Sonia Ruiz de Azúa

Serum IgG Antibodies Against the NR1 Subunit of the NMDA Receptor Not Detected in Schizophrenia

To the Editor: A consensus exists that schizophrenia is not a single disease, but the final pathway of a variety of still unknown neurobiological derangements. Recently, several treatable autoimmune brain disorders have been identified presenting with psychotic symptoms that, in some cases, resemble those found in schizophrenia (1). Antibodies target synaptic proteins, interrupting synaptic transmission in brain networks supporting cognition and emotion. Particularly relevant are auto-antibodies against the NR1 subunit of the N-acetyl methyl D-aspartate receptor (NMDAR), which result in diminished NMDAR activity, now considered a hallmark of schizophrenia (2). In patients harboring these antibodies, initial psychiatric symptoms are usually followed by dyskinetic movements or seizures and decreased respiratory drive, with a reduced level of consciousness, often requiring intensive care (1). However, it could be postulated that a limited form of the disease may result in a milder syndrome, akin to schizophrenia. We tested this hypothesis using sera from patients with their first psychotic episode referred to the regional psychiatric center of the province of Alava, Spain, and from healthy controls. All were enrolled after written informed consent according to protocols approved by the local IRB. Blood was drawn and sera were frozen for subsequent study, blinded to patient-control status. After a one-year follow up, sera of patients who then met DSM-IV-TR criteria for schizophrenia-spectrum disorders were tested for antibodies to NR1 and other cell surface antigens using three criteria (immunohistochemistry on rat brain slices and dissociated rodent hippocampal neurons, and a cell-based assay in which HEK cells recombinantly express NMDAR), as previously reported (1). Patients (n=80) and healthy controls (n=40) did not differ statistically in age (29.4±9.9 and 30.7±9.4 years), or sex (28 and 38 percent women). Anti-NR1 IgG antibodies were not detected in either group. Both had four cases with sera reactive to other, still unidentified, neuronal surface antigens. Our findings and a study of seven patients with schizophrenia (3) fail to support the hypothesis that NMDAR IgG antibodies are present in the sera of patients with schizophrenia. Although another study (4) did report NMDAR antibodies in the sera of some schizophrenia patients, it was performed without a control group and test specificity was lower (only one of the above criteria was applied); differences in the clinical diagnosis could also explain the discrepant findings. It should be noted, however, that our study does not rule out that some patients could have antibodies only in cerebrospinal fluid, but not in serum (1). Additionally, antibodies could be present in patients with acute psychosis not meeting DSM-IV diagnostic criteria at one-year.

Working memory as a predictor of negative symptoms and functional outcome in first episode psychosis

The relationship of neurocognitive course with clinical and functional outcomes in psychosis is not well known, especially in the long term. The aim of the study was to examine the clinical and neuropsychological course of first-episode psychosis patients at 5-year follow-up and analyze the relationship of cognitive performance with clinical and functional outcome. The 5-year follow-up was conducted with 26 first-episode psychosis patients. Psychotic symptoms were measured by the Positive and Negative Syndrome Scale, manic and depressive symptoms by the Young Mania Rating Scale and Hamilton Depression Rating Scale respectively, and psychosocial functioning by the Functioning Assessment Short Test. The cognitive domains were assessed by the Wechsler Adult Intelligence Scale, the Wisconsin Card Sorting Test, the Trail Making Test, the Verbal Fluency Test, the Stroop Colour-Word Test and the Wechsler Memory Scale. Patients showed symptomatic improvement in the follow-up except in negative psychotic symptoms. There was also improvement in most cognitive domains except in working memory and processing speed in the follow-up. Working memory impairment was associated to negative psychotic symptoms and poor functional outcomes. Negative symptoms mediated the relationship between working memory and outcome. Therefore, negative symptoms should be a primary target of treatment to improve functional outcomes.

Relationship between negative symptoms and plasma levels of insulin-like growth factor 1 in first-episode schizophrenia and bipolar disorder patients.

