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PubMed2025

Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links.

OBJECTIVE: To explore potential genetic and/or causal associations between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder. METHODS: We conducted polygenic risk score, genetic correlation, and Mendelian randomization analyses using the latest genome-wide association studies summary statistics and individual genotyping data. Next, a blinded observer examined dopamine transporter imaging binding status-a marker of neurodegeneration-in patients with isolated/idiopathic rapid-eye movement sleep behavior disorder, with (N = 6) and without Post-Traumatic Stress Disorder (N = 32). RESULTS: Polygenic risk scores for Post-Traumatic Stress Disorder were associated with isolated/idiopathic rapid-eye-movement sleep behavior disorder, with each standard deviation increase linked to 14.7% higher odds (odds ratio = 1.15, 95% confidence interval: 1.04 to 1.26, p = 0.005). However, genetic correlation was weak, and Mendelian randomization did not support a potential causal relationship. The proportion of individuals with abnormal dopamine transporter imaging binding status was significantly higher in the Post-Traumatic Stress Disorder group compared to those without the disorder (p=0.01, X2 = 6.62). INTERPRETATION: Polygenic risk scores analysis identified an association between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder, consistent with the result from the small exploratory substudy. The lack of strong genetic correlation or causation may reflect limited sample size. Further research with larger and more diverse cohorts is crucial to clarify the genetic, biological and physiological mechanisms underlying this association.

Journal Article↗
PubMed2006

A genetic screen for behavioral mutations that perturb dopaminergic homeostasis in mice.

Disruption of dopaminergic (DA) systems is thought to play a central role in the addictive process and in the pathophysiology of schizophrenia. Although inheritance plays an important role in the predisposition to these disorders, the genetic basis of this is not well understood. To provide additional insight, we have performed a modifier screen in mice designed to identify mutations that perturb DA homeostasis. With a genetic background sensitized by a mutation in the dopamine transporter (DAT), we used random chemical mutagenesis and screened for mutant mice with locomotor abnormalities. Four mutant lines were identified with quantitatively elevated levels of locomotor activity. Mapping of mutations in these lines identified two loci that alter activity only when dopamine levels are elevated by a DAT mutation and thus would only have been uncovered by this type of approach. One of these quantitative trait loci behaves as an enhancer of DA neurotransmission, whereas the other may act as a suppressor. In addition, we also identified three loci which are not dependent on the sensitized background but which also contribute to the overall locomotor phenotype.

Animals↗
PubMed2006

Genetic influences on behavioral and neuroendocrine responses to predator-odor stress in rats.

The exposure of animals to a variety of stressful events can induce behavioral and physiological responses, which can be modulated by anxiety levels. It is well recognized that genetic factors play a substantial role in both anxiety and stress reactivity. The present study examined the effect of exposure to 2,4,5-trimethylthiazoline (TMT), a component of fox feces, on nociception and corticosterone levels in Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rat strains (which display genetic differences in anxiety models such as the elevated plus-maze and open-field). The influence of two quantitative trait loci (QTL), named Ofil1 and Ofil2, which are known to affect emotionality in LEW versus SHR intercrosses on the responses to TMT was also investigated. LEW and SHR rats of both sexes displayed similar levels of behavioral and neuroendocrine responses after TMT exposure. As expected, TMT odor stress produced analgesia and enhanced corticosterone levels. Ofil1 on chromosome 4 affected stress-induced analgesia in males only. Ofil2 on chromosome 7 had no effect. The results suggest that behaviors measured in classical models of generalized anxiety and reactivity to stress produced by predator odors can be genetically dissociated. Finding a locus with an effect on the behavioral responses to stress represents the starting point in the search for genes responsible for stress-related traits.

Animals↗
PubMed1989

Genetics of factors affecting the life history of Drosophila melanogaster. III. Egg insertion behavior.

A genetic analysis of two laboratory strains of Drosophila melanogaster that displayed opposite oviposition tendencies with respect to egg, insertion behavior was performed. In general, the insertion characteristic appears to be dominant over the noninsertion characteristic and is controlled by a polygenic system associated mostly with chromosomes 2 and 3. The results of this study indicate that these genes may be concentrated at the distal end of chromosome 2L and at the distal end of chromosome 3R, and their presence on both of these chromosome regions is needed to approach the full egg insertion effect, suggesting the presence of interaction among genes in these two regions.

Animals↗
PubMed1975

Behavioral studies using genetically defined mice. A bibliography.

References in this bibliography have been selected from the Subject-Strain Bibliography of Inbred Strains of Mice, maintained at The Jackson Laboratory, which attempts to include all published papers dealing with specific inbred strains of mice, named genes in mice, or named transplantable tumors. We have selected all references which appear to be of behavioral interest, including reports of the effects of neurological mutations, but have omitted genetic studies conducted with these mutants. Studies using "white", "Swiss", or undesignated mice are not included. This bibliography covers literature published from 1922 through late 1973. The authors would like to be informed of omissions, and to receive reprints of omitted papers. The bibliography is divided into three sections. The first section includes all references in which a behavioral measure appears to be the variable of primary interest. This section is divided into 16 behavioral categories: activity, aggression, audiogenic seizures, communication, emotionality, feeding, learning, maternal, memory, psychomotor, regulation, reproduction, biorhythms, sensation, social, and miscellaneous. References are assigned to a category on the basis of their apparent emphasis. The second section includes all references in which the effects of a treatment on behavior appear to be the variables of primary interest. This section is divided into nine treatment categories: age, alcohol, central nervous system, mutations, neonatal and teratogenic, population size, pharmacological agents, genetic selection, and miscellaneous. Where multiple treatments were used, references are assigned to the category of the most important treatment. The third section contains reviews and theoretical references. Each item in the bibliography is assigned to a category in one of the three sections and given a reference number. At the end of each category is a list of the reference numbers from other categories which contain information pertinent to that category. References are arranged alphabetically within each category.

