Josefina Castro-Fornieles

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

BackgroundOur objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group.MethodsTotal antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls.ResultsA decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients.ConclusionsGlutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology.

The child and adolescent first-episode psychosis study (CAFEPS): Design and baseline results ☆

OBJECTIVE The child and adolescent first-episode psychosis study (CAFEPS) is a multicenter, two-year, longitudinal project aiming to evaluate different clinical, neuropsychological, neuroimaging, biochemical, immunological, and genetic variables and treatment and prognostic factors in these patients. This paper describes the methods and rationale behind the study and the general characteristics of the sample. METHOD At six different centers, from March 2003 through November 2005, we consecutively recruited 110 patients, ages 9-17 years, who presented with a first psychotic episode. Controls were recruited from the same geographic areas and were matched for gender and age. RESULTS Patients had lower socioeconomic status (SES) (p=0.018) and parental years of education (p<0.001) than controls. The percentage of patients recruited increased with age (p<0.001) and there was a higher percentage of males (p<0.001). The total mean PANSS score was 89.03+/-20.1, the positive score 23.8+/-6.5 and the negative score 20.02+/-8.8. There were no significant differences between the genders with respect to age, parental years of education, SES, or scores in premorbid adjustment or general functioning. There were statistically significant positive correlations between age and positive symptoms and between all PANSS subscales and the Disability Assessment Schedule, and negative correlations between positive symptoms and global functioning. Diagnoses after the baseline evaluation were: psychotic disorder not otherwise specified (NOS) 35.5%, schizophreniform disorder 24.5%, mood disorder with psychotic symptoms 22.7%, schizophrenia 10%, schizoaffective disorder 2.7%, and other psychotic disorders 4.5%. Patients had worse premorbid adjustment (p<0.001) and global functioning (p<0.001) than controls after controlling for SES. CONCLUSIONS Infancy and adolescence adjustment and global functioning are lower in children and adolescents with psychotic disorders than in controls, severity of symptoms are related to general disability, and the most frequent diagnoses are psychotic disorders NOS.

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

BACKGROUND Increasing evidence supports the important role of illness state and individual characteristics in insight. METHODS Insight, 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. RESULTS (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). CONCLUSION Insight 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.

Neuropsychological Performance in Children and Adolescents with Obsessive-Compulsive Disorder and Influence of Clinical Variables

BACKGROUND Several studies have found impairment in visual memory and visual organization in adults with obsessive-compulsive disorder (OCD), but little is known about the neuropsychological profile of children and adolescents with this disorder. The influence of clinical variables such as age, severity of obsessive-compulsive symptomatology, depressive symptomatology, and pharmacological treatment on cognitive performance in these patients has not been thoroughly studied. METHODS A neuropsychological battery designed for this study was administered to 35 patients with DSM-IV-TR diagnosis of OCD without psychiatric comorbidity aged between 7 and 18 years and 35 gender- and age-matched healthy subjects. RESULTS Children and adolescents with OCD performed significantly worse on verbal and visual memory and velocity. When depressive symptomatology was controlled, impairment in visual memory, visual organization, and velocity again was found, but impairment in verbal memory was not. Neuropsychological impairment was not related to age, obsessive-compulsive severity, and pharmacological treatment. CONCLUSIONS Children and adolescents with OCD without psychiatric comorbidity with acute illness show impairment in visual memory, visual organization, and velocity, similar to adults. The influence of depressive symptomatology is important in cognitive performance. No relation was found between neuropsychology and age, severity of obsessive-compulsive symptomatology, or pharmacological treatment in this study.

