Reduced genual corpus callosal white matter integrity in pathological gambling and its relationship to alcohol abuse or dependence

Abstract

Objective. Magnetic resonance imaging (MRI) studies have demonstrated functional prefrontal cortical (PFC) abnormalities in pathological gambling (PG) and other psychiatric disorders characterized by impaired impulse control; e.g., cocaine dependence and bipolar disorder. These abnormalities are accompanied by impairments in white matter microstructures in the anterior (genual) corpus callosum (CC) in cocaine dependence and bipolar disorder. Prior studies have not examined white matter integrity in PG. We predicted impairments in genual CC white matter in PG. Methods. Nineteen participants with PG and 19 matched control participants underwent diffusion tensor imaging (DTI) to compare white matter integrity in the CC, as assessed using fractional anisotropy (FA). Results. In PG subjects as compared to control subjects, reduced FA values in the left and right genu of the CC were observed. Multiple regression analyses confirmed that PG status – in addition to age and past alcohol abuse/dependence (AA/AD) – was a significant predictor of genual FA values. Among PG participants, left and right genu FA values were negatively correlated with scores on the Behavioral Activation System Fun-Seeking (BAS-FS) subscale. Limitations. Limitations include a reliance on self-report measures of impulsivity and related constructs and a relatively small sample of PG subjects with past AA/AD. Conclusion. Findings of decreased FA values in the genu of the CC in PG subjects suggest that, like with other disorders of behavioral dyscontrol, white matter microstructural abnormalities contribute to the pathophysiology of PG. These differences appear particularly relevant to individuals with remitted AA/AD, highlighting the importance of considering co-occurring substance use disorders when investigating PG.

Key words::

• Pathological gambling
• impulsivity
• alcohol
• diffusion tensor imaging
• corpus callosum

Acknowledgments

The authors would like to acknowledge Robert D Rogers for helpful discussions. The authors would like to acknowledge Katherine VanBuskirk for help with data management and collection. This study was supported in part by NIH grants R01 DA019039, RC1 DA028279, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, the Veterans Integrated Service Network 1 Mental Illness Research, Education, and Clinical Center (MIRECC), and the State of Connecticut, Department of Mental Health and Addiction Services. The contents of the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding agencies.

Statement of interest

The authors report that they have no financial conflicts of interest with respect to the content of this manuscript. Dr Potenza has received financial support or compensation for the following: Dr Potenza consults for and is an advisor to Boehringer Ingelheim; has consulted for and has financial interests in Somaxon; has received research support from the National Institutes of Health, Veteran's Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories, Ortho-McNeil, Oy-Control/Biotie and Glaxo-SmithKline pharmaceuticals; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law offices and the federal public defender's office in issues related to impulse control disorders; provides clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; has performed grant reviews for the National Institutes of Health and other agencies; has guest-edited journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts. The other authors reported no biomedical financial interests or other conflicts of interest.