Peripheral immune factors are elevated in women with current or recent alcohol dependence and associated with altered mood and memory.

BACKGROUND: The adverse effects of alcohol on brain function result, in part, from inflammatory processes. The sex-specific neuropsychiatric consequences and inflammatory status of active alcohol dependence and early remission from dependence have not been investigated. METHODS: Neuropsychiatric symptoms, inflammatory factors, and liver enzymes were compared in a prospective cohort study of adults with (n=51) or without (n=31) a current or recent history of alcohol dependence. RESULTS: Neuropsychiatric profiles were similar in adults with current or recent alcohol dependence regardless of sex. In male and female participants measures of depression (female p<0.05, male p<0.001), anxiety (female p<0.001, male p<0.001), and memory complaints (female p<0.001, male p<0.05) were elevated, relative to non-dependent controls. Significant sex×alcohol dependence history interactions were observed for plasma levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) and brain derived neurotrophic factor (BDNF), with women in the alcohol dependent group exhibiting increased levels of both analytes (p<0.05) relative to controls. Positive correlations between TIMP-1 levels and measures of depression (r2=0.35, p<0.01), anxiety (r2=0.24, p<0.05) and memory complaints (r2=0.44, p<0.01) were found in female, but not male, participants. CONCLUSIONS: Though neuropsychiatric profiles were similar for men and women with current or recent alcohol dependence, plasma factors associated with increases in depression, anxiety, and memory impairment differed and support the need to tailor treatments based on sex.

Plasma Inflammatory Factors Are Associated with Anxiety, Depression, and Cognitive Problems in Adults with and without Methamphetamine Dependence: An Exploratory Protein Array Study.

OBJECTIVES: It is hypothesized that immune factors influence addictive behaviors and contribute to relapse. The primary study objectives were to (1) compare neuropsychiatric symptoms across adults with active methamphetamine (MA) dependence, in early remission from MA dependence, and with no history of substance dependence, (2) determine whether active or recent MA dependence affects the expression of immune factors, and (3) evaluate the association between immune factor levels and neuropsychiatric symptoms. METHODS: A cross-sectional study was conducted using between group comparisons and regression analyses to investigate associations among variables. Eighty-four adults were recruited into control (CTL) (n = 31), MA-active (n = 17), or MA-remission (n = 36) groups. Participants completed self-report measures of anxiety, depression, and memory complaints and objective tests of attention and executive function. Blood samples were collected, and a panel of immune factors was measured using multiplex technology. RESULTS: Relative to CTLs, MA-dependent adults evidenced greater anxiety and depression during active use (p < 0.001) and remission (p < 0.007), and more attention, memory, and executive problems during remission (p < 0.01) but not active dependence. Regression analyses identified 10 immune factors (putatively associated with cytokine-cytokine receptor interactions) associated with anxiety, depression, and memory problems. CONCLUSION: While psychiatric symptoms are present during active MA dependence and remission, at least some cognitive difficulties emerge only during remission. Altered expression of a network of immune factors contributes to neuropsychiatric symptom severity.

Multi-analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection.

BackgroundThe purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms-depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV. MethodsBlood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV-, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers. ResultsCompared with HCV- controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV- group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4-10 plasma immune factors; protein signatures significantly accounted for 19-40% of the variance in depression, anxiety, fatigue, and pain. ConclusionsOverall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in adults with or without HCV.

Screening for depression in patients with hepatitis C using the Beck Depression Inventory-II: do somatic symptoms compromise validity?

OBJECTIVE: The objective of the study was to evaluate the validity of the Beck Depression Inventory-II (BDI-II) when used to measure depression in patients with hepatitis C virus (HCV). METHOD: Factor analysis was utilized to validate the BDI-II in a sample of 671 patients with HCV recruited from a large Veterans Affairs medical center. The data were split randomly: the first half was subjected to exploratory factor analysis, and confirmatory factor analysis was used with the second half to confirm the model. Diagnostic data were retrieved from the electronic medical records. RESULTS: Subjects were 97.0% male, average age was 52.8 years, 16.1% had a cirrhosis diagnosis, 62.9% had a current major depressive disorder diagnosis, and 42.3% endorsed significant depressive symptoms on the BDI-II. A two-factor model was an excellent fit for the data; the factors were labeled Cognitive-Affective and Somatic. Patients scored significantly higher on the Somatic factor than on the Cognitive-Affective factor (P<.001), and this discrepancy increased when comparing patients based on whether they had a diagnosis of cirrhosis. CONCLUSIONS: When screening for depression in HCV patients, questions targeting cognitive and affective symptoms of depression may provide a more valid measurement of depression than questions targeting somatic symptoms of depression, particularly for patients with more advanced liver disease.

Prevalence of liver disease in veterans with bipolar disorder or schizophrenia.

