Neuropsychological Performance and Functional Capacity Following Mild Traumatic Brain Injury in Veterans.

OBJECTIVE: To examine the relationship between neuropsychological functioning and performance-based functional capacity in veterans with a history of mild traumatic brain injury (mTBI), as well as the moderating effects of age and psychiatric symptoms on this relationship. SETTING: Three Veterans Affairs medical centers. PARTICIPANTS: One hundred nineteen Iraq/Afghanistan veterans with a history of mTBI and self-reported cognitive difficulties. DESIGN: Cross-sectional, secondary data analysis of baseline measures in a randomized controlled trial. MAIN MEASURES: The main outcome measure, functional capacity, was assessed using the objective and performance-based University of California San Diego Performance-based Skills Assessment-Brief. A global deficit score (GDS) was created as a composite score for performance on a battery of neuropsychological measures assessing domains of attention, processing speed, executive functioning, and verbal memory performance. Posttraumatic stress disorder (PTSD) symptom severity was assessed using the PTSD Checklist-Military Version, and depressive symptom severity was assessed using the Beck Depression Inventory, Second Edition. RESULTS: Bivariate analyses indicated that worse neuropsychological performance (ie, higher GDS) and greater PTSD symptom severity were associated with worse communication abilities and worse overall functional capacity. Multiple linear regressions demonstrated that GDS and PTSD symptom severity explained 9% of the variance in communication and 10% of the variance in overall functional capacity; however, GDS emerged as the only significant predictor in both regressions. Age, PTSD, and depressive symptom severity did not moderate the relationship between GDS and overall functional capacity. Performance in the verbal learning and memory domain emerged as the strongest neuropsychological predictor of communication and overall functional capacity. CONCLUSIONS: Worse neuropsychological functioning was moderately associated with worse performance-based functional capacity, even when accounting for PTSD symptom severity. Verbal learning and memory was the primary neuropsychological domain driving the relationship with functional capacity; improvement in verbal learning and memory may translate into improved functional capacity.

Cognition during active methamphetamine use versus remission.

OBJECTIVE: To evaluate whether cognitive performance in adults with active methamphetamine use (MA-ACT) differs from cognitive performance in adults in remission from MA use disorder (MA-REM) and adults without a history of substance use disorder (CTLs). METHOD: MA-ACT (n = 36), MA-REM (n = 48), and CTLs (n = 62) completed the Neuropsychological Assessment Battery (NAB). RESULTS: The MA-ACT group did not perform significantly worse than CTLs on any NAB Index. The MA-REM group performed significantly (p < 0.050) worse than CTLs on the NAB Memory Index. The MA-ACT group performed significantly better than CTLs and the MA-REM group on the Executive Functions Index. CONCLUSIONS: Some cognitive deficits are apparent during remission from MA use, but not during active use; this may result in clinical challenges for adults attempting to maintain recovery and continue with treatment.

Change in Learning and Memory Partially Mediates Effects of Compensatory Cognitive Training on Self-Reported Cognitive Symptoms.

OBJECTIVE: To examine associations among compensatory cognitive training (CCT), objective cognitive functioning, and self-reported cognitive symptoms. We examined whether change in objective cognitive functioning associated with participation in CCT at 10-week follow-up mediates change in self-reported cognitive symptoms associated with CCT at 15-week follow-up. SETTING: Three VA outpatient mental health clinics. PARTICIPANTS: Veterans with a history of mild traumatic brain injury who reported cognitive deficits. DESIGN: Randomized controlled trial post hoc causal mediation analysis. MAIN MEASURES: Self-reported cognitive symptoms were measured by the Prospective-Retrospective Memory Questionnaire and the Multiple Sclerosis Neuropsychological Screening Questionnaire. Objective cognitive functioning was measured using a battery of neuropsychological tests. RESULTS: Improvement on the Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall test mediated the association between participation in CCT and decrease in the Prospective-Retrospective Memory Questionnaire total score. Improvement on the HVLT-R Total Recall and HVLT-R Delayed Recall tests both meditated the association between participation in CCT and decrease in the Multiple Sclerosis Neuropsychological Screening Questionnaire total score. No other measures of objective cognitive functioning were significant mediators. CONCLUSION: Patients' perceptions of cognitive symptom improvement due to CCT are partially mediated by learning and memory, though these subjective improvements occur regardless of other changes in objective cognitive functioning associated with CCT.

Predictors of Intervention Adherence in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury.

