Behavioral and psychosocial factors associated with sexual risk in a population of crack cocaine users

The purpose of this dissertation was to examine the relationship between key psychosocial and behavioral components of the Transtheoretical Model and the Theory of Reasoned Action for sexual risk reduction in a population of crack cocaine smokers and sex workers, not in drug treatment. ^ The first study examined the results of an analysis of the association between two principal constructs in the Transtheoretical Model, the processes of change and the stages of change for condom use, in a high risk population. In the analysis of variance for all respondents, the overall F-test revealed that people in different stages have different levels of experiential process use, F(3,317) = 17.79, p = 0.0001 and different levels of behavioral process use, F(3,317) = 28.59, p = .0001. For the experiential processes, there was a significant difference between the precontemplation/contemplation stage, and both the action, and maintenance, stages.^ The second study explored the relationship between the Theory of Reasoned Action “beliefs” and the stages-of-change in the same population. In the analysis of variance for all participants, the results indicate that people in different stages did value the positive beliefs differently, F(3,502) = 15.38, p = .0001 but did not value the negative beliefs differently, F(3,502) = 2.08, p = .10. ^ The third study explored differences in stage-of-change by gender, partner type drug use, and HIV status. Three discriminant functions emerged, with a combined χ2(12) = 139.57, p = <.0001. The loading matrix of correlations between predictors and discriminant functions demonstrate that the strongest predictor for distinguishing between the precontemplation/contemplation stage and the preparation, action, and maintenance stages (first function) is partner type (.962). The loadings on the second discriminant function suggest that once partner type has been accounted for, ever having HIV/AIDS (.935) was the best predictor for distinguishing between the first three stages and the maintenance stage. ^ These studies demonstrate that behavioral change theories can contribute important insight to researchers and program planners attempting to alter HIV risk behavior in high-risk populations. ^

Comparative Behavioral and Neural Effects of Tryptophan and Catecholamine Depletion in Remitted Depression

Background: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catechominergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber’s selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Methods: Using identical neuroimaging procedures with [18F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared to healthy controls in a double-blind, randomized, crossover design. Results: While TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex (PCC). While we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. Conclusions: In conclusion, this study showed that serotonin and catecholamines play common and differential roles in the pathophysiology of depression.

State of the art of integrated therapy approaches in the treatment of schizophrenia: empirical evidence and clinical relevance

Objective: Integrated behavior therapy approaches are defined by the combination of behavioral and or cognitive interventions targeting neurocognition combined with other goal-oriented treatment targets such as social cognition, social skills, or educational issues. The Integrated Psychological Therapy Program (IPT) represents one of the very first behavior therapy approaches combining interventions of neurocognition, social cognition, and social competence. This comprehensive group-based bottom-up and top-down approach consists of five subprograms, each with incremental steps. IPT has been successfully implemented in several countries in Europe, America, Australia and in Asia. IPT worked as a model for some other approaches designed in the USA. IPT was undergone two further developments: based on the social competence part of IPT, the three specific therapy programs focusing residential, occupational or recreational topics were developed. Recently, the cognitive part of INT was rigorously expanded into the Integrated Neurocognitive Therapy (INT) designed exclusively for outpatient treatment: INT includes interventions targeting all neurocognitive and social cognitive domains defined by the NIMH-MATRICS initiative. These group and partially PC-based exercises are structured into four therapy modules, each starting with exercises on neurocognitive domains followed by social cognitive targets. Efficacy: The evidence of integrated therapy approaches and its advantage compared to of one-track interventions was becoming a discussion tool in therapy research as well as in mental health systems. Results of meta-analyses support superiority of integrated approaches compared to one-track interventions in more distal outcome areas such as social functioning. These results are in line with the large body of 37 independent IPT studies in 12 countries. Moreover, IPT research indicates the maintenance of therapy effects after the end of therapy and some evidence generalization effects. Additionally, the international randomized multi-center study on INT with 169 outpatients strongly supports the successful therapy of integrated therapy in proximal and distal outcome such as significant effects in cognition, functioning and negative symptoms. Clinical implication: therapy research as well as expert’s clinical experience recommends integrated therapy approaches such as IPT to be successful agents within multimodal psychiatric treatment concepts. Finally, integrated group therapy based on cognitive remediation seems to motivate and stimulate schizophrenia inpatients and outpatients to more successful and independent life also demanded by the recovery movement.