OBJECTIVE: To assess the prevalence of three liver diseases [hepatitis C virus (HCV), nonalcoholic fatty liver disease and alcohol-induced cirrhosis] in patients (veterans) with/without schizophrenia/schizoaffective disorder and bipolar disorder. METHODS: A retrospective electronic chart review of Veterans Integrated Services Network 20 facilities from January 1, 2001 to December 21, 2006 selected patients to one of two groups: schizophrenia/schizoaffective disorder or bipolar disorder. Patients in both groups were compared with veterans in an equal-sized random sample from the same data set of veterans without psychiatric diagnoses. Logistic regression models evaluated risk for overall liver diseases as well as HCV, nonalcoholic fatty liver disease and alcoholic-induced cirrhosis. RESULTS: Patients with schizophrenia (n=6521) had a higher prevalence of liver disease [22.4% versus 3.2%; odds ratio (OR)=8.73]; HCV (16.5% versus 1.9%; OR=10.21); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=4.09) than matched controls. Patients with bipolar disorder (n=5319) had a higher prevalence of liver disease (21.5% versus 3.5%; OR=7.58); HCV (15.5% versus 2.1%; OR=8.60); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=3.82) than matched controls. Risk factors for liver disease in patients with schizophrenia (versus matched controls) included diabetes (OR=1.29), hypertension (OR=1.27), HIV (OR=3.54), substance use disorder (SUD) (OR=2.28), alcohol use disorder (OR=3.05) and schizophrenia (OR=2.74). Risk factors for development of liver disease for patients with bipolar disorder: diabetes (OR=1.40), HIV (OR=3.66), SUD (OR=2.68), alcohol use disorder (OR=3.22) and bipolar disorder (OR=2.27). CONCLUSIONS: This study in veterans shows that the presence of mental illness and its comorbidities represents a significant risk factor for the diagnosis of liver disease, including HCV and alcohol-related cirrhosis.

Measuring nausea in emergency department patients via the use of exploratory factor analysis.

OBJECTIVES: The objective was to evaluate the applicability of a previously studied multifactorial nausea scale in the emergency department (ED) setting via exploratory factor analysis (EFA). METHODS: Two studies evaluated the validity and factor structure of 18 nausea descriptors scored on 11-point Likert scales. Trained research volunteers administered the scale to 83 men and 123 women in the first sample and to 100 men and 230 women in the second sample. All patients were assessed at enrollment and again at 90 minutes to detect changes in symptom severity. An EFA in the first study used a maximum likelihood estimation method with a principal factor analysis. The second study narrowed the descriptors and evaluated the factor structure with a confirmatory factor analysis (CFA). RESULTS: Two factors were retained in the solution; one contained five items with descriptors of physical symptoms, and a second contained five items with psychological symptoms. CFA determined that the two five-item scales were stable and reliable measures of patient nausea experience. CONCLUSIONS: The scales measure both physical and psychological symptoms of nausea, indicating that the experience is multidimensional.

Adoption of practice guidelines and assessment tools in substance abuse treatment.

BACKGROUND: The gap between research and practice limits utilization of relevant, progressive and empirically validated strategies in substance abuse treatment. METHODS: Participants included substance abuse treatment programs from the Northeastern United States. Structural equation models were constructed with agency level data to explore two outcome variables: adoption of practice guidelines and assessment tools at two points in time; models also included organizational, staffing and service variables. RESULTS: In 1997, managed care involvement and provision of primary care services had the strongest association with increased use of assessment tools, which, along with provision of counseling services, were associated with a greater use of practice guidelines. In 2001, managed care involvement, counseling services and being a stand-alone drug treatment agency were associated with a greater use of assessment tools, which was in turn related to an increase in the use of practice guidelines. CONCLUSIONS: This study provides managers, clinicians and policy-makers with a framework for understanding factors related to the adoption of new technologies in substance abuse treatment.

Facilitating outpatient treatment entry following detoxification for injection drug use: a multisite test of three interventions.

A multisite, randomized trial within the National Drug Abuse Treatment Clinical Trials Network (CTN) was conducted to test 3 interventions to enhance treatment initiation following detoxification: (a) a single session, therapeutic alliance intervention (TA) added to usual treatment; (b) a 2-session, counseling and education, HIV/HCV risk reduction intervention (C&E), added to usual treatment; and (c) treatment as usual (TAU) only. Injection drug users (n=632) enrolled in residential detoxification at 8 community treatment programs were randomized to 1 of the 3 study conditions. TA participants reported entering outpatient treatment sooner and in greater numbers than TAU participants. Reported treatment entry for C&E fell between TA and TAU with no significant differences between C&E and the other conditions. There were no differences among the interventions in retention, as measured by weeks of outpatient treatment for all participants who reported treatment entry. Alliance building interventions appear to be effective in facilitating transfer from detoxification to outpatient treatment, but additional treatment engagement interventions may be necessary to improve retention.

