Oxidative stress in psychiatric disorders : evidence base and therapeutic implications

Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage. This review aims to examine the current evidence for the role of oxidative stress in psychiatric disorders, and its academic and clinical implications. A literature search was conducted using the Medline, Pubmed, PsycINFO, CINAHL PLUS, BIOSIS Previews, and Cochrane databases, with a time-frame extending to September 2007. The broadest data for oxidative stress mechanisms have been derived from studies conducted in schizophrenia, where evidence is available from different areas of oxidative research, including oxidative marker assays, psychopharmacology studies, and clinical trials of antioxidants. For bipolar disorder and depression, a solid foundation for oxidative stress hypotheses has been provided by biochemical, genetic, pharmacological, preclinical therapeutic studies and one clinical trial. Oxidative pathophysiology in anxiety disorders is strongly supported by animal models, and also by human biochemical data. Pilot studies have suggested efficacy of N-acetylcysteine in cocaine dependence, while early evidence is accumulating for oxidative mechanisms in autism and attention deficit hyperactivity disorder. In conclusion, multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders. These data not only suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.

Effects of N-acetylcysteine on substance use in bipolar disorder : a randomized placebo controlled clinical trial

Objective: To evaluate the effect of N-acetylcysteine (NAC) on substance use in a double-blind, placebo-controlled trial of NAC in bipolar disorder. It is hypothesised that NAC will be superior to placebo for reducing scores on the Clinical Global Impressions scale for Substance Use (CGI-SU).

Methods: Participants were randomised to 6-months of treatment with 2 g/day NAC (n = 38) or placebo (n = 37). Substance use was assessed at baseline using the Habits instrument. Change in substance use was assessed at regular study visits using the CGI-SU.

Results: Amongst the 75 participants 78.7% drank alcohol (any frequency), 45.3% smoked tobacco and 92% consumer caffeine. Other substances were used by fewer than six participants. Caffeine use was significantly lower for NAC-treated participants compared with placebo at week 2 of treatment but not at other study visits.

Conclusion: NAC appeared to have little effect on substance use in this population. A larger study on a substance using population will be necessary to determine if NAC may be a useful treatment for substance use.

Cavity

This series of photographs focuses on caves in Western Victoria that have a layer of colonial occupation; caves said to be inhabited by bush rangers, escaped convicts, shipwreck survivors and hermits. The photographer was drawn to a rich vein of sites associated with colonial myths of inhabitation. These include the escaped convict William Buckley; Miss Carmichael, survivor of the wreck of the Lochard in 1878; Bushranger Captain Melville, and elusive enigmatic Black Ranges hermit David Ross. The resulting photographs explore the sensory and psychological resonance of these extraordinary places, what they feel like and how they feed the imagination, the need to feel rooted, to feel at home. Her approach embraces the paradoxical ambivalence of this need and the complex process of negotiating our presence in the land.

Gyration

European Renaissance and Romantic landscape appeared in vistas. The conditions of the industrial revolution and, according to Patrick Maynard and Jonathon Crary, the film camera especially, led to a Modernist re-vision vividly recorded in Xavier Herbert’s contrary Modernist vision, prompted by seeing the Australian bush, its ‘... stunted trees, the mulga and the wilga and the gimlet gum, doing a kind of dance, spinning past, seeming to swing away from the train to the horizon and race ahead, to come back...the same set of trees in endless gyration’.

Manipulating Islam and democracy in Iraq’s ‘Pluralised Authoritarianism’

With the realisation that the initial motives for the 2003 invasion of Iraq – Saddam’s alleged stockpile of Weapons of Mass Destruction (WMD) and his links to Al-Qaeda – were grievous intelligence errors the Bush administration, with varying degrees of success, were able to spin the war’s rasion d’etre and redefine the parameters of victory. A central tenet of this approach was to begin speaking about democracy as if it had always been one of the aims of the war itself. For the first few years, the effort to democratise Iraq appeared to gain some credible momentum: a complex array of political, religious and ethno-sectarian factions formed political parties and civil society movements; uncensored news was enthusiastically consumed across the nation; Iraqi citizens took to the streets to protest key government decisions; and millions of Iraqis voted in relatively free and fair national elections (Davis, 2004, 2007, Isakhan, 2008, 2011b). Central to each of these developments were various Iraqi religious establishments – but especially those of the Shia Arab population of Iraq – who saw no distinction between their Islamic faith and the notion of democracy. Not surprisingly, a body of literature has emerged which has been very optimistic about Iraq’s engagement with both ‘Islam’ and ‘democracy’ in the post-Baathist period, while acknowledging the challenges it faces in creating a stable, egalitarian and democratic society (Al-Musawi, 2006, Cole, 2006, Davis, 2005, Dawisha, 2009, Isakhan, 2011a, Stansfield, 2007).