Evidence-supported psychosocial treatment for dual disorder patients

Results on the effectiveness of psychosocial treatments for patients with comorbid psychiatric and substance use disorders (dual disorders) will be discussed based on relevant meta-analyses and comprehensive reviews. Findings pertaining to severe (e.g., schizophrenia) and mild to moderate (e.g., anxiety disorders) dual disorders will be presented. The heterogeneity in patient characteristics, treatments, settings, and measured outcomes within the studies hinders the extraction of simple conclusions regarding how to effectively integrate psychiatric and addiction-oriented services into one psychosocial treatment. However, promising treatment strategies and interventions include integrative programs that comprise motivational interviewing; disorder-specific cognitive-behavioral interventions; substance use reduction interventions such as relapse prevention or contingency management; and/or family interventions. Such programs are generally superior to control groups (e.g., waiting list, treatment as usual) and are sometimes superior to other active treatments (e.g., skills training) in outcomes of substance use, psychiatric disorders, and social functioning.

Serotonin versus catecholamine deficiency: behavioral and neural effects of experimental depletion in remitted depression

Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catecholaminergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber's selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Using identical neuroimaging procedures with [(18)F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared with healthy controls in a double-blind, randomized, crossover design. Although TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex. Although we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. In conclusion, this study showed that serotonin and catecholamines have common and differential roles in the pathophysiology of depression.

Clinical effectiveness of cognitive behavioral therapy for depression in routine care: A propensity score based comparison between randomized controlled trials and clinical practice

Background: The efficacy of cognitive behavioral therapy (CBT) for the treatment of depressive disorders has been demonstrated in many randomized controlled trials (RCTs). This study investigated whether for CBT similar effects can be expected under routine care conditions when the patients are comparable to those examined in RCTs. Method: N=574 CBT patients from an outpatient clinic were stepwise matched to the patients undergoing CBT in the National Institute of Mental Health Treatment of Depression Collaborative Research Program (TDCRP). First, the exclusion criteria of the RCT were applied to the naturalistic sample of the outpatient clinic. Second, propensity score matching (PSM) was used to adjust the remaining naturalistic sample on the basis of baseline covariate distributions. Matched samples were then compared regarding treatment effects using effect sizes, average treatment effect on the treated (ATT) and recovery rates. Results: CBT in the adjusted naturalistic subsample was as effective as in the RCT. However, treatments lasted significantly longer under routine care conditions. Limitations: The samples included only a limited amount of common predictor variables and stemmed from different countries. There might be additional covariates, which could potentially further improve the matching between the samples. Conclusions: CBT for depression in clinical practice might be equally effective as manual-based treatments in RCTs when they are applied to comparable patients. The fact that similar effects under routine conditions were reached with more sessions, however, points to the potential to optimize treatments in clinical practice with respect to their efficiency.

The Treatment Action Campaign's First Decade: Success Achieved?

South Africa is known to have the largest HIV epidemic in the world with 5.7 million people currently living with HIV, according to UNAIDS. In light of the crisis, South Africa's Treatment Action Campaign (TAC) has led the social movement for increased treatment access for people living with HIV through lobbying the government, multinational pharmaceutical companies, and grassroots campaigning. Since it's founding a decade ago, TAC has been highly acclaimed both regionally and internationally for its success. In order to determine the success of this social movement organization, social movement theories, such as mobilization potential, external political opportunity structure, and framing of the social context of issues will be examined. The assessment of TAC's success will be made based on two outcomes: political outcome and social/cultural outcome. The assessment of TAC's success, using this framework has shown that TAC is a successful social movement organization overall.

