Abstract
Cocaine use disorder (CUD) is a major public health concern with devastating social, economic, and mental health implications. A better understanding of the underlying neurobiology and phenotypic variations in individuals with CUD is necessary for the development of effective and targeted treatments. In this study, 39 women and 54 men with CUD completed a 6-min resting-state functional magnetic resonance imaging scan after intranasal oxytocin (OXY) or placebo administration. Graph-theory network analysis was used to quantify functional connectivity changes caused by OXY in striatum, anterior cingulate cortex (ACC), insula, and amygdala nodes of interest. OXY increased connectivity in the right ACC and left amygdala in males, whereas OXY increased connectivity in the right ACC and right accumbens in females. Machine learning was then used to associate treatment response (placebo minus OXY) in nodes of interest with years of cocaine use and severity of childhood trauma separately for males and females. Childhood trauma and years of cocaine use were associated with OXY-induced changes in ACC connectivity for both men and women, but connectivity changes in the amygdala were associated with years of cocaine use in men and connectivity changes in the right insula were associated with years of cocaine use in women. These findings suggest that salience network nodes (ACC and insula) are potential OXY treatment targets in CUD, with the amygdala as a treatment target for men and the accumbens as a treatment target for women.
Highlights
Gender differences in addictive and affective disorders are well established [1, 2]
None met the threshold for significance, head motion was included in the two primary analyses below as a precaution given that only six head motion parameters were used as nuisance variables in preprocessing
The present study has shown that OXY-related connectivity changes in components of the salience network, anterior cingulate cortex (ACC), and insula are important for understanding individual variations in childhood trauma severity and cocaine use severity
Summary
Gender differences in addictive and affective disorders are well established [1, 2] Both gonadal and stress hormones can modulate brain function, leading to different levels of susceptibility to neuropsychiatric disorders and treatment response. Biomedical research focused on understanding hormonal modulation and gender differences in brain function may be advanced by including. Oxytocin and Cocaine Use Disorder neuroimaging markers of functional brain organization One such marker is resting-state functional brain connectivity (RSFC), which uses functional magnetic resonance imaging (fMRI) to image the brain while an individual is alert and awake but not engaged in any particular cognitive task; that is, when the brain is at “rest.” This continuous resting-state fMRI (rsfMRI) paradigm can reveal brain regions that are temporally synchronized with other brain regions to characterize brain regions that seem to activate (or deactivate) in unison, revealing additional phenotypes that are not captured with current behavioral assessments or neurobiological markers. Not all studies have shown an association between compromised RSFC and years of use [5], the collective findings point to RSFC as a promising imaging biomarker for relapse risk or other behaviors implicated in the addiction process [17]
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