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PubMed1997

Stress hypertension: the "wrong" genes in the "wrong" environment.

Jim Henry demonstrated an animal's society can induce an increase in blood pressure and its cardiovascular sequale. He recognized that the stress required to elevate blood pressure was a function of the genetically determined behavioral traits of the mice used. He termed some strains aggressive, others peaceable. Being highly inbred (indeed isogenic strains) it was intriguing to find that the behavior of these genetically identical individuals could differ markedly once placed in a society that decreased territory. A dominant or "king" mouse emerged. Other non-dominant males were aggressive and striving to be king. Adrenal medullary systems were activated and renins high. Others huddled in one cage and appeared to have given up. Jim called them depressed. Their adrenal cortex was hyperplastic suggesting pituitary adrenal axis activation as in depression, their renin was low and corticosterone high. In rats, careful selection of a strain genetically aggressive had to be combined with titration of societal stress to reliably induce hypertension. Its likely that humans retain some, if not all, of these variations, i.e. some respond to stress with an increase in blood pressure and others do not, some respond via the sympathetic pathway and others by adrenal cortical activation. The suggestion that African American's high blood pressures is due to stress is relevant to the Henry paradigm and the known genetic influences on sodium retention in blacks. The integration of this paradigm with the genetically increased sensitivity to the blood pressure raising effects of dietary sodium in blacks is proposed and discussed.

Animals↗
PubMed2001

Genetic association analysis of behavioral inhibition using candidate loci from mouse models.

Genes influence the development of anxiety disorders, but the specific loci involved are not known. Genetic association studies of anxiety disorders are complicated by the complexity of the phenotypes and the difficulty in identifying appropriate candidate loci. We have begun to examine the genetics of behavioral inhibition to the unfamiliar (BI), a heritable temperamental predisposition that is a developmental and familial risk factor for panic and phobic disorders. Specific loci associated with homologous phenotypes in mouse models provide compelling candidate genes for human BI. We conducted family-based association analyses of BI using four genes derived from genetic studies of mouse models with features of behavioral inhibition. The sample included families of 72 children classified as inhibited by structured behavioral assessments. We observed modest evidence of association (P = 0.05) between BI and the glutamic acid decarboxylase gene (65 kDA isoform), which encodes an enzyme involved in GABA synthesis. No significant evidence of association was observed for the genes encoding the adenosine A(1A) receptor, the adenosine A(2A) receptor, or preproenkephalin. This study illustrates the potential utility of using candidate genes derived from mouse models to dissect the genetic basis of BI, a possible intermediate phenotype for panic and phobic disorders.

Animals↗
PubMed1996

Seasonal changes in mood and behavior. The role of genetic factors.

BACKGROUND: Seasonal rhythms in mood and behavior (seasonality) have been reported to occur in the general population. Seasonal affective disorder, a clinically diagnosed syndrome, is believed to represent the morbid extreme of a spectrum of seasonality. Two types of seasonality have been clinically described: one characterized by a winter pattern and a second by a summer pattern of depressive mood disturbance. METHODS: By using methods of univariate and multivariate genetic analysis, we examined the relative contribution of genetic and environmental factors to the risk of seasonality symptoms that were assessed by a mailed questionnaire of 4639 adult twins from a volunteer-based registry in Australia. RESULTS: Seasonality was associated with a winter rather than a summer pattern of mood and behavioral change. In each behavioral domain (ie, mood, energy, social activity, sleep, appetite, and weight), a significant genetic influence on the reporting of seasonal changes was found. Consistent with the hypothesis of a seasonal syndrome, genetic effects were found to exert a global influence across all behavioral changes, accounting for at least 29% of the variance in seasonality in men and women. CONCLUSIONS: There is a tendency for seasonal changes in mood and behavior to run in families, especially seasonality of the winter type, and this is largely due to a biological predisposition. These findings support continuing efforts to understand the role of seasonality in the development of mood disorders.

Adult↗
PubMed2001

From simple to complex oscillatory behavior in metabolic and genetic control networks.

