Inmaculada Baeza

Trait and State Attributes of Insight in First Episodes of Early-Onset Schizophrenia and Other Psychoses: A 2-Year Longitudinal Study

BACKGROUNDnIncreasing evidence supports the important role of illness state and individual characteristics in insight.nnnMETHODSnInsight, as measured with the Scale to Assess Unawareness of Mental Disorder, over the first 2 years of early-onset first-episode psychosis and its correlations with clinical, socio-demographic, cognitive, and structural brain variables are studied.nnnRESULTSn(1) insight at 2 years is poorer in schizophrenia spectrum disorders (SSDs) than in subjects with other psychoses; (2) the more severe the psychosis, the worse the insight. In SSD, depressive symptoms, poorer baseline executive functioning, lower IQ, longer duration of untreated psychosis (DUP), and poorer premorbid infancy adjustment are associated with poorer insight; frontal and parietal gray matter (GM) reductions at baseline correlate with worse insight into having psychotic symptoms at 2 years; (3) insight into having a mental disorder (Scale to Assess Unawareness of Mental Disorder [SUMD]1) at 1 year, DUP, and baseline IQ are the most consistent variables explaining different aspects of insight at 2 years in SSD patients. IQ and SUMD1 at 1 year, together with left frontal and parietal GM volumes, explain 80% of the variance of insight into having specific psychotic symptoms in SSD patients (adjusted R(2) = 0.795, F = 15.576, P < .001).nnnCONCLUSIONnInsight is a complex phenomenon that depends both on severity of psychopathology and also on disease and subject characteristics, such as past adjustment, IQ, DUP, cognitive functioning, frontal and parietal GM volumes, and age, gender, and ethnicity.

Second-Generation Antipsychotic Use in Children and Adolescents: A Six-Month Prospective Cohort Study in Drug-Naïve Patients

OBJECTIVEnTo assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths.nnnMETHODnThis study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (meanxa0= 14.6 ± 2.9 years). Of those, 248 (88.8%) received a single antipsychotic (risperidone, olanzapine, or quetiapine) and completed 2 visits, and 178 (63.8%) completed the 6-month follow-up. Patients had schizophrenia-spectrum disorders (44.5%), mood-spectrum disorders (23.2%), disruptive behavioral disorders (17.3%), or other disorders (15.1%). Fifteen age- and gender-matched, healthy, nonmedicated individuals served as a comparison group.nnnRESULTSnFrom baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (nxa0= 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (nxa0= 44; 11.5 kg and 1.08 BMI z score), and quetiapine (nxa0= 47; 6.3 kg and 0.54 BMI z score), but not in healthy control participants (-0.11 kg and 0.006 BMI z score). Fasting metabolic parameters increased significantly with risperidone (glucose [3.8] mg/dL, insulin [4.9] mU/L, homeostasis model assessment of insulin resistance [HOMA-IR: 1.2], triglycerides [15.6] mg/dL), and olanzapine (glucose [5.0] mg/dL, total cholesterol [21.2] mg/dL, and low-density lipoprotein cholesterol [44.6] mg/dL), but not with quetiapine or in healthy control participants. The percentage of research participants considered to be at risk of adverse health outcome increased during the 6 months from 8.9% to 29.2% for risperidone (pxa0< .0001), 6.8% to 38.1% for olanzapine (pxa0<xa0.0001), and 6.3%xa0to 4.0% for quetiapine (pxa0= .91).nnnCONCLUSIONnOlanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporalxa0side effect patterns.

Duration of untreated psychosis predicts functional and clinical outcome in children and adolescents with first-episode psychosis: A 2-year longitudinal study

