Marilyn Huckans

Cortical activation during delay discounting in abstinent methamphetamine dependent individuals

BackgroundMethamphetamine (MA)-dependent individuals prefer smaller immediate over larger delayed rewards in delay discounting (DD) tasks. Human and animal data implicate ventral (amygdala, ventral striatum, ventrolateral prefrontal cortex insula) and dorsal (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex and posterior parietal cortex) systems in DD decisions. The ventral system is hypothesized to respond to the salience and immediacy of rewards while the dorsal system is implicated in the process of comparison and choice.MethodsWe used functional Magnetic Resonance Imaging to probe the neural correlates of DD in 19 recently abstinent MA-dependent patients and 17 age- and gender-matched controls.ResultsHard DD choices were associated with greatest activation in bilateral middle cingulate, posterior parietal cortex (PPC), and the right rostral insula. Control subjects showed more activation than MA patients bilaterally in the precuneus and in the right caudate nucleus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Magnitude of discounting was correlated with activity in the amygdala, DLPFC, posterior cingulate cortex and PPC.ConclusionsOur findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions. Patients addicted to MA, who strongly prefer smaller immediate over larger delayed rewards, activate the dorsal cognitive control system in order to overcome their preference. Activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting, suggesting that heavily discounting MA-dependent individuals may be more responsive to the negative salience of delayed rewards than controls.

GLOBAL AND LOCAL MORPHOMETRIC DIFFERENCES IN RECENTLY ABSTINENT METHAMPHETAMINE-DEPENDENT INDIVIDUALS

Methamphetamine (MA) is associated with behavioral and cognitive deficits that may be related to macrostructural abnormalities. Quantitative anatomical comparisons between controls and methamphetamine-dependent individuals have produced conflicting results. We examined local and global differences in brain structure in 61 abstinent methamphetamine-dependent individuals and 44 controls with voxel-based morphometry and tissue segmentation. We related regional differences in gray matter density and whole brain segmentation volumes to performance on a behavioral measure of impulsivity and group membership using multiple linear regression. Within the MA group, we related cortical and subcortical gray matter density to length of abstinence. Controls had greater density relative to MA in bilateral insula and left middle frontal gyrus. Impulsivity was higher in the MA group and, within all subjects, impulsivity was positively correlated with gray matter density in posterior cingulate cortex and ventral striatum and negatively correlated in left superior frontal gyrus. Length of abstinence from MA was associated with greater amygdalar density. Earlier age of first use of MA (in subjects who initiated use before age 21) was associated with smaller intracranial volume. The findings are consistent with multiple possible mechanisms including neuroadaptations due to addictive behavior, neuroinflammation as well as dopaminergic and serotonergic neurotoxicity.

Depressive symptoms in patients with chronic hepatitis C are correlated with elevated plasma levels of interleukin-1β and tumor necrosis factor-α

Studies suggest that cytokines have a role in the biology of depression. In this study, we evaluated depression and cytokine levels in patients with and without chronic hepatitis C (HCV) to better assess how chronic infection alters cytokines levels and may contribute to depressive symptomotology. Twenty-three adults with (n = 16) and without (n = 7) HCV were recruited through the Portland VA Medical Center. Research participants were excluded for current substance abuse, psychotic disorder, liver cirrhosis, or interferon (IFN) therapy. Participants completed the Beck Depression Inventory-II (BDI-II) and a blood draw to evaluate plasma cytokine levels [i.e., interleukin (IL)-1β, IL-10 and tumor necrosis factor (TNF)- α]. T-tests were performed to compare cytokine levels in patients with versus those without HCV. HCV patients showed higher TNF-α values compared to patients without HCV (group means = 7.94 vs. 3.41 pg/mL, respecitively, p = 0.047). There were no significant differences between the groups for the other cytokines assessed. In patients with HCV, TNF-α and IL-1β levels (but not IL-10) were correlated with BDI-II scores [r = 0.594, p = 0.020 and r = 0.489, p = 0.055 (trend), respectively]. Taken together, these results show an association between severity of depressive symptoms and expression of proinflammatory cytokines in patients with HCV. Future studies should investigate how inflammatory mediators play a role in the expression of specific depressive symptoms in patients with chronic infection. Patients with HCV represent an interesting model to examine this relationship.

