Polysubstance Use: Diagnostic Challenges and Patterns of Use
Polysubstance Use: Diagnostic Challenges and Patterns of Use
Imaging studies suggest that the abuse of multiple substances may have a cumulative or synergistic adverse effect on brain function and neurocognition. Abstinent polysubstance abusers have reduced gray matter in the right temporal pole and medial frontal lobe, including the superior, cingulate, and paracingulate gyri. Abé et al. employed high-field brain magnetic resonance spectroscopy to study differences in brain metabolite concentrations in polysubstance abuse. Polysubstance abusers were defined as meeting DSM-IV criteria for dependence on alcohol in addition to one or more psychostimulants (mostly cocaine). At 1-month abstinence, polysubstance abusers had significantly lower concentrations of N-acetylaspartate, creatine, myoinositol, and choline-containing metabolites in the dorsolateral prefrontal cortex than alcohol-dependent individuals, who did not differ from healthy controls. This suggests cocaine may be more injurious than alcohol. Amongst polysubstance abusers, levels of N-acetylaspartate metabolites in this region were strongly correlated with deficits in visuospatial and working memory performance. This suggests that long-lasting memory deficits in polysubstance abusers may be the result of persistent abnormalities in neuronal integrity. Myoinositol abnormalities have been detected in the temporal cortex, cerebellar vermis, and lenticular nucleus, but these were not associated with cognitive performance. In neither of the studies were these abnormalities related to the severity of consumption.
The relationships between brain function and drug doses may differ according to age, the substances abused, or how 'dose' is measured. Dose-related abnormalities in frontal N-acetylaspartate have been reported in adolescent polysubstance abusers compared to cannabis-dependent individuals and controls, suggesting a greater vulnerability to neurotoxicity in younger polysubstance users. Dose-response relationships were observed for methamphetamine and cannabis, but only in polysubstance users, suggesting a synergistic effect of combined use. Dose-related alterations in cortical serotonin signalling have also been observed in long-term abstinent polysubstance users, but these were specific to 3,4-methylenedioxymethamphetamine (MDMA), suggesting a unique role in serotonin neurotoxicity. Other studies have shown dose-dependent associations between MDMA and brain activity in the parahippocampal gyrus and superior parietal lobule during memory encoding but not retrieval. Taken together, recent findings suggest psychostimulant abuse in polysubstance users is particularly injurious. However, these studies, and other recent investigations of inhibitory control and decision-making, find no difference in the behavioural performance between polysubstance abusers and controls. This contrasts with the body of neuropsychological evidence of impairments resulting from substance abuse.
Some have interpreted the discrepancy between neural and behavioural outcomes as reflecting the engagement of compensatory processes to achieve equivalent performance. It is also possible that neuropsychological tasks adapted and simplified for the scanner lack sensitivity or that neuroimaging studies lack sufficient sample sizes for adequate statistical power. Large differences have been reported in behavioural performance between polysubstance abusers and controls on standardized neuropsychological tests of working memory, inhibition, cognitive flexibility, self-regulation, and decision-making (administered outside the scanner). Test performance correlated with resting brain metabolism in the right middle temporal pole (working memory), right calcarine and bilateral posterior cingulate (self-regulation), and right middle and superior frontal cortices (decision-making). However, only severity of cocaine use was related to brain metabolism (right middle temporal pole). Therefore, although polysubstance abuse is clearly associated with deficits in brain function and cognition, elucidating more specific relationships is made difficult by the methodological differences between studies, differences in the wide range of substances abused, and possibly reduced statistical power in neuroimaging studies.
Imaging and Neuropsychology Studies
Imaging studies suggest that the abuse of multiple substances may have a cumulative or synergistic adverse effect on brain function and neurocognition. Abstinent polysubstance abusers have reduced gray matter in the right temporal pole and medial frontal lobe, including the superior, cingulate, and paracingulate gyri. Abé et al. employed high-field brain magnetic resonance spectroscopy to study differences in brain metabolite concentrations in polysubstance abuse. Polysubstance abusers were defined as meeting DSM-IV criteria for dependence on alcohol in addition to one or more psychostimulants (mostly cocaine). At 1-month abstinence, polysubstance abusers had significantly lower concentrations of N-acetylaspartate, creatine, myoinositol, and choline-containing metabolites in the dorsolateral prefrontal cortex than alcohol-dependent individuals, who did not differ from healthy controls. This suggests cocaine may be more injurious than alcohol. Amongst polysubstance abusers, levels of N-acetylaspartate metabolites in this region were strongly correlated with deficits in visuospatial and working memory performance. This suggests that long-lasting memory deficits in polysubstance abusers may be the result of persistent abnormalities in neuronal integrity. Myoinositol abnormalities have been detected in the temporal cortex, cerebellar vermis, and lenticular nucleus, but these were not associated with cognitive performance. In neither of the studies were these abnormalities related to the severity of consumption.
The relationships between brain function and drug doses may differ according to age, the substances abused, or how 'dose' is measured. Dose-related abnormalities in frontal N-acetylaspartate have been reported in adolescent polysubstance abusers compared to cannabis-dependent individuals and controls, suggesting a greater vulnerability to neurotoxicity in younger polysubstance users. Dose-response relationships were observed for methamphetamine and cannabis, but only in polysubstance users, suggesting a synergistic effect of combined use. Dose-related alterations in cortical serotonin signalling have also been observed in long-term abstinent polysubstance users, but these were specific to 3,4-methylenedioxymethamphetamine (MDMA), suggesting a unique role in serotonin neurotoxicity. Other studies have shown dose-dependent associations between MDMA and brain activity in the parahippocampal gyrus and superior parietal lobule during memory encoding but not retrieval. Taken together, recent findings suggest psychostimulant abuse in polysubstance users is particularly injurious. However, these studies, and other recent investigations of inhibitory control and decision-making, find no difference in the behavioural performance between polysubstance abusers and controls. This contrasts with the body of neuropsychological evidence of impairments resulting from substance abuse.
Some have interpreted the discrepancy between neural and behavioural outcomes as reflecting the engagement of compensatory processes to achieve equivalent performance. It is also possible that neuropsychological tasks adapted and simplified for the scanner lack sensitivity or that neuroimaging studies lack sufficient sample sizes for adequate statistical power. Large differences have been reported in behavioural performance between polysubstance abusers and controls on standardized neuropsychological tests of working memory, inhibition, cognitive flexibility, self-regulation, and decision-making (administered outside the scanner). Test performance correlated with resting brain metabolism in the right middle temporal pole (working memory), right calcarine and bilateral posterior cingulate (self-regulation), and right middle and superior frontal cortices (decision-making). However, only severity of cocaine use was related to brain metabolism (right middle temporal pole). Therefore, although polysubstance abuse is clearly associated with deficits in brain function and cognition, elucidating more specific relationships is made difficult by the methodological differences between studies, differences in the wide range of substances abused, and possibly reduced statistical power in neuroimaging studies.
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