A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety.

Studies of the association between polymorphisms of the serotonin transporter gene (5-HTT) and trait anxiety have produced inconsistent results, raising questions about the strength of the relationship and the methodological conditions under which the relationship holds. We conducted a meta-analysis of existing studies to provide formal statistical measures of the strength of the linked polymorphic region of the serotonin transporter gene (5-HTTLPR)-anxiety relationship. For the entire collection of 26 studies, results provided no support for a relationship between anxiety and the presence of the short form of the 5-HTTLPR polymorphism. There was strong evidence of the presence of moderating variables, however, and subsequent analysis revealed that choice of the measure of trait anxiety was significant. Studies using the Neuroticism scale of Costa and McCrae were found to produce a small positive effect (d=0.23). Other potential moderators (country of study origin, type of subject) did not have a meaningful impact on d statistics. These findings indicate that 5-HTTLPR may in fact have a small but reliable influence on personality, particularly in the manifestation of trait anxiety when measured with a neuroticism scale based on the five-factor model of personality. Our results suggest that the success of future personality genetics research will be maximized by the use of personality measures from both the psychobiological and five-factor models.

DRD4 and novelty seeking: results of meta-analyses.

Studies of the association between polymorphisms within and near the dopamine D4 receptor (DRD4) gene and novelty seeking (NS) have produced inconsistent results, raising questions about the strength of the relationship and the methodological conditions under which the relationship holds. We conducted three meta-analyses of existing studies to provide formal statistical measures of the strength of the DRD4-NS relationship. Results provided no support for a relationship between NS and the presence of the 7-repeat allele of the VNTR polymorphism. A small positive effect, however, was found for long repeats of the same polymorphism. The most promising findings were obtained for the relationship with the -521 C/T promoter polymorphism, for which the analysis showed an effect size of 0.32. The positive findings are consistent with a polygenic model of influence on fundamental personality dimensions.

A functional polymorphism within the mu-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 mu-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.

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.

Differential episodic and semantic memory performance in Alzheimer's disease and vascular dementias.

Differential performance on measures of episodic and semantic memory were examined in AD, cortical vascular dementia (CVaD), subcortica] vascular dementia (SVaD), and controls. Groups were matched on age, education, and gender; dementia groups also were matched on severity. Recognition/retrieval differences were found only between SVaD and AD groups, not between CVaD and AD. Thus, recognition/retrieval differences are likely secondary to subcortical pathology rather than to vascular etiology per se. Similarly, significant numbers of memory errors were associated with cortical pathology, regardless of etiology. Error rate differences were found only between SVaD and AD groups, not between CVaD and AD. Finally, rapid forgetting was unique to AD; however, since no difference was found between SVaD and AD, rapid forgetting may occur only as AD progresses. No semantic memory measure differentiated AD from either CVaD or SVaD subjects. Results suggest that some previously reported episodic differences may be due to cortical versus white matter subcortical pathology, rather than to AD versus vascular etiology.

Material-specific memory in traumatic brain injury: differential effects during acquisition, recall, and retention.

Material-specific memory refers to the ability to learn and recall new episodic information on the basis of the nature of the stimulus material (e.g., verbal vs. nonverbal-visuospatial). Structural equation modeling was used to analyze data from a sample of patients with traumatic brain injury to compare 3 models of memory functioning: material-specific, material-specific plus general, and general (non-material-specific). The models were examined separately for acquisition, delayed free recall, and retention aspects of memory. Results suggest that, at least in a population with traumatic brain injury, the acquisition of new information takes place in a material-specific memory fashion, delayed free recall involves both material-specific and general (non-material-specific) memory components, but retention relies primarily on general (non-material-specific) memory processes.

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 Alzheimer's 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.

A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease.

OBJECTIVE: To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD. DESIGN: A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls. RESULTS: The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE epsilon4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset. CONCLUSION: The reduced or absent risk for AD conferred by APOE in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author's dataset the opposite effects of APOE and CST3 genotype on risk for AD with increasing age suggest that CST3 is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.

The genetic association between Cathepsin D and Alzheimer's disease.

The aspartyl protease Cathepsin D has previously been suggested to play a role in the Alzheimer's disease (AD) process because of its ability to cleave the beta-amyloid precursor protein and the possibility that it may be one of the 'secretase' enzymes. A functional C-->T polymorphism in the Cathepsin D gene (CATD) has been reported to be associated with increased risk for AD in Caucasian case-control studies; specifically, the T-carrying genotypes confer increased risk. We have examined this association in our own Caucasian dataset of 210 AD cases and 120 controls, and in an additional Hispanic dataset comprising 79 AD cases and 112 controls. In Hispanics we find a modest interaction between CATD genotype and age of onset on risk for AD, such that the non-T-carrying genotype confers increased risk. In our Caucasian dataset we find no evidence for association between the CATD polymorphism and AD, although we do observe a small tendency towards an increase in the T-carrying genotypes in the case group, consistent with previous studies. We conducted an aggregate analysis of the published Caucasian datasets and found evidence that this CATD polymorphism (or another locus in linkage disequilibrium) does contribute significant, but small (<2%) risk for AD.

A taxometric analysis of MMPI-2 Infrequency scales [F and F(p)] in clinical settings.