Psychiatric and substance use disorders comorbidities in veterans with hepatitis C virus and HIV coinfection.

PURPOSE OF REVIEW: A growing number of veterans in the Veterans Health Administration are coinfected with HIV and hepatitis C virus. This review covers timely research relative to comorbid conditions that are common in this population including psychiatric diagnoses, substance use disorders and neurocognitive problems. RECENT FINDINGS: Current literature on the psychiatric, substance use disorders and cognitive problems of the coinfected population show that not only are rates of morbidity higher in the coinfected population but that this affects antiviral treatments as well. There is new evidence that brain injuries and infiltration of the virus into the central nervous system may be responsible for cognitive dysfunction. Cotesting, particularly in hepatitis C infected individuals, is not done routinely despite shared risk factors. SUMMARY: With this understanding of the comorbidities of the coinfected population, integrated healthcare models involving mental health, internal medicine, substance abuse treatment and internal medicine are crucial to work with these medically and psychologically complex patients.

The cognitive effects of hepatitis C in the presence and absence of a history of substance use disorder.

The aim of the study was to determine whether infection with the hepatitis C virus (HCV) is associated with cognitive impairment beyond the effects of prevalent comorbidities and a history of substance use disorder (SUD). Adult veterans were recruited from the Portland Veterans Affairs Medical Center into three groups: (1) HCV+/SUD+ (n = 39), (2) HCV+/SUD- (n = 24), and (3) HCV-/SUD- (n = 56). SUD+ participants were in remission for > or =90 days, while SUD- participants had no history of SUD. Groups did not significantly differ in terms of rates of psychiatric or medical comorbidities. Procedures included clinical interviews, medical record reviews, and neuropsychological testing. Significant group differences were found in the domains of Verbal Memory, Auditory Attention, Speeded Visual Information Processing, and Reasoning/Mental Flexibility (p

Organizational Readiness for Change and opinions toward treatment innovations.

Program administrators and staff in treatment programs participating in the National Drug Abuse Treatment Clinical Trials Network completed surveys to characterize participating programs and practitioners. A two-level random-effects regression model assessed the influence of Organizational Readiness for Change (ORC) and organizational attributes on opinions toward the use of four evidence-based practices (manualized treatments, medication, integrated mental health services, and motivational incentives) and practices with less empirical support (confrontation and noncompliance discharge). The ORC scales suggested greater support for evidence-based practices in programs where staff perceived more program need for improvement, better Internet access, higher levels of peer influence, more opportunities for professional growth, a stronger sense of organizational mission, and more organizational stress. Support for confrontation and noncompliance discharge, in contrast, was strong when staff saw less opportunity for professional growth, weaker peer influence, less Internet access, and perceived less organizational stress. The analysis provides evidence of the ORC's utility in assessing agency strengths and needs during the implementation of evidence-based practices.

Client and counselor attitudes toward the use of medications for treatment of opioid dependence.

Attitudes, perceived social norms, and intentions were assessed for 376 counselors and 1,083 clients from outpatient, methadone, and residential drug treatment programs regarding four medications used to treat opiate dependence: methadone, buprenorphine, clonidine, and ibogaine. Attitudes, social norms, and intentions to use varied by treatment modality. Methadone clients and counselors had more positive attitudes toward the use of methadone, whereas their counterparts in residential and outpatient settings had neutral or negative assessments. Across modalities, attitudes, perceived social norms, and intentions toward the use of buprenorphine were relatively neutral. Assessments of clonidine and ibogaine were negative for clients and counselors in all settings. Social normative influences were dominant across settings and medications in determining counselor and client intentions to use medications, suggesting that perceptions about beliefs of peers may play a critical role in use of medications to treat opiate dependence.

Direct care workers in the National Drug Abuse Treatment Clinical Trials Network: characteristics, opinions, and beliefs.

OBJECTIVE: Individuals with direct care responsibilities in 348 drug abuse treatment units were surveyed to obtain a description of the workforce and to assess support for evidence-based therapies. METHODS: Surveys were distributed to 112 programs participating in the National Drug Abuse Treatment Clinical Trials Network (CTN). Descriptive analyses characterized the workforce. Analyses of covariance tested the effects of job category on opinions about evidence-based practices and controlled for the effects of education, modality (outpatient or residential), race, and gender. RESULTS: Women made up two-thirds of the CTN workforce. One-third of the workforce had a master's or doctoral degree. Responses from 1,757 counselors, 908 support staff, 522 managers-supervisors, and 511 medical staff (71% of eligible participants) suggested that the variables that most were most consistently associated with responses were job category (19 of 22 items) and education (20 of 22 items). Managers-supervisors were the most supportive of evidence-based therapies, and support staff were the least supportive. Generally, individuals with graduate degrees had more positive opinions about evidence-based therapies. Support for using medications and contingency management was modest across job categories. CONCLUSIONS: The relatively traditional beliefs of support staff could inhibit the introduction of evidence-based practices. Programs initiating changes in therapeutic approaches may benefit from including all employees in change efforts.

