Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: a multicentre 1H-MRS study (OPTiMiSE).

Conventional antipsychotic medication is ineffective in around a third of patients with schizophrenia, and the nature of the therapeutic response is unpredictable. We investigated whether response to antipsychotics is related to brain glutamate levels prior to treatment. Proton magnetic resonance spectroscopy was used to measure glutamate levels (Glu/Cr) in the anterior cingulate cortex (ACC) and in the thalamus in antipsychotic-naive or minimally medicated patients with first episode psychosis (FEP, n = 71) and healthy volunteers (n = 60), at three sites. Following scanning, patients were treated with amisulpride for 4 weeks (n = 65), then 1H-MRS was repeated (n = 46). Remission status was defined in terms of Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores. Higher levels of Glu/Cr in the ACC were associated with more severe symptoms at presentation and a lower likelihood of being in remission at 4 weeks (P < 0.05). There were longitudinal reductions in Glu/Cr in both the ACC and thalamus over the treatment period (P < 0.05), but these changes were not associated with the therapeutic response. There were no differences in baseline Glu/Cr between patients and controls. These results extend previous evidence linking higher levels of ACC glutamate with a poor antipsychotic response by showing that the association is evident before the initiation of treatment.

Trajectories of symptom dimensions in short-term response to antipsychotic treatment in patients with a first episode of non-affective psychosis.

BACKGROUND: Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data. METHOD: This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables. RESULTS: Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension. CONCLUSIONS: Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.

Three-year longitudinal population-based volumetric MRI study in first-episode schizophrenia spectrum patients.

BACKGROUND: Schizophrenia is a chronic brain disorder associated with structural brain abnormalities already present at the onset of the illness. Whether these brain abnormalities might progress over time is still under debate. METHOD: The aim of this study was to investigate likely progressive brain volume changes in schizophrenia during the first 3 years after initiating antipsychotic treatment. The study included 109 patients with a schizophrenia spectrum disorder and a control group of 76 healthy subjects. Subjects received detailed clinical and cognitive assessment and structural magnetic resonance imaging (MRI) at regular time points during a 3-year follow-up period. The effects of brain changes on cognitive and clinical variables were examined along with the impact of potential confounding factors. RESULTS: Overall, patients and healthy controls exhibited a similar pattern of brain volume changes. However, patients showed a significant lower progressive decrease in the volume of the caudate nucleus than control subjects (F 1,307.2 = 2.12, p = 0.035), with healthy subjects showing a greater reduction than patients during the follow-up period. Clinical and cognitive outcomes were not associated with progressive brain volume changes during the early years of the illness. CONCLUSIONS: Brain volume abnormalities that have been consistently observed at the onset of non-affective psychosis may not inevitably progress, at least over the first years of the illness. Taking together with clinical and cognitive longitudinal data, our findings, showing a lack of brain deterioration in a substantial number of individuals, suggest a less pessimistic and more reassuring perception of the illness.

Global and regional cortical thinning in first-episode psychosis patients: relationships with clinical and cognitive features.

BACKGROUND: The thickness of the cortical mantle is a sensitive measure for identifying alterations in cortical structure. We aimed to explore whether first episode schizophrenia patients already show a significant cortical thinning and whether cortical thickness anomalies may significantly influence clinical and cognitive features. METHOD: We investigated regional changes in cortical thickness in a large and heterogeneous sample of schizophrenia spectrum patients (n=142) at their first break of the illness and healthy controls (n=83). Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using brains2. The contribution of sociodemographic, cognitive and clinical characterictics was investigated. RESULTS: Patients showed a significant total cortical thinning (F=17.55, d=-0.62, p<0.001) and there was a diffuse pattern of reduced thickness (encompassing frontal, temporal and parietal cortices) (all p's<0.001, d's>0.53). No significant group×gender interactions were observed (all p's>0.15). There were no significant associations between the clinical and pre-morbid variables and cortical thickness measurements (all r's<0.12). A weak significant negative correlation between attention and total (r=-0.24, p=0.021) and parietal cortical thickness (r=-0.27, p=0.009) was found in patients (thicker cortex was associated with lower attention). Our data revealed a similar pattern of cortical thickness changes related to age in patients and controls. CONCLUSIONS: Cortical thinning is independent of gender, age, age of onset and duration of the illness and does not seem to significantly influence clinical and functional symptomatology. These findings support a primary neurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia.

Prognostic value of cognitive functioning for global functional recovery in first-episode schizophrenia.

BACKGROUND: It has become widely accepted that cognitive deficits in schizophrenia are related to functional outcome. However, it remains to be seen whether these associations are relevant for predicting which cases will have a global functional recovery. In this study, we attempt to determine whether global functional recovery (integrating social and occupational outcomes) after first-episode schizophrenia (FES) can be predicted by cognitive variables. METHOD: A total of 131 FES patients with functional deficits (n=97) and functional recovery (n=34) as determined at 1-year follow-up were examined. Neuropsychological, sociodemographic, pre-morbid and clinical data at baseline were analysed using independent groups comparisons and a logistic regression method. RESULTS: Sustained attention and negative symptoms emerged as significant predictors of good global functional outcome. Although the model revealed a high accuracy (91%) in the classification of patients with functional deficits, it was unacceptably low (26%) in the classification of patients with global functional recovery. CONCLUSIONS: The limitations found in the prediction of a favourable global functional outcome may well be an indication for a need to address the role of other factors not commonly included in longitudinal studies of long-term outcomes in schizophrenia.

