Publications (60) View all
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Article: Persistent infection with neurotropic herpes viruses and cognitive impairment.
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ABSTRACT: BACKGROUND: Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n=1852). Method Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens. RESULTS: PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 × 10-5 and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (β = -0.25, p = 7.28 × 10-10). There were no significant interactions between exposure and group status. CONCLUSIONS: Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status.Psychological Medicine 09/2012; · 6.16 Impact Factor -
Article: Heritability of functioning in families with schizophrenia in relation to neurocognition.
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ABSTRACT: The role of daily functioning is an integral part of the schizophrenia (SZ) phenotype and deficits in this trait appear to be present in both affected persons and some unaffected relatives; hence we have examined its heritability in our cohort of African American schizophrenia families. There is now ample evidence that deficits in cognitive function can impact family members who are not themselves diagnosed with SZ; there is some, but less evidence that role function behaves likewise. We evaluate whether role function tends to "run in families" who were ascertained because they contain an African American proband diagnosed with SZ. We analyzed heritability for selected traits related to daily function, employment, living situation, marital status, and Global Assessment Scale (GAS) score; modeling age, gender, along with neurocognition and diagnosis as covariates in a family based African-American sample (N=2488 individuals including 979 probands). Measures of role function were heritable in models including neurocognitive domains and factor analytically derived neurocognitive summary scores and demographics as covariates; the most heritable estimate was obtained from the current GAS scores (h2=0.72). Neurocognition was not a significant contributor to heritability of role function. Commonly assessed demographic and clinical indicators of functioning are heritable with a global rating of functioning being the most heritable. Measures of neurocognition had little impact on heritability of functioning overall. The family covariance for functioning, reflected in its heritability, supports the concept that interventions at the family level, such as evidenced-based family psychoeducation may be beneficial in schizophrenia.Biological Psychiatry 05/2012; 139(1-3):105-9. · 8.28 Impact Factor -
Article: An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis.
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ABSTRACT: While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3',5'-monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants. Birhinal assessments of odor-detection threshold sensitivity to lyral and citralva were acquired in youths experiencing prodromal symptoms (n=17) and controls at low risk for developing psychosis (n=15). Citralva and lyral are odorants that differ in cAMP activation; citralva is a strong cAMP activator and lyral is a weak cAMP activator. The overall group-by-odor interaction was statistically significant. At-risk youths showed significantly reduced odor detection thresholds for lyral, but showed intact detection thresholds for citralva. This odor-specific threshold deficit was uncorrelated with deficits in odor identification or discrimination, which were also present. ROC curve analysis revealed that olfactory performance correctly classified at-risk and low-risk youths with greater than 97% accuracy. This study extends prior findings of an odor-specific hyposmia implicating cAMP-mediated signal transduction in schizophrenia and unaffected first-degree relatives to include youths at clinical risk for developing the disorder. These results suggest that dysregulation of cAMP signaling may be present during the psychosis prodrome.Biological Psychiatry 04/2012; 138(2-3):280-4. · 8.28 Impact Factor -
Article: Being right is its own reward: load and performance related ventral striatum activation to correct responses during a working memory task in youth.
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ABSTRACT: The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. Intrinsically motivated subjects performing challenging cognitive tasks engage reinforcement circuitry including VS even in the absence of external feedback or incentives. However, little is known about how such VS responses develop with age, relate to task performance, and are influenced by task difficulty. Here we used fMRI to examine VS activation to correct and incorrect responses during a standard n-back working memory task in a large sample (n=304) of healthy children, adolescents and young adults aged 8-22. We found that bilateral VS activates more strongly to correct than incorrect responses, and that the VS response scales with the difficulty of the working memory task. Furthermore, VS response was correlated with discrimination performance during the task, and the magnitude of VS response peaked in mid-adolescence. These findings provide evidence for scalable intrinsic reinforcement signals during standard cognitive tasks, and suggest a novel link between motivation and cognition during adolescent development.NeuroImage 03/2012; 61(3):723-9. · 5.89 Impact Factor -
Article: Age group and sex differences in performance on a computerized neurocognitive battery in children age 8−21.
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ABSTRACT: Objective: Examine age group effects and sex differences by applying a comprehensive computerized battery of identical behavioral measures linked to brain systems in youths that were already genotyped. Such information is needed to incorporate behavioral data as neuropsychological “biomarkers” in large-scale genomic studies. Method: We developed and applied a brief computerized neurocognitive battery that provides measures of performance accuracy and response time for executive-control, episodic memory, complex cognition, social cognition, and sensorimotor speed domains. We tested a population-based sample of 3,500 genotyped youths ages 8–21 years. Results: Substantial improvement with age occurred for both accuracy and speed, but the rates varied by domain. The most pronounced improvement was noted in executive control functions, specifically attention, and in motor speed, with some effect sizes exceeding 1.8 standard deviation units. The least pronounced age group effect was in memory, where only face memory showed a large effect size on improved accuracy. Sex differences had much smaller effect sizes but were evident, with females outperforming males on attention, word and face memory, reasoning speed, and all social cognition tests and males outperforming females in spatial processing and sensorimotor and motor speed. These sex differences in most domains were seen already at the youngest age groups, and age group × sex interactions indicated divergence at the oldest groups with females becoming faster but less accurate than males. Conclusions: The results indicate that cognitive performance improves substantially in this age span, with large effect sizes that differ by domain. The more pronounced improvement for executive and reasoning domains than for memory suggests that memory capacities have reached their apex before age 8. Performance was sexually modulated and most sex differences were apparent by early adolescence. (PsycINFO Database Record (c) 2012 APA, all rights reserved)Neuropsychology 02/2012; 26(2):251-265. · 3.82 Impact Factor