We present an overview of mechanisms responsible for simple or complex oscillatory behavior in metabolic and genetic control networks. Besides simple periodic behavior corresponding to the evolution toward a limit cycle we consider complex modes of oscillatory behavior such as complex periodic oscillations of the bursting type and chaos. Multiple attractors are also discussed, e.g., the coexistence between a stable steady state and a stable limit cycle (hard excitation), or the coexistence between two simultaneously stable limit cycles (birhythmicity). We discuss mechanisms responsible for the transition from simple to complex oscillatory behavior by means of a number of models serving as selected examples. The models were originally proposed to account for simple periodic oscillations observed experimentally at the cellular level in a variety of biological systems. In a second stage, these models were modified to allow for complex oscillatory phenomena such as bursting, birhythmicity, or chaos. We consider successively (1) models based on enzyme regulation, proposed for glycolytic oscillations and for the control of successive phases of the cell cycle, respectively; (2) a model for intracellular Ca(2+) oscillations based on transport regulation; (3) a model for oscillations of cyclic AMP based on receptor desensitization in Dictyostelium cells; and (4) a model based on genetic regulation for circadian rhythms in Drosophila. Two main classes of mechanism leading from simple to complex oscillatory behavior are identified, namely (i) the interplay between two endogenous oscillatory mechanisms, which can take multiple forms, overt or more subtle, depending on whether the two oscillators each involve their own regulatory feedback loop or share a common feedback loop while differing by some related process, and (ii) self-modulation of the oscillator through feedback from the system's output on one of the parameters controlling oscillatory behavior. However, the latter mechanism may also be viewed as involving the interplay between two feedback processes, each of which might be capable of producing oscillations. Although our discussion primarily focuses on the case of autonomous oscillatory behavior, we also consider the case of nonautonomous complex oscillations in a model for circadian oscillations subjected to periodic forcing by a light-dark cycle and show that the occurrence of entrainment versus chaos in these conditions markedly depends on the wave form of periodic forcing. (c) 2001 American Institute of Physics.

Journal Article↗
PubMed1997

Genetic aspects of childhood behavioral disorders.

The evidence is reviewed to support the concept that many disruptive, childhood and adolescent behavioral disorders including ADHD, Tourette syndrome, learning disabilities, substance abuse, oppositional defiant disorder and conduct disorder, are part of a spectrum of inter-related behaviors that have a strong genetic component, are polygenically inherited, share a number of genes in common that affect dopamine, serotonin and other neurotransmitters, and are transmitted from both parents. Some of the implications of this hypothesis in relation to diagnosis and treatment are reviewed, including the possibility that the genes involved may be increasing in frequency.

Adolescent↗
PubMed2002

The challenges of genetic tests for human behavior.

OBJECTIVE: To review the potential benefits and adverse effects of genetic tests that may develop, that effectively predict mental illness or variation from the norm on behavior traits. METHOD: A review is offered of the history of genetic-based political policies and racial discrimination. The current status of genetic research in mental disorders is described. Anticipated genetic progress, and derivative tests and limits on their predictive power are considered. RESULTS: There does exist a potential for invidious stigmatization and discrimination, based on genotypes of individuals and allele frequencies in communities, in various transactions such as health care access, employment and education, as well as in more intimate decisions including choice of spouse and decisions to become a parent. CONCLUSIONS: The major uses of valid genetic tests for human behavioral traits will be for development of knowledge on pathophysiology of illness, and for development of new treatment and educational strategies to deal with illness. Some extension of genetic tests into predictions about specific individuals may well occur. Awareness of the potential for discrimination, and a determination to develop culturally sensitive and fair applications of genetic tests, is required to avoid adverse effects on individuals and communities.

Behavior↗
PubMed1975

A genetic analysis of phototactic behavior in Drosophila melanogaster I. Selection in the presence of inversions.

The effectiveness of selection for positive and negative phototactic behavior in populations of Drosophila melanogaster heterozygous for various multiple inversions was compared using the method of realized heritability. Selection in the presence of FM6, SM1 or TM3 alone was as effective as in populations carrying no inversions. However, the presence of FM6 and TM3 together reduced the effectiveness of selection for photopositive behavior and FM6 and SM1 and TM3 restricted the response to selection for negative phototactic behavior. The results are discussed in terms of the organization of genes influencing phototactic behavior in this species.

Animals↗
PubMed1997

Genetics of suicides. Family studies and molecular genetics.

Suicidal behavior, like so much else in psychiatry, tends to cluster in families. Clinical studies show that a family history of suicide is associated with a raised risk of both attempts at suicide and completed suicide. Twin studies show that monozygotic twins have a greater concordance for suicidal behavior than dizygotic twins. Adoption studies also suggest that there may be genetic factors in suicide. Most recently, molecular genetic studies report that polymorphisms of the tryptophan hydroxylase gene are associated with suicidal behavior.

Adolescent↗
PubMed2004

The genetic basis for smoking behavior: a systematic review and meta-analysis.