OBJECTIVE: The purpose of this study was to determine modifiable predictors of intervention adherence in a study of group-based Compensatory Cognitive Training (CCT) for Iraq/Afghanistan War veterans with a history of mild traumatic brain injury (mTBI). METHODS: One hundred twenty-three veterans enrolled in a randomized controlled trial of a 10-week CCT intervention (54 assigned to CCT) and were evaluated at baseline, 5 weeks, 10 weeks, and 15 weeks. CCT adherence was determined by the number of CCT sessions attended, with more sessions indicative of greater adherence. Baseline demographic and clinical characteristics, and subjective and objective neuropsychological performance, were examined in relation to CCT session attendance. RESULTS: Older age and worse attention performance at baseline were associated with higher CCT attendance rates. CONCLUSIONS: This study generates preliminary evidence for potential modifiable neuropsychological factors that may improve engagement in CCT interventions.

Randomized controlled trial protocol for project BRIDGE: A telephone-administered motivational interviewing intervention targeting risky sexual behavior in older people living with HIV.

PURPOSE: By 2020, 70% of people living with HIV in the United States will be greater than 50 years of age. As many as 37% of sexually active older people living with HIV (OPLWH) engage in HIV transmission sexual behaviors. In spite of repeated calls for secondary prevention interventions to reduce condomless sex in OPLWH, no age-appropriate, evidence-based secondary prevention interventions exist for this group. Furthermore, many OPLWH face barriers to engaging in face-to-face secondary prevention services because of HIV- and age-related stigma, comorbid mental and physical health conditions that complicate travel, or geographic isolation. High rates of depression in OPLWH may further complicate engagement in interventions intended to reduce HIV transmissions. Telephone-administered motivational interviewing may be a feasible and efficacious intervention for this population. METHODS: This randomized controlled trial will test the efficacy of a 5-session telephone-administered motivational interviewing plus behavioral skills training (teleMI+BST) intervention versus a 5-session telephone-administered coping effectiveness training (teleCET) control intervention to reduce condomless sex in OPLWH. A diverse sample of 336 OPLWH will be recruited across the U.S. The primary analysis will test the efficacy of teleMI+BST to reduce occasions of non-condom protected anal and vaginal intercourse with HIV serodiscordant sex partners. Secondary analyses will examine the efficacy of teleMI+BST to reduce depressive symptoms in mildly depressed OPLWH. CONCLUSION: This is the first large-scale RCT intended to reduce HIV sexual transmission risk behavior in OPLWH and will add to the literature on secondary prevention telehealth interventions for people living with HIV. ClinicalTrials.gov Identifier: NCT03004170. This trial has been conducted by the approval of the Institutional Review Board. Participants provided verbal consent to participate in this trial.

Partial MHC/neuroantigen peptide constructs attenuate methamphetamine-seeking and brain chemokine (C-C motif) ligand 2 levels in rats.

There are no medications that target the neurotoxic effects or reduce the use of methamphetamine. Recombinant T-cell receptor ligand (RTL) 1000 [a partial major histocompatibility complex (pMHC) class II construct with a tethered myelin peptide], addresses the neuroimmune effects of methamphetamine addiction by competitively inhibiting the disease-promoting activity of macrophage migration inhibitory factor to CD74, a key pathway involved in several chronic inflammatory conditions, including substance use disorders. We previously reported that RTL constructs improve learning and memory impairments and central nervous system (CNS) inflammation induced by methamphetamine in mouse models. The present study in Lewis rats evaluated the effects of RTL1000 on maintenance of self-administration and cue-induced reinstatement using operant behavioral methods. Post-mortem brain and serum samples were evaluated for the levels of inflammatory factors. Rats treated with RTL1000 displayed significantly fewer presses on the active lever as compared to rats treated with vehicle during the initial extinction session, indicating more rapid extinction in the presence of RTL1000. Immunoblotting of rat brain sections revealed reduced levels of the pro-inflammatory chemokine (C-C motif) ligand 2 (CCL2) in the frontal cortex of rats treated with RTL1000, as compared to vehicle. Post hoc analysis identified a positive association between the levels of CCL2 detected in the frontal cortex and the number of lever presses during the first extinction session. Taken together, results suggest that RTL1000 may block downstream inflammatory effects of methamphetamine exposure and facilitate reduced drug seeking-potentially offering a new strategy for the treatment of methamphetamine-induced CNS injury and neuropsychiatric impairments.

Methamphetamine use alters human plasma extracellular vesicles and their microRNA cargo: An exploratory study.

