Table 2:
Findings from sex/gender comparisons in reviewed papers
| Study | Domains; Task | Behavioral Comparisons & Covariates | Direct Comparison SM Men v. SM Women | Interaction Effect and/or Group Differences | Brain-Behavior Associations |
|---|---|---|---|---|---|
| McClernon 2008 | Approach; Smoking-related visual cues | Sex/gender differences not reported Covariate(s): Age, FTND, SJWQ craving & negative affect |
Smoking > Control Cue W > M: R Putamen, BL cuneus, L temporal cortex, L Motor/SMA M > W: L Hippocampus and L OFC |
--- |
M: Cue reactivity in the hippocampus was positively associated with negative affect W: No brain-behavior associations |
| Claus 2011 | Approach; Taste Cue Task | Sex/gender differences not reported Covariate(s): ADS |
Alcohol > Control Beverage Whole brain analysis: No main effect of sex/gender ROI Analysis: M > W in L Amygdala |
--- | Not reported |
| Potenza 2012 | Approach & Negative Emotionality; Stress & Drug Imagery Script |
No sex/gender difference in cocaine use or cue-elicited craving, anxiety, heart rate Covariate(s): None |
---- |
3-way interaction of sex, diagnostic group, and condition: R temporal cortex, putamen, amygdala, hippocampus, insula, PCC, Fusiform cortex, L caudate, NAcc, dlPFC, SMA, BL Broca’s Area, OFC Directions explored separately: Drug Condition: M: CUD > HC in ACC, PCC, L thalamus, BL insula, BL caudate, BL hippocampus, BL putamen, BL dlPFC, BL vmPFC, BL OFC W: CUD < HC: Cerebellum, BL ACC, BL PCC, L Primary Sensory & Motor, Parietal Cortex Stress Condition: M: CUD > HC in cerebellum, ACC, NAcc, thalamus, insula; CUD < HC in precuneus W: CUD > HC in ACC, PCC, BL vmPFC, BL dmPFC, L dlPFC, BL insula, BL OFC, BL amygdala, BL hippocampus, R NAcc |
Drug > Neutral: M: Positive association between craving and reactivity in the hippocampus, insula, PCC, dlPFC, dmPFC, temporal and parietal cortices, cerebellum W: Positive association between craving and reactivity in the midbrain, hippocampus, vlPFC, temporal cortex, cerebellum, thalamus Stress Condition > Neutral: M: Positive association between craving and reactivity in the BL occipital cortex W: No brain-behavior associations |
| Nikolova 2013 | Approach; Number-guessing |
M > W problem drinking Covariate(s): Current Axis 1 Diagnosis, Age |
Positive > Negative Feedback CA haplotype carriers only: M > W in BL NAcc reactivity |
--- |
M: Increased NAcc reactivity mediated an association between CA haplotype and increased problematic drinking W: Decreased R NAcc reactivity mediated an association between CA haplotype and decreased problematic drinking |
| Wetherill 2013 | Approach; Smoking-related audio/visual cues |
M > W: CPD & Pack-years W > M: Cue-elicited craving Covariate(s): CPD |
Smoking > Neutral Cue M > W: Activity in BL clusters in the hippocampus and amygdala to smoking cues |
--- | Craving was not associated with brain reactivity in either men or women |
| Mendrek 2014 | Approach; Smoking-related visual cues |
No sex/gender differences in basal or cue-induced craving, depressive symptoms Covariate(s): None |
Smoking-related > Smoking Unrelated Cues No sex/gender differences |
---- | Not reported |
| Padula 2015 |
Approach & Negative Emotionality; Emotional Faces |
Sex/gender differences not reported Covariate(s): Age, Handedness, Task Accuracy |
Not reported | Interaction effect: Fearful > Neutral faces: M AUD > M HC while W AUD < W HC in the BL OFC Happy > Neutral Faces: M AUD > M HC while W AUD < W HC in L caudate, L OFC, L Parietal cortex and R Occipital cortex |
Not reported |
| Wetherill 2015 | Approach; Backward-Masked Cue Task |
No sex/gender differences in cannabis use behaviors or craving M > W # weekly drinkers Covariate(s): Age, weekly quantity and frequency of substance use; HAM-D/A |
No sex/gender differences | ---- |
M: Baseline cannabis craving positively associated with striatum activation to cannabis cues W: Baseline cannabis craving positively correlated with bilateral anterior insula activation to cannabis cues; inversely correlated with the L lateral OFC activity |
| Canterberry 2016 |
Approach & Negative Emotionality; Emotional Stimuli |
No sex/gender differences in demographics, cocaine use behavior, or other clinical variables; No sex/gender differences on arousal rating to cues Covariate(s): Depression symptomology, education, state anxiety, CPD |
Arousing Positive > Neutral Cues M > W in the R OFC Arousing Negative > Neutral Cues No sex/gender differences |
