. The primary PNS group was characterized by earlier age-onset, lower smoking rates, and more common clozapine use. Resilience and egalitarian/democratic parenting were negatively correlated with symptoms related to motivation/pleasure and blunted expression. More blunted expression-related symptoms and longer DUP in the first episode significantly predicted primary/secondary PNS at follow-up. Using the data from total negative symptom scores and DUP, Receiver Operating Characteristic analyses significantly differentiated primary/secondary PNS groups from the non-PNS counterparts. PNS associated with blunted expression and low motivation/pleasure in the first episode could persist into clinical follow-up. Effective pharmacological treatment and psychosocial interventions are needed in youth.

BDNF Val66Met polymorphism is associated with negative symptoms in early-onset schizophrenia spectrum and other psychotic disorders

Background and ObjectivesTo investigate the clinical characteristics of adolescents with early-onset full psychotic disorders either with Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) or DRD2/ANKK1 Taq1A (rs1800497) polymorphisms. Method101 cases with early-onset schizophrenia (EOS) or other psychotic spectrum disorders (SSD) and 150 healthy controls were included in the current study. Using the Positive and Negative Symptom Scale (PANSS), patient subgroups were compared for their psychotic symptoms, age-onset, duration of untreated illness, and family history of psychiatric disorders. The real-time polymerase chain reaction (RT-PCR) was implemented for genotyping procedures. ResultsStudy groups and patient subgroups were similar regarding their sociodemographic characteristics (16.4 ± 2.6 years, 62.2% male for all participants). Results did not reveal any difference between patients and healthy controls for DRD2/ANKK1 Taq1A and BDNF Val66Met genotypes. Patients with A1A2 (Gly/Lys) allele reported higher rates of substance use compared to A2A2 (Glu/Glu) counterparts. Other clinical variables were found similar. EOS/SSD group with Val66Met heterozygote allele revealed lower levels of negative symptoms than Val/Val homozygotes. Conversely, the age onset of full psychotic disorder, total positive symptom score, and total general psychopathology score of PANSS were found comparable between Val/Met and Val/Val groups. In the logistic regression model, Glu/Lys genotypes remained significant for the presence of substance use. ConclusionThe interaction between substance use and the DRD2 gene should be investigated for the development of early-onset psychotic disorders. BDNF Val66Met polymorphism also could be a disease-modifying factor for the presence of negative symptoms.

Time to Clinical Response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study.

Objectives: We investigated the time course of clinical response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study (TEOSS). Methods: TEOSS randomized 119 predominantly outpatient youth ages 8-19 years with schizophrenia or schizoaffective disorder to 8 weeks of treatment with molindone, risperidone, or olanzapine. We used proportional hazards regression to determine whether these three antipsychotics differed in the time until clinical response, defined as the time from treatment initiation to the point of achieving a Clinical Global Impressions-Improvement (CGI-I) scale score of 1 ("very much improved") or 2 ("much improved") that was maintained until week 8. Results: Of the 116 youth who initiated treatment, 56 (48%) achieved clinical response. Among clinical responders, the median (±interquartile range) time until clinical response was 4.0 (±4.0) weeks for olanzapine, 4.5 (±4.0) weeks for risperidone, and 6.0 (±4.0) weeks for molindone. There were no significant differences in time course for clinical response between medications (p = 0.84). Youth without symptom improvement (CGI-I ≥ 4) after 3 weeks were more likely to be clinical nonresponders at week 8 (relative risk ratio = 1.98, 95% confidence interval 1.29-3.05), compared with youth with at-least-minimal symptom improvement after 3 weeks when looking at all antipsychotics combined. Conclusion: To our knowledge, our study is the first to investigate medication differences in treatment response timing in early onset schizophrenia spectrum disorders. Clinical response times for molindone, risperidone, and olanzapine were not significantly different. Furthermore, while lack of early improvement predicted clinical nonresponse, whether or not to continue antipsychotic treatment after 3 or more weeks without symptom improvement should be based on clinical judgment after weighing potential risks, benefits, and alternatives. ClinicalTrials.gov Identifier: NCT00053703.

