Igor Bombin

Brain morphology and neurological soft signs in adolescents with first-episode psychosis.

BACKGROUND Adolescents with first-episode psychosis have increased severity of neurological soft signs when compared with controls, but it is unclear whether increased severity of neurological soft signs is an expression of specific structural brain deficits. AIMS To examine whether increased severity of neurological soft signs was associated with decreased brain volumes in adolescents with first-episode psychosis. METHOD Brain scans were obtained for 70 adolescents (less than 18 years of age) with first-episode psychosis (duration of positive symptoms less than 6 months). Volumes were assessed using voxel-based morphometry and through segmentation of anatomical structures. RESULTS Increased severity of sensory integration neurological soft signs correlated with smaller right and left thalamus volume, whereas increased severity of sequencing of complex motor acts neurological soft signs correlated with smaller right caudate volume. CONCLUSIONS Neurological soft signs may be an easy-to-assess marker of region-specific structural brain deficits in adolescents with first-episode psychosis.

Association study between obsessive-compulsive disorder and serotonergic candidate genes.

BACKGROUND To date, research examining the relationship between serotonergic genes and obsessive-compulsive disorder (OCD) has yielded conflicting results. The purpose of this study is to investigate the association between four serotonergic polymorphisms (STin2 VNTR and 5-HTTLPR of the SLC6A4 gene, and A-1438G (rs6311) and T102C (rs6313) of the HTR2A gene) and OCD. METHODS 99 OCD patients, 456 non-OCD psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS All groups showed Hardy-Weinberg equilibrium for the analyzed genetic variability. A-1438G and T102C polymorphisms were in complete linkage disequilibrium. OCD patients showed an excess of STin2.12 carriers (12/12, 12/10, and 12/9 genotypes) compared with healthy controls (chi(2) (1)=7.21, corrected p=0.021; OR=3.38, 95% CI=1.32-8.62) and non-OCD psychiatric patients (chi(2) (1)=6.70, corrected p=0.030; OR=3.24, 95% CI=1.27-8.26). However, no differences were found between non-OCD patients and healthy controls (chi(2) (1)=0.05, corrected p>1; OR=1.04, 95% CI=0.72-1.51). No significant differences were found with respect to A-1438G and 5-HTTLPR polymorphisms. CONCLUSIONS Our data provide supporting evidence of an association between the STin2 VNTR polymorphism of the SLC6A4 gene and OCD.

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.

Neuropsychological functioning in adolescents with first episode psychosis: a two-year follow-up study.

Cognitive deficits are a core feature of psychotic disorders. Both in adult and adolescent populations, studies have shown that patients with psychosis have poorer cognitive functioning than controls. The cognitive domains that seem to be affected are mainly attention, working memory, learning and memory, and executive function. However, with regard to the trajectory of cognitive function throughout the illness, there is still a dearth of prospective data in patients who develop psychosis during adolescence. In this article, neuropsychological functioning was assessed in a sample of 24 first episodes of early onset psychosis (EOP) and 29 healthy adolescents at baseline and after a two-year follow-up. Patients with EOP showed lower scores than controls in overall cognitive functioning and in all specific domains assessed (attention, working memory, executive function, and learning and memory) both at baseline and the two-year follow-up. When changes in cognitive functioning over two years were assessed, patients and controls showed significant improvement in almost all cognitive domains. However, this improvement disappeared in the patient group after controlling for improvement in symptomatology. Our findings support a neurodevelopmental pathological process in this sample of adolescents with psychosis.

Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses

BACKGROUND The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders. Method Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls. RESULTS EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405). CONCLUSIONS Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

Neurological soft signs in adolescents with first episode psychosis: two-year followup.

Neurological soft signs were assessed in 24 first episodes of early onset psychosis and 30 healthy adolescents over a 2-year period. Patients presented more neurological soft signs than controls and showed a significant decrease in some Neurological Evaluation Scale scores over the followup period. This decrease in the patient group was influenced by changes in symptomatology.

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.

Functional impairment as a defining feature of: amnestic MCI cognitive, emotional, and demographic correlates

BACKGROUND Early definitions of mild cognitive impairment (MCI) excluded the presence of functional impairment, with preservation of a persons ability to perform activities of daily living (ADL) as a diagnostic criterion. However, recent studies have reported varying degrees of functional impairment associated with MCI. Hence, we aimed to test the potential functional impairment associated with MCI and its predictors. METHODS Sixty-nine healthy elderly subjects, 115 amnestic single-domain MCI subjects (a-MCI), and 111 amnestic multi-domain MCI subjects (md-MCI) were assessed using a battery of neuropsychological tests including measures of attention, memory, working memory, executive functions, language, and depression. Additionally, functional ability was assessed by both qualitative (WHO-DAS II) and quantitative (CHART) instruments. Cognitive and functional performance was compared between groups, and regression analyses were performed to identify predictors of functional ability. RESULTS The md-MCI group was more impaired than the a-MCI group, and both were more impaired than healthy subjects in all cognitive measures, in total CHART score, CHART cognitive and mobility subscores, and WHO-DAS II communication and participation subscales. For the rest of the functional measures, the md-MCI group was more impaired than healthy controls. Prediction of functional ability by cognitive measures was limited to md-MCI subjects and was higher for the CHART than for the WHO-DAS II. The WHO-DAS II was largely influenced by depressive symptoms. CONCLUSIONS Functional impairment is a defining feature of MCI and is partially dependent on the degree of cognitive impairment. Quantitative measures of functional ability seem more sensitive to functional impairment in MCI than qualitative measures, which seem to be more related to depression.

Predominance of Symptoms Over Time in Early-Onset Psychosis: A Principal Component Factor Analysis of the Positive and Negative Syndrome Scale

BACKGROUND Early-onset psychosis is a symptomatically nonspecific and heterogeneous entity composed of several diagnoses. This study examined the dimensional structure of symptoms and the temporal stability of this structure during a 6-month follow-up. METHOD A principal component factor analysis of the Positive and Negative Syndrome Scale was conducted at baseline, 4 weeks, and 6 months in a sample of 99 first-episode psychotic patients (mean age = 15.5 years). RESULTS The factor analysis produced a 5-dimension solution (Positive, Negative, Depression, Cognitive, Hostility) that explained 62.4% of the variance at baseline, 63.4% at 4 weeks, and 65.1% at 6 months. Negative dimension was the most consistent and stable over time and was predominant at baseline (23.9%) and at 4 weeks (25.7%). Depression was predominant at 6 months (31.1%). CONCLUSIONS There is a stable 5-dimension structure of symptoms in early-onset psychosis with varying predominance of symptoms over time. Negative symptoms are a core feature of psychosis and are thus important diagnostic criteria.