Longer duration of untreated psychosis (DUP) in adult patients with first-episode psychosis (FEP) has been associated with poor clinical and social outcomes. We aimed to estimate the influence of DUP on outcome at 2-year follow-up in subjects with an early-onset (less than 18 years of age) FEP of less than 6 months duration. A total of 80 subjects (31.3% females, mean age 16.0±1.8 years) were enrolled in the study. The influence of DUP on outcome was estimated using multiple regression models (two linear models for influence of DUP on the C-GAF at 2 years and C-GAF change through the follow-up period, and a logistic model for influence of DUP on 41 PANSS remission at 2 years in schizophrenia patients (n=47)). Mean DUP was 65.3±54.7 days. Median DUP was 49.5 days. For the whole sample (n=80), DUP was the only variable significantly related to C-GAF score at 2-year follow-up (Beta=-0.13, p<0.01), while DUP and premorbid adjustment (Beta=-0.01, p<0.01; and Beta=-0.09, p=0.04, respectively) were the only variables significantly related to C-GAF change. In schizophrenia patients, DUP predicted both C-GAF score at 2 years and C-GAF change, while in patients with affective psychosis (n=22), DUP was unrelated to outcome. Lower baseline C-GAF score (OR=0.91, p<0.01) and shorter DUP (OR=0.98, p=<0.01) were the only variables that significantly predicted clinical remission in schizophrenia patients. In conclusion, longer DUP was associated with lower C-GAF at 2 years, less increase in C-GAF, and lower rates of clinical remission in early-onset FEP. Our findings support the importance of early detection programs, which help shorten DUP.

Psychiatric disorders in child and adolescent offspring of patients with schizophrenia and bipolar disorder: A controlled study

BACKGROUNDnEarly clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively.nnnMETHODSnSZ and BP parents with offspring aged 7-17years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations.nnnRESULTSnWe found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP-offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP-offspring, and BP-offspring presented a higher prevalence of depression than CC-offspring.nnnCONCLUSIONSnThe higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP.

Can positive family factors be protective against the development of psychosis

Genetic and environmental factors are both involved in the aetiology of psychotic disorders. The aim of this study was to assess if positive and negative environmental factors, together with psychotic family antecedents, are associated with the recent development of psychosis. We also investigated the interactions between family history of psychosis and positive and negative family environment. The sample comprised 110 children and adolescents, who had suffered a first psychotic episode and 98 healthy controls. All subjects were interviewed about their socioeconomic status, family history of psychosis and family environment (Family Environment Scale, FES). Early onset psychosis was significantly associated with a family history of psychosis. Family environment was perceived as more negative and less positive among patients than among controls. A negative family environment increased the risk of psychosis independently of the family history of psychosis. However, there was a significant protective effect of a positive family environment for persons with a family history of psychosis. This effect was not seen in subjects without a family history of psychosis. Therefore, our results support the importance of considering both family history of psychosis and family environment in the early stages of psychosis.

A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis

BACKGROUNDnThe relationship between duration of untreated psychosis (DUP) and executive function (EF) in patients with first-episode psychosis (FEP) is controversial. We aim to assess the influence of DUP on changes in EF over a 2-year period in subjects with early-onset FEP (first psychotic symptom before age 18) and less than 6 months of positive symptoms.nnnMETHODSnA total of 66 subjects were included in the study (19 females [28.8%], mean age 16.2 ± 1.6 years). The influence of DUP on changes in EF over the 2-year follow-up (expressed as a composite score of 5 cognitive abilities: attention, working memory, cognitive flexibility, response inhibition, and problem solving) was estimated using a multivariate linear regression model after removing the effect of intelligence quotient and controlling for age, gender, diagnosis, premorbid adjustment, severity of positive and negative symptoms at baseline, global functioning at baseline, and mean daily antipsychotic dosage during follow-up.nnnRESULTSnMean DUP was 65.0 ± 6.9 days (95% confidence interval [CI], 51.2, 78.8). Median DUP was 47.5 days (range 2-180 days). Negative symptoms at baseline was the only variable significantly associated with EF at baseline (10.9% of explained variance [e.v. 10.9%], p=0.007). Only shorter DUP (e.v. 8.7%, p=0.013) and greater severity of baseline negative symptoms (e.v. 10.0%, p=0.008) were significantly associated with greater improvement in EF.nnnCONCLUSIONSnIn early-onset FEP, shorter DUP was associated with greater improvement in EF over a 2-year follow-up period.

Premorbid impairments in early-onset psychosis: differences between patients with schizophrenia and bipolar disorder.

