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.

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.