Arousing Positive > Neutral M: No significant differences W: CUD < HC in OFC, vACC, PCC, angular gyrus Arousing Negative > Neutral M: No significant differences W: CUD < HC OFC, ACC, fusiform cortex, L temporal cortex, putamen |
Not reported |
| Konova 2016 | Approach; Monetary Reward |
M < W task reaction time; No sex/gender differences in cue-elicited cocaine craving or cocaine use behaviors; Female cocaine users more likely to report lifetime mood disorders relative to male cocaine users Covariate(s): Age, BDI scores, and reaction times |
W < M in R Hippocampus, BL PCC, L temporal cortex |
SUD W < SUD M, HC W in R primary Motor SUD W > SUD M, HC W in L Broca’s Area |
No sex/gender differences in brain-behavior associations |
| Zanchi 2016 | Approach; Smoking-related audio-visual cues |
No sex/gender differences in smoking behavior or cue-elicited craving Covariate(s): None |
Smoking > Neutral Cue W > M: Activity in the dlPFC, Broca’s Area, dACC, and temporal and occipital cortices |
Sex/gender difference in dlPFC, Broca’s Area, dACC, and precuneus was greater in smokers relative to non-smokers | Craving was not associated with brain reactivity in either M or W |
|
Dumais 2017 Study 1 |
Approach; Smoking-related audio-visual cues |
M > W pack-years No sex/gender differences in basal or cue-induced raving Covariate(s): Pack-years |
Smoking > Neutral M > W reactivity in the NAcc and vmPFC |
---- |
M: Change in pre- to post- scan craving was positively correlated with NAcc reactivity W: No brain-behavior associations |
|
Dumais 2017 Study 2 |
Approach; Smoking-related visual cues |
M > W cigarettes per day No sex/gender differences in basal or cue-induced craving Covariate(s): CPD |
Smoking > Neutral M > W in bilateral vmPFC |
--- | M: Positive association between post-SC craving in and entire ROI mask (encompassing all listed regions) W: No brain-behavior associations |
| Sawyer 2019 |
Approach & Negative Emotionality; Emotional Stimuli |
AUD W < AUD M average # daily alcoholic drinks & sensation-seeking AUD W > AUD M delayed memory scores & Wechsler Memory Scale Covariate(s): None |
Tested but region-specific results not reported |
Happy and Erotic > Neutral: AUD M < HC M in BL OFC, BL dlPFC, L parietal cortex, BL SMA, L Occipital cortex, L precuneus, L cuneus, L dACC, L cerebellum; W either did not exhibit these decreases or exhibited increases Aversive and Gruesome > Neutral: AUD M < HC M in L dmPFC, R OFC and L dlPFC, BL SMA, L parietal cortex, L temporal cortex, L cerebellum; W either did not exhibit these decreases or exhibited increases |
Not reported |
| Molokotos 2020 |
Approach; Smoking-related visual cues |
No sex/gender differences in smoking behavior or demographics Covariate(s): Discriminability on PRT task |
Not reported | --- |
M: Out-of-scanner PRT response bias positively associated with L caudate reactivity W: No association between PRT and brain reactivity |
| Prashad 2020 | Approach; Visual Drug Cue |
M > W number of alcohol drinking days and number of drinks W > M subjective cannabis craving Covariate(s): None |
No sex/gender differences in neural response | --- | Not reported |
| Zhang 2020 | Approach; Cocaine-related visual cues |
No sex/gender differences in cocaine use measures or craving CUD W > CUD M on BDI score, age Covariate(s): Age, Years of drinking, BDI scores |
Whole brain analysis: No sex/gender differences ROI: PAG Activity: No sex/gender differences PAG Connectivity No sex/gender differences |
--- |
PAG Activity: No sex/gender differences PAG Connectivity M: PAG -- vmPFC connectivity positively associated with craving W: PAG – vmPFC connectivity negatively associated with craving Granger Causality analysis: M: PAG → vmPFC W: vmPFC → PAG |
| Oscar-Berman 2021 |
Approach & Negative Emotionality; Emotional Faces |
AUD W < AUD M Duration of Heavy Drinking in Years AUD W > AUD M HAM-D/A Covariate(s): None |
Whole brain analysis: No sex/gender differences ROI analysis No sex/gender differences |
Whole brain analysis: Positive > Fixation HC W > AUD W, differences in L temporal cortex, but not between in M Negative > Fixation AUD M > HC M, differences in L FEF, but not in W ROI analysis: Emotion X Group X Sex/Gender: In HC M and AUD W: Greater reactivity to positive faces (vs. fixation) relative to negative and neutral faces compared to AUD men and HC women in L hippocampus |
Not reported |
| Claus 2022 |
Approach & Negative Emotionality; Alcohol & Negative Cues |