Antipsychotic Treatment in Child and Adolescent First-Episode Psychosis: A Longitudinal Naturalistic Approach

OBJECTIVE The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a naturalistic longitudinal study of early-onset first psychotic episodes. This report describes the antipsychotic treatment during the first year and compares the most frequently used agents after 6 months. METHODS Participants were 110 patients, aged 9-17 years, with a first psychotic episode attended consecutively at six different centers. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions (CGI), Disability Assessment Schedule (DAS), and Global Assessment of Function (GAF) scales were administered at baseline and at 6 months and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale only at 6 months. RESULTS Diagnoses at baseline were 38.2% psychotic disorder not otherwise specified, 39.1% schizophrenia-type disorder, 11.8% depressive disorder with psychotic symptoms, and 10.9% bipolar disorder, manic episode with psychotic symptoms. The most frequently used antipsychotic agents were risperidone (n = 50), quetiapine (n = 18), and olanzapine (n = 16). Patients who were prescribed olanzapine or quetiapine had more negative and general symptoms. Using the baseline score as covariate, no significant differences were found in the reductions on any scale in patients treated with risperidone, quetiapine, or olanzapine for 6 months. Weight increase was greater with olanzapine than with risperidone (p = 0.020) or quetiapine (p = 0.040). More neurological side effects appeared with risperidone than with olanzapine (p = 0.022). All side effects were mild or moderate. CONCLUSIONS Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, are the most used in our context in first psychotic episodes in children and adolescents. These three obtain similar clinical improvement, but differ in their side effects.

Cerebral activation in children and adolescents with obsessive–compulsive disorder before and after treatment: A functional MRI study

BACKGROUND Structural and functional fronto-striatal abnormalities are involved in the pathophysiology of obsessive-compulsive disorder (OCD). The aims of the present study were: (a) to investigate possible regional brain dysfunction in premotor cortico-striatal activity in drug-naïve children and adolescents with OCD; (b) to correlate brain activation with severity of obsessive-compulsive symptomatology; and (c) to detect possible changes in brain activity after pharmacological treatment. METHOD Twelve children and adolescents (age range 7-18 years; seven male, five female) with DSM-IV obsessive-compulsive disorder and twelve healthy subjects matched for age, sex and intellectual level were studied. Functional magnetic resonance imaging data were obtained during the performance of simple and complex sequences. RESULTS Comparing the complex motor condition with the simple control condition, both patients and controls showed a pattern of cerebral activation involving the fronto-parietal cortex and basal ganglia. Compared with controls, OCD patients presented significantly higher brain activation bilaterally in the middle frontal gyrus. After 6 months of pharmacological treatment and with clear clinical improvement, activation in the left insula and left putamen decreased significantly. CONCLUSION In a paediatric OCD sample that was treatment naïve and without another psychiatric disorder we showed hyperactivation of the circuits that mediate symptomatic expression of OCD. The cerebral activation decreases after treatment and clinical improvement.

The Human Cerebral Cortex Flattens during Adolescence

The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this process, 52 healthy male and female adolescents (11–17 years old) were neuroimaged twice using magnetic resonance imaging, approximately 2 years apart. Using a novel morphometric analysis procedure combining the FreeSurfer and BrainVisa image software suites, we quantified global and lobar change in cortical thickness, outer surface area, the gyrification index, the average Euclidean distance between opposing sides of the white matter surface (gyral white matter thickness), the convex (“exposed”) part of the outer cortical surface (hull surface area), sulcal length, depth, and width. We found that the cortical surface flattens during adolescence. Flattening was strongest in the frontal and occipital cortices, in which significant sulcal widening and decreased sulcal depth co-occurred. Globally, sulcal widening was associated with cortical thinning and, for the frontal cortex, with loss of surface area. For the other cortical lobes, thinning was related to gyral white matter expansion. The overall flattening of the macrostructural three-dimensional architecture of the human cortex during adolescence thus involves changes in gray matter and effects of the maturation of white matter.

DRD3, but not COMT or DRD2, genotype affects executive functions in healthy and first-episode psychosis adolescents†

Catechol‐O‐methyltransferase (COMT) and dopamine receptors 2 (DRD2) and 3 (DRD3) have been associated with a higher risk of developing psychosis and with dopaminergic system (DAS) regulation. Frontal cognitive functioning has been proven to be a useful endophenotype for psychosis and it is partially controlled by the DAS. Val158Met (rs4680, COMT), Taq IA (rs1800497, DRD2) and Ser9Gly (rs6280; DRD3) polymorphisms were analyzed in a sample of 84 adolescent Caucasian patients with first‐episode psychosis (ages 11–17) and 85 healthy Caucasian controls (ages 10–17). A comprehensive neuropsychological battery, assessing attention, working memory, memory, and executive functions, was administered to the entire sample. The relationship between neuropsychological scores and genotype was determined. Subjects with the DRD3 Gly/Gly genotype showed significantly poorer performance than Ser/Ser subjects in executive functioning tasks (P = 0.002; adjusted R2 = 0.031), with no significant differences in the other cognitive paradigms. Neither COMT nor DRD2 polymorphisms significantly contributed to variance in cognition in our adolescent sample. The DRD3 Ser9Gly polymorphism seems to be involved with prefrontal cognition. This effect seems to be heterogeneous in terms of cognitive paradigms. The lack of association between COMT and DRD2 genotypes and cognition in our sample may be partially explained by the young age of the sample and the clinical heterogeneity of the patients.