Altered empathy-related resting-state functional connectivity in adolescents with early-onset schizophrenia and autism spectrum disorders.

Empathy refers to the ability to understand other people's feelings and reacting emotionally to others. Impaired empathy has been reported in both individuals with schizophrenia and autism spectrum disorders (ASD). Despite overlaps, few studies have directly examined the neural mechanisms of impaired empathy in these two clinical groups. We used resting-state fMRI to investigate the neural correlates of empathic functioning in adolescents with ASD (N = 11), early-onset schizophrenia (EOS) (N = 20), and typically developing (TD) controls (N = 26). Their parents completed the Griffith Empathy Measure (GEM) to assess the adolescents' empathic capacity. We found that EOS and ASD participants both exhibited impaired empathy as measured by the GEM, especially in cognitive empathy (post-hoc ps < 0.05). Regions-of-interest-based functional connectivity revealed decreased connectivity between the salience network (SN) (i.e., the anterior insula and the anterior cingulate cortex) and core regions of the mentalizing network (e.g., the temporal-parietal junction and the precuneus), and among the SN and the bilateral superior temporal gyri (STG) and the left cerebellum in EOS participants. Subsequent comparisons revealed reduced grey matter volume in the STG bilaterally in both clinical groups. Increased resting-state functional connectivity within the social brain network was correlated with higher parent-reported scores of empathic capacity in TD adolescents, but such a brain-phenotype relationship was absent in the two clinical groups. These findings indicate that structural alterations and disturbed resting-state functional connectivity in the core empathy network may be the neural correlates of social cognitive deficits in individuals with EOS and ASD.

Recovery and Recovering in Older Adults with Schizophrenia: A 5-Tier Model

RationaleThere are little recent data on clinical recovery in older adults with schizophrenia. This exploratory study uses an empirically measurable construct to address this issue. MethodsFrom an original sample of 248 community-dwelling persons aged 55 and over with early-onset schizophrenia spectrum disorder, a subsample of 102 persons was reassessed at a mean of 52 months. Clinical recovery required meeting criteria for its two components: clinical remission and community integration. ResultsProspective analysis generated a 5-tier taxonomy of recovery in which 12% remained persistently in clinical recovery at both baseline and follow-up (Tier 1) and 18% never met criteria of clinical recovery (Tier 5). The remaining 70% exhibited a variety of components of clinical recovery at baseline and follow-up (Tiers 2, 3, and 4). ConclusionThe findings generated a dynamic picture of recovery, with most persons being in varying states of “recovering.” The 5-tier taxonomy of recovery adumbrated potential treatment strategies for each tier.

Childhood-Onset Schizophrenia and Early-onset Schizophrenia Spectrum Disorders: An Update.

The clinical severity, impact on development, and poor prognosis of childhood-onset schizophrenia may represent a more homogeneous group. Positive symptoms in children are necessary for the diagnosis, and hallucinations are more often multimodal. In healthy children and children with a variety of other psychiatric illnesses, hallucinations are not uncommon and diagnosis should not be based on these alone. Childhood-onset schizophrenia is an extraordinarily rare illness that is poorly understood but seems continuous with the adult-onset disorder. Once a diagnosis is confirmed, aggressive medication treatment combined with family education and individual counseling may prevent further deterioration.

1.4 TIME UNTIL CLINICAL IMPROVEMENT IN THE TREATMENT OF EARLY-ONSET SCHIZOPHRENIA SPECTRUM DISORDERS STUDY (TEOSS)

There is little research on how long to wait for clinical improvement before changing antipsychotic drugs in early-onset schizophrenia. The Treatment of Early-Onset Schizophrenia Spectrum Disorders Study (TEOSS) randomized 119 youth ages 8–19 years with schizophrenia, schizoaffective disorder, or schizophreniform disorder to 8 weeks of treatment with molindone, risperidone, or olanzapine. Until recently, the publications using TEOSS data found that response rates did not significantly differ for the 3 antipsychotic drugs.