No sex/gender differences in alcohol use behaviors W > M in craving, sadness, fear affect, and perceived stress; M > W in self-efficacy Covariate(s): None |
Alcohol > Neutral Cues Whole brain analysis: W > M in the bilateral somatosensory cortex/precuneus, L dlPFC, and vmPFC ROI analysis: No main effect of sex/gender Negative > Neutral Cues Whole brain analysis: No main effect of sex/gender ROI analysis: W > M in L NAcc – vACC and L NAcc – medial OFC connectivity |
--- | Not reported |
| Smith 2023 |
Approach & Negative Emotionality; Stress & Drug Imagery Script |
SUD M > SUD W years of substance use SUD W > SUD M history of trauma, lifetime PTSD, anxiety ratings to drug cues with same pattern at the trend-level for stress cues; No sex/gender main effect on craving, heart rate, anxiety Covariate(s): CTQ and significant sex differences in any demographic variable included as a covariate in all analyses |
Drug Cues (Drug > Neutral): No sex/gender differences Stress Cues (Stress > Neutral): M > W in the BL caudate, thalamus, hypothalamus, R hippocampus, and L putamen |
--- |
Drug Cues: M: Positive association between reactivity in the putamen and caudate and # of follow-up days of substance use W: Inverse association between reactivity in the L dlPFC and L insula and future number of days used Stress Cues: M: No brain-behavior associations W: Inverse association between reactivity in the vmPFC and future days of substance use |
| Luo 2013 |
Executive Function; Stop Signal Paradigm |
No sex/gender differences in craving or task performance W > M # days used cocaine M > W # years of alcohol use Covariate(s): Years of cocaine and alcohol use, amount of cocaine and alcohol use in the month before admission |
Not reported | --- |
Stop Error > Stop Success M: Decreased left insula and dACC activation predicted relapse and earlier time to relapse W: Decreased thalamic and dACC activation predicted relapse and earlier time to relapse |
| Zhang 2014 |
Executive Function; Stop Signal Paradigm |
Sex/gender differences in cocaine use measures, craving, and task performance not assessed
Covariate(s): Days of abstinence |
Stop Error > Stop Success Not reported |
Not reported |
M: No brain-behavior associations W: Thalamus – vmPFC connectivity was positively correlated with the amount of cocaine use in the month before admission |
| Swartz 2021 | Executive Function; Stop Signal Paradigm |
No significant first-order correlation between sex/gender and AUDIT scores or age Sex/gender differences in other clinical measures (anxiety, mood) not statistically tested M < W RT on ‘Go’ Trials Covariate(s): Diagnosis of mood or anxiety disorder, self-reported use of cannabis in the previous 90 days |
Correct Stop > Correct Go No sex/gender differences Incorrect Stop > Correct Go: M > W reactivity in the primary motor cortex/somatosensory cortex, parietal cortex, precuneus, lateral occipital cortex Correct stop > Incorrect stop No sex/gender differences |
--- |
M: Negative association between reactivity in the somatosensory and lateral occipital cortex and AUDIT score W: Positive association between reactivity and AUDIT score in the somatosensory and lateral occipital cortex |
| Li 2005 |
Negative Emotionality; Stress Imagery Script |
No sex/gender differences in cue-elicited heart rate, anxiety, craving, or vividness rating of imagery No sex/gender differences in cocaine measures Covariate(s): None |
W > M: L FEF, L vACC, R PCC, L Broca’s Area, L insula |
--- |
M: No brain-behavior associations W: R PCC reactivity inversely correlated with cocaine craving and positively correlated with change in heart rate |
| Gorka 2019 |
Negative Emotionality; Threat Startle Response |
Sex/gender differences in demographics, alcohol use behaviors, craving, or task performance not reported Covariate(s): None |
No main effect of sex/gender | No interaction effect | No Brain X Sex/Gender Interaction of behavioral measures |
| Chang 2002 | Resting | Sex/gender differences in methamphetamine use behavior, demographics, or behavior not reported Covariate(s): None |
Not reported | Interaction Effect: W: MD > HC R occipital cortex and midline structure (pineal gland) M: MD < HC R occipital cortex and midline structure (pineal gland) |
Not reported |
| Tanabe 2008 | Resting |
No sex/gender differences in smoking behavior or age Covariate(s): None |
No main effect of sex/gender | ---- | Not reported |
| Wetherill 2014 | Resting |
M > W CPD Covariate(s): None |
