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Addict Biol. 2017 Feb 1. doi: 10.1111/adb.12492. [Epub ahead of print]

Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions.

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  • 1The National Center on Addiction and Substance Abuse, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
  • 2Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
  • 3Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
  • 4Connecticut Mental Health Center, New Haven, CT, USA.
  • 5Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
  • 6Yale Child Study Center, Yale University School of Medicine, New Haven, CT, USA.


Alterations in neural structure have been reported in both cocaine-use disorder and gambling disorder, separately, suggesting similarities across addiction diagnoses. Individual variation in neural structure has also been associated with impulsivity, a dimensional construct implicated in addictions. This study combines categorical (diagnosis-based) and dimensional (transdiagnostic) approaches to identify neural structural alterations linked to addiction subtypes and trait impulsivity, respectively, across individuals with gambling disorder (n = 35), individuals with cocaine-use disorder (n = 37) and healthy comparison individuals (n = 37). High-resolution T1-weighted data were analyzed using modulated voxel-based morphometry (VBM). Statistical analyses were conducted using whole-brain general-linear models, corrected for family-wise error (pFWE < .05). Categorical analyses indicated a main effect of diagnostic group on prefrontal (dorsal anterior cingulate and ventromedial prefrontal cortex) gray matter volumes (GMVs), involving decreased GMVs among cocaine-use disorder participants only. Dimensional analyses indicated a negative association between trait impulsivity and cortical (insula) and subcortical (amygdala and hippocampus) GMVs across all participants. Conjunction analysis indicated little anatomical overlap between regions identified as differentiating diagnostic groups and regions covarying with impulsivity. These data provide first evidence of neural structural differences between gambling disorder and an illicit substance-use disorder. They further indicate dissociable effects of diagnostic groupings and trait impulsivity on neural structure among individuals with behavioral and drug addictions. Study findings highlight the importance of considering both categorical and dimensional (e.g. Research Domain Criteria; RDoC) analysis approaches within the context of addictions research.


cocaine; pathological gambling; voxel-based morphometry

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