Distinguishing prodromal stage of bipolar disorder and early onset schizophrenia spectrum disorders during adolescence

Prodromal symptoms of bipolar disorder (BD) and early onset schizophrenia spectrum disorder (EOSSD) overlap. To date, there has been no study directly comparing the prodromal stage of both disorders. Thus, the current study is aimed at determining which prodromal symptom clusters differentiate BD and EOSSD. One hundred twenty one adolescents (33 BD-1, 30 EOSSD, 58 healthy controls) were evaluated for the presence of 79 prodromal symptoms, divided into 7 prodromal symptom clusters. Great than 2 subsyndromal manic symptoms and ADHD comorbidity were significantly more specific for BD than schizophrenia; brief limited intermittent psychotic symptoms (BLIPS) were more likely to be part of EOSSD. In contrast, attenuated psychotic symptoms, and negative symptoms were not specifically related to the diagnosis of EOSSD. In conclusion, subsyndromal manic symptoms, BLIPS, and ADHD might be useful for predicting the trajectory of an emerging affective disorder versus schizophrenia and thus valuable for early detection, and intervention strategies.

A Longitudinal Study of Illness Awareness in Older Adults With Schizophrenia

Impaired insight is common in schizophrenia and may be affected by changes that occur with aging. There have been a few nonprospective investigations of insight in older adults with schizophrenia (OAS). This study examines the temporal fluctuations that occur with insight-defined as "awareness of mental illness" (dichotomized into presence or absence)-along with associated factors that influence illness awareness (IA) in OAS. The sample consisted of 103 persons derived from an initial sample of 250 community-dwelling persons aged 55 and over with early-onset schizophrenia spectrum disorder. Mean follow-up was 53 months. We examined 27 potential predictor variables of IA along with 5 covariates in bivariate analysis. The significant variables were then examined using multiple regression analyses. 23% of persons transitioned between presence and absence of IA, 62% had persistent IA, and 15% never had IA. At baseline, fewer negative symptoms (blunted affect), higher cognitive functioning (conceptualization), younger age, higher educational levels, and more physical disorders were associated significantly with higher rates of IA at follow-up. Baseline IA did not predict any variables at follow-up. IA is often unstable in later life, with nearly one-fourth of persons showing fluctuations. Although younger age predicted IA over time, other factors associated with aging, such as cognitive functioning and physical disorders, had additional independent effects on IA. The impact of IA on clinical and functional variables attenuated over time, suggesting that for many OAS, IA may have a limited role in enhancing long-term outcomes.

Predictors and Moderators of Antipsychotic-Related Weight Gain in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study.

Antipsychotic-related weight gain is a common clinically relevant side effect when treating psychotic disorders in pediatric populations, yet few predictors and no moderators of antipsychotic-related weight gain are known. The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study randomized 119 youths (age 8-19 years) with schizophrenia or schizoaffective disorder to 8 weeks of antipsychotic treatment with molindone, risperidone, or olanzapine and assessed treatment response and side effects. In this secondary analysis, we used multivariable linear regression and receiver operating characteristic analysis to investigate predictors and moderators of weight change and percent weight change from baseline to week 8. Treatment assignment was the most discriminant predictor of weight change [F(2, 66) = 17.00, p < 0.001] and percent weight change [F(2, 66) = 16.85, p < 0.001]. Mean weight gain was 0.74 (standard deviation ±3.51) kg for molindone, 4.13 ± 3.79 kg for risperidone, and 7.29 ± 3.44 kg for olanzapine. After adjusting for treatment assignment, lower pretreatment hemoglobin A1C (HgbA1C) predicted more weight gain [F(1, 55) = 4.71, p = 0.03]. Diagnosis (schizoaffective vs. schizophrenia) moderated weight change [F(2, 63) = 6.02, p = 0.004] and percent weight change [F(2, 63) = 5.26, p = 0.008] such that schizoaffective diagnosis predicted larger weight gain for youths in the risperidone treatment arm. Age, sex, family income, baseline weight, and symptoms neither predicted nor moderated weight change or percent weight change. We identified prognostic subgroups and novel risk factors for antipsychotic-related weight gain. We confirmed that antipsychotic choice is extremely important for predicting future weight gain. We also found that younger age did not predict greater weight gain, in contrast to prior studies. Our findings require replication in an independent sample because we did not adjust for multiple comparisons to minimize false negatives. ClinicalTrials.gov Identifier: NCT00053703.