Attitudes toward the integration of smoking cessation treatment into drug abuse clinics.

This article examines the variables associated with the presence of smoking cessation interventions in drug abuse treatment units, as well as staff attitudes toward the integration of smoking cessation services as a component of care. Surveys were administered to 106 organizations, 348 treatment clinics, and 3,786 employees in agencies that participated in the National Drug Abuse Treatment Clinical Trials Network. Organizational factors, attributes of the treatment setting, and staff attitudes toward smoking cessation treatment were assessed. Use of smoking cessation interventions was associated with the number of additional services offered at clinics, residential detoxification services, and attitudes of the staff toward smoking cessation treatment. Staff attitudes toward integrating smoking cessation services in drug treatment were influenced by the number of pregnant women admitted, the number of ancillary services provided, the attitudes of staff toward evidence-based practices, and whether smoking cessation treatment was offered as a component of care.

Elimination of methadone benefits in the Oregon Health Plan and its effects on patients.

OBJECTIVES: This prospective study assessed the impacts of a policy change to Oregon's Medicaid program (Oregon Health Plan; OHP) that eliminated methadone benefits for 60 percent of active methadone patients. Recipients of OHP Standard (expanded Medicaid benefits, which were discontinued after the policy change) self-selected into two groups: those who paid for methadone after the policy change and those who terminated treatment. OHP Plus beneficiaries (traditional Medicaid) did not lose benefits. METHODS: A total of 149 patients participated in the study, and interviews were conducted at baseline (time of policy change) and one, three, and 12 months after the policy change. Patients were assessed with the Addiction Severity Index (ASI), Timeline Follow Back assessment, and chart review. RESULTS: Patients who left treatment because they were unable to pay for methadone services showed significant elevations in ASI composite scores for drug and legal problems at baseline and at two and three months after the policy change. The patients who attempted to self-pay experienced significantly more employment problems than the other two groups. The OHP Standard recipients who paid for their methadone treatment over the year were more likely to have additional resources to pay for methadone, be employed, and have stable housing. CONCLUSIONS: The elimination of methadone treatment benefits in the OHP had substantial negative impacts for patients with the greatest indicators of need.

Adoption of naltrexone to treat alcohol dependence.

Three surveys (1997, 1999, and 2001) of outpatient substance abuse treatment centers in Connecticut, Massachusetts, Rhode Island, Maine, Vermont, and New Hampshire examined organizational characteristics that influenced the adoption of naltrexone. Structural equation modeling with manifest variables assessed predictors related to the use of naltrexone. Use of naltrexone increased over time from 14% in 1997 to 25% in 2001. In 1997, programs funded by managed care were more likely, and clinics that provided only substance abuse services were less likely to use psychiatric medication and naltrexone. In subsequent years, counselor education level and organization size also influenced use of naltrexone.

Predictors of aggression across three generations among sons of alcoholics: relationships involving grandparental and parental alcoholism, child aggression, marital aggression and parenting practices.

OBJECTIVE: This longitudinal study uses a three-generation database involving measures of grandparental and parental alcohol use disorder (AUD), marital aggression and aggression to offspring to predict early and later childhood aggression of third generation offspring. Given the importance of aggressive, undercontrolled behavior in the etiology of alcoholism, the purpose of this study was to construct a statistical model of intergenerational aggression and alcoholism among family members. METHOD: Participants were a population-based sample of 186 young sons of alcoholics and both biological parents and 120 nonsubstance abusing families and their age-matched sons drawn from the same neighborhoods. Extensive family data were collected at baseline and at 6 years postbaseline. Structural equation modeling evaluated retrospective and prospective relationships between grandparental and parental predictors of the sons' childhood aggression when they were 3-5 and 9-11 years of age. RESULTS: The final model showed that grandparental marital aggression predicted development of parental antisocial behavior, which predicted parental alcoholism and marital aggression and partially mediated level of child aggression among their sons as preschoolers. Significant autostabilities in level of child aggression, parental AUD and marital aggression were present in families over the 6-year interval. Marital aggression was a more important predictor of son's preschool aggression; direct parental aggression to the child was more important at 9-11. Child aggression at 3-5 also was a partial mediator of level of parent-to-child aggression at 9-11. CONCLUSIONS: Results indicate continuity of aggression across three generations and also indicate that the child's pathway into risk for later AUD is not simply mediated by parental alcoholism, but is carried by other comorbid aspects of family functioning, in particular aggression.