Table 1.

Summary of neuroimaging studies of social stress in human drug addiction

Reference	Social stress type (measure)	Substance use/disorder	Sample	Paradigm (social stress or other)	Imaging tool/procedure	Analysis type	Prime brain regions	Brain-behavior associations
Past social stress/trauma
(Van Dam et al. 2014)	Childhood maltreatment (CTQ)	Alcohol, cocaine, and/or cannabis	79 in-treatment SUD; 98 CON	N/A	3T MRI VBM	Whole-brain; ROI	CM (controlling for SUD): ↓L hippocampus, ↓parahippocampus, ↓anterior fusiform gyrus	↓CM-related gray matter volume, ↑severity of substance use after initial relapse
(Bachi et al. 2018)	Childhood maltreatment (CTQ)	Cocaine	24 CUD + CM; 23 CUD-CM; 29 CON	N/A	3T MRI VBM	Whole-brain	CUD + CM > CON| CUD-CM: ↓R lateral OFC CUD + CM > CON: ↓middle temporal gyrus	↓R lateral OFC, ↑depression and ↓constraint
(Elton et al. 2015)	Childhood maltreatment (CTQ)	Cocaine	20 male CUD + CM; 18 male CUD-CM	Guided imagery induction. Post-task: anxiety, craving	3T fMRI BOLD	Whole-brain; ROI	Stress > neutral script (CUD + CM): ↓L dorsal-anterior precuneus, ↓L supplementary motor area CTQ score-by-craving rating interaction: ↓rostral ACC	↓L precuneus and ↓L supplementary motor area, ↑physical and emotional abuse
(Ieong and Yuan 2018)	Childhood maltreatment (Adverse Childhood Experiences; (Felitti et al. 1998))	Heroin and/or nicotine	7 heroin (abstinent >3 months)-nicotine dependence +CM; 7 nicotine dependence +CM; 7 CON	Reading the mind in the eyes	Continuous wave; functional near-infrared spectroscopy; Resting-state FC	ROI	Heroin-nicotine dependence > nicotine dependence: ↑OFC, ↑mPFC, ↓dorsolateral PFC	N/A
(Casement et al. 2015)	Stressful life events in late adolescence (Life Event Questionnaire for Adolescents (Masten et al. 1994) and Interpersonal Problem Situations Inventory for Urban Adolescents; (Farrell et al. 1998))	Alcohol (problematic use)	152 males	Reward-guess task	3T fMRI BOLD	ROI	Stress scores; severity of alcohol use, association with reward: Anticipation of reward and reward outcome = ↓mPFC	↓mPFC, ↑cumulative life stress events and ↑severity of alcohol use
(Poppa et al. 2019)	PTSD (lifetime sexual trauma; Life Stressors Checklist-Revised; (Wolfe and Kimerling 1997))	Methamphetamine and/or cocaine	14 female SUD-PTSD; 29 female SUD	Interoceptive-exteroceptive attention	3T fMRI FC of task-modulated networks	Whole-brain	SUD-PTSD > SUD: ↓OFC network located in the mid-posterior insula, angular gyrus, precuneus, and lateral prefrontal cortex areas	↓OFC network strength, ↑sexual violence exposure across all participants
(Gawrysiak et al. 2017)	Trauma history (lifetime; Addiction Severity Index; (McLellan et al. 1992))	Cocaine	18 CUD-trauma; 16 CUD	N/A	3T fMRI Resting-stateFC	Seed-based (amygdala)	Trauma: ↑amygdala and limbic-striatal regions connectivity	N/A
Social stress induction
(Seo et al. 2011)	N/A	Alcohol (social drinking)	20 males; 23 females	Guided imagery induction	3T fMRI BOLD	Whole-brain	Stress script (both): ↑L dorsal striatum Stress script (male > female): ↑mPFC, ↑rostral ACC, ↑posterior insula, ↑putamen, ↑amygdala ↑hippocampus, ↑parahippocampal gyrus	↑dorsal striatum, ↑craving in males
(Li et al. 2005)	N/A	Cocaine	17 male CUD; 10 female CUD	Guided imagery induction. Post-task: Anxiety, craving	1.5T fMRI BOLD	Whole-brain; ROI	Stress script (both): ↑mid temporal gyrus Stress script (female > male): ↑middle, medial, inferior frontal cortical areas, ↑anterior cingulate, ↑insula, ↑middle and inferior frontal cortices, ↑R posterior cingulate cortex	↑L anterior cingulate and ↑R posterior cingulate cortices, ↓craving rating during stress imagery in female CUDs
(Li et al. 2006)	N/A	Cocaine	17 male CUD; 10 female CUD	Guided imagery induction	1.5T fMRI BOLD	ROI	Stress script (both): ↑R inferior frontal cortex, ↑mPFC, ↑R anterior cingulate	↑mPFC and ↓L posterior cingulate cortex, ↓socialization in female CUDs
(Sinha et al. 2005)	N/A	Cocaine	20 CUD; 8 CON	Guided imagery induction	1.5T fMRI BOLD	Whole-brain	Stress script (CUD): ↓ medial orbitofrontal/anterior cingulate region, ↓R postcentral gyrus, ↓R fusiform gyrus, ↓L precentral gyrus, ↓medial FG, ↓L hippocampus, ↑caudate, ↑ dorsal striatum	↑caudate and ↑dorsal striatum, ↑stress-induced cocaine craving ratings