T152. NRN1 GENE AND FUNCTIONAL MRI: ASSOCIATION ANALYSIS IN SCHIZOPHRENIA PATIENTS AND HEALTHY SUBJECTS

BackgroundAlterations of synaptic plasticity are currently accepted to play a critical role in schizophrenia (SZ). Among genes of neuronal plasticity there is Neuritin1 gene (NRN1), which has been associated with SZ, age at onset and differences in general cognitive performance in this disorder. However, little is known about the brain imaging correlates of NRN1 gene. We aimed: i) to investigate the association of NRN1 with schizophrenia-spectrum disorders (SZ-SD), exploring its role in age at onset through a family-based study, ii) to examine the brain functional correlates of NRN1 sequence variants through a neuroimaging genetics approach using a case-control design.MethodsA family-based association analysis was carried out with a sample of 588 individuals from 159 families (74 early onset / 85 adult onset) with an offspring with a diagnosis of SZ-SD. An independent sample consisting of 45 subjects (26 patients / 19 controls) was used to perform a case-control neuroimaging genetics analysis. DNA was extracted from blood/buccal mucosa samples and eleven Single Nucleotide Polymorphisms (SNPs) in NRN1 were genotyped. The linkage disequilibrium between the SNPs was estimated in the family-based sample with Haploview v4.1. Three haplotype blocks were defined: 1) rs2208870, rs12333117, rs582186, 2) rs645649, rs582262, 3) rs3763180, rs10484320, rs4960155, rs9379002, rs9405890, rs1475157. PLINK-v1.06 was used for the tabulation of possible individual haplotype phases and for the family-based association analyses (Transmission Disequilibrium Test). To explore the brain functional correlates of NRN1, the subjects belonging to case-control sample underwent a single MRI scanning session and performed a virtual reality spatial navigation task (Salgado-Pineda et al. 2016). The standard atlas provided in the FSL package was used to define three separate ROIs (left and right hippocampus and medial frontal region (mPFC)) and the mean value of activation per each subject was used to test the effect of each SNP/haplotypes by means of a linear regression. All the analyses were adjusted by age, sex and premorbid intelligence coefficient (IQ-TAP).ResultsTwo haplotypes including SNP4 and SNP5 (rs645649-rs582262) were associated with early onset SZ-SD: the haplotype CG was undertransmitted from parents to patients (p=0.011, OR (95%CI=0.08(0.01–0.71) - protective haplotype), while the haplotype GG showed an overtransmission trend (p=0.055, OR (95%CI=3.83 (1.40–10.48)). No effect was observed in the adult onset subsample.No differences between patients and controls were observed in the activation of the three ROIs. Within patients, an effect of the haplotype CG (SNP4-5) was detected in the mPFC: carriers of no copies of the protective haplotype showed a higher mean activation (n=15, mean(SD)=-1.17(17.37)) than individuals with at least one copy of the haplotype (n=9, mean(SD)=-21.19(21.94)) (⎕=-0.507 p=0.035).DiscussionFirst, our family-based results are consistent with evidence of a genetic association between NRN1 gene and SZ-SD and extend the knowledge on that NRN1 has a selective impact on early age at onset (Fatjó-Vilas et al. 2016). Second, our data suggest that NRN1 is involved in the regulation of the de-activation of mPFC in patients with SZ during a spatial navigation task. This result is of special interest since mPFC is an area included in the Default Mode Network (DMN) and alterations in this network have been highly documented in SZ patients during performance of different tasks (Pomarol-Clotet et al. 2008; Mannell et al. 2010; Salgado-Pineda et al. 2011).AcknowledgementsFundación Alicia Koplowitz.

