April D. Thames

Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: A meta-analysis

BACKGROUND Neurocognitive functioning in schizophrenia has received considerable attention because of its robust prediction of functional outcome. Psychiatric symptoms, in particular negative symptoms, have also been shown to predict functional outcome, but have garnered much less attention. The high degree of intercorrelation among all of these variables leaves unclear whether neurocognition has a direct effect on functional outcome or whether that relationship to functional outcome is partially mediated by symptoms. METHODS A meta-analysis of 73 published English language studies (total n=6519) was conducted to determine the magnitude of the relationship between neurocognition and symptoms, and between symptoms and functional outcome. A model was tested in which symptoms mediate the relationship between neurocognition and functional outcome. Functional outcome involved measures of social relationships, school and work functioning, and laboratory assessments of social skill. RESULTS Although negative symptoms were found to be significantly related to neurocognitive functioning (p<.01) positive symptoms were not (p=.97). The relationship was moderate for negative symptoms (r=-.24, n=4757, 53 studies), but positive symptoms were not at all related to neurocogniton (r=.00, n=1297, 25 studies). Negative symptoms were significantly correlated with functional outcome (r=-.42, p<.01), and again the correlation was higher than for positive symptoms (r=-.03, p=.55). Furthermore, our findings support a model in which negative symptoms significantly mediate the relationship between neurocognition and functional outcome (Sobel test p<.01). CONCLUSIONS Although neurocognition and negative symptoms are both predictors of functional outcome, negative symptoms might at least partially mediate the relationship between neurocognition and outcome.

Medication and finance management among HIV-infected adults: The impact of age and cognition

This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report.

Disorganization and Reality Distortion in Schizophrenia: A Meta-Analysis of the Relationship between Positive Symptoms and Neurocognitive Deficits

BACKGROUND Factor analytic studies have shown that in schizophrenia patients, disorganization (e.g., conceptual disorganization and bizarre behavior) is a separate dimension from other types of positive symptoms such as reality distortion (delusions and hallucinations). Although some studies have found that disorganization is more strongly linked to neurocognitive deficits and poor functional outcomes than reality distortion, the findings are not always consistent. METHODS A meta-analysis of 104 studies (combined n=8015) was conducted to determine the magnitude of the relationship between neurocognition and disorganization as compared to reality distortion. Additional analyses were conducted to determine whether the strength of these relationships differed depending on the neurocognitive domain under investigation. RESULTS The relationship between reality distortion and neurocognition was weak (r=-.04; p=.03) as compared to the moderate association between disorganization and neurocognition (r=-.23; p<.01). In each of the six neurocognitive domains that were examined, disorganization was more strongly related to neurocognition (rs range from -.20 to -.26) than to reality distortion (rs range from .01 to -.12). CONCLUSIONS The effect size of the relationship between neurocognition and disorganization was significantly larger than the effect size of the relationship between neurocognition and reality distortion. These results hold across several neurocognitive domains. These findings support a dimensional view of positive symptoms distinguishing disorganization from reality distortion.

Longitudinal Change in Cognitive Function and Medication Adherence in HIV-Infected Adults

Neuropsychological (NP) dysfunction has been linked to poor medication adherence among HIV-infected adults. However, there is a dearth of research examining longitudinal changes in the relationship between NP status and adherence rates. We hypothesized that declines in NP functioning would be associated with a corresponding decline in medication adherence while stable NP functioning would be associated with stable or improving adherence rates. Participants included 215 HIV-infected adults who underwent cognitive testing at study entry and six months later. Compared to the NP stable group, the NP decline group showed a greater drop in adherence rates. Further analysis revealed that, beyond global NP, learning and memory was significantly associated with changes in adherence rates. These findings further support the link between cognitive functioning and medication adherence and illustrates the importance of documenting changes in cognitive abilities for identifying individuals at risk for poor adherence.

Neurocognitive functioning in HIV-1 infection: effects of cerebrovascular risk factors and age

This study examined the interactive effects of cerebrovascular risks, advancing age, and HIV infection on neurocognition, and explored whether pharmacological treatment of cerebrovascular risk factors attenuated neurocognitive dysfunction. Participants included 98 HIV-seropositive adults (cerebrovascular risk: 23.5%; age > 50: 27.6%). Cerebrovascular risk was associated with slower processing speed even after controlling for age effects (b = −2.071; p =.04), and the interaction of age and cerebrovascular risk was associated with poorer verbal fluency (b = 1.276, p =.002). Participants with pharmacologically untreated cerebrovascular risk demonstrated reduced processing speed, learning/memory, and executive functioning relative to those on medication. Poor cerebrovascular health confers significant risk for HIV+ individuals, and this effect may be of greater consequence than advancing age. The cognitive impact of risk appears to be more pronounced in the absence of adequate pharmacological treatment.

Depression, Cognition, and Self-Appraisal of Functional Abilities in HIV: An Examination of Subjective Appraisal Versus Objective Performance

Depression frequently co-occurs with HIV infection and can result in self-reported overestimates of cognitive deficits. Conversely, genuine cognitive dysfunction can lead to an under-appreciation of cognitive deficits. The degree to which depression and cognition influence self-report of capacity for instrumental activities of daily living (IADLs) requires further investigation. This study examined the effects of depression and cognitive deficits on self-appraisal of functional competence among 107 HIV-infected adults. As hypothesized, higher levels of depression were found among those who over-reported problems in medication management, driving, and cognition when compared to those who under-reported or provided accurate self-assessments. In contrast, genuine cognitive dysfunction was predictive of under-reporting of functional deficits. Together, these results suggest that over-reliance on self-reported functional status poses risk for error when diagnoses require documentation of both cognitive impairment and associated functional disability in everyday life.

