Archival Report
Elevated Brain Iron in Cocaine Use Disorder as Indexed by Magnetic Field Correlation Imaging

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Abstract

Background

Iron homeostasis is a critical biological process that may be disrupted in cocaine use disorder (CUD). In the brain, iron is required for neural processes involved in addiction and can be lethal to cells if unbound, especially in excess. Moreover, recent studies have implicated elevated brain iron in conditions of prolonged psychostimulant exposure. Thus, the purpose of this study was to examine iron in basal ganglia reward regions of individuals with CUD using an advanced imaging method called magnetic field correlation (MFC) imaging.

Methods

MFC imaging was acquired in 19 non-treatment-seeking individuals with CUD and 19 healthy control individuals (both male and female). Region-of-interest analyses for MFC group differences and within-group correlations with age and years of cocaine use were conducted in the globus pallidus internal segment (GPi), globus pallidus external segment, putamen, caudate nucleus, thalamus, and red nucleus.

Results

Individuals with CUD had significantly elevated MFC compared with control individuals within the GPi. In control individuals, MFC significantly increased with age in the GPi, globus pallidus external segment, putamen, and caudate nucleus. Conversely, there were no significant MFC within-group correlations in the CUD group.

Conclusions

Individuals with CUD have excess iron in the GPi, as indexed by MFC, and lack the age-related gradual iron deposition seen in normal aging. Because the globus pallidus is critical for the transition of goal-directed behavior to compulsive behavior, significantly elevated iron in the GPi may contribute to the persistence of CUD. These findings implicate dysregulation of brain iron homeostasis in CUD and support pursuing this new line of research.

Section snippets

Participants

A total of 25 non-treatment-seeking cocaine users were recruited from the community. Of these individuals, 6 were excluded owing to severe motion artifacts in their neuroimaging data. All remaining 19 individuals (79% male) met the DSM-IV-TR criteria for cocaine dependence and had a positive urine drug screen for cocaine at the time of assessment (Multi-Drug Screen Test Dip Card; W.H.P.M. Inc., Irwindale, CA). A total of 19 age-matched healthy control individuals (58% male) without a history of

Demographics and MFC Index of Brain Iron

The two groups did not significantly differ in age or gender ratio (Table 1). The CUD group had a moderate level of depressive symptoms (Beck Depression Inventory score: mean = 11.1, SD = 9.9). In the CUD group, 3 individuals had a history of posttraumatic stress disorder, 3 individuals had a previous episode of major depressive disorder (2 of them with a suicide attempt), 1 individual had a history of panic disorder, and 1 individual met criteria for generalized anxiety disorder. In the CUD

Discussion

Brain iron homeostasis is a critical biological mechanism that has been underexamined in CUD, with only one prior study to date (19). Using MFC imaging to index brain iron, we demonstrated that individuals with CUD have significantly elevated MFC values in the GPi (32.9% increase) compared with control individuals, with a similar trend in the GPe (13.4% increase). Moreover, unlike in control individuals, there were no significant correlations of MFC with age in the CUD group within the GPi,

Acknowledgments and Disclosures

Funding was provided by the Klingenstein Third Generation Foundation (to VA) and the Litwin Foundation (to JAH).

JHJ and JAH are inventors with patents related to MFC imaging that are owned by New York University and licensed to Siemens Healthcare. VA, CAH, CEM, and WHD report no biomedical financial interests or potential conflicts of interest.

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      Citation Excerpt :

      A strength of our study is that we conducted a multimodal brain iron assessment using the iron-sensitive R2* metric and the more iron-specific MFC metric that is independent of some of the non‑iron mechanisms affecting R2* (Jensen et al., 2009, 2006; Jensen and Helpern, 2014). While both metrics correlate with putative postmortem iron concentration in healthy brain (Adisetiyo et al., 2012; Langkammer et al., 2010), variance in their sensitivity and specificity for iron in different brain regions have been demonstrated (Adisetiyo et al., 2018) and are reflected in our findings (Table 3). Confounds such as tissue microstructure, calcification and water and protein content affect R2* and MFC differently (Brown et al., 2014; Dusek et al., 2013; Jensen and Helpern, 2014) which underscores the advantage of multimodal assessment of brain iron in that this approach capitalizes on the strengths of each modality for improved brain iron detection.

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