T27. DYSFUNCTIONAL ATTITUDES IN ADOLESCENTS WITH EARLY-ONSET PSYCHOSIS: PRELIMINARY RESULTS

BackgroundDysfunctional attitudes such as defeatist performance beliefs (DPB) and asocial beliefs (AB) have been linked to negative symptoms and functional outcome in chronic schizophrenia (Campellone et al., 2016; Grant and Beck, 2010) and in adults with recent onset schizophrenia (Ventura et al., 2014). Adolescents with early-onset psychosis (EOP) are at major risk of having persistent negative symptoms (Puig et al., 2017) but no previous study has examined dysfunctional attitudes in this population. We aimed: (1) to examine if more DPB and AB were present in adolescents with EOP compared with normal controls, and (2) to study the relationships between DPB and AB with symptoms and functioning.MethodsSample: 15 adolescents with EOP (11♀, age=15.33 ± 1.23) and 10 healthy controls (8♀, age=15.60 ± 1.51), participants in a trial about cognitive and behavioral social skills treatment in EOP developing in Hospital Clínic of Barcelona (baseline data). Patients were under antipsychotic meds. Inclusion criteria: having an early-onset schizophrenia spectrum disorder diagnosed between 9–18 years-old (schizophrenia, schizoaffective disorder, psychosis n.o.s.); being within the 5 first years after the disease onset; clinical stability. Exclusion criteria: IQ<70; comorbid substance dependence disorder; neurological disorders. Instruments: PANSS (Kay et al., 1987), Calgary Depression Scale (CDS, Addington et al., 1990), Children’s Global Assessment Scale (C-GAS, Shaffer et al., 1983), Social and Role Functioning Scales (GF:S, GF:R, Cornblatt et al., 2007), Life Skills Profile - Adolescent version (Puig et al., 2013), Dysfunctional Attitudes Scale - Spanish version (DAS, Sanz et al., 1993); Asocial Beliefs Scale (Grant and Beck, 2010). DPB was extracted from the DAS scale following Beck et al. (2013). Groups were compared with T-test or Chi-square tests. Pearson correlations were computed for examining relationships between variables.ResultsEOP and control groups were homogeneous in age (t=-0.49, p=0.632) and sex (X2=0.15, p=0.702). All subjects were living with their parents. Family SES was lower in EOP group (X2=10.69, p=0.030). All subjects but one patient were studying although patients had repeated more courses (t=4.00, p=0.001). EOP subjects had a predominance of negative symptoms (positive symptoms=14.07 ± 3.85; negative symptoms=23.50 ± 13.79; general symptoms=31.86 ± 7.28). Mean score of CDS in EOP was low (3.77 ± 4.76). EOP group had lower scores in all functional measures than controls (C-GAS: 51.14 ± 9.38 vs 93.70 ± 4.45, GF:S: 5.71 ± 1.07 vs 9.00 ± 0.47, GF:R: 5.21 ± 1.12 vs 8.80 ± 0.42, LSP: 67.64 ± 12.30 vs 44.13 ± 3.60; t>6.67, p<0.001). Regarding dysfunctional attitudes, EOP group had higher scores in dysfunctional attitudes scales than healthy controls (DPB: 55.60 ± 19.57 vs 33.00 ± 9.37, AB: 6.67 ± 3.42 vs 3.00 ± 2.11; t>3.02, p<0.006). In EOP, DPB and AB scores were negatively correlated with functioning (DPB: C-GAS r=-0.60, GF:S r=-0.66, GF:R r=-0.66, LSP r=0.65; p<0.002; AB: C-GAS r=-0.45, GF:S r=-0.55, GF:R r=-0.49, LSP r=0.53; p<0.029). No significant correlation were found between dysfunctional attitudes and negative symptoms in EOP.DiscussionThese preliminary results showed that adolescents with EOP had higher levels of dysfunctional attitudes than controls. Accordantly to recent literature, defeatists performance beliefs and asocial beliefs were correlated with poorer functioning. However, dysfunctional attitudes were not associated with negative symptoms. It might be that dysfunctional attitudes do not contribute to negative symptoms but in functional outcome in youngs with EOP although larger samples are required. Acknowledgments: Fundación Alicia Kolplowitz.