W > M connectivity between the hippocampus/amygdala and bilateral AI, vACC, & L parietal cortex | --- | Not reported |
| Beltz 2015 | Resting |
No sex/gender differences in smoking behavior Covariate(s): Age, CO in analyses related to nicotine dependence/tolerance |
W > M in Default Mode Network (PCC, dACC, BL parietal cortex) | --- |
M: No brain-behavior associations W: Positive correlation between nicotine tolerance and connectivity within the reward network (bilateral striatum, OFC) |
| Li 2016 | Resting | Sex/gender differences in alcohol use measures, craving, and behavior not reported Covariate(s): Age |
W > M BEN in L primary motor, BL somatosensory, BL temporal, L parietal, and R occipital cortices, precuneus, R cerebellum | Smokers had less widespread resting BEN difference between men and women relative to HC |
M: Positive association between BEN and years-smoking in R premotor/SMA; Negative association with R cuneus, L occipital cortex, R OFC; Further correlations between BEN and CPD, FTND) (see Li et al
supplemental material) W: Positive association between BEN and years-smoking in R amygdala, BL Broca’s area, R primary motor, BL temporal, parietal, occipital cortices; further correlations between BEN and CPD, FTND) (see Li et al supplemental material) |
| MS Maria 2017 | Resting |
No sex/gender differences in demographics, smoking behavior or dependence Covariate(s): None |
No sex/gender differences | Not reported |
W: No brain-behavior associations M: Positive association between EVC and FTND in R insula; trend-level positive association between DIV and FTND in the L NAcc |
| Zhang 2017 | Resting |
M > F years of tobacco use Compared to HC, W but not men smokers reported greater narcotics and marijuana use Covariate(s): Age, Years of marijuana use, Days of marijuana use in the prior month |
Not reported |
No interaction effect. M and W analyzed separately: M: Smokers > Nonsmokers: None Nonsmokers > Smokers: None W: Smokers > Nonsmokers: SMA, somatosensory and parietal cortices, anterior insula; Smokers < Nonsmokers: PCC/precuneus |
M: BNM-SMA connectivity negatively correlated with FTND W: No brain-behavior associations |
| Manza 2018 | Resting | Sex/gender effects on cannabis use measures and craving not reported Covariate(s): None |
No sex/gender differences | No sex/gender differences | Not reported |
| Zhang 2018 | Resting | Sex/gender effects on methamphetamine use, craving, task performance not reported Covariate(s): Age, Smoking status |
Not reported | Interaction effect: M: CD < HC MH-dmPFC connectivity W: CD > HC MH-dmPFC connectivity |
M: No brain-behavior associations W: MH-dmPFC connectivity is negatively associated with craving |
| Canessa 2021 | Resting |
No sex/gender differences in alcohol use behavior No sex/gender differences in out-of-scanner task performance; Covariate(s): Age, smoking status |
Not reported | No Sex X Group effects | No Sex X Group X Decision-latency effects on resting-state metrics |
ADS = Alcohol Dependence Scale; AUD = Alcohol Use Disorder; AUDIT = Alcohol Use Disorders Identification Test; BDI = Beck Depression Inventory; BEN = Brain Entropy; BL = Bilateral; BNM = Basal Nucleus of Meynert; CA = haplotype of GAL gene; CD = Cocaine-dependent; CO = Carbon monoxide CPD = Cigarettes smoked per day; CTQ.= Childhood Trauma Questionnaire; CUD = Cocaine Use Disorder; dACC = dorsal anterior cingulate cortex; DIV = Diversity coefficient; dlPFC = dorsolateral prefrontal cortex; dmPFC; = dorsomedial prefrontal cortex; EVC = Eigenvector centrality; FTND= Fagerstrom Test for Nicotine Dependence; FEF = Frontal eye field; HAM-D/A = Hamilton Depression Rating scale; Hamilton Anxiety Rating Scale; HC = healthy control L = Left; M = Men; MD = Methamphetamine-dependent; MH = Medial hypothalamus; NAcc = Nucleus Accumbens; OFC = Orbitofrontal cortex; R = Right; Pack-years = Quantification of the amount an individual has smoked, calculated by the number of packs smoked per day multiplied by the number of years the individual has smoked; PAG = Periaqueductal gray; PCC= Posterior cingulate cortex; PTSD = Post-Traumatic Stress Disorder; PRT = Probabilistic reward task; SJWQ = Shiffman-Jarvik Withdrawal Questionnaire; ROI = Region of Interest; RT = Reaction Time; SM = Substance misuse; SMA = Supplemental motor area; SUD = Substance use disorder; vACC= Ventral anterior cingulate cortex; vlPFC = Ventrolateral prefrontal corte; vmPFC= Ventromedial prefrontal cortex; W = Women