Considerable evidence indicates that smoking behavior is under a degree of genetic influence. We conducted a systematic review of candidate gene studies of smoking behavior and, where sufficient studies existed, combined reported data using meta-analytic techniques. A total of 41 studies were identified by the search strategy, of which 28 contributed to the meta-analysis. The meta-analysis included data on the DRD2, DAT, 5HTT, and CYP2A6 genes and smoking behavior. Categorical data were extracted on smoking status (never-smoker, ex-smoker, current smoker). Continuous data were extracted on number of cigarettes smoked per day. Evidence indicated effects of the DRD2 Taq1A polymorphism and smoking initiation, the 5HTT LPR and CYP2A6 reduced-activity polymorphisms and smoking cessation, and the DRD2 Taq1A and CYP2A6 reduced-activity polymorphisms and cigarette consumption. The evidence for an effect of specific genes was modest, however, and evidence indicated substantial between-study heterogeneity in most cases, with the exception of the effects of the 5HTT and CYP2A6 genes on smoking cessation. When a random-effects model was applied to analyses in which evidence indicated significant heterogeneity, the effects were in all cases no longer statistically significant. The evidence for a contribution of specific genes to smoking behavior remains modest. Implications for the design of future studies are discussed, such as the need for the development of more specific phenotypes to increase the genetic signal in candidate gene studies.

Genetic Predisposition to Disease↗
PubMed2006

Self-surveillance for genetic predisposition to cancer: behaviors and emotions.

PURPOSE/OBJECTIVES: To describe the kinds of self-monitoring activities and the emotional responses associated with those activities in patients with a genetic predisposition to multiple endocrine neoplasia type 2a (MEN2a) or familial adenomatous polyposis (FAP). RESEARCH APPROACH: Thematic analysis of the transcripts of patient interviews conducted for two previous grounded theory investigations of participation in lifelong surveillance for patients with cancer predisposition syndromes and their family members. SETTING: In the original studies, participants were recruited through a high-risk gastrointestinal cancer clinic (for FAP) and pediatric and adult endocrinology clinics (for MEN2a) at two eastern U.S. medical centers and by patient referral. PARTICIPANTS: 58 transcripts of interviews with 29 patients; 17 diagnosed with FAP or the variants of Gardner syndrome and attenuated FAP and 12 patients diagnosed with MEN2a. METHODOLOGIC APPROACH: Informants participated in two hour-long, in-depth interviews and completed a self-administered sociodemographic questionnaire. MAIN RESEARCH VARIABLES: Types of self-surveillance activities. FINDINGS: Patients engage in an elaborate set of self-surveillance activities that are grouped into five categories of behavior: Medication Appraisal, Phenotype Tracking, Intake and Output Monitoring, Laboratory and Treatment Recording, and Tracking of Visits. Self-surveillance behaviors are grouped independent of type of syndrome, penetrance, age, or gender of the patient. Each category comprises a variety of behaviors that correspond with treatment recommendations and understanding of the disorder. CONCLUSIONS: Self-surveillance may be driven by a combination of anticipation and the need for control and understanding. INTERPRETATION: Findings from the study could be used to create an assessment tool to evaluate the extent to which patients are involved in day-to-day self-monitoring. Clinicians may use the categories to better understand patients' knowledge deficits and the emotional impact of enhanced vigilance. Self-surveillance activities performed by patients with MEN2a and FAP also may be performed by patients with other cancer predisposition syndromes.

Adenomatous Polyposis Coli↗
PubMed1987

The "battle of the sexes": a genetic model with limit cycle behavior.

A two-locus genetic model, based on Dawkins "sex war" game, with the fitness of the genotypes at each locus depending on the gene frequencies at the other, is shown to give rise to a stable limit cycle. The mathematical analysis involves averaging techniques and elliptic integrals.

Animals↗
PubMed2006

Genetic contribution to suicidal behaviors and associated risk factors among adolescents in the U.S.

This paper examines genetic contribution to suicidal behaviors and other risk factors associated with suicidal behavior among adolescents in the U.S. Using adolescent twin data in the National Longitudinal Study of Adolescent Health (N = 1448), we compared concordance in suicidal ideation and attempt among monozygotic (MZ) and dizygotic (DZ) twins. Heritability of risk factors for suicidal behaviors also was examined using Pearson correlation and mixed-model analyses. A trend of higher concordance in suicidal ideation and attempt was found among MZ than DZ twins but the difference was not statistically significant by the stringent test of bootstrapping analysis. Evidence of heritability was found for several suicide risk factors. The percentage of variance explained by heritability was larger among female twins for depression, aggression, and quantity of cigarettes smoked in comparison to heritability estimates for male twins. However, estimated heritability was larger among male than female twins for alcohol use and binge drinking. Heritability influence was negligible among both sexes for other drug use. Risk factors for suicidal behaviors among adolescents may be heritable. Gender differences found in the heritability of some suicide risk factors suggest these genetic contributions are gender specific. Future research examining potential interactions between expression of genetic influence and particular environmental contexts may enhance prevention and intervention efforts.

Adolescent↗