Efficacy of Cognitive Rehabilitation Therapies for Mild Cognitive Impairment (MCI) in Older Adults: Working Toward a Theoretical Model and Evidence-Based Interventions

To evaluate the efficacy of cognitive rehabilitation therapies (CRTs) for mild cognitive impairment (MCI). Our review revealed a need for evidence-based treatments for MCI and a lack of a theoretical rehabilitation model to guide the development and evaluation of these interventions. We have thus proposed a theoretical rehabilitation model of MCI that yields key intervention targets–cognitive compromise, functional compromise, neuropsychiatric symptoms, and modifiable risk and protective factors known to be associated with MCI and dementia. Our model additionally defines specific cognitive rehabilitation approaches that may directly or indirectly target key outcomes–restorative cognitive training, compensatory cognitive training, lifestyle interventions, and psychotherapeutic techniques. Fourteen randomized controlled trials met inclusion criteria and were reviewed. Studies markedly varied in terms of intervention approaches and selected outcome measures and were frequently hampered by design limitations. The bulk of the evidence suggested that CRTs can change targeted behaviors in individuals with MCI and that CRTs are associated with improvements in objective cognitive performance, but the pattern of effects on specific cognitive domains was inconsistent across studies. Other important outcomes (i.e., daily functioning, quality of life, neuropsychiatric symptom severity) were infrequently assessed across studies. Few studies evaluated long-term outcomes or the impact of CRTs on conversion rates from MCI to dementia or normal cognition. Overall, results from trials are promising but inconclusive. Additional well-designed and adequately powered trials are warranted and required before CRTs for MCI can be considered evidence-based.

Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: a 16-week prospective study.

OBJECTIVE This study evaluated the distinctive clinical and biological manifestations of depressive symptom subtypes (i.e., cognitive-affective and somatic) in Veterans with hepatitis C viral infection (HCV) before and during interferon-alpha (IFN) based antiviral therapy. METHODS Thirty-two Veterans with HCV and no prior history of IFN therapy were followed prospectively during the first 16weeks of therapy to evaluate depressive symptoms and to determine if baseline cytokine and serotonin levels predicted subsequent changes in depressive scores. RESULTS IFN therapy resulted in a significant increase in total depressive symptoms from baseline (week 0) to week 16, with neurovegetative and somatic symptoms of depression including loss of appetite, fatigue and irritability increasing within the first two weeks of therapy and continuing to increase throughout IFN therapy. When depressive symptoms were evaluated using a two-factor (i.e., Cognitive-Affective and Somatic) model, the Cognitive-Affective factor score did not change significantly following IFN therapy initiation, while the Somatic factor score showed a significant increase from week 0 to week 16. Veterans with the largest increases in somatic symptoms from week 0 to week 2 had significantly higher levels of tumor necrosis factor-alpha (TNF-α) and lower levels of serotonin at baseline, as compared to Veterans with minimal or no increase in somatic symptoms. CONCLUSION Somatic symptoms of depression can be significantly exacerbated during IFN therapy and may be predicted by higher TNF-α levels and lower serotonin levels at baseline.

A pilot study examining effects of group-based cognitive strategy training treatment on self-reported cognitive problems, psychiatric symptoms, functioning, and compensatory strategy use in OIF/OEF combat veterans with persistent mild cognitive disorder and history of traumatic brain injury

We aimed to determine whether group-based Cognitive Strategy Training (CST) for combat veterans with mild cognitive disorder and a history of traumatic brain injury (TBI) has significant posttreatment effects on self-reported compensatory strategy usage, functioning, and psychiatric symptoms. Participants included 21 veterans returning from conflicts in Iraq or Afghanistan with a diagnosis of Cognitive Disorder, Not Otherwise Specified and a history of combat-related TBI. Participants attended 6- to 8-week structured CST groups designed to provide them training in and practice with a variety of compensatory cognitive strategies, including day planner usage. Of the participants, 16 completed pre- and posttreatment assessment measures. Following CST, participants reported significantly increased use of compensatory cognitive strategies and day planners; an increased perception that these strategies were useful to them; increased life satisfaction; and decreased depressive, memory, and cognitive symptom severity. Group-based CST is a promising intervention for veterans with mild cognitive disorder, and randomized controlled trials are required to further evaluate its efficacy.