(Kober et al. 2017)	N/A	Nicotine	11 smokers in mindfulness training; 12 smokers in freedom from smoking treatment	Guided imagery induction	1.5T fMRI BOLD	Whole-brain	Stress script (both): ↑↓cluster in amygdala, anterior insula, mid insula, hippocampus, parahippocampal gyrus, thalamus, middle occipital gyrus, midbrain, cerebellum, and R posterior insula; ↑↓cluster across cuneus/precuneus, posterior cingulate cortex	↑neural activity during stress, ↓post-treatment cigarettes per day reduction. Protracted effect in similar brain regions at 3 months follow-up
(Maurage et al. 2012)	N/A	Alcohol	22 AUD; 22 CON	Cyberball	3T fMRI BOLD	Whole-brain	AUD > CON (social exclusion): ↑R insula, ↓R ventral PFC, ↓L medial FG AUD > CON (re-inclusion post social exclusion): ↑L dorsal ACC, ↑parahippocampal gyrus	N/A
(Hanlon et al. 2018)	N/A	Cocaine	18 CUD; 25 CON	Cyberball	3T fMRI BOLD	Whole-brain	CUD > CON (social exclusion > inclusion): ↑R medial FG/pregenual cingulate ↑L ventral FG, ↑R caudate	N/A
(Bach et al. 2019a, b)	N/A	Opioid	19 OMT; 20 CON	Cyberball	3T fMRI VBM	Whole-brain; ROI	OMT > CON (VBM): ↓anterior insula, ↓L inferior FG, ↓R frontal lobe, ↓R inferior FG	↓L insula, ↓reduced feelings of inclusion during inclusion trial and ↑feelings of exclusion during inclusion trial. ↓L insula, ↑social interaction anxiety symptoms
(Bach et al. 2019a, b)	N/A	Opioid	17 OMT; 21 CON	Cyberball	3 T fMRI BOLD	Whole-brain	OMT > CON (social exclusion and inclusion): ↓ superior and middle occipital and lingual gyri, ↓ cunei, ↓L fusiform gyrus	N/A
(Beard et al. 2021)	N/A	Alcohol and/or cannabis use	181 adolescents	Cyberball	3T fMRI BOLD	Whole-brain: ROI	Exclusion > inclusion: ↑dorsal ACC, ↑subgenual ACC, ↑anterior insula	↓dorsal ACC and ↑anxiety, ↑substance use later in adolescence ↓dorsal ACC and ↑distress (game-related), ↑substance use later in adolescence ↑anterior insula, ↑substance use in females
(Charlet et al. 2014)	N/A	Alcohol	33 AUD; 33 CON	Facial emotion recognition (aversive faces)	3T fMRI BOLD & VBM	ROI	AUD > CON (BOLD): ↓ FG, ↑L rostral ACC, ↑L anterior cingulate cortex/ medial FG, ↑R precuneus AUD > CON (VBM): ↓FG, ↓ rostral ACC, ↓frontal regions (ACC, insula, temporal, occipital gyri)	↑L rostral ACC, ↑days of abstinence and ↓days of binge drinking. ↑FG activation, ↑lifetime drinking
(Bedi et al. 2009)	N/A	MDMA (administration)	9 individuals with past MDMA use	Facial emotion recognition (aversive faces)	3T fMRI BOLD	Whole-brain; ROI	MDMA 1.5 mg/kg > MDMA 0.75 mg/kg |Placebo (angry > neutral faces): ↓L amygdala MDMA 0.75 mg/kg > MDMA 1.5 mg/kg|Placebo (happy > neutral): ↑R ventral striatum	↑R ventral striatum, no effect on self-reported sociability in MDMA (0.75 mg/kg)
(Flanagan et al. 2019)	N/A	Alcohol, cannabis and/or cocaine	10 couples (n = 20) w/one partner w/ hazardous drinking or SUD	Relationship conflict	3T fMRI BOLD	ROI	Female > male (conflict > neutral): ↑R amygdala-L inferior FG and mid-cingulate connectivity, ↑L OFC-R mid temporal gyrus connectivity Male > female (conflict > neutral): ↑R OFC-R, amygdala/hippocampus connectivity Group (conflict): ↑R OFC-R frontal pole connectivity	↑R amygdala and L prefrontal cortex FC during the conflict or neutral cues, ↑intimate partner violence victimization and perpetration
(Dagher et al. 2009)	N/A	Nicotine	15 nicotine smokers	Montreal imaging stress task. Post-task: Cue-reactivity	3 T fMRI BOLD	Whole-brain; ROI	Stressful > non-stressful: ↓hippocampus, ↓amygdala, ↓bed nucleus of the stria terminalis, ↓hypothalamus, ↓nucleus accumbens Stressful > non-stressful (smoking cue-reactivity): ↑dorsomedial PFC, ↑dorsal caudate, ↑dorsomedial thalamus, ↑hippocampus	↑hippocampus, ↑amygdala, and ↑nucleus accumbens, ↑cue-reactivity and ↑ craving response

Notes: Childhood Trauma Questionnaire (CTQ; (Bernstein et al. 2003)) Substance use disorder (SUD); Control (CON); Magnetic resonance imaging (MRI); Voxel-based morphometry (VBM); Childhood maltreatment (CM); Left (L); Cocaine use disorder (CUD); Right (R); Orbitofrontal cortex (OFC); Functional magnetic resonance imaging (fMRI); Blood-oxygen-level-dependent (BOLD); Region-of-interest (ROI); Anterior cingulate cortex (ACC); Functional connectivity (FC); Prefrontal cortex (PFC); Medial PFC (mPFC); Post-traumatic stress disorder (PTSD); Frontal gyrus (FG); Alcohol use disorder (AUD); Opioid methadone treatment (OMT); 3,4-Methylenedioxymethamphetamine (MDMA)