Iron but not folic acid supplementation reduces the risk of low birthweight in pregnant women without anaemia: a case-control study.

OBJECTIVE: To assess whether iron and folic acid supplementation reduce the risk of low birthweight (LBW) in women without anaemia. DESIGN: Case-control study. SETTING: University Hospital of Cantabria. STUDY POPULATION: Cases were 322 mothers without anaemia delivering a singleton infant of less than 2500 g. Controls were 934 mothers without anaemia delivering a term non-small-for-gestational-age infant. DATA COLLECTION: Data on iron and folic acid supplementation were obtained from prenatal chart record and personal interview. Data on risk factors for LBW were also gathered. RESULTS: Agreement between the two sources of information was good (82% for folic acid and 94% for iron). Odds ratios yielded from the two sources were very close. Folic acid only (15 mg/day) was unrelated to LBW, whereas iron supplementation (80 mg ferrous sulphate) was associated with a lower risk of LBW (odds ratio (OR) 0.58, 95% CI 0.34 to 0.98), adjusted for smoking, maternal education, body mass index, obstetric diseases during pregnancy, weight gain during pregnancy, and previous LBW. The results of iron plus folic acid were similar to those for iron (OR 0.56, 95% CI 0.33 to 0.96). There was a significant trend towards a lower risk of LBW (p<0.001) with the duration of iron supplementation. After stratifying by the type of LBW, the trend was also significant for any kind of LBW. CONCLUSIONS: Iron supplementation is associated with a lower risk of LBW in pregnant women without anaemia.

Cannabis abuse is associated with decision-making impairment among first-episode patients with schizophrenia-spectrum psychosis.

BACKGROUND: Cannabis use appears to be a risk factor for schizophrenia. Moreover, cannabis abusers show impaired decision-making capacities, linked to the orbitofrontal cortex (OFC). Although there is substantial evidence that first-episode schizophrenia patients show impairments in cognitive tasks associated with the dorsolateral prefrontal cortex (DLPFC), it is not clear whether decision making is impaired at schizophrenia onset. In this study, we examined the association between antecedents of cannabis abuse and cognitive impairment in cognitive tasks associated with the DLPFC and the OFC in a sample of first-episode patients with schizophrenia-spectrum disorders. METHOD: One hundred and thirty-two patients experiencing their first episode of a schizophrenia-spectrum psychosis were assessed with a cognitive battery including DLPFC-related tasks [backward digits, verbal fluency (FAS) and the Trail Making Test (TMT)] and an OFC-related task [the Iowa Gambling Task (GT)]. Performance on these tasks was compared between patients who had and had not abused cannabis before their psychosis onset. RESULTS: No differences were observed between the two groups on the performance of any of the DLPFC-related tasks. However, patients who had abused cannabis before their psychosis onset showed a poorer total performance on the gambling task and a lower improvement on the performance of the task compared to no-abusers. CONCLUSIONS: Pre-psychotic cannabis abuse is associated with decision-making impairment, but not working memory and executive function impairment, among first-episode patients with a schizophrenia-spectrum psychosis. Further studies are needed to examine the direction of causality of this impairment; that is, does the impairment make the patients abuse cannabis, or does cannabis abuse cause the impairment?

Pretreatment predictors of cognitive deficits in early psychosis.

BACKGROUND: Predicting cognitive deficits in early psychosis may well be crucial to identify those individuals most in need of receiving intensive intervention. As yet, however, the identification of potential pretreatment predictors for cognitive performance has been hampered by inconsistent findings across studies. We aimed to examine the associations of functional and clinical pretreatment variables with cognitive functioning after a first psychotic episode. METHOD: One hundred and thirty-one patients experiencing first-episode psychosis were assessed for psychopathology, pre-morbid functioning, duration of illness, age of onset, and family history of psychosis and neurocognitive functioning. Multiple regression analyses were conducted for six basic cognitive dimensions known to be affected in this population: verbal learning, verbal memory, verbal comprehensive abilities, executive functioning, motor dexterity and sustained attention. RESULTS: Pre-morbid functioning was the main predictor for five out of the six basic cognitive domains. Pre-morbid social adjustment difficulties were associated with worse performance in executive functioning, motor dexterity and sustained attention. Academic functioning was associated with verbal comprehension, and verbal learning and memory. Gender, age of onset, duration of untreated psychosis, and family history of psychosis had no or limited value as predictors of neurocognitive outcome. CONCLUSIONS: Poor pre-morbid functioning was related to a worse performance in the six basic cognitive dimensions evaluated; however, this accounted for only a small amount of the explained variance. Cognitive impairment is a prominent feature in patients with early psychosis regardless of favorable prognostic features such as short duration of illness, female gender, later age of onset, and non-family history of psychosis.