The typology of overreporting, which is a deliberate attempt to amplify symptoms, simulate psychopathology, or understate coping capacities, was examined using taxometric procedures with Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Infrequency scales [F and F(p)] in psychiatric inpatient and Veterans Affairs (VA) medical center treatment settings. Overreporting was identified as a taxon using several taxometric procedures, and the multiple estimates of the taxon base rate were consistent within each sample. Mean base-rate estimates were .27 and .19 for the psychiatric inpatient and VA medical center settings, respectively. Overall classification rates ranged from .80 to .97 across the 2 settings, which supports the use of F and F(p) in the identification of overreporting on the MMPI-2 in psychiatric inpatient and VA medical center settings.

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 Alzheimer's 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.

Utilization and outcome in an overnight psychiatric observation program at a Veterans Affairs Medical Center.

OBJECTIVE: The effectiveness of an overnight psychiatric observation program was evaluated. The program was designed to avoid unnecessary hospitalization of patients experiencing acute psychiatric crises. METHODS: Of 110 patients admitted to the observation unit at a Veterans Affairs medical center over a six-month period in 1996, the charts of 92 patients were retrospectively reviewed. Characteristics of patients referred to the program were documented, inpatient hospitalization rates and suicide rates in the six-month periods before and after admission to the observation unit were examined, and variables related to the need for hospitalization immediately after observation were explored. RESULTS: Most of the 92 patients (98 percent) were referred from the medical center's emergency room. At the time of observation, 80 percent of the patients were unemployed, 55 percent expressed suicidal or homicidal ideation, 49 percent were intoxicated or at risk for alcohol withdrawal, and 41 percent were homeless. The most frequent psychiatric diagnosis was substance abuse or dependence (77 percent). The large majority of patients (88 percent) were referred the next day to other outpatient programs for follow-up and treatment, which avoided costly inpatient treatment. In the six months before admission to the observation program, the mean number of inpatient psychiatric bed days was 9.8, compared with 2.7 days in the six-month period after discharge from the observation program. No increase in suicide gestures or attempts was noted among the patients. No variables significantly predicted admission to inpatient care after the observation period. CONCLUSIONS: Overnight observation programs may provide a cost-effective alternative to traditional inpatient treatment for some individuals with psychiatric disorders.

The opioid receptor system and alcoholism: a genetic perspective.

Over the past decade, mounting evidence has implicated the endogenous opioid receptor system as a central player in the etiology of alcohol drinking behavior in animals and alcoholism in humans. Much of this work is a product of a pharmacological approach, where differences in opioid receptor pharmacology have been found to predict drinking behavior in animal models of alcoholism, including rats and mice selectively bred for alcohol preference and avoidance. This review considers the opioid receptor system and alcoholism from a genetic standpoint, and discusses investigation into opioid receptor pharmacology in animal models of alcoholism as work that paved the way for the more recent molecular genetic studies implicating the delta-, and particularly, the mu opioid receptors as genetically linked to alcoholism-associated phenotypes in animal models of the disease. These genetic studies are set within the broader context of the candidate gene approach for alcoholism, where opioid receptor genes are taken to be partial, rather than complete, risk factors for alcoholism. Building upon these findings, the recent genetic association between alcoholism and the mu opioid receptor gene in humans is discussed. Finally, the translation of such genetic association studies between opioid receptor genes and alcoholism to a pharmacogenetic approach, allowing for the evaluation of putative relationships between genotype and pharmacological response profiles, is suggested to address the etiological question of what the molecular mechanism is underlying opioid receptor genetic risk for alcoholism phenotypes.

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.

Association of a functional mu-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.

The alpha-2 macroglobulin gene is not associated with Alzheimer's disease in a case-control sample.

Genetic association has recently been reported between alleles in the alpha-2-macroglobulin (A2M) gene and the occurrence of Alzheimer's disease (AD) in familial and sporadic samples. We have investigated the A2M intronic deletion polymorphism in a case-control study of 295 unrelated clinic and community-based AD cases, and compared these to a sample of 113 unrelated control individuals recruited as part of an epidemiological study. Our results show no association between A2M and AD in either case sample. Furthermore, A2M is not predictive of AD in an interactive fashion when considering APOE, race or gender. In a subset of our larger sample we have also investigated the A2M Val1000lle polymorphism, and again find no evidence for association. We conclude that there is no genetic association between A2M and AD in our case-control sample.

Changes in personality characteristics in women treated in a therapeutic community.

We examined changes in mood and personality characteristics in a sample of cocaine-dependent women being treated in a therapeutic community (TC). Forty-six women completed the Beck Depression Inventory (BDI), the Hamilton Anxiety Scale (HAM-A), and the Millon Clinical Multiaxial Inventory-II (MCMI-II) on admission and 12 months after discharge from the TC. On admission, the group was characterized by clinically significant scores on the BDI, HAM-A, and the MCMI-II Avoidant, Dependent, Antisocial, Passive-aggressive, Self-defeating, and Borderline scales. On follow-up, significant improvement in functioning was suggested by decreases in scale scores on the BDI, HAM-A, and MCMI-II Avoidant, Dependent, Self-Defeating, and Borderline Scales, but not for the MCMI-II Antisocial and Passive-Aggressive scales. These results suggest substantial positive effects of TC treatment on personality characteristics and functioning, but also indicate that TC treatment may not habilitate all critical personality deficits.