Elena de la Serna

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.

Predictors of suicide attempt in early-onset, first-episode psychoses: a longitudinal 24-month follow-up study.

OBJECTIVE To study the prevalence of suicide attempts and factors associated with risk for suicide during the first episode of psychosis, and to identify early predictors of suicide attempts over a 24-month follow-up period in an early-onset, first-episode psychosis cohort. METHOD 110 subjects in their first episode of psychosis aged between 9 and 17 years were assessed by using the DSM-IV diagnostic interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and a battery of clinical instruments at baseline and at 12 and 24 months. Patients were enrolled in the study from March 2003 through November 2005. Suicide attempts and level of suicidality at each assessment were evaluated by using the Clinical Global Impression for Severity of Suicidality and the Hamilton Depression Rating Scale. Subjects were classified as being at high, low, or no risk of suicide, depending on their scores on certain items of these scales. Clinical associations between the outcome measures high risk for suicide during acute episode and suicide attempts during follow-up were investigated by 2 sets of logistic regression analyses. RESULTS The 24-month prevalence of suicide attempters was 12.4%. History of suicide attempts prior to psychotic episode (OR = 20.13; 95% CI, 1.83-220.55; P = .01), severe depressive symptoms (OR = 8.78; 95% CI, 1.15-67.11; P = .003), and antidepressant treatment (OR = 15.56; 95% CI, 2.66-90.86; P = .002) were associated with being classified as high suicide risk at baseline. The categorization of high suicide risk at baseline predicted suicide attempts during follow-up (OR = 81.66; 95% CI, 11.61-574.35; P = .000). CONCLUSIONS Suicide is a major concern in early-onset first-episode psychosis. Suicidal behavior and depressive symptoms at psychosis onset are important signs to be aware of to prevent suicide attempts during the early period after first-episode psychosis.

Two-year diagnostic stability in early-onset first-episode psychosis.

BACKGROUND Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). AIM To describe diagnostic stability and the variables related to diagnostic changes. METHODS Participants were 83 patients (aged 9-17 years) with an EO-FEP consecutively attended. They were assessed with a structured interview (Kiddie-Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version) and clinical scales at baseline and after 2 years. RESULTS The global consistency for all diagnoses was 63.9%. The small group of bipolar disorder had high stability (92.31%) as did the group with schizophrenia spectrum disorders (90.00%). Depressive disorder had lower stability (37.50%) and the lowest values were for psychotic disorder not otherwise specified (11.76%) and brief psychotic disorder (0%).The most frequent diagnostic shift was to schizophrenia spectrum and bipolar disorders. One group of patients did not meet the criteria for any diagnosis at follow-up. Independent predictors of change to schizophrenia spectrum disorders were lower scores on the Childrens Global Assessment Scale (CGAS) and the Hamilton Depression Rating Scale. Predictors of not having a diagnosis at follow-up were the CGAS and the Strauss-Carpenter Outcome Scale. CONCLUSIONS Global diagnostic stability was 63.9%. Bipolar and schizophrenia spectrum disorders were the most stable diagnoses, while depressive disorder and other psychosis the least stable. Psychosocial functioning at baseline was a good predictor of diagnosis at follow-up. These data show the need for longitudinal follow-up in EO-FEP before a stable diagnosis is reached.

Intrinsic connectivity networks from childhood to late adolescence: Effects of age and sex

Highlights • We assessed intrinsic connectivity of networks underlying cognition in youth.• Evidence of age effects on intrinsic connectivity was found across all networks.• Intrinsic connectivity showed no effect of sex, nor age by sex interactions.

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

BACKGROUND Early 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. METHODS SZ 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. RESULTS We 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. CONCLUSIONS The 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.

Cognitive functioning in children and adolescents in their first episode of psychosis: differences between previous cannabis users and nonusers.

To investigate the relationship between cognition and prior cannabis use in children and adolescents presenting a first episode of psychosis. A total of 107 patients with first episode of psychosis and 96 healthy controls, aged 9 to 17 years, were interviewed about their previous substance use and to assess their cognitive functions. Patients were assessed while not using cannabis by means of a comprehensive neuropsychological battery. They were divided into 2 groups depending on the history of prior cannabis use: cannabis users (CU) and cannabis nonusers (CNU). Significant differences were found in all areas evaluated between the 3 groups. Both CU and CNU patients obtained lower scores than controls on verbal learning and memory and working memory. Patients with prior cannabis use performed better on some tests of attention (Continuous performance test (CPT) number of correct responses, p = 0.002; CPT average reaction time, p < 0.001) and executive functions (Trail Making Test, part B (TMT-B) number of mistakes, p < 0.001; Wisconsin Card Sorting Test (WCST) number of categories completed, p < 0.001) than CNU patients. CU patients performed better than CNU subjects on some cognitive measures. This may indicate lower individual vulnerability for psychosis in CU patients in whom cannabis use can be a precipitating factor of psychotic episodes.

Cognitive reserve as a predictor of two year neuropsychological performance in early onset first-episode schizophrenia

INTRODUCTION The concept of cognitive reserve (CR) has been defined as individual differences in the efficient utilization of brain networks which allow some people to cope better than others with brain pathology. CR has been developed mainly in the field of aging and dementia after it was observed that there appears to be no direct relationship between the degree of brain pathology and the severity of clinical manifestations of this damage. The present study applies the concept of CR to a sample of children and adolescents with a first episode of schizophrenia, aiming to assess the possible influence of CR on neuropsychological performance after two year follow-up, controlling for the influence of clinical psychopathology. METHODS 35 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (SSD) and 98 healthy controls (HC) matched for age and gender were included. CR was assessed at baseline, taking into account premorbid IQ, educational-occupational level and leisure activities. Clinical and neuropsychological assessments were completed by all patients at two year follow-up. RESULTS The CR proxy was able to predict working memory and attention at two year follow-up. Verbal memory and cognitive flexibility were not predicted by any of the variables included in the regression model. The SSD group obtained lower scores than HC on CR. CR measures correctly classified 79.8% of the sample as being SSD or HC. CONCLUSIONS Lower scores on CR were observed in SSD than in HC and the CR measure correctly classified a high percentage of the sample into the two groups. CR may predict SSD performance on working memory and attention tasks.