Influencia del hábito tabáquico familiar en la hospitalización infantil por enfermedades respiratorias en los dos primeros años de vida / Influence of parental smoking on pediatric hospitalization for respiratory illness among children aged less than 2 years

Scanear (AU)

Papel de los equipos de atención primaria en la hospitalización infantil de los niños menores de 2 años / Role of primary care teams in the admission to hospital of children under two years old

Objetivo. Determinar si la conformación de los equipos de atención primaria con la realización del programa de salud del niño sano da lugar a una disminución del riesgo de hospitalización en los niños menores de 2 años, respecto al sistema sanitario tradicional de consultorio o ambulatorio. Diseño. Estudio epidemiológico de casos-referencia. Casos: 40 por ciento de los niños hospitalizados menores de 24 meses en plantas de hospitalización pediátricas o neonatal del Hospital Universitario Marqués de Valdecilla. Referencia: 15 por ciento de los recién nacidos vivos en dicho hospital. Recogida de información mediante entrevista personal y consulta de la tarjeta sanitaria. Período de estudio: abril de 1995 a mayo de 1996. Resultados. Los niños menores de 2 años controlados habitualmente por un médico perteneciente a un equipo de atención primaria presentan una disminución del riesgo de hospitalización para todos los diagnósticos clínicos de 0,57 (IC del 95 por ciento, 0,35-0,93), tras haber ajustado por diferentes factores de confusión como educación materna, clase social, etnia, edad materna, consumo de tabaco materno, lactancia natural al nacimiento, ingreso al nacimiento. Se observó una disminución del riesgo de hospitalización por fiebre sin localización aparente en aquellos niños controlados habitualmente por un médico de equipo (RR ajustado, 0,41; IC del 95 por ciento, 0,19-0,90). Conclusión. Las ventajas de la reforma en la asistencia sanitaria en el ámbito pediátrico, con la conformación de los equipos de atención primaria y la realización de las actividades que ello conlleva, se traduce en una disminución del riesgo de hospitalización para aquellos niños menores de 2 años cuyo control habitual es realizado por un pediatra perteneciente a un equipo de atención primaria (AU)

[Role of primary care teams in hospitalization of children under 2 years of age?]. / Papel de los equipos de atención primaria en la hospitalización infantil de los niños menores de 2 años.

OBJECTIVE: To determine whether the structure of primary care teams on carrying out the healthy child health programme leads to a drop in the risk of admission to hospital of children under two, in comparison with the traditional clinic or out-clinic health system. DESIGN: Case-reference epidemiological study. CASES: 40% of the children under 24 months admitted to paediatric or neonate floors of the Marqués de Valdecilla University Hospital. Reference: 15% of the recently born children alive in this hospital. Information was gathered through face-to-face interview and by examining health cards. The study ran from April 1995 to May 1996. RESULTS: Children under two monitored habitually by a doctor belonging to a primary care team showed a drop in risk of hospital admission for all clinical diagnoses of 0.57 (95% CI, 0.35-0.93), after adjustment due to various confusion factors such as maternal education, social class, ethnic background, mother's age, mother's tobacco consumption, natural breast-feeding at birth, admission at birth. There was a drop of risk of hospital admission for high temperature without apparent cause in those children monitored habitually by a team doctor (adjusted RR = 0.41; 95% CI, 0.19-0.90). CONCLUSIONS: The advantages of the paediatric health care reform with the structuring of the primary care teams and the accompanying activities performed lead to a drop in the risk of hospital admission of those children under two years old who are habitually monitored by a doctor belonging to a primary care team.

Risk factors for low birth weight: results from a case-control study in southern Spain.

The main objective of this study is to examine the effect of several variables, including altitude of maternal residence, on delivering a low birth weight (LBW) newborn. A case-control study was done. Two hundred forty cases (single newborn weighing less than 2,500 g) and 374 controls (single newborn weighing more than 2,499 g) were included. Information was gathered from the clinical chart of delivering women, through a personal interview and the Spanish Census Bureau (for altitude). Predictors of LBW were assessed through stepwise logistic regression analysis. Several well-known LBW risk factors were identified: hypertension, weight gain during pregnancy, body size (mainly maternal prepregnancy weight), low social class, primiparity, and several conditions (spontaneous delivery, abruptio placentae). Altitude was an independent predictor of LBW at term (more than 37 weeks of gestational age) but not for preterm LBW. Nevertheless, a relationship between altitude and birth weight was not found in controls, although a moderate decreasing gradient with altitude was observed. The limitations of these findings are discussed.

Comparison of two copper IUDs: the MLCu375 and the Nova-T.

A comparative randomized trial was carried out on two intrauterine contraceptive devices: the Nova-T and the MLCu375. The IUDs were used by 1116 and 1237 women respectively, over a period of 2 years. The reasons for IUD removal were analyzed after one and two years using the life-table method. Statistically significant differences were found in the rates for pregnancy, expulsion and removal for bleeding and/or pain favoring the MLCu375 IUD.