Methamphetamine (MA) is the largest drug threat across the globe, with health effects including neurotoxicity and cardiovascular disease. Recent studies have begun to link microRNAs (miRNAs) to the processes related to MA use and addiction. Our studies are the first to analyse plasma EVs and their miRNA cargo in humans actively using MA (MA-ACT) and control participants (CTL). In this cohort we also assessed the effects of tobacco use on plasma EVs. We used vesicle flow cytometry to show that the MA-ACT group had an increased abundance of EV tetraspanin markers (CD9, CD63, CD81), but not pro-coagulant, platelet-, and red blood cell-derived EVs. We also found that of the 169 plasma EV miRNAs, eight were of interest in MA-ACT based on multiple statistical criteria. In smokers, we identified 15 miRNAs of interest, two that overlapped with the eight MA-ACT miRNAs. Three of the MA-ACT miRNAs significantly correlated with clinical features of MA use and target prediction with these miRNAs identified pathways implicated in MA use, including cardiovascular disease and neuroinflammation. Together our findings indicate that MA use regulates EVs and their miRNA cargo, and support that further studies are warranted to investigate their mechanistic role in addiction, recovery, and recidivism.

Trace amine-associated receptor gene polymorphism increases drug craving in individuals with methamphetamine dependence.

BACKGROUND: Methamphetamine (MA) is a potent agonist at the trace amine-associated receptor 1 (TAAR1). This study evaluated a common variant (CV) in the human TAAR1 gene, synonymous single nucleotide polymorphism (SNP) V288V, to determine the involvement of TAAR1 in MA dependence. METHODS: Participants (n = 106) with active MA dependence (MA-ACT), in remission from MA dependence (MA-REM), with active polysubstance dependence, in remission from polysubstance dependence, and with no history of substance dependence completed neuropsychiatric symptom questionnaires and provided blood samples. In vitro expression and function of CV and wild type TAAR1 receptors were also measured. RESULTS: The V288V polymorphism demonstrated a 40% increase in TAAR1 protein expression in cell culture, but message sequence and protein function were unchanged, suggesting an increase in translation efficiency. Principal components analysis resolved neuropsychiatric symptoms into four components, PC1 (depression, anxiety, memory, and fatigue), PC2 (pain), PC3 (drug and alcohol craving), and PC4 (sleep disturbances). Analyses of study group and TAAR1 genotype revealed a significant interaction for PC3 (craving response) (p = 0.003). The control group showed no difference in PC3 associated with TAAR1, while adjusted mean craving for the MA-ACT and MA-REM groups, among those with at least one copy of V288V, was estimated to be, respectively, 1.55 (p = 0.036) and 1.77 (p = 0.071) times the adjusted mean craving for those without the TAAR1 SNP. CONCLUSIONS: Neuroadaptation to chronic MA use may be altered by TAAR1 genotype and result in increased dopamine signaling and craving in individuals with the V288V genotype.

Neuroinflammation in addiction: A review of neuroimaging studies and potential immunotherapies.

Addiction is a worldwide public health problem and this article reviews scientific advances in identifying the role of neuroinflammation in the genesis, maintenance, and treatment of substance use disorders. With an emphasis on neuroimaging techniques, this review examines human studies of addiction using positron emission tomography to identify binding of translocator protein (TSPO), which is upregulated in reactive glial cells and activated microglia during pathological states. High TSPO levels have been shown in methamphetamine use but exhibits variable patterns in cocaine use. Alcohol and nicotine use, however, are associated with lower TSPO levels. We discuss how mechanistic differences at the neurotransmitter and circuit level in the neural effects of these agents and subsequent immune response may explain these observations. Finally, we review the potential of anti-inflammatory drugs, including ibudilast, minocycline, and pioglitazone, to ameliorate the behavioral and cognitive consequences of addiction.

Functional MRI and delay discounting in patients infected with hepatitis C.

Hepatitis C virus-infected (HCV+) adults evidence increased rates of psychiatric and cognitive difficulties. This is the first study to use functional magnetic resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. To determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit differences in brain activation during a delay discounting task (DDT), a measure of one's tendency to choose smaller immediate rewards over larger delayed rewards-one aspect of impulsivity. Twenty adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. Mixed effects regression analyses of hard versus easy trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less activation in the left lateral occipital gyrus, precuneus, and superior frontal gyrus. There were also significant interactive effects for hard-easy contrasts in the bilateral medial frontal gyrus, left insula, left precuneus, left inferior parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a positive relationship between impulsivity and activation, while the HCV+ group exhibited a negative relationship. Within the HCV+ group, those with high viral load chose immediate rewards more often than those with low viral load, regardless of choice difficulty; those with low viral load chose immediate rewards more often on hard choices relative to easy choices. Results show that HCV+ patients exhibit greater impulsive behavior when presented with difficult choices, and impulsivity is negatively related to activation in regions important for cognitive control. Thus, interventions that decrease impulsive choice may be warranted with some HCV+ patients.