Multidisciplinary treatment of fibromyalgia: does cognitive behavior therapy increase the response to treatment?

OBJECTIVE Multidisciplinary treatments (MTs) are usually recommended for reducing fibromyalgia (FM) symptoms and include physical exercise, drug management, education, and cognitive behavior therapy (CBT). However, there is no evidence that CBT adds efficacy to the other therapeutic components. This randomized controlled trial analyzed the response of FM patients to two MTs, with and without CBT, according to the presence of concurrent symptoms. METHODS Eighty-three women with FM were randomly assigned to MT or combined MT and CBT. The MT included medical intervention, physical training, education, and discussion of the syndrome. The CBT focused on coping with stress, modifying lifestyles, and changing pain behaviors. Demographic and clinical data, information regarding tender points, and questionnaire responses about functional capability [Fibromyalgia Impact Questionnaire (FIQ)], health status [36-item Short Form Health Survey (SF-36)], and mental health [Symptom Checklist-90-Revised (SCL-90-R)] were obtained at the beginning, at the end of the 15-week treatment, and at 6-month follow-up. Subgroups are identified in relation to treatment response. RESULTS Sixty-six women (80%) completed treatment. Although the variance of the total sample had changed at posttreatment (F=2.67, P=.031), there was no significant effect for the TimexTreatment interaction (F=1.65, P=.16). Univariate tests detected a significant fall in the FIQ score. The subgroup of patients with fatigue showed a better response with MT+CBT than with MT. At 6-month follow-up, the statistical differences had been maintained. Intention-to-treat analysis ratified these results. CONCLUSIONS MT improves functional capability and reduces symptom impact. CBT increases mildly the effect of MT in patients with fatigue.

Comorbid anxiety in children and adolescents with bipolar spectrum disorders: prevalence and clinical correlates.

OBJECTIVE Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder. We aimed to examine the prevalence and correlates of comorbid anxiety disorders among youth with bipolar disorder. METHOD As part of the Course and Outcome of Bipolar Youth study, 446 youth, ages 7 to 17 years, who met DSM-IV criteria for bipolar I disorder (n = 260) or bipolar II disorder (n = 32) or met operationalized criteria for bipolar disorder not otherwise specified (n = 154) were included. Subjects were evaluated for current and lifetime Axis I psychiatric disorders at intake using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime version, and standardized instruments were used to assess functioning and family history. RESULTS Forty-four percent (n = 194) of the sample met DSM-IV criteria for at least 1 lifetime anxiety disorder, most commonly separation anxiety (24%) and generalized anxiety disorders (16%). Nearly 20% met criteria for 2 or more anxiety disorders. Overall, anxiety disorders predated the onset of bipolar disorder. Subjects with bipolar II disorder were more likely than subjects with bipolar I disorder or bipolar disorder not otherwise specified to have a comorbid anxiety disorder. After adjusting for confounding factors, youth with bipolar disorder with anxiety were more likely to have bipolar II disorder; longer duration of mood symptoms; more severe ratings of depression; and family history of depression, hopelessness, and somatic complaints during their worst lifetime depressive episode than those without anxiety. CONCLUSIONS Comorbid anxiety disorders are common in youth with bipolar disorder, and they most often predate bipolar disorder onset. Bipolar II disorder, a family history of depression, and more severe lifetime depressive episodes distinguish youth with bipolar disorder with comorbid anxiety disorders from those without. Careful consideration should be given to the assessment of comorbid anxiety in youth with bipolar disorder.