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

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. 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 2years, and composite scores of total performances were calculated. The analyses were performed with a linear mixed model. 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. Though at different levels, the EOS group and the controls had a similar cognitive course over 2years. Some baseline characteristics (psychotic symptoms, DUP, remission, and hospitalization) had no influence on cognition within the first 2years 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.

Glucocorticoids and the risk of schizophrenia spectrum disorder in childhood and adolescence – A Danish nationwide study

Glucocorticoids can have psychosis as a potential side effect, but have also been suggested to yield protective effects due to anti-inflammatory properties. Nonetheless, knowledge is sparse on the association between glucocorticoid treatment and development of psychosis, which we aimed to study in this first large-scale longitudinal study.Among all individuals born in Denmark 1995–2003 (n=597,257), we compared individuals who had redeemed ≥1 prescription for glucocorticoids to an active comparator group and a non-exposed group concerning subsequent development of schizophrenia spectrum disorders until 2013. Hazard rate ratios (HRR) were estimated using Cox regression adjusted for calendar year, age, gender, urbanization, somatic diseases, parental educational level and psychiatric history.The risk for a subsequent diagnosis of early-onset schizophrenia spectrum disorder (N=1141) was increased after exposure to both non-systemic (HRR=1.47; 95%-CI=1.25–1.73; N=371) and systemic glucocorticoids (HRR=1.66; 95%-CI=1.13–2.43; N=34), when compared to non-exposed individuals. Similar elevated risks were observed when comparing to the active comparator group, for schizophrenia and acute psychosis, and within an older cohort. The risk of psychosis was elevated the most within the first year after exposure to glucocorticoids (P<0.001) without any indication for a dose-response association. However, in individuals with asthma, exposure to glucocorticoids did not further increase the risk of psychosis.Glucocorticoid exposure was associated with an increased risk for psychotic disorders, which may be explained by an effect of the underlying somatic disease, such as asthma. A potential beneficial effect of glucocorticoids on psychotic symptoms should be investigated in clinical trials.

Predictors of treatment response and drop out in the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study

The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) compared the efficacy of risperidone, olanzapine, and molindone over 8 weeks in 119 youths age 8–19 years with early-onset schizophrenia or schizoaffective disorder. From this large dataset, we examined predictors of treatment response and drop out using stepwise regression and receiver operating characteristics curve (ROC) analysis. Treatment response was defined as having both a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) score and a Clinical Global Impression-Improvement (CGI-I) score < 3. More severe baseline symptoms, having a history of being in an early education program, and previous prescription of a mood stabilizer increased the likelihood of responding to treatment. Anhedonia and poor community functioning predicted a reduction in symptom severity on the PANSS. Random assignment to different antipsychotic treatment was not predictive of outcome. Parental report of aggressive behaviors at baseline and being African American were associated with a greater likelihood of drop out. Our results suggest youth with more severe psychotic symptoms are most likely to benefit from treatment with antipsychotics and that aggressive youth may require additional support to improve treatment adherence. Further investigation is needed to understand potentially modifiable predictors of response like early education programs.