title: Neuroimaging study of sex differences in the neuropathology of cocaine abuse.
abstract: BACKGROUND
  Female and male substance abusers differ in their disease patterns and clinical outcomes. An important question in addiction neuroscience thus concerns the neural substrates underlying these sex differences.
  
  
  OBJECTIVE
  This article aims to examine what is known of the neural mechanisms involved in the sex differences between substance abusers.
  
  
  METHODS
  We reviewed neuroimaging studies that addressed sex differences in cerebral perfusion deficits after chronic cocaine use and in regional brain activation during pharmacologic challenge and cue-induced craving. We also present results from a preliminary study in which cocaine-dependent men and women participated in script-guided imagery of stress- and drug cue-related situations while blood oxygenation level-dependent signals of their brain were acquired in a 1.5T scanner. Spatial pre-processing and statistical analysis of brain images were performed. Regional brain activation was compared between stress and drug cue trials in men versus women.
  
  
  RESULTS
  The results of our study showed greater activation in the left uncus and right claustrum (both, statistical threshold of P = 0.01, uncorrected; extent = 10 voxels) in men (n = 5) during drug cue trials compared with stress trials. No brain regions showed greater activation during stress trials compared with drug cue trials. In contrast, women (n = 6) showed greater activation in the right medial and superior frontal gyri during stress trials compared with drug cue trials at the same statistical threshold. No brain regions showed more activation during drug cue trials than during stress trials.
  
  
  CONCLUSIONS
  The studies reviewed underscore the need to consider sex-related factors in examining the neuropathology of cocaine addiction. Our preliminary results also suggest important sex differences in the effect of stress- and drug cue-associated brain activation in individuals with cocaine use disorder.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA. chiang-shan.li@yale.edu
authors.forename: Chiang-shan Ray
authors.initials: CS
authors.lastname: Li
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kemp
authors.forename: Verica
authors.initials: V
authors.lastname: Milivojevic
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
mesh_terms: D000328:Adult; D001007:Anxiety / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D019970:Cocaine-Related Disorders / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019018:Imagery, Psychotherapy; D008297:Male; D012737:Sex Factors; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology