Oxytocin-Induced Changes in Intrinsic Network Connectivity in Cocaine Use Disorder: Modulation by Gender, Childhood Trauma, and Years of Use

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.

Heterogeneity in response to repeated intranasal oxytocin in schizophrenia and autism spectrum disorders: A meta‐analysis of variance

“…Some examples include, for instance, genotype (e.g. the single nucleotide polymorphism rs53576 in the promoter of the OXTR gene) (Chen et al, 2020; Feng et al, 2015) and early life adversity (Joseph et al, 2019; van Zuiden et al, 2017), the latter being common in patients with schizophrenia (Popovic et al, 2019). Most likely these factors moderate the response to intranasal OT by affecting the regulation of the expression of OT receptors (Kraaijenvanger et al, 2019).…”

“…First, both schizophrenia (Liang & Greenwood, 2015) and ASD (Mottron & Bzdok, 2020) are highly heterogeneous disorders; thus, it is plausible that intranasal OT might benefit specific subsets of patients where a deficit in OT signalling might contribute to symptoms to a greater extent. Second, a number of inter‐individual factors have also been shown to moderate the response to intranasal OT, such as (epi)genetic variation (Chen et al, 2020; Feng et al, 2015) and childhood trauma (Joseph et al, 2019; van Zuiden et al, 2017), likely through effecting on the capacity of the OT receptor to respond to OT binding (Kraaijenvanger et al, 2019). Hence, to properly evaluate the therapeutic potential of a daily‐repeated intranasal OT treatment regime in patients with schizophrenia and ASD, it is important to investigate whether subgroups of patients may show a differential response to treatment that is masked by mean group level analyses.…”

Machine learning approaches for parsing comorbidity/heterogeneity in antisociality and substance use disorders: A primer

“…In two of these studies, subtyping was based on symptom severity, with supervised SVMs aiming to categorize individuals with more versus less severe symptom characteristics: Wetherill et al (2018) attained 88% accuracy in predicting the severity of nicotine use disorder via within-network connectivity of various resting-state networks, while Steele et al (2017) reported between 69%-80% prediction accuracy using structural MRI data to categorize adolescents into those with low/high psychopathic traits. Two additional studies used regression-based approaches to predict continuous variation in alcohol use severity (Fede et al, 2019), and years of cocaine use (Joseph et al, 2019), via resting-state functional connectivity metrics. Finally, one additional study, presented as a conference paper took a quite different approach that is worth expanding on here: Zilverstand et al (2018) combined unsupervised methods with clustering techniques to identify cocaine-dependent and nondependent individuals who showed similar covariation patterns in their resting-state functional connectivity dynamics.…”

Oxytocin moderates corticolimbic social stress reactivity in cocaine use disorder and healthy controls

“…However, these effects are often moderated by childhood trauma history, sex, or both. Moreover, prior studies investigating the effect of OT on brain response in substance-using populations have focused on cue reactivity [ 14 , 19 , 20 ] or the resting state [ 21 ], but to our knowledge, no prior studies used a social stress task in an fMRI setting. Given that the stress pathway is implicated in addictive behaviors and that OT can attenuate stress responses in humans, the present study used a social stress task adapted for the MRI environment, the Montreal Imaging Stress Task (MIST, [ 22 ]), in healthy controls (HC) and individuals with cocaine use disorder (CUD) who were not seeking treatment.…”