However, there have been virtually no studies which have sought to question this optimism in the light of more recent events. Addressing this lacuna, this paper documents the last few years (2006- 2011) which have seen many elements within the Iraqi political elite – most notably the Maliki government and his State of Law Coalition (SLC) – demonstrate what has been referred to in literature on other Arab states alternatively as ‘liberalised autocracy’ (Brumberg, 2002), ‘semi-authoritarianism’ (Ottaway, 2003) or ‘pluralised authoritarianism’ (Posusney and Angrist, 2005). That is to say, that these states consolidate their incumbency while putting in place measures that can be considered more or less liberal. To do this, the regime actually utilises (and controls) nominally democratic mechanisms such as elections, media freedoms, political opposition and civil society as part of their strategy to retain power. Of particular interest here are the ways in which the Maliki government – and Shia Arab Iraqi political factions more broadly – have manipulated both ‘Islam’ and ‘democracy’ towards such ‘pluralised authoritarianism’.

Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.

Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.

Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.

Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

Telescope

Telescope is a feature length time lapse of reflections, changes in sunlight of my backyard, assembled over 20 years. Telescope starts in Super 8 and ends with digital video, shot mostly while the family were themselves at work, somewhere else. It is an emptied landscape. When people think of Australia they imagine open space and bush. But really most Australians inhabit or were born in suburban spaces, often with backyards with fences, big enough for fruit trees, lawns and clotheslines. I consider this a place of absence that speaks to many things that our culture avoids.The backyard as emblem of a White Australia that hit its highpoint in the 1950s, for example. Australia is a migrant culture settled by waves of newcomers escaping, running away from somewhere else, leaving to forget. Another story concerns the continued invisibility of the indigenous people. When the British first planted the Union Jack on Australian soil and said "there is nothing here" they set up a tradition of denial as our founding principle. This still plagues us. What is festering in Australian backyards are these denials and erasures that I try to bring out in the soundtrack, that plays like the radio that meanders through a lazy Sunday afternoon. Such sounds try to tell stories of absence, of occupation, and of a nostalgia for an Australia that no longer exists, but still palpably reverberates around the suburban backyard.

The Max Bell Gallery (Gallery X series) Bishop and Reis

 An interactive exhibition, which recreates the Max Gallery and re-interprets two of Geelong's most renowned paintings (View of Geelong and A Bush Burial) through digital animation

Liquid landscape (Headland)

A complex structure floats on an undulating colour field. This could be a description of any landscape painting where the built environment, human culture, intersects with the natural world. In Stephen Bush's "Cumberland" (2010) an appropriated landscape supports a log cabin - centrally and ideally placed in a picturesque, alpine landscape. The cabin though, has no relationship to the ground plane, above which it hovers, while its shadows fall in the opposite direction to the buildings and mountains behind it. Bush fetishizes paint, exploring its plasticity and exploiting the viewer's gullibility (as do I). My work realises Bush's aesthetic in three dimensions, extending it to meet with the act of looking, and asks the viewer to merge with the work of art.

Effects of N-acetyl cysteine on cognitive function in bipolar disorder

Aims

Bipolar disorder is characterized by progressive changes in cognition with declines in executive functioning, memory and sustained attention. Current pharmacotherapies for bipolar disorder target mood symptoms but have not addressed these cognitive changes resulting in euthymic individuals who still experience cognitive deficits. N-acetyl cysteine (NAC) has been shown to have effects on antioxidant status, glutamate transmission, inflammation and neurogenesis. Adjunctive treatment with NAC improves the symptoms experienced by those with bipolar disorder, particularly depression, and it was hypothesized that cognition may also be improved following NAC treatment.
Methods

As part of a larger randomized, double-blind, placebo-controlled trial, participants in the current report were tested at baseline and 6 months to assess changes in cognitive function following either 2000 mg of NAC daily or placebo.
Results

This study failed to find changes in cognitive function following treatment with NAC compared to placebo.
Conclusions

While an important pilot study, this study had a small sample size and included a limited battery of cognitive tests. Further investigations on the effects of NAC on cognitive performance in bipolar disorder are required.