Relationship between clinical and neuropsychological characteristics in child and adolescent first degree relatives of subjects with schizophrenia

INTRODUCTION Studies have shown higher rates of psychopathology and cognitive difficulties among relatives of schizophrenia patients than among the general population. This study aimed to analyze the relationship between clinical and neuropsychological characteristics in children and adolescents at high genetic risk for schizophrenia. METHODS Participants were 26 children and adolescent first-degree relatives of subjects diagnosed with schizophrenia (high-risk [HR] group) and 20 controls whose parents and siblings did not meet DSM-IV criteria for any psychotic disorder. These two groups were matched by age, sex and socio-economic status and clinical and neuropsychological assessments were completed by all participants. RESULTS Among HR children 42.3% were diagnosed with one or more DSM-IV axis I psychiatric disorders. The most common diagnoses were attention deficit/hyperactivity disorder (ADHD) (34.6%) and generalized anxiety disorder (3.8%) There were significant differences between HR children and controls with respect to prodromal symptoms, behavioral problems and premorbid adjustment, as well as on the majority of intelligence subscales, working memory and logical memory. When differences between HR with ADD (HR-ADD), HR without ADD (HR-NADD) and controls were analyzed, significantly higher scores on clinical scales of prodromal symptoms, behavioral problems and premorbid adjustment were found in HR-ADD than in HR-NADD or controls. There were no significant differences in cognitive domains between HR-ADD and HR-NADD, but there were between HR-ADD and controls and between HR-NADD and controls on the Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index and GAI. CONCLUSIONS Compared to controls, HR children showed more clinical symptoms and cognitive abnormalities. HR children with ADD had worse clinical symptoms than did HR without ADD, although there were no differences in terms of cognitive abnormalities. Both HR groups seem to have similar deficits in neuropsychological performance.

Comparison between young siblings and offspring of subjects with schizophrenia: clinical and neuropsychological characteristics.

INTRODUCTION High rates of psychopathology and worse performance in cognitive areas have been described in high risk (HR) first degree relatives of subjects with schizophrenia. The present study aimed to examine clinical and neuropsychological characteristics in two different groups of first degree relatives of patients with schizophrenia - one of siblings (HRs), and one of offspring (HRo) - and compare them with healthy controls (HC). METHODS Participants were 30 HRo, 26 HRs and 33 HC, all aged between 7 and 16 years. Clinical and neuropsychological assessments were completed by all participants. RESULTS No significant differences were observed between HR groups in DSM-IV diagnoses. The most prevalent diagnosis in both HR samples was attention deficit/hyperactivity disorder (ADHD) followed by oppositional defiant disorder and generalized anxiety disorder. Both HR groups obtained worse scores than HC on prodromal symptoms, premorbid adjustment and behavioral problem scales. In cognitive areas, HRo performed worse than HC on most WISC-IV index scores, logical memory, visual memory and perceptual organization, whereas HRs only performed worse in WISC-IV indexes, logical memory and perceptual organization. Most of these differences remained stable after controlling for ADHD. The comparison between HRo and HRs showed significant differences in prodromal symptoms and working memory after controlling for ADHD. CONCLUSION Similar abnormalities in HRo and HRs were found in relation to clinical and neuropsychological variables. Subtle differences were found between HR groups with HRo showing difficulties in more clinical and neuropsychological areas than HRs and HC. This suggests that, the specific kind of family relationship should to be taken into account in future HR research.

Two-Year Follow-Up of Cognitive Functions in Schizophrenia Spectrum Disorders of Adolescent Patients Treated with Electroconvulsive Therapy

OBJECTIVE The aim of the current study was to investigate the long-term cognitive effects of electroconvulsive therapy (ECT) in a sample of adolescent patients in whom schizophrenia spectrum disorders were diagnosed. METHODS The sample was composed of nine adolescent subjects in whom schizophrenia or schizoaffective disorder was diagnosed according to DSM-IV-TR criteria on whom ECT was conducted (ECT group) and nine adolescent subjects matched by age, socioeconomic status, and diagnostic and Positive and Negative Syndrome Scale (PANSS) total score at baseline on whom ECT was not conducted (NECT group). Clinical and neuropsychological assessments were carried out at baseline before ECT treatment and at 2-year follow-up. RESULTS Significant differences were found between groups in the number of unsuccessful medication trials. No statistically significant differences were found between the ECT group and the NECT group in either severity as assessed by the PANSS, or in any cognitive variables at baseline. At follow-up, both groups showed significant improvement in clinical variables (subscales of positive, general, and total scores of PANSS and Clinical Global Impressions-Improvement). In the cognitive assessment at follow-up, significant improvement was found in both groups in the semantic category of verbal fluency task and digits forward. However, no significant differences were found between groups in any clinical or cognitive variable at follow-up. Repeated measures analysis found no significant interaction of time×group in any clinical or neuropsychological measures. CONCLUSIONS The current study showed no significant differences in change over time in clinical or neuropsychological variables between the ECT group and the NECT group at 2-year follow-up. Thus, ECT did not show any negative influence on long-term neuropsychological variables in our sample.