Reduced striatal volume in cocaine-dependent patients
Research Highlights
► Cocaine dependence is associated with reduced gray matter volumes in the striatum. ► Gray matter volume of the amygdala is reduced with years of cocaine use. ► The study links structural changes in cocaine addicts with previous animal research.
Introduction
Structural neuroadaptations in the central nervous system are related to the changes in behavior and brain function associated with cocaine dependence. Much of the research on these neuroadaptations has focused on dopamine circuitry and particularly on the ventral striatum (Koob et al., 1994, White and Kalivas, 1998). For example, animal and human studies have shown altered functional activity in the ventral striatum associated with cocaine consumption (Lyons et al., 1996, Porrino et al., 2002, Porrino et al., 2007, Volkow et al., 2006, Risinger et al., 2005, Hanlon et al., 2009). Chronic effects of cocaine on the striatum have also been reflected in the concentration of dopamine receptors (Volkow et al., 1993), dendrites and dendritic spines (Robinson and Kolb, 2004). A central role for the striatum in drug addiction is suggested by its involvement in drug incentive salience processes (Robinson and Berridge, 2003, Robinson and Berridge, 2008), drug-related neuroadaptations (Koob and Le Moal, 2008), and in the proposed change in the locus of behavioral control from the ventral to dorsal striatum associated with drug-seeking behavior after chronic drug self-administration (see Everitt and Robbins, 2005, Everitt et al., 2008). Therefore, theories of addiction and the empirical animal literature lead to the prediction of changes in the striatum in cocaine-dependent patients.
Neurobiological differences related to cocaine addiction at the macrostructural brain level are widespread across the brain as shown by voxel-based morphometry (VBM). Previous studies on the morphometric changes associated with drug use and abuse which applied VBM have reported gray matter (GM) reductions in the volume of the orbitofrontal cortex, the anterior cingulate cortex, the insula, the superior temporal cortex (Matochik et al., 2003, Franklin et al., 2002, Lim et al., 2008) and the cerebellum (Sim et al., 2007). Although the studies cited above have suggested that structural changes should be found in the striatum, they have not been reported by means of VBM. It is possible that the micro-structural changes observed in animal studies may not be detectable by a macro-structural technique such as VBM. However, the possibility of detecting structural changes in important subcortical structures such as the striatum by means of this non-invasive tool in human studies would prove valuable as it could provide an assay of cocaine's effects while linking the human and animal literatures.
A few human studies on the structural changes associated with cocaine addiction have specifically analyzed brain volume differences in the striatum (Jacobsen et al., 2001, Martínez et al., 2004) by means of manual volume segmentation. Jacobsen et al. (2001) showed an increased volume of the caudate head and putamen while Martínez et al. (2004) found no such differences. This lack of consensus in human research may reflect methodological and sample characteristic differences between studies. Compared to these previous studies, the present investigation was restricted to a sample of cocaine-dependent males for two main reasons. First, gender considerably influences GM values, even in healthy subjects (Good et al., 2001, Giedd et al., 1996, Filipek et al., 1994, Ahsan et al., 2007); therefore limiting analyses to one gender should reduce unwanted variance. Second, and more importantly, gender differences in cocaine dependence have been described in perfusion abnormalities (Levin et al., 1994), treatment outcomes (Weiss et al., 1997), patterns of abuse (Griffin et al., 1989), situations that lead to consumption (Waldrop et al., 2007) and the brain's stress response (Li et al., 2005). Particularly, it seems that some cocaine-related phenomena, like craving, specifically involve the striatum in males (Kilts et al., 2004, Kilts et al., 2001). Therefore, it seems plausible that cocaine neuroadaptations may depend on gender, and that striatum changes might be more pronounced in males. Therefore, we hypothesized that we would find GM volume changes in those brain areas functionally affected by cocaine addiction which are dependent on dopaminergic neurotransmission, and our main expectations focused on the striatum.
Section snippets
Participants
Twenty male cocaine-dependent patients and 16 matched controls participated in this study. The cocaine patients were recruited from the Addiction Treatment Service of San Agustín in Castellón, Spain. The inclusion criteria included cocaine dependence based on the DSM-IV criteria. Control subjects were required to have no diagnosis of substance abuse or dependence. The exclusion criteria for all the participants included neurological illness, prior head trauma, positive HIV status, diabetes,
Group differences
Whole brain voxel-wise analyses with an age-adjusted ANCOVA showed significantly reduced GM in the left striatum (x, y, z MNI coordinates = − 5, 2, –1; T-value = 4.46, p < 0.001; cluster size = 833) and the right supramarginal gyrus (x, y, z MNI coordinates = 50, –60, 32, T-value = 5.20, p < 0.001; cluster size = 1086) for the cocaine group. Fig. 1 charts voxel means for these clusters revealing that the percentage of volume change between controls and patients was 14.8% for the striatum and 12.1% for the
Discussion
We provide the first evidence of gray matter (GM) volume reduction in the striatum of cocaine-dependent patients by means of VBM as well as a volume reduction in the right supramarginal gyrus. The detection of striatal volume reduction in the cocaine group in this report may be explained by sample characteristics or methodological improvements. For example, unlike prior studies that applied this same image-analysis technique (http://dbm.neuro.uni-jena.de/vbm/) to substance-dependence
Financial disclosures
The authors report no biomedical financial interests or potential conflicts of interest.
Acknowledgments
We thank the professional group at the Addictive Behaviors Unit San Agustín of Castellón (UCA, Unidad de Conductas Adictivas San Agustín de Castellón) for their collaboration. This study was supported by grants from FEPAD (Fundación para el Estudio, Prevención y Asistencias a la Drogodependencia), from the “National Plan of Drugs” (Plan Nacional de Drogas) and from the funding agency CONSOLIDER-INGENIO 2010 Program (CSD2007-00012).
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