Previous studies have suggested that insulin-like growth factor-1 (IGF-1) is altered in schizophrenia. The objective of this study was to investigate whether plasma IGF-1 levels were altered at the onset of psychiatric disorders such as schizophrenia or bipolar disorder. We focused at the first psychotic episode (FPE) and during 1-year follow-up. We also studied if IGF-1 levels were related to clinical symptoms. 50 patients and 43 healthy controls matched by age, gender and educational level were selected from the Basque Country catchment area in Spain. Plasma IGF-1 levels were measured at FPE and 1 month, 6 months and one year later. Patient symptoms were assessed at the same disease stages using the Positive and Negative Symptoms Scale (PANSS), the Global Assessment of Functioning (GAF), the Hamilton Depression Rating Scale (HDRS21) and the Young Mania Rating Scale (YMRS). A statistically significant increase in the plasma levels of IGF-1 was found in the whole cohort of patients one month after FPE compared to matched controls (219.84 ng/ml vs 164.15 ng/ml; p=0.014), as well as in schizophrenia patients alone at that stage (237.60 ng/ml vs 171.60 ng/ml; p=0.039). In turn, negative symptoms in both groups of patients were positively correlated with IGF-1 levels both at FPE (β=0.521; p<0.001) and after 1 year (β=0.659; p=0.001), being patients diagnosed with schizophrenia the main contributors to this relationship. These results indicate that there is a significant change in the plasma levels of IGF-1 at the initial stages of schizophrenia but not in bipolar disorder, and suggest that IGF-1 could have role in the pathophysiology of negative symptoms.

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.

Autoconcepto físico y estilos de vida en la adolescencia

Healthy lifestyles are associated with both physical self-concept and psychological well-being, at least during the adolescence. In this study the results confirm the relation.

Plasma brain-derived neurotrophic factor levels, learning capacity and cognition in patients with first episode psychosis

BackgroundCognitive impairments are seen in first psychotic episode (FEP) patients. The neurobiological underpinnings that might underlie these changes remain unknown. The aim of this study is to investigate whether Brain Derived Neurotrophic Factor (BDNF) levels are associated with cognitive impairment in FEP patients compared with healthy controls.Methods45 FEP patients and 45 healthy controls matched by age, gender and educational level were selected from the Basque Country area of Spain. Plasma BDNF levels were assessed in healthy controls and in patients. A battery of cognitive tests was applied to both groups, with the patients being assessed at 6 months after the acute episode and only in those with a clinical response to treatment.ResultsPlasma BDNF levels were altered in patients compared with the control group. In FEP patients, we observed a positive association between BDNF levels at six months and five cognitive domains (learning ability, immediate and delayed memory, abstract thinking and processing speed) which persisted after controlling for medications prescribed, drug use, intelligence quotient (IQ) and negative symptoms. In the healthy control group, BDNF levels were not associated with cognitive test scores.ConclusionOur results suggest that BDNF is associated with the cognitive impairment seen after a FEP. Further investigations of the role of this neurotrophin in the symptoms associated with psychosis onset are warranted.

