Chronic Cocaine Use and White Matter Coherence: A Diffusion Tensor Imaging Study.

OBJECTIVE: Chronic substance use and its effects on brain function and structure has long been of interest to clinicians and researchers. Prior cross-sectional comparisons of diffusion tensor imaging (DTI) metrics have suggested deleterious effects of chronic substance use (i.e., cocaine use) on white matter coherence. However, it is unclear how these effects may replicate across geographic regions when examined with similar technologies. In this study, we sought to conduct a replication of previous work in this area and determine whether there are any patterns of persistent differences in white matter microstructure between individuals with a history of cocaine use disorder (CocUD, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and healthy controls. METHOD: A total of 46 participants (21 healthy controls, 25 chronic cocaine users) were recruited from the Richmond, Virginia metropolitan area. Information regarding past and current substance use was collected from all participants. Participants also completed structural and DTI scans. RESULTS: Consistent with previous DTI studies, significant differences were found between fractional anisotropy (FA) and axial diffusivity (AD) CocUD and controls, with CocUD showing lower FA and AD in the right inferior and superior longitudinal fasciculus, the genu, body, and splenium of the corpus callosum, and the anterior, posterior, and superior corona radiata, among several other regions. These differences were not significant for other diffusivity metrics. Lifetime alcohol consumption was greater in the CocUD group, but lifetime alcohol consumption did not show a significant linear relationship with any of the DTI metrics in within-group regression analyses. CONCLUSIONS: These data align with previously reported declines in white matter coherence in chronic cocaine users. However, it is less clear whether comorbid alcohol consumption results in an additive deleterious effect on white matter microstructure.

A Spatio-temporal Model for Detecting the Effect of Cocaine Use Disorder on Functional Connectivity.

Drug addiction can lead to many health-related problems and social concerns. Researchers are interested in the association between long-term drug usage and abnormal functional connectivity. Functional connectivity obtained from functional magnetic resonance imaging data promotes a variety of fundamental understandings in such association. Due to the complex correlation structure and large dimensionality, the modeling and analysis of the functional connectivity from neuroimage are challenging. By proposing a spatio-temporal model for multi-subject neuroimage data, we incorporate voxel-level spatio-temporal dependencies of whole-brain measurements to improve the accuracy of statistical inference. To tackle large-scale spatio-temporal neuroimage data, we develop a computational efficient algorithm to estimate the parameters. Our method is used to first identify functional connectivity, and then detect the effect of cocaine use disorder (CUD) on functional connectivity between different brain regions. The functional connectivity identified by our spatio-temporal model matches existing studies on brain networks, and further indicates that CUD may alter the functional connectivity in the medial orbitofrontal cortex subregions and the supplementary motor areas.

Continuum of depressive and manic mixed states in patients with bipolar disorder: quantitative measurement and clinical features.

Bipolar mixed states combine depressive and manic features, presenting diagnostic and treatment challenges and reflecting a severe form of the illness. DSM-IV criteria for a mixed state require combined depressive and manic syndromes, but a range of mixed states has been described clinically. A unified definition of mixed states would be valuable in understanding their diagnosis, mechanism and treatment implications. We investigated the manner in which depressive and manic features combine to produce a continuum of mixed states. In 88 subjects with bipolar disorder (DSM-IV), we evaluated symptoms and clinical characteristics, and compared depression-based, mania-based, and other published definitions of mixed states. We developed an index of the extent to which symptoms were mixed (Mixed State Index, MSI) and characterized its relationship to clinical state. Predominately manic and depressive mixed states using criteria from recent literature, as well as Kraepelinian mixed states, had similar symptoms and MSI scores. Anxiety correlated significantly with depression scores in manic subjects and with mania scores in depressed subjects. Discriminant function analysis associated mixed states with symptoms of hyperactivity and negative cognitions, but not subjective depressive or elevated mood. High MSI scores were associated with severe course of illness. For depressive or manic episodes, characteristics of mixed states emerged with two symptoms of the opposite polarity. This was a cross-sectional study. Mixed states appear to be a continuum. An index of the degree to which depressive and manic symptoms combine appears useful in identifying and characterizing mixed states. We propose a depressive or manic episode with three or more symptoms of the opposite polarity as a parsimonious definition of a mixed state.

Bupropion and cognitive-behavioral therapy for smoking cessation in women.

Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women. It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered. This study used a two level factorial design to examine the independent and interactive effects of medication (bupropion 300 mg/day vs. placebo) and psychotherapy (cognitive-behavioral therapy [CBT] vs. supportive therapy [ST]). In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments, we examined medication compliance and its role in the efficacy of bupropion. Participants were 154 women, aged at least 30 years and smoking more than 10 cigarettes/day. Compliance with study medication was assessed using Medication Event Monitoring Systems (MEMS) over 7 weeks of treatment. Psychological interventions were delivered in 60-min weekly group sessions. Longitudinal analysis of abstinence outcomes from end of treatment (EOT) through 12 months after treatment revealed a significant interaction of medication and therapy. Higher abstinence rates at EOT and 3-, 6-, 9-, and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT (44%, 24%, 30%, 23%, 17%) rather than with ST (18%, 1%, 8%, 5%, 2%). The bupropion-CBT combination, however, was not clearly superior to placebo, regardless of therapy assignment. Higher rates of medication compliance were positively predictive of abstinence, and this effect was most evident in the placebo condition. Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women.