Differential predictors of medication adherence in HIV: findings from a sample of African American and Caucasian HIV-positive drug-using adults.

Modest or even occasional nonadherence to combined antiretroviral therapy (cART) can result in adverse clinical outcomes. African Americans demonstrate lower rates of adherence than Caucasians or Latinos. Identifying factors that influence medication adherence among African Americans is a critical step toward reducing HIV/AIDS disease progression and mortality. In a sample of 181 African American (n=144) and Caucasian (n=37) HIV-positive drug-using individuals [age (M=42.31; SD=6.6) education (M=13.41; SD=2.1)], we examined the influence of baseline drug use, literacy, neurocognition, depression, treatment-specific social support, and patient satisfaction with health care provider on medication adherence averaged over the course of 6 months (study dates 2002-2006). Our findings suggest differential baseline predictors of medication adherence for African Americans and Caucasians, such that patient satisfaction with provider was the strongest predictor of follow-up medication adherence for African Americans whereas for Caucasians depressive symptoms and treatment-specific social support were predictive of medication adherence (after controlling for duration of drug use).

Effects of Stereotype Threat, Perceived Discrimination, and Examiner Race on Neuropsychological Performance: Simple as Black and White?

The purpose of the current study was to examine the predictive roles of stereotype threat and perceived discrimination and the mediating role of examiner-examinee racial discordance on neuropsychological performance in a non-clinical sample of African American and Caucasian individuals. Ninety-two African American (n = 45) and Caucasian (n = 47) adults were randomly assigned to either a stereotype threat or non-threat condition. Within each condition, participants were randomly assigned to either a same race or different race examiner. All participants underwent neuropsychological testing and completed a measure of perceived discrimination. African Americans in the stereotype threat condition performed significantly worse on global NP (Mz = -.30, 95% confidence interval [CI] [-0.07, -0.67] than African Americans in the non-threat condition (Mz = 0.09, CI [0.15, 0.33]. African Americans who reported high levels of perceived discrimination performed significantly worse on memory tests when tested by an examiner of a different race, Mz = -1.19, 95% CI [-1.78, -.54], than African Americans who were tested by an examiner of the same race, Mz = 0.24, 95% CI [-0.24, 0.72]. The current study underscores the importance of considering the role of contextual variables in neuropsychological performance, as these variables may obscure the validity of results among certain racial/ethnic groups.

Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C

Objective: This study examined neurologic abnormalities (as measured by proton magnetic resonance spectroscopy imaging and diffusion tensor imaging), neurocognitive performance, and fatigue among a sample of adults with hepatitis C virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural brain abnormalities and neurocognitive compromise consistent with frontostriatal dysfunction as well as increased fatigue compared to controls. Method: Participants were 76 individuals diagnosed with HCV and 20 controls who underwent a comprehensive neurocognitive evaluation and clinical assessments. A subset of the HCV+ participants (n = 29) and all controls underwent MRI. Results: Individuals diagnosed with chronic HCV infection demonstrated greater fractional anisotropy in the striatum as well as greater mean diffusivity in the fronto-occiptal fasciculus and external capsule compared to HCV− controls. HCV+ participants also demonstrated lower levels of N-acetylaspartate in bilateral parietal white matter and elevations in myo-inosital (mI) in bilateral frontal white matter compared to HCV− controls (all p values < 0.05). HCV+ participants also demonstrated significantly poorer neuropsychological performance, particularly in processing speed and verbal fluency. HCV+ patients reported higher levels of fatigue than controls, and fatigue was significantly correlated with diffusivity in the superior fronto-occipital fasciculus, elevations in mI in frontal white matter, and overall cognitive performance. Conclusions: Our results suggest that HCV-associated neurologic complications disrupt frontostriatal structures, which may result in increased fatigue and poorer cognitive performance, particularly in those cognitive domains regulated by frontostriatal regions.

Ebola: translational science considerations

We are currently in the midst of the most aggressive and fulminating outbreak of Ebola-related disease, commonly referred to as “Ebola”, ever recorded. In less than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over 10,000 people, indiscriminately of gender or age, with a fatality rate of about 50%. Whereas at its onset this Ebola outbreak was limited to three countries in West Africa (Guinea, where it was first reported in late March 2014, Liberia, where it has been most rampant in its capital city, Monrovia and other metropolitan cities, and Sierra Leone), cases were later reported in Nigeria, Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US (i.e., Dallas, Texas; New York City) by late October 2014. World and US health agencies declared that the current Ebola virus disease (EVD) outbreak has a strong likelihood of growing exponentially across the world before an effective vaccine, treatment or cure can be developed, tested, validated and distributed widely. In the meantime, the spread of the disease may rapidly evolve from an epidemics to a full-blown pandemic. The scientific and healthcare communities actively research and define an emerging kaleidoscope of knowledge about critical translational research parameters, including the virology of EBOV, the molecular biomarkers of the pathological manifestations of EVD, putative central nervous system involvement in EVD, and the cellular immune surveillance to EBOV, patient-centered anthropological and societal parameters of EVD, as well as translational effectiveness about novel putative patient-targeted vaccine and pharmaceutical interventions, which hold strong promise, if not hope, to curb this and future Ebola outbreaks. This work reviews and discusses the principal known facts about EBOV and EVD, and certain among the most interesting ongoing or future avenues of research in the field, including vaccination programs for the wild animal vectors of the virus and the disease from global translational science perspective.