Variables socioculturales en la construcción del autoconcepto fisico

Resumen Mediante este estudio se buscaba identificar diferencias en el autoconcepto físico relacionadas con la edad y con variables culturalmente mediadas tales como el género, la práctica deportiva, los hábitos de vida saludable o los hábitos alimentarios y, así mismo, precisar relaciones entre el desarrollo del autoconcepto físico y algunas influencias socioculturales. Participaron en el estudio 540 estudiantes, con edades comprendidas entre los 12 y los 23 años de edad, de los cuales 284 eran mujeres y 256 hombres; todos ellos residían en la Comunidad Autónoma del País Vasco; 418 cursaban Educación Secundaria mientras que 122 realizaban estudios universitarios. Respondieron por escrito a un cuestionario sobre sus hábitos de vida y cumplimentaron el Cuestionario de Autoconcepto Físico (CAF) de Goñi, Ruiz de Azúa y Liberal (2004) y el Cuestionario de Influencias sobre el Modelo Estético Corporal (CIMEC-26), de Toro, Salamero y Martínez (1995). Los datos obtenidos ofrecen una visión, mucho más compleja que la hasta ahora disponible sobre los cambios asociados con la edad. Permiten destacar el hecho de que la evolución del autoconcepto físico no es homogénea ya que cada una de sus dimensiones (habilidad, condición, atractivo y fuerza) sigue pautas evolutivas propias. El autoconcepto físico es más alto en los hombres que en las mujeres y los mejores índices están asociados con la práctica deportiva (y más en concreto con la práctica deportiva socializada), con los hábitos de vida saludables, con una alimentación sana y con una percepción subjetiva de buena salud. Se ha podido comprobar también que quienes ofrecen un mejor autoconcepto físico son quienes, a su vez, muestran una menor vulnerabilidad a la presión de los modelos estéticos imperantes. La importancia de esta nueva información se percibe al relacionarla con problemas de acuciante actualidad como son los trastornos de la imagen corporal; pero se trata, al mismo tiempo, de una información que se podrá precisar en la medida en que se disponga de instrumentos más afinados para medir empíricamente la influencia mediática y de otros factores culturales sobre el autoconcepto físico.

The 2nd Schizophrenia International Research Society Conference, 10-14 April 2010, Florence, Italy: summaries of oral sessions.

The 2nd Schizophrenia International Research Society Conference, was held in Florence, Italy, April 10-15, 2010. Student travel awardees served as rapporteurs of each oral session and focused their summaries on the most significant findings that emerged from each session and the discussions that followed. The following report is a composite of these reviews. It is hoped that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

Manic and depressive symptoms and insight in first episode psychosis

Insight impairment is common early in the course of psychosis. Most studies have focused on the relationship between insight and depression, although manic symptoms are also frequent in psychoses. The main aim of this study was to examine the relationship between insight dimensions and manic and depressive symptoms in first-episode psychosis. A group of inpatients in their first psychotic episodes (n=124) were evaluated using the Scale to Assess Unawareness of Mental Disorder, Young Mania Rating Scale and Hamilton Depression Rating Scale. To study the effect of clinical, manic and depressive symptoms on insight, awareness of mental disorder, awareness of the achieved effects of medication, and awareness of the social consequences of having a mental disorder were modelled using ordinal logistic regression techniques. Results showed that greater awareness of mental disorder was significantly related to higher age at first episode together with higher scores for negative and depressive symptoms. The opposite was found to be true in presentations with a higher severity of disease and manic symptoms. The model fitting unawareness of the achieved effects of medication identified the same significant variables, except in the case of negative symptoms. Finally, the model assessing the social consequences of having a mental disorder showed unawareness to be greater when manic symptoms and disease severity were high.

Opposite cannabis-cognition associations in psychotic patients depending on family history

The objective of this study is to investigate cognitive performance in a first-episode psychosis sample, when stratifying the interaction by cannabis use and familial or non-familial psychosis. Hierarchical-regression models were used to analyse this association in a sample of 268 first-episode psychosis patients and 237 controls. We found that cannabis use was associated with worse working memory, regardless of family history. However, cannabis use was clearly associated with worse cognitive performance in patients with no family history of psychosis, in cognitive domains including verbal memory, executive function and global cognitive index, whereas cannabis users with a family history of psychosis performed better in these domains. The main finding of the study is that there is an interaction between cannabis use and a family history of psychosis in the areas of verbal memory, executive function and global cognition: that is, cannabis use is associated with a better performance in patients with a family history of psychosis and a worse performance in those with no family history of psychosis. In order to confirm this hypothesis, future research should explore the actual expression of the endocannabinoid system in patients with and without a family history of psychosis.