SWM task accuracy and reaction time were calculated for SWM and simple attention conditions. Group differences in neuropsychological test scores and SWM task performance were examined with one-way ANOVAs. We followed up significant ANOVAs with Tukey’s all pairwise t-tests between the three groups. Imaging data were processed and analyzed using the Analysis of Functional NeuroImages package . We first applied a motion-correction algorithm to the time series data . Second, we correlated the time series data with a set of reference vectors that represented the block design of the task and accounted for delays in hemodynamic response , while covarying for estimated motion and linear trends. Next, we transformed imaging data to standard coordinates then resampled the functional data into 3.5 mm3 voxels. Finally, we applied a spatial smoothing Gaussian filter to account for anatomic variability. After processing functional data, we examined average BOLD response to the SWM task in each group using one sample t-tests, and determined regions that showed greater response to SWM relative to simple attention , reduced response during SWM relative to rest , and greater simple attention response than SWM response. We next compared response during SWM relative to simple attention between groups with ANOVAs, and performed pairwise comparisons between groups. We performed group comparisons on the whole brain, rather than discrete regions thought to be activated by the task, because previous studies by our group and others have suggested neural reorganization and use of alternate brain systems during working memory among individuals with AUD. To control for Type I error in group analyses, we required significant voxels to form clusters ≥1072 μl , yielding a cluster-wise α < .0167 . We utilized the Talairach Daemon and AFNI to confirm gyral labels for clusters.
Previous research has suggested that neuropsychological deficits among adult marijuana users are associated with lingering effects of recent use, and that these impairments dissipate with extended abstinence . To understand whether group differences in the current study relate to recent cannabis growers use, we performed post-hoc regressions within the MAUD group. First, we extracted the average fit coefficient for each MAUD participant from each cluster where we observed a difference between MAUD and control or AUD teens. Next, we used regression analyses to examine whether days since last marijuana use predicted brain response within each group difference cluster.Mental health in young adulthood is the strongest predictor of mental health in adulthood. Mental health vulnerabilities present in young adulthood can be exacerbated by marijuana use, thus potentially hindering or delaying a successful transition to adulthood. Considering motives of marijuana use may provide insight into the associations between marijuana use and mental health in young adults. The purpose of this dissertation was to: 1) understand the associations between motives of marijuana use and symptoms of depression, symptoms of anxiety, and overall psychological distress in young adults, and 2) examine whether these associations vary by gender. Data come from the Cannabis, Health and Young Adult Study , a longitudinal study of young adults, in Los Angeles, who use marijuana for medical and/or recreational purposes. Exploratory and confirmatory analyses were performed to validate the factor structure of the instrument used to operationalize motives of marijuana use for the study. Multiple linear regressions were used to determine how motives of use are associated to mental health outcomes. Indirect effects between motives of use and mental health outcomes through frequency of use were also assessed.
Finally, gender was tested as a moderator for both direct and indirect associations between motives of use and mental health outcomes. Results validate the factor structure of the amended Comprehensive Marijuana Motive Questionnaire. Furthermore, results indicate that the coping motive of use is positively, significantly associated with mental health outcomes. The motives of conformity, pain, and attention are indirectly associated with symptoms of depression through frequency of use. Gender influences the association between the motive of social anxiety with symptoms of depression and overall psychological distress whereas women who endorse this motive of use report more symptoms of depression and overall psychological distress than men. None of the moderated mediation analyses were significant. These results emphasize the importance of considering motive of use in the development of interventions targeting marijuana use and mental health in young adults. These findings also highlight the need for gender specific interventions as men and women engage in use differently, and with different consequences to their mental health.Mental health in young adulthood is the strongest predictor of mental health in adulthood. Mental health vulnerabilities present in young adulthood can be exacerbated by marijuana use, thus potentially hindering or delaying a successful transition to adulthood. Considering motives of marijuana use may provide insight into the associations between marijuana use and mental health in young adults. The purpose of this dissertation was to: 1) understand the associations between motives of marijuana use and symptoms of depression, symptoms of anxiety, and overall psychological distress in young adults, and 2) examine whether these associations vary by gender. Data come from the Cannabis, Health and Young Adult Study , a longitudinal study of young adults, in Los Angeles, who use marijuana for medical and/or recreational purposes. Exploratory and confirmatory analyses were performed to validate the factor structure of the instrument used to operationalize motives of marijuana use for the study.
