Bret E. Fuller

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 <or = .05). Post hoc comparisons indicated that HCV+/SUD- patients performed significantly worse than HCV-/SUD- controls on tests measuring verbal learning, auditory attention, and reasoning/mental flexibility, but only HCV+/SUD+ patients did worse than HCV-/SUD- controls on tests of speeded visual information processing. Results indicate that chronic HCV is associated with cognitive impairment in the absence of a history of SUD. The most robust deficits appear to be in verbal learning and reasoning/mental flexibility. (JINS, 2009, 15, 69-82.).

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.

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.

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.

The 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.

A longitudinal study evaluating the effects of interferon-alpha therapy on cognitive and psychiatric function in adults with chronic hepatitis C.

OBJECTIVE To prospectively evaluate for changes in objective cognitive performance (attention, memory, and executive function) and psychiatric symptom severity (depression, anxiety, fatigue, and pain) in patients before, during and after interferon-alpha based therapy (IFN) for chronic hepatitis C virus infection (HCV). METHODS 33 HCV+ adults were evaluated two months before IFN initiation (baseline), three months into IFN, and six months following IFN termination (IFN+ Group). 31 HCV+ adults who did not undergo IFN therapy were evaluated at baseline and six months later (IFN- Group). At each evaluation, participants completed the Neuropsychological Assessment Battery (NAB) Attention, Memory and Executive Functions Modules, the Beck Depression Inventory, Second Edition (BDI), Generalized Anxiety Disorder Inventory (GADI), Fatigue Severity Scale (FSS), and Brief Pain Inventory (BPI). RESULTS Compared with the IFN- Group, the IFN+ Group experienced significantly (p<0.050) increased symptoms of depression, anxiety, fatigue and pain during IFN therapy relative to baseline. In the IFN+ Group, psychiatric symptoms generally returned to baseline levels following IFN termination. Sustained viral response was associated with significantly lower depression and fatigue. No significant changes in cognitive performance were observed. CONCLUSIONS During IFN, patients with HCV evidence significantly increased psychiatric symptoms, including symptoms of depression, anxiety, fatigue and pain. These psychiatric symptoms are generally short-term and remit following IFN termination, with increased benefit if viral clearance is achieved. However, IFN is not associated with significant declines in objective cognitive performance during or following IFN.

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.

Efficacy of motivational enhancement therapy on alcohol use disorders in patients with chronic hepatitis C: a randomized controlled trial.

AIMS To determine the efficacy of motivational enhancement therapy (MET) on alcohol use in patients with the hepatitis C virus (HCV) and an alcohol use disorder (AUD). DESIGN Randomized, single-blind, controlled trial comparing MET to a control education condition with 6-month follow-up. SETTING Patients were recruited from hepatitis clinics at the Minneapolis, Minnesota and Portland, Oregon Veterans Affairs Health Care Systems, USA. PARTICIPANTS AND INTERVENTION Patients with HCV, an AUD and continued alcohol use (n = 139) were randomized to receive either MET (n = 70) or a control education condition (n = 69) over 3 months. MEASUREMENTS Data were self-reported percentage of days abstinent from alcohol and number of standard alcohol drinks per week 6 months after randomization. FINDINGS At baseline, subjects in MET had 34.98% days abstinent, which increased to 73.15% at 6 months compared to 34.63 and 59.49% for the control condition. Multi-level models examined changes in alcohol consumption between MET and control groups. Results showed a significant increase in percentage of days abstinent overall (F(1120.4)  = 28.04, P < 0.001) and a significant group × time effect (F(1119.9)  = 5.23, P = 0.024) with the MET group showing a greater increase in percentage of days abstinent at 6 months compared with the education control condition. There were no significant differences between groups for drinks per week. The effect size of the MET intervention was moderate (0.45) for percentage of days abstinent. CONCLUSION Motivational enhancement therapy (MET) appears to increase the percentage of days abstinent in patients with chronic hepatitis C, alcohol use disorders and ongoing alcohol use.

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.

AAC to support conversation in persons with moderate Alzheimer's disease.

Even though we know that external memory aids support communication in Alzheimer’s disease, the components of the communication aids for individuals with Alzheimer’s disease have not been studied systematically. The goal of these two pilot experiments was to examine differences in conversational performance of adults with Alzheimer’s disease related to the presence and absence of an aid, the type of symbol embedded in the aid, and the presence or absence of voice output. In Experiment 1, 30 adults with moderate-to-severe Alzheimer’s disease participated in 10-min conversations with and without personalized AAC boards. There was no effect of AAC, regardless of symbol type, and a deleterious effect of voice output. In Experiment 2, modified spaced-retrieval training preceded conversations, standardized prompts were presented, and semantically-based dependent variables were examined. For the 11 participants in the second experiment, there was a significant effect of AAC, showing that the presence of AAC was associated with greater use of targeted words during personal conversations. We discuss new information about the contribution of AAC for persons with Alzheimer’s disease, and demonstrate how the applied research process evolves over the course of a long-term commitment to a scientific investigation.

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

Purpose of review A growing number of veterans in theVeterans 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.