Behavioral Profile of the Novel Cannabinoid Agonist AM4054

Although cannabinoid drugs have been used for thousands of years both recreationally and therapeutically, little has been known about their mechanisms of action until recently. Since the discovery of the endogenous cannabinoid CB1 receptor in 1988, the behavioral profile of cannabinoid receptor ligands has been much more thoroughly defined. Cannabinoid CB1 agonists have been shown to produce a variety of behavioral effects including suppression of locomotion, catalepsy, hypothermia, and analgesia. Research has also demonstrated that these behavioral effects can be inhibited by CB1 receptor antagonists including SR 141716 and AM 251. Although behavioral indicators of anxiety including thigmotaxis have been observed in several different paradigms, there is inconclusive and often times contradictory evidence to define the role of anxiety in CB1 receptor activation. The present study addressed the behavioral profile of AM 4054, a novel full agonist at the CB1 receptor, as well as the ability of the CB1 antagonist AM 251 to reverse these effects. To further identify and expand research on the suppression of locomotion and induction of thigmotaxis with the administration of a CB1 agonist, experiment 1 was conducted in the open field. In this experiment, each rat (n=40) was randomly assigned one of the five treatments: vehicle, 0.16, 0.32, 0.64, or 1.25 mg/kg AM 4054. After a 30 minute pre-treatment, each subject was tested in the open field for 18 minutes. Results indicated that AM 4054 produced a dose-related suppression of locomotion as well as the subtle presence of thigmotaxis in two out of four doses. In experiment 2, subjects (n=40) received either vehicle or 2.0 or 4.0 mg/kg AM 251 60 minutes prior to testing. After 30 minutes, the subjects were given either a 0.3 mg/kg dose of AM 4054 or vehicle. After a total pretreatment duration of 60 minutes, the animals were tested on a battery of tasks including an 18 minute session in locomotor boxes. Experiment 2 was a continuation of a previous study conducted in the same lab, which confirmed the effects of AM 4054 on this tetrad of tasks as being consistent with other cannabinoid agonists. In this experiment the effects of AM 4054 were reversed by the administration of the CB1 antagonist AM 251. Past studies have shown that AM 4054 is a highly potent drug with behavioral actions similar to other cannabinoid CB1 agonists. Furthermore, AM 4054 can be a useful drug in future studies, and has potential therapeutic value for the treatment of various conditions.

History of Maltreatment and Psychiatric Impairment in Children in Outpatient Psychiatric Treatment

There is increasing evidence that childhood victimization and attachment disruptions impact a child’s development. In this study, children and adolescents from an outpatient psychiatric clinic were assessed, measuring history of trauma, history of out-of-home placement, initial diagnoses, and CBCL internalizing and externalizing problem scores. Multiple regression analyses showed that both violent abuse trauma (physical/sexual abuse) and victim trauma (physical abuse/sexual abuse/witnessing domestic violence/witnessing community violence) are prevalent among patients with externalizing severity problems; concluding that diagnosis alone may not account for a history of victimization, but externalizing problem severity does. Overall, the study is consistent with past literature that it is important to acknowledge a child’s history of maltreatment and out-of-home placement when understanding their psychiatric development and diagnosis.

Chronic volatile substance abuse among the adult Kickapoo traditional tribe of Texas: Disease and disability profiles, neuropsychosocial consequences, and social implications for treatment

The purpose of this study, based on secondary data from attendees at a substance abuse clinic for the Kickapoo Healing Grounds in Eagle Pass, Texas, is two fold: (1) to elucidate neuro-behavioral performance of volatile substance abusers in the Kickapoo tribe and (2) to determine factors associated with their treatment completion and rehabilitation as measured by their employment at follow-up. Volatile substance abuse (VSA) is associated with a host of neurological manifestations, and secondary prevention or clinical treatment and rehabilitation remains the mainstay of control efforts. Very little is known about VSA in general, and especially among Native American populations. It is anticipated that the results will help determine and assist other tribes and non-tribal substance abuse centers with treatment planning for volatile substance abusers among Native American populations. ^

Physician and patient determinants of the treatment of sleep difficulties in U.S. outpatient settings

The prevalence of sleep difficulties among the patients seen in the primary care settings is about 30%. This problem increases with age and is more common among females than males. Variations are noticed in prescription choices for different patients with sleep difficulties. Many factors affect a physician's prescription decision while chosen from a wide array of available medications. Both pharmacological and behavioral therapies are available for the treatment of sleep difficulties. It is important to know the impact of use of different types of prescriptions on health outcomes related to sleep difficulties. Thus the knowledge of prescription patterns among different types of patients (e.g. age, gender, race, insurance type etc.) becomes important for determining a clinical guideline. This study is designed to assist in evidence-based policymaking on understanding the variations in physician prescriptions for sleep difficulties and reasons for such variations. ^ A modified version of the model suggested by Eisenberg was used as a theoretical framework for this study to predict the factors influencing treatment of sleep difficulties. Multivariate logistic regression methods were used to analyze the 1996–2001 National Ambulatory Medical Care Survey data. ^ This study found that increased age, female gender, white race, established patients, and mental comorbidity were associated with significantly increased likelihood for prescription of some type of therapy for sleep difficulties in US outpatient settings. Patients with private insurance were associated with lower likelihood of receipt of many therapies. Psychiatrists were more likely to prescribe some kind of treatment as well as more expensive therapies for sleep difficulty as compared to other physician specialties. HMO enrolled patient visits were more likely to be associated with receipt of behavioral therapy. This study also found that 32% of patients with sleep difficulties received no type of therapy during their visits. Only 5% of the patients received behavioral therapy only. Almost three-quarters of the patients receiving some kind of medication prescription were prescribed benzodiazepines. The study results also suggest a need for wider coverage of behavioral therapy by payers in US outpatient settings. ^

