Association of Hippocampal Glutamate Levels With Adverse Outcomes in Individuals at Clinical High Risk for Psychosis.

Importance: Preclinical and human data suggest that hippocampal dysfunction plays a critical role in the onset of psychosis. Neural hyperactivity in the hippocampus is thought to drive an increase in subcortical dopamine function through glutamatergic projections to the striatum. Objective: To examine the association between hippocampal glutamate levels in individuals at clinical high risk for psychosis and their subsequent clinical outcomes. Design, Setting, and Participants: This cross-sectional study of 86 individuals at clinical high risk for psychosis and 30 healthy control individuals, with a mean follow-up of 18.5 months, was conducted between November 1, 2011, and November 1, 2017, at early detection services in London and Cambridge, United Kingdom. Main Outcomes and Measures: Concentrations of glutamate and other metabolites were measured in the left hippocampus using 3-T proton magnetic resonance spectroscopy at the first clinical presentation. At follow-up, clinical outcomes were assessed in terms of transition or nontransition to psychosis using the Comprehensive Assessment of the At-Risk Mental State criteria and the level of overall functioning using the Global Assessment of Function scale. Results: Of 116 total participants, 86 were at clinical high risk for psychosis (50 [58%] male; mean [SD] age, 22.4 [3.5] years) and 30 were healthy controls (14 [47%] male; mean [SD] age, 24.7 [3.8] years). At follow-up, 12 clinical high-risk individuals developed a first episode of psychosis whereas 74 clinical high-risk individuals did not; 19 clinical high-risk individuals showed good overall functioning (Global Assessment of Function ≥65), whereas 38 clinical high-risk individuals had a poor functional outcome (Global Assessment of Function <65). Compared with clinical high-risk individuals who did not become psychotic, clinical high-risk individuals who developed psychosis showed higher hippocampal glutamate levels (mean [SD], 8.33 [1.48] vs 9.16 [1.28] glutamate levels; P = .048). The clinical high-risk individuals who developed psychosis also had higher myo-inositol levels (mean [SD], 7.60 [1.23] vs 6.24 [1.36] myo-inositol levels; P = .002) and higher creatine levels (mean [SD], 8.18 [0.74] vs 7.32 [1.09] creatine levels; P = .01) compared with clinical high-risk individuals who did not become psychotic, and higher myo-inositol levels compared with healthy controls (mean [SD], 7.60 [1.23] vs 6.19 [1.51] myo-inositol levels; P = .005). Higher hippocampal glutamate levels in clinical high-risk individuals were also associated with a poor functional outcome (mean [SD], 8.83 [1.43] vs 7.76 [1.40] glutamate levels; P = .02). In the logistic regression analyses, hippocampal glutamate levels were significantly associated with clinical outcome in terms of transition and nontransition to psychosis (ß = 0.48; odds ratio = 1.61; 95% CI, 1.00-2.59; P = .05) and overall functioning (ß = 0.53; odds ratio = 1.71; 95% CI, 1.10-2.66; P = .02). Conclusions and Relevance: The findings indicate that adverse clinical outcomes in individuals at clinical high risk for psychosis may be associated with an increase in baseline hippocampal glutamate levels, as well as an increase in myo-inositol and creatine levels. This conclusion suggests that these measures could contribute to the stratification of clinical high-risk individuals according to future clinical outcomes.

Dynamic relationship between multiple START assessments and violent incidents over time: a prospective cohort study.

BACKGROUND: Dynamic risk factors need to be assessed repeatedly over time rather than at a single time point to examine the relationship with violence. This predictive validity study sought to examine the degree of dynamic change in risk assessed in a group of mentally disordered offenders and the relationship between change and the occurrence of violence. METHODS: Routine structured assessments of Strengths and Vulnerabilities on the Short-Term Assessment of Risk and Treatability (START) instrument (n = 475) were linked prospectively with 275 violent incidents using logistic regression in a sample of 50 patients. RESULTS: Stability within patients estimated using the intra-class correlation coefficient was high (>.80) for both Strengths and Vulnerabilities. In the overall sample, a 10 point increase in START Vulnerabilities score was associated with a three-fold increased risk of violence (OR = 3.1; 95% CI, 1.47-7.46) but there was no association for Strengths score (OR = 0.91, 95% CI, 0.34-2.47). When examined within patients, both Vulnerabilities (OR = 1.77, 95% CI, 0.56-5.54) and Strengths (OR = 2.26, 95% CI, 0.38-13.42) were associated with an increased risk of violence but in both cases precision was low due to reduced sample sizes. CONCLUSIONS: Risk factors which are considered to have the capacity to fluctuate dynamically did not do so substantially in this group of mentally disordered offenders. When fluctuations did occur there was some tentative evidence that they are associated with violent outcomes and could guide the use of prevention measures.

Support for healthy breastfeeding mothers with healthy term babies.

BACKGROUND: There is extensive evidence of important health risks for infants and mothers related to not breastfeeding. In 2003, the World Health Organization recommended infants be exclusively breastfed until six months of age, with breastfeeding continuing as an important part of the infant's diet till at least two years of age. However, breastfeeding rates in many countries currently do not reflect this recommendation. OBJECTIVES: To assess the effectiveness of support for breastfeeding mothers. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 October 2011). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing extra support for healthy breastfeeding mothers of healthy term babies with usual maternity care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: Of the 67 studies that we assessed as eligible for inclusion, 52 contributed outcome data to the review (56,451 mother-infant pairs) from 21 countries. All forms of extra support analysed together showed an increase in duration of 'any breastfeeding' (includes partial and exclusive breastfeeding) (risk ratio (RR) for stopping any breastfeeding before six months 0.91, 95% confidence interval (CI) 0.88 to 0.96). All forms of extra support together also had a positive effect on duration of exclusive breastfeeding (RR at six months 0.86, 95% CI 0.82 to 0.91; RR at four to six weeks 0.74, 95% CI 0.61 to 0.89). Extra support by both lay and professionals had a positive impact on breastfeeding outcomes. Maternal satisfaction was poorly reported. AUTHORS' CONCLUSIONS: All women should be offered support to breastfeed their babies to increase the duration and exclusivity of breastfeeding. Support is likely to be more effective in settings with high initiation rates, so efforts to increase the uptake of breastfeeding should be in place. Support may be offered either by professional or lay/peer supporters, or a combination of both. Strategies that rely mainly on face-to-face support are more likely to succeed. Support that is only offered reactively, in which women are expected to initiate the contact, is unlikely to be effective; women should be offered ongoing visits on a scheduled basis so they can predict that support will be available. Support should be tailored to the needs of the setting and the population group.