John A. Schinka

Association of a functional μ‐opioid receptor allele (+118A) with alcohol dependency

Genetic association studies have implicated the TaqI A1 allele of the human dopamine D2 receptor gene (DRD2) as a risk-determining factor for alcohol dependency. However, as alcoholism is a disease of polygenic inheritance, the percentage of overall disease variance explained by the TaqI A1 allele is small. In searching for other genetic loci that may, either alone or in combination with DRD2, enhance prediction of alcoholism, we have found a novel association between a functional coding variant (+118A) within the human mu-opioid receptor gene and alcohol dependency. However, no association was detected between the DRD2 TaqI A1 allele and alcoholism in our sample nor did we find synergy between +118A and TaqI A1 alleles on prediction of risk for the disease. These results suggest that, at the molecular level, the endogenous mu-opioid receptor system is a contributing factor to the etiology of alcoholism.

A functional polymorphism within the μ-opioid receptor gene and risk for abuse of alcohol and other substances

Genetic association studies investigating the role of the +118A allele of the human μ-opioid receptor gene in risk for alcohol dependency have produced inconsistent findings, possibly because of the failure to recognize sampling methodology difficulties inherent in association studies of polygenic disorders. We examined the frequency of the AA genotype and A allele in several groups of substance-dependent cases, unrestricted controls, and super controls screened for the use of alcohol and cigarettes. Our findings and analyses suggest that the OPRM1 +118 polymorphism is a general risk gene for substance dependence, but is not specific to a particular substance. The nature of the conferred risk is likely to be in use of multiple substances, but it is not yet determined if the risk could be expressed in severity of use of any particular substance. The contribution of the gene to risk for substance dependence is small, and is detected most easily in studies that use control samples that are screened for all forms of substance dependence.

Pre-MCI and MCI: neuropsychological, clinical, and imaging features and progression rates.

OBJECTIVE To compare clinical, imaging, and neuropsychological characteristics and longitudinal course of subjects with pre-mild cognitive impairment (pre-MCI), who exhibit features of MCI on clinical examination but lack impairment on neuropsychological examination, to subjects with no cognitive impairment (NCI), nonamnestic MCI (naMCI), amnestic MCI (aMCI), and mild dementia. METHODS For 369 subjects, clinical dementia rating sum of boxes (CDR-SB), ApoE genotyping, cardiovascular risk factors, parkinsonism (UPDRS) scores, structural brain MRIs, and neuropsychological testing were obtained at baseline, whereas 275 of these subjects received an annual follow-up for 2-3 years. RESULTS At baseline, pre-MCI subjects showed impairment on tests of executive function and language, higher apathy scores, and lower left hippocampal volumes (HPCV) in comparison to NCI subjects. Pre-MCI subjects showed less impairment on at least one memory measure, CDR-SB and UPDRS scores, in comparison to naMCI, aMCI and mild dementia subjects. Follow-up over 2-3 years showed 28.6% of pre-MCI subjects, but less than 5% of NCI subjects progressed to MCI or dementia. Progression rates to dementia were equivalent between naMCI (22.2%) and aMCI (34.5%) groups, but greater than for the pre-MCI group (2.4%). Progression to dementia was best predicted by the CDR-SB, a list learning and executive function test. CONCLUSION This study demonstrates that clinically defined pre-MCI has cognitive, functional, motor, behavioral and imaging features that are intermediate between NCI and MCI states at baseline. Pre-MCI subjects showed accelerated rates of progression to MCI as compared to NCI subjects, but slower rates of progression to dementia than MCI subjects.

Memory Patterns and Executive Functioning in Mild Cognitive Impairment and Alzheimer's Disease

The present study examined the similarities in the pattern of cognitive loss in Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI). We administered a battery of neuropsychological tests to individuals with these disorders as well as to a group of cognitively intact controls. The battery included measures of memory acquisition, consolidation, and retrieval, as well as tests of language, visuospatial ability, psychomotor speed, and executive functioning. All subjects (N =62) were evaluated in a memory disorder clinic and were diagnosed by a consensus procedure. Multivariate and univariate statistical methods were used to examine differences in level of performance on all neuropsychological tests and in the pattern of performance for memory measures. We found a significant difference between controls and the MCI and AD groups in terms of consolidation, but not in acquisition or retrieval. The MCI and AD groups did not differ in the pattern of memory processing. Also, the only non-memory neurocognitive domain in which MCI group differed significantly from the control group was executive functioning. Our findings suggest that the pattern of loss of memory function of MCI patients parallels that of AD patients. Also, our finding that executive functioning was the only other neurocognitive domain in which the control and MCI groups differed significantly is in contrast to traditional clinical lore that implicates language dysfunction and/or visuospatial deficits early in AD. These findings provide preliminary evidence that consolidation deficits and subtle declines in executive functioning may be the most useful cognitive markers for the early direction of AD.

