Paradoxical Decrease in Striatal Activation on an fMRI Reward Task Following Treatment in Youth with Co-morbid Cannabis Dependence/Major Depression.

Reward behavior, including reward behavior involving drugs, has been shown to be mediated by the ventral striatum and related structures of the reward system. The aim of this study was to assess reward-related activity as shown by fMRI before and after treatment among youth with comorbid cannabis dependence and major depression. We hypothesized that the reward task (Delgado et al., 2003) would elicit activation in the reward system, and that the level of activation in response to reward would increase from the beginning to the end of the 12-week treatment study as levels of depressive symptoms and cannabis use decreased. Six subjects were recruited from a larger treatment study in which all received Cognitive Behavioral Therapy/Motivational Enhancement Therapy (CBT/MET), and also were randomized to receive either fluoxetine or placebo. Each of the six subjects completed an fMRI card- guessing/reward task both before and after the 12-week treatment study. As hypothesized, the expected activation was noted for the reward task in the insula, prefrontal, and striatal areas, both before and after treatment. However, the participants showed lower reward-related activation after treatment relative to pre-treatment, which is opposite of what would be expected in depressed subjects who did not demonstrate a comorbid substance use disorder. These paradoxical findings suggest that the expected increase in activity for reward associated with treatment for depression was overshadowed by a decrease in reward-related activation associated with treatment of pathological cannabis use in these comorbid youth. These findings emphasize the importance of comorbid disorders in fMRI studies.

Developing an Institutional Informational Base and Bibliographical Clearinghouse.

Successful management and implementation of the diverse functions of the International Network of Person-Centered Medicine (INPCM) require a comprehensive and efficient informational base to advance quality of patient care though timely and rapid distribution of knowledge via publications, conferences, and education programs in concert with catalyzing research through systematic efficient data acquisition, storage, retrieval, and analysis. This study describes the structure and functions of the proposed INPCM's information system.

PTSD contributes to teen and young adult cannabis use disorders.

BACKGROUND: Previous studies involving adults suggest that Post Traumatic Stress Disorder (PTSD) increases the prevalence of cannabis use disorders (CUD) (cannabis dependence and cannabis abuse). However, little work with PTSD and CUD has been conducted involving adolescents, despite the fact that CUD typically have their onset during adolescence. This study addresses the effect of PTSD on CUD among teenagers transitioning to young adulthood. METHOD: The subjects in this ongoing study were the offspring of adult men with a lifetime history of a substance use disorder (SUD) (SUD+probands, N=343) vs those with no lifetime history of a SUD (SUD-probands, N=350). The participants were initially recruited when the index sons of these fathers were 10-12 years of age, and subsequent assessments were conducted at age 12-14, 16, 19, 22, and 25. Other variables examined were an index of behavioral undercontrol associated with future risk for developing SUD, known as the Transmissible Liability Index, or TLI, and affiliation with deviant peers. Multivariate logistic regression and path analyses were conducted. RESULTS: Of these 693 subjects, 31 subjects were diagnosed with PTSD, and 161 were diagnosed with a CUD. The CUD subjects included 136 male participants and 25 female participants, including 103 (64%) Caucasian participants and 58 (36%) participants of other races. Logistic regression demonstrated that the development of a CUD was associated with deviance of peers (Wald=63.4, p=0.000), the TLI (Wald=28.8, p=0.000), African American race (Wald=14.2, p=0.000), PTSD (Wald=12.7, p=0.000), male gender (Wald=12.0, p=0.001), household SES (Wald=9.2, p=0.002), and being an offspring of a SUD+proband (Wald=6.9, p=0.009). Path analyses demonstrated that PTSD is directly associated with the presence of a CUD and with peer deviance, that higher peer deviance is associated with the presence of a CUD, and that PTSD mediated the association between peer deviance and CUD. CONCLUSIONS: These findings suggest that PTSD contributes to the etiology of CUD among teenagers making the transition to young adulthood beyond the effects of deviant peers, the TLI (Transmissible Liability Index, a measure of risk for SUD), and demographic factors.

Divalproex utility in bipolar disorder with co-occurring cocaine dependence: a pilot study.

OBJECTIVE: The aim of this open-label pilot study was to evaluate the utility of divalproex in decreasing cocaine use and stabilizing mood symptoms among patients with bipolar disorder with comorbid cocaine dependence. METHOD: Fifteen patients enrolled in the study and seven met final inclusion criteria of DSM-IV/SCID diagnoses of bipolar I disorder and comorbid cocaine dependence with active cocaine use. Patients were started on open-label divalproex. After stabilization on divalproex sodium, weekly assessments were undertaken for 8weeks. Subjects also attended dual recovery counseling. RESULTS: The results revealed significant improvement on % cocaine abstinent days, dollars spent on cocaine, ASI's drug use severity index, % alcohol abstinent days, drinks per drinking day, marijuana use and cigarettes smoking. They also had significant improvement on manic, depressive, and sleep symptoms and on functioning. There were no reported adverse events or increases in liver function tests. CONCLUSION: The results of this open-label study point to the potential utility of divalproex in patients with bipolar disorder and primary cocaine dependence. Double-blind, placebo-controlled studies to fully evaluate the efficacy of divalproex in this high risk clinical population are warranted.