Measured Gene–Environment Interactions and Mechanisms Promoting Resilient Development

ABSTRACT— Childhood maltreatment elevates risk for antisocial behavior, depression, and other problems over the life span, but a subset of maltreated individuals avoids maladaptive development and shows resilience. Resilience reflects a dynamic confluence of factors that promotes positive adaptation despite exposure to adverse experiences. Recent replicated findings of gene–environment interactions (abbreviated G × E) involving maltreatment have identified two genes, monoamine oxidase A ( MAOA ) and serotonin transporter ( 5-HTT ), that moderate the association between childhood maltreatment and psychopathology. Accordingly, G × E raise new questions about potential biological mechanisms by which some individuals are able to cope adaptively and function relatively well despite experiencing early adversity. We summarize advances toward greater specification of G × E mechanisms, including genetic and environmental moderation of G × E effects and imaging genomics that provide clues regarding resilience processes in development.     

An evaluation of recollection and familiarity in Alzheimer’s disease and mild cognitive impairment using receiver operating characteristics

There is a need to investigate exactly how memory breaks down in the course of Alzheimer’s disease (AD). Examining what aspects of memorial processing remain relatively intact early in the disease process will allow us to develop behavioral interventions and possible drug therapies focused on these intact processes. Several recent studies have worked to understand the processes of recollection and familiarity in patients with mild cognitive impairment (MCI) and very mild AD. Although there is general agreement that these patient groups are relatively unable to use recollection to support veridical recognition decisions, there has been some question as to how well these patients can use familiarity. The current study used receiver operating characteristic (ROC) curves and a depth of processing manipulation to understand the effect of MCI and AD on the estimates of recollection and familiarity. Results showed that patients with MCI and AD were impaired in both recollection and familiarity, regardless of the depth of encoding. These results are discussed in relation to disease pathology and in the context of recent conflicting evidence as to whether familiarity remains intact in patients with MCI. The authors highlight differences in stimuli type and task difficulty as possibly modulating the ability of these patients to successfully use familiarity in support of memorial decisions.     

Bayesian Risk Assessment in Genetic Testing for Autosomal Dominant Disorders with Age-Dependent Penetrance

Risk assessment is an essential component of genetic counseling and testing, and the accuracy of risk assessment is critical for decision making by consultands. However, it has been shown that genetic risk calculations may have high error rates in practice. Risk calculations for autosomal dominant disorders are frequently complicated by age-dependent penetrance and sensitivities of less than 100% in genetic testing. We provide methods of risk calculation for prototypical pedigrees of a family at risk for an autosomal dominant disorder with age-dependent penetrance. Our risk calculations include scenarios in which the sensitivity of genetic testing is less than 100%, and in which the sensitivity of genetic testing varies for different family members at risk. Our Bayesian methods permit autosomal dominant disease probabilities to be calculated accurately, taking into account all relevant information. Our methods are particularly useful for hereditary cancer syndromes, in which genetic testing can seldom achieve 100% sensitivity. Our methods can be applied to many different scenarios, including those where the sensitivity of genetic testing varies for different family members at risk. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.     

The Therapeutic Frame: On the Need for Flexibility

A fundamental function of the therapeutic frame is protection of the therapeutic process from the intrusion of elements antithetical to the best interest of the client and detrimental to treatment outcome. It is argued that dogmatic interpretation of the frame promotes conformity rather than growth in the client, blinds the therapist to legitimate issues of client diversity, and constricts the therapist's ability to be appropriately responsive to the client. It is suggested that while the frame is essential to maintain the focus of treatment on the welfare of the client, inflexible adherence undermines this purpose.     

The role of psychosocial context, age, and intelligence in memory performance of older men.

The hypothesis that psychosocial contextual factors contribute to developmental changes in memory was examined using 326 male World War II veterans. Availability of young adult intelligence scores made it possible to separate the contributions of contextual variables and age to maintenance of general intelligence from their direct contributions to performance on 4 memory tasks. Being younger, healthier, more educated, more introverted, more intellectually active, and more satisfied with social support predicted less intellectual decline and, indirectly, better memory performance. Age, personality, locus of control, and extent of social support directly contributed to performance on 1 or more memory tasks. Age contributions were consistent with Craik's (1986) proposed continuum of task demands for self-initiated effort. Possible elaborations of Craik's hypothesis to accommodate contextual variables are suggested.     

Scopolamine-induced deficits in spontaneous alternation performance: attenuation with lateral ventricle injections of glucose.

This experiment determined whether centrally administered glucose can attenuate scopolamine-induced deficits in spontaneous alternation performance. All rats were surgically prepared with indwelling cannulae directed at the lateral ventricle. Thirty min prior to alternation tests, rats received systemic (ip) injections of saline or scopolamine (3 mg/kg). Ten or thirty min prior to training, the rats also received a direct injection into the lateral ventricle of either artificial cerebrospinal fluid (CSF) or glucose (3 micrograms in 1 microliter). Scopolamine significantly impaired spontaneous alternation performance relative to controls. Additional treatment with ICV glucose 30 min, but not 10 min prior to testing, significantly attenuated the scopolamine-induced deficit. These results add support to the view that glucose acts directly on brain systems to attenuate behavioral effects of cholinergic antagonists.     

Glucose effects on mecamylamine-induced memory deficits and decreases in locomotor activity in mice.

Peripheral glucose administration attenuates the effects of muscarinic cholinergic antagonists on several measures, including spontaneous alternation, inhibitory avoidance, and locomotor activity. The present study examined glucose interactions with mecamylamine, a nicotinic cholinergic antagonist, on these measures. Mecamylamine (5 mg/kg, sc) significantly impaired spontaneous alternation performance. Glucose (100 mg/kg, ip) administered with mecamylamine attenuated the impairment. Treatment with hexamethonium (5 and 10 mg/kg, sc), a peripheral nicotinic blocker, did not impair performance. Pretraining treatment with mecamylamine, but not hexamethonium, significantly reduced later retention latencies on inhibitory avoidance tests. Glucose, administered with mecamylamine prior to training, significantly attenuated the impaired test performance. Mecamylamine, but not hexamethonium, significantly decreased locomotor activity. In contrast to the attenuating effects of glucose on the other measures above, glucose administered with mecamylamine potentiated the decreased locomotor activity. These findings demonstrate that glucose influences the behavioral effects of a nicotinic cholinergic antagonist in a manner generally similar to that of muscarinic cholinergic antagonists, and supports previous evidence that circulating glucose interacts with central cholinergic functions.