Individuals with an at risk mental state (ARMS) are at greatly increased risk of developing a psychotic illness. Risk of transition to psychosis is associated with regionally reduced cortical gray matter volume. There has been considerable interest in the interaction between psychosis risk and substance use. In this study we investigate the relationship between alcohol, cannabis and nicotine use with gray matter volume in ARMS subjects and healthy volunteers. Twenty seven ARMS subjects and 27 healthy volunteers took part in the study. All subjects underwent volumetric MRI imaging. The relationship between regional gray matter volume and cannabis use, smoking, and alcohol use in controls and ARMS subjects was analysed using voxel-based morphometry. In any region where a significant relationship with drug was present, data were analysed to determine if there was any group difference in this relationship. Alcohol intake was inversely correlated with gray matter volume in cerebellum, cannabis intake was use was inversely correlated with gray matter volume in prefrontal cortex and tobacco intake was inversely correlated with gray matter volume in left temporal cortex. There were no significant interactions by group in any region. There is no evidence to support the hypothesis of increased susceptibility to harmful effects of drugs and alcohol on regional gray matter in ARMS subjects. However, alcohol, tobacco and cannabis at low to moderate intake may be associated with lower gray matter in both ARMS subjects and healthy volunteers—possibly representing low-level cortical damage or change in neural plasticity.
Individuals with an At Risk Mental State (ARMS) are at increased risk of developing psychosis (Phillips et al., 2000). They have also been shown to have reduced gray matter compared to healthy volunteers (Pantelis et al., 2003 and Borgwardt et al., 2007), and, with transition to psychosis, show a further reduction in gray matter volume (Pantelis et al., 2003 and Takahashi et al., 2009), findings which have been confirmed by recent meta-analyses (Smieskova et al., 2010 and Fusar-Poli et al., 2011). The cause of these changes is not known, but it has been suggested that reductions in gray matter volume might occur, in part, because of increased sensitivity in ARMS subjects to the potentially toxic effects of drugs and alcohol (Welch et al., 2010). Cannabis, tobacco and alcohol have been implicated in brain volume changes in patients with schizophrenia (Sullivan et al., 2000, Nesvag et al., 2007, Szeszko et al., 2007, Tregellas et al., 2007, Bangalore et al., 2008, Rais et al., 2008a, McClernon, 2009 and Van Haren et al., 2010), and there is some evidence that moderate levels of intake may be associated with reduced gray matter volume in individuals at genetic risk of schizophrenia, and even in healthy volunteers (McClernon, 2009, Gallinat et al., 2006, Sasaki et al., 2009, Verbaten, 2009 and Lorenzetti et al., 2010). Here, using data acquired during an earlier study (Stone et al., 2009), we investigate the hypothesis that the degree of recent cannabis, alcohol and tobacco use is negatively associated with gray matter volume in a dose-dependent manner, and that ARMS subjects show a stronger negative association between substance use and gray matter volume than healthy volunteers due to increased sensitivity to neurotoxic effects.
Alcohol, tobacco and cannabis at low to moderate intake may be associated with lower gray matter in both ARMS subjects and healthy volunteers—possibly representing low-level cortical damage or change in neural plasticity. The present study does not support the hypothesis that ARMS subjects are at greater risk of gray matter changes associated with substance intake, although it is possible that at higher levels of intake, or with prolonged use, a differential effect may emerge.
