Astrocytes have a higher antioxidant potential in comparison to neurons. Pathways associated with this selective advantage include the transcriptional regulation of antioxidant enzymes via the action of the Cap'n'Collar transcription factor Nrf2 at the antioxidant response element (ARE). Here we show that Nrf2 overexpression can reengineer neurons to express this glial pathway and enhance antioxidant gene expression. However, Nrf2-mediated protection from oxidative stress is conferred primarily by glia in mixed cultures. The antioxidant properties of Nrf2-overexpressing glia are more pronounced than those of neurons, and a relatively small number of these glia (Ͻ 1% of total cell number added) could protect fully cocultured naive neurons from oxidative glutamate toxicity associated with glutathione (GSH) depletion. Microarray and biochemical analyses indicate a coordinated upregulation of enzymes involved in GSH biosynthesis (xCT cystine antiporter, ␥-glutamylcysteine synthetase, and GSH synthase), use (glutathione S-transferase and glutathione reductase), and export (multidrug resistance protein 1) with Nrf2 overexpression, leading to an increase in both media and intracellular GSH. Selective inhibition of glial GSH synthesis and the supplementation of media GSH indicated that an Nrf2-dependent increase in glial GSH synthesis was both necessary and sufficient for the protection of neurons, respectively. Neuroprotection was not limited to overexpression of Nrf2, because activation of endogenous glial Nrf2 by the small molecule ARE inducer, tert-butylhydroquinone, also protected against oxidative glutamate toxicity.

Economics and mental health are intertwined. Apart from the accumulating evidence of the huge economic impacts of mental ill‐health, and the growing recognition of the effects that economic circumstances can exert on mental health, governments and other budget‐holders are putting increasing emphasis on economic data to support their decisions. Here we consider how economic evaluation (including cost‐effectiveness analysis, cost‐utility analysis and related techniques) can contribute evidence to inform the development of mental health policy strategies, and to identify some consequences at the treatment or care level that are of relevance to service providers and funding bodies. We provide an update and reflection on economic evidence relating to mental health using a lifespan perspective, analyzing costs and outcomes to shed light on a range of pressing issues. The past 30 years have witnessed a rapid growth in mental health economics, but major knowledge gaps remain. Across the lifespan, clearer evidence exists in the areas of perinatal depression identification‐plus‐treatment; risk‐reduction of mental health problems in childhood and adolescence; scaling up treatment, particularly psychotherapy, for depression; community‐based early intervention and employment support for psychosis; and cognitive stimulation and multicomponent carer interventions for dementia. From this discussion, we pull out the main challenges that are faced when trying to take evidence from research and translating it into policy or practice recommendations, and from there to actual implementation in terms of better treatment and care.

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The 3-year outcome in phase-specific early intervention compared favourably with that of standard psychiatric care, particularly with respect to functional outcome and reduction in hospitalizations, suicides and disengagements. However, intervention did not appear to reduce the rate of relapse.