BACKGROUNDnDespite the large body of research on premorbid impairments in schizophrenia, studies comparing different early-onset psychoses are scarce.nnnAIMSnTo examine premorbid impairments in first episodes of early-onset bipolar and schizophrenia disorders.nnnMETHODnWe compared premorbid adjustment and other premorbid variables such as IQ and developmental abnormalities in a cohort of children and adolescents (N=69) with bipolar disorder (BP) or schizophrenia (SZ) experiencing their first psychotic episode and in a healthy control group (N=91).nnnRESULTSnSchizophrenia patients showed more social impairment in childhood than bipolar patients (p<0.05) and healthy controls (p<0.001) and had higher rates of developmental abnormalities (p<0.05) than healthy controls. Between childhood and early adolescence, schizophrenia and bipolar patients showed a greater decline in academic adjustment than healthy controls, more specifically in adaptation to school (p<0.01).nnnCONCLUSIONSnEarly-onset schizophrenia patients show more early social impairment than early-onset bipolar patients. Intellectual premorbid abnormalities are less specific and probably more linked to early-onset psychosis.

Predictors of schizophrenia spectrum disorders in early-onset first episodes of psychosis: a support vector machine model

Identifying early-onset schizophrenia spectrum disorders (SSD) at a very early stage remains challenging. To assess the diagnostic predictive value of multiple types of data at the emergence of early-onset first-episode psychosis (FEP), various support vector machine (SVM) classifiers were developed. The data were from a 2-year, prospective, longitudinal study of 81 patients (age 9–17xa0years) with early-onset FEP and a stable diagnosis during follow-up and 42 age- and sex-matched healthy controls (HC). The input was different combinations of baseline clinical, neuropsychological, magnetic resonance imaging brain volumetric and biochemical data, and the output was the diagnosis at follow-up (SSD vs. non-SSD, SSD vs. HC, and non-SSD vs. HC). Enhanced recursive feature elimination was performed for the SSD vs. non-SSD classifier to select and rank the input variables with the highest predictive value for a diagnostic outcome of SSD. After validation with a test set and considering all baseline variables together, the SSD vs. non-SSD, SSD vs. HC and non-SSD vs. HC classifiers achieved an accuracy of 0.81, 0.99 and 0.99, respectively. Regarding the SSD vs. non-SSD classifier, a combination of baseline clinical variables (severity of negative, disorganized symptoms and hallucinations or poor insight) and neuropsychological variables (impaired attention, motor coordination, and global cognition) showed the highest predictive value for a diagnostic outcome of SSD. Neuroimaging and biochemical variables at baseline did not add to the predictive value. Thus, comprehensive clinical/cognitive assessment remains the most reliable approach for differential diagnosis during early-onset FEP. SVMs may constitute promising multivariate tools in the search for predictors of diagnostic outcome in FEP.

Functional deterioration from the premorbid period to 2 years after the first episode of psychosis in early-onset psychosis

The aim of the study was to analyze changes in functional adjustment from childhood to 2xa0years after the first episode of psychosis (FEP) in patients with early-onset schizophrenia spectrum disorders (SSD) and affective psychoses (AFP) and a good or intermediate level of premorbid adjustment. We followed 106 adolescents (aged 12–17xa0years) with FEP for 2xa0years after recruitment. Premorbid adjustment in childhood was assessed in 98 patients with the childhood subscale of the Cannon-Spoor Premorbid Adjustment Scale (c-PAS). Global functioning was assessed 2xa0years after the FEP with the Children’s Global Assessment Scale (c-GAS) or the Global Assessment of Functioning scale (GAF), as appropriate. Functional deterioration was defined as a downward shift in the level of functional adjustment from childhood to 2 years after the FEP. In patients with good or intermediate premorbid adjustment, functional deterioration was observed in 28.2xa0% (26.5xa0% of the AFP group, 29.4xa0% of the SSD group). Longer duration of untreated psychosis (Betaxa0=xa00.01; Pxa0=xa00.01) and higher symptom severity at the FEP, as measured with the Clinical Global Impression Scale (Betaxa0=xa01.12; Pxa0=xa00.02), significantly predicted the presence of functional deterioration, accounting for 21.4xa0% of the variance. Irrespective of diagnosis (SSD or AFP), almost one-third of adolescents with FEP and good or intermediate premorbid adjustment showed functional deterioration from the premorbid period to 2xa0years after the FEP.

Clinical high risk for psychosis in children and adolescents: a systematic review

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 18xa0years. 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.