Research on major depression has confirmed that it is caused by an array of biopsychosocial and lifestyle factors. Diet, exercise and sleep are three such influences that play a significant mediating role in the development, progression and treatment of this condition. This review summarises animal and human-based studies on the relationship between these three lifestyle factors and major depressive disorder, and their influence on dysregulated pathways associated with depression, namely neurotransmitter processes, immuno-inflammatory pathways, hypothalamic-pituitary-adrenal (HPA) axis disturbances, oxidative stress and antioxidant defence systems, neuroprogression, and mitochondrial disturbances. Increased attention in future clinical studies on the influence of diet, sleep and exercise on major depressive disorder and investigations of their effect on physiological processes will help to expand our understanding and treatment of major depressive disorder. Mental health interventions, taking into account the bidirectional relationship between these lifestyle factors and major depression are also likely to enhance the efficacy of interventions associated with this disorder.

Biomarkers are regularly used in medicine to provide objective indicators of normal biological processes, pathogenic processes or pharmacological responses to therapeutic interventions, and have proved invaluable in expanding our understanding and treatment of medical diseases. In the field of psychiatry, assessment and treatment has, however, primarily relied on patient interviews and questionnaires for diagnostic and treatment purposes. Biomarkers in psychiatry present a promising addition to advance the diagnosis, treatment and prevention of psychiatric diseases. This review provides a summary on the potential of peripheral biomarkers in major depression with a specific emphasis on those related to inflammatory/immune and oxidative stress/antioxidant defences. The complexities associated with biomarker assessment are reviewed specifically around their collection, analysis and interpretation. Focus is placed on the potential of peripheral biomarkers to aid diagnosis, predict treatment response, enhance treatment-matching, and prevent the onset or relapse of major depression.

The ATD technique is a valid method of manipulating central 5-HT levels. The second article in this series will review the application of ATD in depression, anxiety and other psychiatric conditions.

Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice. Conventional dependence management, benzodiazepine tapering, is commonly a protracted process over several weeks or months. It is often associated with significant withdrawal symptoms and craving leading to patient drop out and return to use. Accordingly, there is a worldwide need to find effective pharmacotherapeutic interventions for benzodiazepine dependence. One drug of increasing interest is the GABAA benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus intravenous infusions of low dose flumazenil used either with or without benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term symptoms in the months following withdrawal. Preliminary data suggest that continuous intravenous or subcutaneous flumazenil infusion for 4 days significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous infusion was shown to be tissue compatible so the development of a longer acting (i.e. several weeks) depot flumazenil formulation has been explored. This could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae. Preliminary in vitro water bath and in vivo biocompatibility data in sheep show that such an implant is feasible and so is likely to be used in clinical trials in the near future.

Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.

BACKGROUND: Curcumin, the principal curcuminoid derived from the spice turmeric, influences several

The monoamine neurotransmitter serotonin (5-HT) has an important role in both the pathophysiology and treatment of anxiety and panic attacks.1,2 The strongest evidence that a specific abnormality of the serotonin system predisposes or contributes to anxiety comes from studies of the 5-HT 1A receptor. 'Knockout' mice bred without 5-HT 1A receptors in the cerebral cortex and limbic system show increased anxiety behaviours 3 and patients with panic disorder have been shown by challenge testing to have subsensitivity of these receptors. 4 Furthermore, the azapirone 5-HT 1A agonist buspirone is licensed for the treatment of generalised anxiety disorder in the UK. In a systematic review of 36 trials of patients treated for generalised anxiety disorder azapirones, including buspirone, were found to be superior to placebo in short-term studies (4-9 weeks). 5The development of select radiotracers for the 5-HT 1A receptor now allows a direct examination of this receptor system in living patients with panic disorder. Neumeister et al 6 reported the first full positron emission tomography (PET) study of 5-HT 1A binding in 16 unmedicated patients with panic disorder and 15 healthy controls. Regions of interest examined were limited to the anterior cingulate cortex, posterior cingulate cortex, anterior insula, mesiotemporal cortex, anterior temporopolar cortex and midbrain raphe -all areas of high 5-HT 1A binding. Lower 5-HT 1A binding occurred in anterior cingulate, posterior cingulate and raphe only in patients with panic disorder. Seven of the 16 patients with panic disorder had comorbid depression, although there was no difference in 5-HT 1A binding between the patients with panic disorder with comorbid depression and those without. The radiotracer used for Neumeister et al's study [18 F]-FCWAY, gives a reliable signal subcortically, but quantification in cortical areas is limited because of retained fluoride signal in bone. 7A further recent PET study using [11 C]WAY-100635 found reduced 5-HT 1A binding in social anxiety disorder. 8 That study compared 12 unmedicated male patients with social anxiety disorder with 18 healthy controls. Six of these patients had comorbid agoraphobia. Six regions of interest were examined a priorireduction of 5-HT 1A binding was found in the amygdala, anterior cingulate, insula, medial orbitofrontal cortex and raphe. After Bonferroni correction only the differences in the amygdala and anterior cingulate cortex remained significant. There was no significant correlation between state or trait anxiety scores and regional 5-HT 1A binding potential in both groups.In this study, we used the PET tracer [ 11 C]WAY-100635 which allows in vivo quantification of 5-HT 1A receptors with exquisite delineation and precision.9,10 Specifically, we wished to confirm the findings of Neumeister et al, 6 extend the findings to look at more regions of interest and finally examine the effect of SSRI treatment. Our specific hypothesis was that patients with panic disorder would have reductions in 5-HT 1A receptor ...

Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal (HPA) disturbances, lowering inflammation, and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.