Studies on behavioral regulations of morphine tolerance in rats

Opioids remain the drugs of choice in chronic pain treatment, but opioid tolerance, defined as a decrease in analgesic effect after prolonged or repeated use, dramatically limits their clinical utility. Opioid tolerance has classically been studied by implanting spinal catheters in animals for drug administration. This procedure has significant morbidity and mortality, as well as causing an inflammatory response which decreases the potency of opioid analgesia and possibly affects tolerance development. Therefore, we developed and validated a new method, intermittent lumbar puncture (Dautzenberg et al.), for the study of opioid analgesia and tolerance. Using this method, opioid tolerance was reliably induced without detectable morbidity. The dose of morphine needed to induce analgesia and tolerance using this method was about 100-fold lower than that required when using an intrathecal catheter. Only slight inflammation was found at the injection site, dissipated within seven mm. ^ DAMGO, an opioid μ receptor agonist, has been reported to inhibit morphine tolerance, but results from different studies are inconclusive. We evaluated the effect of DAMGO on morphine tolerance using our newly-developed ILP method, as well as other intrathecal catheter paradigms. We found that co-administration of sub-analgesic DAMGO with morphine using ILP did not inhibit morphine tolerance, but instead blocked the analgesic effects of morphine. Tolerance to morphine still developed. Tolerance to morphine can only be blocked by sub-analgesic dose of DAMGO when administered in a lumbar catheter, but not in cervical catheter settings. ^ Finally, we evaluated the effects of Gabapentin (GBP) on analgesia and morphine tolerance. We demonstrated that GBP enhanced analgesia mediated by both subanalgesic and analgesic doses of morphine although GBP itself was not analgesic. GBP increased potency and efficacy of morphine. GBP inhibited the expression, but not the development, of morphine tolerance. GBP blocked tolerance to analgesic morphine but not to subanalgesic morphine. GBP reversed the expression of morphine tolerance even after tolerance was established. These studies may begin to provide new insights into mechanisms of morphine tolerance development and improve clinical chronic pain management. ^

Examination of the influence of behavioral, normative and control beliefs on the adherence to a prescribed renal diet among elderly populations with chronic to end-stage renal disease

The 1999-2004 prevalence of chronic kidney disease in adults 20 year or older (15.5 million) is an estimated 7.69%. The risk of developing CKD is exacerbated by diabetes, hypertension and/or a family history of kidney disease. African Americans, Hispanics, Pacific Islanders, Native Americans, and the elderly are more susceptible to higher incidence of CKD. The challenges of aging coupled with co-morbidities such as kidney disease raises the potential for malnutrition among elderly (for the purpose of this study 55 years or older) populations. Lack of adherence to prescribed nutrition guidelines specific to renal failure jeopardizes body homeostasis and increases the likelihood of future morbidity and resultant mortality. The relationship and synergy that exists between diet and disease is evident. Clinical experience with renal patients has indicated the importance of adherence to diet therapy specific to kidney disease. Extension investigation of diet adherence among endstage renal disease patients revealed a sizeable dearth in the current literature. This thesis study was undertaken to help reduce that void. The study design is qualitative and descriptive. Support, cooperation, and collaboration were provided by the University of Texas Nephrology Department, University of Texas Physicians, and DaVita Dialysis Centers. Approximately 105 male and female chronic to end-stage kidney disease patients were approached to participate in elicitation interviews in dialysis treatment facilities regarding their present diet beliefs and practices. Eighty-five were recruited and agreed to participate. Inclusion criteria required individuals to be between 35-90 years of age; capable of completing a 5-10 minute interview; and English speaking. Each kidney patient was asked seven (7) non-leading questions developed from the constructs of the Theory of Planned Behavior. The study presents a descriptive comparison of behavioral, normative, and control beliefs that influence adherence to renal diets by age, race, and gender. The study successfully concluded that behavioral, normative, and control beliefs of chronic to end-stage renal patients promoted execution and adherence to prescribed nutrition. This study provides valuable information for dietitians, technicians, nurses, and physicians to assess patient compliance toward prescribed nutrition and the means to support or improve that performance. ^