The relationship between interleukin-6 and functional connectivity in methamphetamine users.

Methamphetamine (MA) causes an increase in pro-inflammatory cytokines in animal models and in humans. Resulting activation of microglia and neuro-inflammation could, via effects on reward networks, mediate behavioral characteristics of addiction. We examined the relationship between interleukin-6 (IL-6) and corticolimbic and striatolimbic resting-state functional connectivity (RSFC). Thirty adults diagnosed with MA dependence and 20 control subjects underwent a resting-state functional magnetic resonance imaging (fMRI) scan and gave a blood sample for determination of plasma IL-6 levels. Seed-based RSFC analyses were performed to examine the interactive effect of group and IL-6 on ventral striatal and prefrontal connectivity. Within the MA group, IL-6 levels were positively related to striatolimbic RSFC but negatively related to corticostriatal RSFC. Our findings with IL-6 support the idea that inflammation may at least partly mediate the link among MA use disorder, RSFC, and behavior, possibly via effects on mesolimbic and mesocortical dopaminergic systems.

Sensory sensitivity in operation enduring freedom/operation Iraqi freedom veterans with and without blast exposure and mild traumatic brain injury.

To examine factors associated with noise and light sensitivity among returning Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with a self-reported history of mild traumatic brain injury (mTBI) due to blast exposure, we compared the self-report of noise and light sensitivity of 42 OEF/OIF Veterans diagnosed with mTBI resulting from combat blast-exposure to that of 36 blast-exposed OEF/OIF Veterans without a history of mTBI. Results suggest a statistically significant difference between Veterans with and without a history of mTBI in the experience of noise and light sensitivity, with sensory symptoms reported most frequently in the mTBI group. The difference remains significant even after controlling for symptoms of PTSD, depression, and somatization. These data suggest that while psychological distress is significantly associated with the complaints of noise and light sensitivity, it may not fully account for the experience of sensory sensitivity in a population with mTBI history.

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.

Mental Health Does Not Moderate Compensatory Cognitive Training Efficacy for Veterans With a History of Mild Traumatic Brain Injury.

OBJECTIVE: To examine the potential moderating effects of mental health symptoms on the efficacy of compensatory cognitive training (CCT) for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans with a history of mild traumatic brain injury (mTBI). DESIGN: Secondary analysis of a randomized controlled trial of CCT. Posttraumatic stress disorder, depression, and substance dependence symptom severity were examined as potential moderators of CCT efficacy for subjective cognitive complaints, use of cognitive strategies, and objective neurocognitive performance. SETTING: Three Veterans Affairs medical centers. PARTICIPANTS: Participants included veterans with history of mTBI (N=119): 50 participated in CCT and 69 received usual care (UC). INTERVENTION: CCT is a 10-week group-based (90 minutes per session) manualized cognitive rehabilitation intervention. MAIN OUTCOME MEASURES: Objective (neuropsychological functioning) and subjective (self-report) cognitive functioning and use of cognitive strategies. RESULTS: Baseline mental health symptoms did not moderate CCT efficacy: veterans who received CCT reported significantly greater improvement in cognitive difficulties and use of cognitive strategies compared with the UC group, regardless of baseline mental health symptom severity. The CCT group also demonstrated significant improvements on neuropsychological measures of attention, learning, and executive functioning compared with the UC group, regardless of baseline mental health symptom severity. CONCLUSIONS: CCT is efficacious for improving objective cognitive functioning and compensatory strategy use for veterans with a history of mTBI, regardless of the severity of comorbid psychiatric symptoms.

Compensatory Cognitive Training for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans With Mild Traumatic Brain Injury.