Hepatitis C testing and infection rates in bipolar patients with and without comorbid substance use disorders

OBJECTIVES To determine and compare hepatitis C (HCV) screening and testing rates among four groups: those with (i) bipolar disorder [BD group (history of BD but no substance use disorder)]; (ii) substance use disorders [SUD group (history of SUD but no BD)]; (iii) co-occurring disorders [DD group (history of both BD and an SUD)]; and (iv) a control group (no history of either bipolar disorder or substance use disorder). Our hypothesis was that HCV antibody testing rates and HCV prevalence would be higher in the BD, SUD, and DD groups than the control group. METHODS Data were retrospectively collected on 325,410 patients seen between 1998 and 2004 within facilities and clinics of the Veterans Integrated Service Network (VISN) 20 Northwest Veterans Health Care Administration from electronic medical records. HCV screening and prevalence rates were compared between the BD, SUD, DD, and control groups. Odds ratios and relative risks were determined and compared between groups. RESULTS Patients in the BD, SUD, and DD groups had been tested at a higher rate than controls and were at increased risk for HCV infection compared with controls. These high-risk groups had a 1.31-fold, 4.86-fold, and 5.46-fold increase in the relative risk of HCV infection, respectively. Overall, compared to the control group, the relative risk of a patient having HCV if he or she had BD (with or without an SUD) was 3.6. CONCLUSIONS Patients with BD and comorbid SUD had an over fourfold increase in relative risk for HCV than our control group and a similar risk as patients in our SUD group. Furthermore, even if bipolar patients did not have a comorbid SUD (the BD group), their relative risk of HCV was significantly higher than that of the control group. This suggests that patients with BD, particularly those with a comorbid SUD, should be screened and tested for HCV.

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.).

Discounting of delayed rewards and executive dysfunction in individuals infected with hepatitis C

Objective: Determine whether adults with hepatitis C (HCV), regardless of substance use disorder, are more likely to discount delayed rewards than adults without hepatitis C, and explore the relationship between delay discounting and neuropsychological functioning. Methods: Procedures included clinical interviews, neuropsychological testing, and a delay discounting task. Results: Regardless of substance abuse history, adults with hepatitis C were significantly more likely to choose smaller immediate rewards over larger delayed rewards. Delay discounting correlated with performance on executive functioning tasks. Conclusions: Increased discounting is associated with broad executive dysfunction, suggesting that HCV-associated executive dysfunction may lead to altered decision-making style.

Integrated hepatitis C virus treatment : addressing comorbid substance use disorders and HIV infection

Objectives:To examine hepatitis C virus (HCV) and HIV testing patterns within the Northwest Veterans Integrated Service Network (VISN 20). Methods:Using a comprehensive VISN 20 database, we retrospectively reviewed medical records of 293 445 veterans. Results:32.8% of patients were tested for HCV, 5.5% were tested for HIV, and 4.3% were co-tested. Of those tested, 12.3% were HCV positive, 5.4% were HIV positive, and 1.6% were co-infected. 79.1% of HIV-positive patients were tested for HCV, 29.2% of whom tested positive. 34.8% of HCV-positive patients were tested for HIV, 4.9% of whom tested positive. Of those tested, HCV-positive patients were significantly more likely than HCV-negative patients to test positive for HIV; HIV-positive patients were no more likely to test positive for HCV than HIV-negative patients. HIV-positive patients with substance use disorders (SUD) were significantly more likely to test HCV positive than those without. Within the total sample, veterans with SUD were significantly more likely to be tested for both diseases and to test positive for HCV but not HIV. After controlling for other categories of SUD, veterans with a history of cocaine abuse compared with those without were at an increased risk of HIV infection and co-infection. Conclusion:79.1% of HIV-positive but only 34.8% of HCV-positive veterans were co-tested, suggesting barriers to HIV testing may exist in VISN 20. Results also indicate that HCV-positive patients are at increased risk for HIV infection and that HIV-positive patients with SUD are at increased risk of HCV infection; routine co-testing for these patients is therefore warranted. Given significant co-infection rates, HCV and HIV screening and testing should be increasingly integrated. Increased infection rates among patients with SUD also warrant integration of HCV and HIV screening and testing into mental health and addiction programmes.