Defining Mild Cognitive Impairment: Impact of Varying Decision Criteria on Neuropsychological Diagnostic Frequencies and Correlates

OBJECTIVE To examine the impact of varying decision criteria on neuropsychological diagnostic frequencies and on their correlates. DESIGN Descriptive and correlational study. SETTING Florida Alzheimers Disease Research Center. PARTICIPANTS A sample of 373 individuals with comprehensive baseline analyses participating in a longitudinal study of cognitive decline and early Alzheimer disease. MEASUREMENTS Mild cognitive impairment (MCI) diagnoses were made on the basis of four sets of decision criteria created by crossing two approaches: varying the number of impaired test results required for a diagnosis within any domain (1 test versus 2) and varying the performance level required to determine impairment (1.5 or 2 standard deviations [SDs] below the normative mean) for any test. RESULTS Under each criteria set, single-domain amnestic MCI was the most frequent MCI diagnosis. MCI global and subtype diagnosis frequencies were inversely related to the stringency of the criteria. The single test-1.5 SD criterion identified the largest number of cases as qualifying for an MCI diagnosis, and the two test-2.0 SD cutoff identified the fewest. Across all sets of criteria, the authors found significant positive associations between neuropsychological diagnoses and Clinical Dementia Rating score categories. Significant relationships between diagnoses and both apolipoprotein E (APOE) genotype and magnetic resonance imaging ratings of medial temporal atrophy (MTA) application were found only for the two test-1.5 SD and two test-2.0 SD cutoffs. CONCLUSION MCI diagnosis frequencies are substantively affected by the stringency of the criteria, but the relative rankings of MCI subtype diagnoses are fairly consistent regardless of the stringency of the criteria. Significant associations of neuropsychological diagnoses with independent markers such as APOE genotype and MTA are only found with more stringent criteria, suggesting that a coherent network of associations reflecting cognitive decline occurs with more restrictive definitions for impairment.

Research Validity Scales for the NEO-PI-R: Additional Evidence for Reliability and Validity

We examined the reliability and validity of the research validity scales (Schinka, Kinder, & Kremer, 1997) for the NEO-Personality Inventory-Revised (NEO-PI-R) in a clinical sample. The Negative Presentation Management (NPM) and Positive Presentation Management (PPM) scales were found to have satisfactory internal consistency reliability. Support for the validity of these scales was provided by the pattern of convergent and discriminant correlations with respective Personality Assessment Inventory (PAI) validity scales. Finally, PAI profiles of individuals with invalid NPM scores were found to differ significantly from those with valid NPM scores. Comparisons of the invalid profiles with profiles from other clinical samples provided additional support for the use of the NPM scale as a measure of negative impression management.

Person-Environment Congruence and Personality Domains in the Prediction of Job Performance and Work Quality.

This study examined the contributions of the 5-Factor Model (FFM; P. T. Costa & R. R. McCrae, 1992) and RIASEC (J. L. Holland, 1994) constructs of consistency, differentiation, and person-environment congruence in predicting job performance ratings in a large sample (N = 514) of employees. Hierarchical regression analyses conducted separately by gender indicated that the interaction of differentiation with Agreeableness and Conscientiousness explained statistically significant variance in work performance for men, and that the interaction of congruence with Agreeableness, Artistic, and Social subscales was statistically significantly related to work performance in women. Findings suggested that the most successful model of job performance prediction would be substantially more complex than simple RIASEC or FFM approaches, and would likely incorporate interactions with constructs of worker adjustment, person-environment fit, types of work environments, and gender.

Gender-specific association of the angiotensin converting enzyme gene with Alzheimer's disease

Epidemiological studies have demonstrated that risk factors for vascular disease are also risk factors for Alzheimers disease (AD). The gene for the angiotensin converting enzyme (ACE) has recently been reported to be associated with risk for AD. We have investigated the possibility of such an association in 98 clinic-based and 73 community-based AD cases versus 175 community-based controls and find a gender-specific association of ACE genotype with AD in the female clinic population. These data suggest that gender may interact with genetic factors to influence risk for AD. Gender-specific risk for AD has been previously reported, and a biological rationale for involvement of ACE in the AD process is supported by studies exploring the relationship between AD and vascular risk factors such as hypertension. However, the results may also be a consequence of the known anomalies that arise in genetic association studies as a consequence of sample selection.

Association between Alzheimer's disease and a functional polymorphism in the Myeloperoxidase gene

A polymorphism in the Myeloperoxidase gene (MPO) has previously been demonstrated to be associated with gender-specific risk in an Alzheimers Disease (AD) autopsy sample. We have investigated this polymorphism in our own samples of 226 Caucasian cases and 166 controls and 59 Hispanic cases and 75 controls. In Caucasians we find a significant association between MPO genotype and AD (P = 0.03), although we do not observe any effects of gender or any interaction with the APOE gene. Specifically, the MPO GG genotype contributes a 1.57-fold increased risk for AD. In Hispanics there was no effect of MPO genotype, or of MPO genotype in interaction with age or gender, on diagnosis of AD.

Elderly norms for the Hopkins Verbal Learning Test-Revised.

The present study evaluates the effects of age, education, and gender in a representative sample of older adults and provides normative data for community-dwelling elderly. Age and gender had significant effects on HVLT-R performance. We provide age- and gender-adjusted normative data. Surprisingly, education level did not affect HVLT-R performance, indicating that education-adjusted norms are not necessary for this measure within this age range. We evaluated a subsample of subjects census-matched on age, education, and gender. These subjects did not differ in overall performance from our entire sample. Therefore, the normative data provided in this paper can be considered to be census-comparable for age, education, and gender.