OBJECTIVE: The purpose of the study was to evaluate the efficacy of group-based compensatory cognitive training (CCT) for Operation Enduring Freedom (OEF)/Operation Iraqi Freedom(OIF)/Operation New Dawn (OND) Veterans with a history of mild traumatic brain injury. METHOD: One hundred nineteen OEF/OIF/OND Veterans with history of mild traumatic brain injury participated at 3 sites, and 50 of the Veterans were randomized to CCT group, while 69 Veterans were randomized to the usual care control group. The CCT group participated in 10 weeks of CCT. Both CCT and usual care groups were assessed at baseline, 5 weeks (midway through CCT), 10 weeks (immediately following CCT), and 15 weeks (5-week follow-up) on measures of subjective cognitive complaints, use of cognitive strategies, psychological functioning, and objective cognitive performance. RESULTS: Veterans who participated in CCT reported significantly fewer cognitive and memory difficulties and greater use of cognitive strategies. They also demonstrated significant improvements on neurocognitive tests of attention, learning, and executive functioning, which were 3 of the cognitive domains targeted in CCT. CONCLUSIONS: Findings indicate that training in compensatory cognitive strategies facilitates behavioral change (ie, use of cognitive strategies) as well as both subjective and objective improvements in targeted cognitive domains.

Parallel Effects of Methamphetamine on Anxiety and CCL3 in Humans and a Genetic Mouse Model of High Methamphetamine Intake.

BACKGROUND: Methamphetamine (MA) abuse causes immune dysfunction and neuropsychiatric impairment. The mechanisms underlying these deficits remain unidentified. METHODS: The effects of MA on anxiety-like behavior and immune function were investigated in mice selectively bred to voluntarily consume high amounts of MA [i.e., MA high drinking (MAHDR) mice]. MA (or saline) was administered to mice using a chronic (14-day), binge-like model. Performance in the elevated zero maze (EZM) was determined 5 days after the last MA dose to examine anxiety-like behavior. Cytokine and chemokine expressions were measured in the hippocampus using quantitative polymerase chain reaction (qPCR). Human studies were also conducted to evaluate symptoms of anxiety using the General Anxiety Disorder-7 Scale in adults with and without a history of MA dependence. Plasma samples collected from human research participants were used for confirmatory analysis of murine qPCR results using an enzyme-linked immunosorbent assay. RESULTS: During early remission from MA, MAHDR mice exhibited increased anxiety-like behavior on the EZM and reduced expression of chemokine (C-C motif) ligand 3 (ccl3) in the hippocampus relative to saline-treated mice. Human adults actively dependent on MA and those in early remission had elevated symptoms of anxiety as well as reductions in plasma levels of CCL3, relative to adults with no history of MA abuse. CONCLUSIONS: The results highlight the complex effects of MA on immune and behavioral function and suggest that alterations in CCL3 signaling may contribute to the mood impairments observed during remission from MA addiction.

Everyday problems with executive dysfunction and impulsivity in adults recovering from methamphetamine addiction.

OBJECTIVES: Compared with non-addicted controls (CTLs), adults in remission from methamphetamine addiction (MA-REM) evidence impairments on objective measures of executive functioning and impulsivity. METHODS: To evaluate the impact of these impairments in MA-REM adults, demographically matched groups (MA-REM, n=30; CTLs, n=24) completed objective and self-report measures of executive functioning and impulsivity. RESULTS: MA-REM adults demonstrated significantly (p < 0.050) greater objective and subjective problems with executive functioning and impulsivity. CONCLUSIONS: These results suggest that adults in MA-REM are aware of their deficits and that these deficits have significant impact in everyday life.

Comparing the Neuropsychological Test Performance of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with and without Blast Exposure, Mild Traumatic Brain Injury, and Posttraumatic Stress Symptoms.

To compare neuropsychological test performance of Veterans with and without mild traumatic brain injury (MTBI), blast exposure, and posttraumatic stress disorder (PTSD) symptoms. We compared the neuropsychological test performance of 49 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans diagnosed with MTBI resulting from combat blast-exposure to that of 20 blast-exposed OEF/OIF Veterans without history of MTBI, 23 OEF/OIF Veterans with no blast exposure or MTBI history, and 40 matched civilian controls. Comparison of neuropsychological test performance across all four participant groups showed a complex pattern of mixed significant and mostly nonsignificant results, with omnibus tests significant for measures of attention, spatial abilities, and executive function. The most consistent pattern was the absence of significant differences between blast-exposed Veterans with MTBI history and blast-exposed Veterans without MTBI history. When blast-exposed Veteran groups with and without MTBI history were aggregated and compared to non-blast-exposed Veterans, there were significant differences for some measures of learning and memory, spatial abilities, and executive function. However, covariation for severity of PTSD symptoms eliminated all significant omnibus neuropsychological differences between Veteran groups. Our results suggest that, although some mild neurocognitive effects were associated with blast exposure, these neurocognitive effects might be better explained by PTSD symptom severity rather than blast exposure or MTBI history alone.

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.

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.