Multiple linear regressions were used to determine how motives of use are associated to mental health outcomes. Indirect effects between motives of use and mental health outcomes through frequency of use were also assessed. Finally, gender was tested as a moderator for both direct and indirect associations between motives of use and mental health outcomes. Results validate the factor structure of the amended Comprehensive Marijuana Motive Questionnaire. Furthermore, results indicate that the coping motive of use is positively, significantly associated with mental health outcomes. The motives of conformity, pain, and attention are indirectly associated with symptoms of depression through frequency of use. Gender influences the association between the motive of social anxiety with symptoms of depression and overall psychological distress whereas women who endorse this motive of use report more symptoms of depression and overall psychological distress than men. None of the moderated mediation analyses were significant. These results emphasize the importance of considering motive of use in the development of interventions targeting marijuana use and mental health in young adults. These findings also highlight the need for gender specific interventions as men and women engage in use differently, and with different consequences to their mental health.The advent of combination anti-retroviral therapy has transformed human immuno deficiency virus infection and its effects on the central nervous system . HIV infection is now a chronic disease with multiple interacting causes of morbidity. Although neurocognitive impairment remains common in some HIV cohorts , neurocognitive deficits now tend to be milder than in the preART era. Identifying persons with milder NCI is more difficult than identifying frank dementia and tends to require comprehensive and costly assessments. Even the milder forms of NCI may be associated with problems with everyday functioning. This highlights the importance of identifying, assessing and intervening in HIV-infected persons at risk for impaired and/or worsening neurocognitive function. Ascertaining biomarkers of HIV-associated NCI is one promising approach to detecting those at risk for NCI, particularly if these biomarkers are obtained as part of routine clinical care. Clinical investigation of biomarkers is also relevant to improve understanding of the biomedical mechanisms underlying NCI in the ART era. The Veterans Aging Cohort Study Index was developed as a composite marker of disease severity among HIV-infected persons based on routine clinical blood tests. It integrates age,“traditional” biomarkers of HIV disease and “nontraditional” biomarkers, including markers of renal and liver function, anemia,grow rack and hepatitis C virus coinfection. The VACS Index has been consistently associated with increased risk of death in HIV-infected persons. It has also been linked to poor health outcomes, including increased risk for hospitalizations and medical intensive care unit admissions,fragility fractures,frailty, and concurrent extremity strength. Prior work by our group found the cross-sectional association of the VACS Index with NCI to be significant but small, and particularly weak among Hispanics.The overall goal of the present study was to extend prior cross-sectional findings to examine the ability of the VACS Index to predict neurocognitive change and incident NCI in a large and well-characterized cohort of HIV-infected persons.
We did so by examining the association between baseline VACS Index scores and subsequent neurocognitive change; whether longitudinal changes in the VACS Index corresponded to changes in neurocognitive function; and whether VACS Index scores predicted time to incident NCI in a subgroup of participants who were neurocognitively normal at baseline.Participants included 655 HIV-infected individuals followed for up to 6 years in National Institutes of Health–funded cohort studies at the University of California, San Diego, HIV Neuro behavioral Research Program from 14 April 1999 to 11 May 2012. Studies were approved by the university’s institutional review board. All participants provided informed consent for participation in these cohort studies and agreed for their data to be used for future studies assessing the impact of HIV on the nervous system. Exclusion criteria included histories of neurological or severe psychiatric conditions. Inclusion criteria were being HIV infected , having ≥2 study visits with valid global neurocognitive scores, having laboratory data available to compute the VACS Index within 3 months of neurocognitive data, being primarily English speaking, providing informed consent, and being free of sensory or physical problems that would interfere with neurocognitive testing. Forty-five percent of the sample had previously undergone neurocognitive testing.Routine clinical chemistry panels, complete blood cell counts, rapid plasma reagin, HCV antibody, and CD4+ T-cell counts were performed at a Clinical Laboratory Improvement Amendments–certified, or equivalent, laboratory. HIV RNA levels in plasma were measured by means of reverse transcription polymerase chain reaction . CNS penetration effectiveness was ascertained as described elsewhere . Self-reported data were gathered on duration of HIV infection, nadir CD4+ T-cell count, history of ART, and duration of current ART. HCV status was based on HCV antibody testing and/or self-report. The VACS Index was computed as described elsewhere, with higher scores indicating worse disease status.The neurocognitive battery comprised 15 measures covering 7 neurocognitive domains . Raw test scores were transformed into scaled scores adjusted for repeated testing,which were then converted into T scores adjusted for demographics. The adjusted T scores for each test were then averaged to derive global and domain T scores, which were used for analyses in the overall sample. To determine whether the VACS Index predicted time to incident NCI, we converted the adjusted T scores for each test into deficit scores, ranging from 0 to 5 and averaged these scores to derive global deficit scores. Consistent with previous studies, NCI was defined as a global deficit score of ≥0.50.We assessed current mood symptoms via the Beck Depression Inventory and used published cutoff scores to determine severity of depression symptoms. Current and lifetime history of major depressive and substance use disorders were obtained using structured diagnostic interviews that follow criteria of the Diagnostic and Statistical Manual of Mental Disorders. Presence of a “substance use disorder” was defined as meeting criteria for abuse or dependence for alcohol, cannabis, and any of the following substances: opioids, methamphetamine, cocaine, sedatives, and hallucinogens. Data on lifetime intravenous drug use were ascertained by self-report.Three analytic approaches were used. First, to evaluate effects of baseline VACS Index scores on changes in neurocognitive function over time, we used a mixed effects linear regression with subject-specific random intercepts and slopes, which assumes that participants have different baseline T scores and varying trajectories of change in T scores over time . The model regressed mean global T scores on time . Individual slopes were obtained from the model and used as outcomes in a linear regression with baseline VACS Index as predictor. The slopes estimated the average changes in global T scores with every year passed. A second set of analyses was used to evaluate the association of the VACS Index as a time-dependent predictor of longitudinal cognitive status based on adjusted T scores.Because the model on global T scores was significant, we investigated the association of the VACS Index as a time-dependent predictor with changes in domain T scores using a similar approach and evaluated the impact of potential covariates.