In vivo longitudinal studies of spinal cord injury and vascular endothelial growth factor treatment

Approximately 12,000 new cases of spinal cord injury (SCI) are added each year to the estimated 259,000 Americans living with SCI. The majority of these patients return to society, their lives forever changed by permanent loss of sensory and motor function. While there are no FDA approved drugs for the treatment of SCI or a universally accepted standard therapy, the current though controversial treatment includes the delivery of high dosages of the corticosteroid methyliprednisolone sodium succinate, surgical interventions to stabilize the spinal column, and physical rehabilitation. It is therefore critically important to fully understand the pathology of injury and determine novel courses and rationally-based therapies for SCI. ^ Vascular endothelial growth factor (VEGF) is an attractive target for treating central nervous system (CNS) injury and disease because it has been shown to influence angiogenesis and neuroprotection. Preliminary studies have indicated that increased vasculature may be associated with functional recovery; therefore exogenous delivery of a pro-angiogenic growth factor such as VEGF may improve neurobehavioral outcome. In addition, VEGF may provide protection from secondary injury and result in increased survival and axonal sprouting. ^ In these studies, SCI rats received acute intraspinal injections of VEGF, the antibody to VEGF, or vehicle control. The effect of these various agents was investigated using longitudinalmulti-modal magnetic resonance imaging (MRI), neuro- and sensory behavioral assays, and end point immunohistochemistry. We found that rats that received VEGF after SCI had increased tissue sparing and improved white matter integrity at the earlier time points as shown by advanced magnetic resonance imaging (MRI) techniques. However, these favorable effects of VEGF were not maintained, suggesting that additional treatments with VEGF at multiple time points may be more beneficial, Histological examinations revealed that VEGF treatment may result in increased oligodendrogenesis and therefore may eventually lead to remyelination and improved functional outcome. ^ On the neurobehavioral studies, treatments with VEGF and Anti-VEGF did not significantly affect performance on tests of open-field locomotion, grid walk, inclined plane, or rearing. However, VEGF treatment resulted in significantly increased incidence of chronic neuropathic pain. This phenomenon could possibly be attributed to the fact that VEGF treatment may promote axonal sprouting and also results in tissue sparing, thereby providing a substrate for the growth of new axons. New connections made by these sprouting axons may involve components of pathways involved in the transmission of pain and therefore result in increased pain in those animals. ^

Goals, plans, and behavior changes: A relevant part of the post-treatment cancer experience

Background. Colorectal cancer (CRC) survivors have to manage treatment side effects, psychosocial issues, and co-morbidities, as well as modify their lifestyles to decrease risk of recurrence and prolong life. Identifying survivors’ goals and key factors that influence their goals will highlight the issues cancer survivors face post-treatment and the resources needed to help them engage in health-promoting behaviors.^ Objectives and methods. This dissertation examines the health-related goals of post-treatment CRC survivors using two studies: (1) a qualitative study to identify and describe the health goals of CRC survivors during the transition from active treatment to post-treatment survivorship and follow-up care; and (2) a cross-sectional survey to identify CRC survivors’ goals, and key factors that influence their goals.^ Results. (1) The 41 qualitative interviews indicated participants’ health-related goals were to be healthy, get back to normal, and not have a cancer recurrence. Most of the CRC survivors reported they maintained healthy behaviors, made healthy behavior changes, or had goals to change their behavior. Respondents were empowered to improve their health by maintaining follow-up care and regular health screenings, and many were managing treatment side effects in an effort to improve functional abilities. (2) The cross-sectional study found that CRC survivors’ most prevalent goals were related to healthy behaviors (i.e., eat a healthy diet and engage in physical activity), and cancer care or disease management (i.e., keep up with health screenings and monitor symptoms). Goals that survivors identified as important were similar to goals they perceived were important to their providers (i.e., goals related to cancer care, disease management). Certain goals were statistically associated with age, barriers to achieving goals, social support and health-related quality of life.^ Conclusions. CRC survivors have health-promoting goals post-treatment and are interested in making health behavior changes. Goals ranged from cancer care/surveillance and disease management to healthy lifestyle modifications. Patients may need help resolving or managing treatment side effects or co-morbidities prior to implementing health promoting behaviors. Healthcare providers’ recommendations may be a powerful resource to encourage survivors to engage in health-promoting behaviors. Self-management and goal setting support could be an appropriate strategy to assist patients with achieving their post-treatment health goals.^