Get sober; stay sober.

In the decades since alcoholism became widely recognized as a disease (Jellinek, 1960), evidence for alcohol-induced physical damage has accumulated both in quantity and in detail. Prominent amongst the affected organ systems at-risk is the brain, which responds to alcohol in a variety of ways. Free radicals formed during metabolism of alcohol damage the brain. Acetaldehyde, which is generated from ethanol, is highly reactive and toxic. This metabolite cross-links brain enzymes, reducing or eliminating the normal functions of those proteins. Neurotransmitter systems are altered not only through these mechanisms, but by adaptation to the neuromodulatory effects of ethanol itself (Heinz et al., 2003). Furthermore, it is possible to visualize damage to different types of brain cells microscopically (Miguel-Hidalgo and Rajkowska, 2003) and, in particular, changes in the number and size of glia (Miguel-Hidalgo et al., 2002). The alcohol-soaked brain shrinks heterogeneously. The damage involves both white (Rohlfing et al., 2006) and grey matter: one of the most severely affected regions is the frontal cortex (Gazdzinski et al., 2005) which, when damaged, leads to impaired cognitive capacity that may further compromise the individual's judgement and motivation to remain sober. The situation often appears dismal from the view of the patient and the provider of treatment, and patients are often discouraged by the physical and cognitive difficulties of achieving and maintaining sobriety. However, data acquired in recent years provide hope and, when presented appropriately, potentially offer renewed motivation for patients to get sober. There is anecdotal support that patients are helped by knowing that there have been improvements in their brain volume, neurochemistry and cognition, and that even showing alcoholics the results from a separate, published group of similarly affected individuals can provide motivation. Dieter Meyerhoff and Timothy Durazzo (University of California and the Veterans' Administration at San Francisco, personal communication) report that many of the alcohol-dependent subjects in their studies begin treatment with the belief that 'the damage is done' and are surprised to learn of the significant volumetric and neurochemical recoveries to be achieved after only a few weeks. Several of their study participants have explicitly stated that this information is encouraging and assists in their motivation to stay sober, at least in the short term. Against this background, Andreas Bartsch and colleagues report combined measurements of neurochemicals, brain volumetrics and neurocognitive function in a longitudinal study involving one group of patients in this issue of Brain (page 36). Briefly, …