The impact of acute and chronic stress on the hypothalamic-pituitary-adrenal (HPA) axis is reviewed and evidence presented that corticotrophin releasing factor (CRF) is the stress neurotransmitter which plays an important role in the activation of the central sympathetic and serotonergic systems. The activity of CRF is expressed through specific receptors (CRF 1 and 2) that are antagonistic in their actions and widely distributed in the limbic regions of the brain, as well as in the hypothalamus, and on immune cells.

The mechanism whereby chronic stress, via the CRF induced activation of the dorsal raphe nucleus, can induce a change in the serotonergic system, involves an increase in the 5HT2A and a decrease in the 5HT1A receptor mediated function. Such changes contribute to the onset of anxiety and depression. In addition, the hypersecretion of glucocorticoids that is associated with chronic stress and depression desensitises the central glucocorticoid receptors to the negative feedback inhibition of the HPA axis. This indirectly results in the further activation of the HPA axis.

The rise in pro-inflammatory cytokines that usually accompanies the chronic stress response results in a further stimulation of the HPA axis thereby adding to the stress response. While CRF would appear to play a pivotal role, evidence is provided that simultaneous changes in the serotonergic and noradrenergic systems, combined with the activation of peripheral and central macrophages that increase the pro-inflammatory cytokine concentrations in the brain and blood, also play a critical role in predisposing to anxiety and depression. Neurodegenerative changes in the brain that frequently occur in the elderly patient with major depression, could result from the activation of indoleaminedioxygenase (IDO), a widely distributed enzyme that converts tryptophan via the kynenine pathway to for the neurotoxic end product quinolinic acid.

The recognition of the importance of evaluating the quality of life of patients with schizophrenia highlighted the importance ofdeveloping appropriate instruments. In this paper we review the available quality of life instruments focusing on their conceptual framework, structure, administration and psychometric properties. First, we address the generic instruments that have been validated for schizophrenic populations, namely the World Health Organization Quality of Life Assessment (WHOQOL), the Medical Outcome Study (MOS) 36-Item Short-Form Health Survey (SF-36) and the EuroQoL-5 Dimensions (EQ-5D). Then, we focus on instruments that have been specifically developed for patients with schizophrenia and other or severe mentally illness such as the Quality of Life Scale (QLS), the Quality of Life Interview (QoLI), the Lancashire Quality of Life Profile (LQoLP), the Sevilla Quality of Life Questionnaire (SQLQ), the Personal Evaluation of Transitions in Treatment (PETIT), and the Quality of Life Questionnaire in Schizophrenia (S-QoL).