Animals↗
PubMed1986

Genetic complexity of host-selection behavior in Drosophila.

Genetic variation for settling responses to different types of food and for oviposition behavior exists within natural populations of Drosophila tripunctata. After flies from two isofemale strains and F(2) derived from crosses between them were released in the wild and recaptured at either mushroom or tomato baits, the oviposition preferences of females for these foods were determined in the laboratory. Whereas settling behavior and oviposition-site preference were negatively correlated in the parental strains, there was no association of these behaviors in the F(2) generation. Furthermore, lines produced by crossing these two strains followed by inbreeding did not manifest such a negative correlation. Together, these results indicate that two important aspects of host selection are under independent genetic control. These findings caution against using a single component of the process of host selection as indicative of the probability that a particular resource will be utilized in the field, and they bear on the question of how speciation based on genetic variation for host selection may be accomplished.

Journal Article↗
PubMed1998

Longitudinal genetic analysis of problem behaviors in biologically related and unrelated adoptees.

The genetic and environmental influences on problem behaviors at two assessment points, three years apart, and their stability were studied in a sample of international adoptees, initially aged 10 to 15 years. Parents of 111 pairs of adopted biological siblings, 221 pairs of adopted nonbiological siblings and 1484 adopted singletons completed the Child Behavior Checklist (75 pairs, 154 pairs and 1080 singletons respectively at second assessment). At first assessment, genetic factors accounted for more than 50% of the variance in the Externalizing, Aggressive Behavior, Attention Problems and Social Problems scales. Shared environmental influences explained 40% of the variance in the Total Problem scale and less for all other scales. Nonshared environmental influences were most important for the Internalizing scale and its subscales, and for the Thought Problems and Delinquent Behavior scales. At the second assessment, genetic factors explained most of the variance in the Total Problem, Externalizing and Aggressive Behavior scales, while nonshared environmental influences explained most of the variance in all other scales. Shared environmental influences explained 33% of the variance in the Internalizing scale and less for the other scales. The stability of the Externalizing scale over time was caused mostly by genetic factors, while nonshared environmental factors mostly caused the stability of the Internalizing scale.

Adolescent↗
PubMed1993

X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism.

We have identified a large Dutch kindred with a new form of X-linked nondysmorphic mild mental retardation. All affected males in this family show very characteristic abnormal behavior, in particular aggressive and sometimes violent behavior. Other types of impulsive behavior include arson, attempted rape, and exhibitionism. Attempted suicide has been reported in a single case. The locus for this disorder could be assigned to the Xp11-21 interval between DXS7 and DXS77 by linkage analysis using markers spanning the X chromosome. A maximal multipoint lod score of 3.69 was obtained at the monoamine oxidase type A (MAOA) locus in Xp11.23-11.4. Results of 24-h urine analysis in three affected males indicated a marked disturbance of monoamine metabolism. These data are compatible with a primary defect in the structural gene for MAOA and/or monoamine oxidase type B (MAOB). Normal platelet MAOB activity suggests that the unusual behavior pattern in this family may be caused by isolated MAOA deficiency.

Adult↗
PubMed2003

Imaging neuronal activity during zebrafish behavior with a genetically encoded calcium indicator.

Genetically encoded calcium indicators, such as cameleon, have offered the promise of noninvasively monitoring activity of neurons, but no one has demonstrated whether these indicators can report calcium transients in neurons of behaving vertebrates. We show that cameleon can be expressed at high levels in sensory and spinal cord neurons in zebrafish by using neural-specific promoters in both transient expression experiments and in a stable transgenic line. Using standard confocal microscopy, calcium transients in identified motoneurons and spinal interneurons could be detected during escape behaviors produced by a touch on the head of the fish. Small movements of the restrained fish during the behavior did not represent a major problem for analyzing the calcium responses because of the ratiometric nature of cameleon. We conclude that cameleon can be used to noninvasively study the activity of neurons in an intact, behaving vertebrate. The ability to introduce an indicator genetically allows for studies of the functional roles of local interneurons that cannot easily be monitored with other approaches. Transgenic lines such as the one we generated can also be crossed into mutant lines of fish to study both structural and functional consequences of the mutations.

Animals↗
PubMed1994

Human parental behavior: evidence for genetic influence and potential implication for gene-culture transmission.

A large sample of adult twins (1117 pairs), who were concordant for having had children were asked to report on their child-rearing practices. A 14-item version of the Parental Bonding Instrument (PBI) was used to assess rearing practices of parent twins. The two factors of Care and Overprotection, commonly found in other studies, were recovered from this analysis of the PBI's parent form. Model-fitting analyses indicate that human parental behavior is under significant genetic influence. Findings further suggest that this influence is sex limited, with a higher heritability in mothers than in fathers, and that it may result partly from the expression of dominant genes. For both PBI factors and both parents, the best-fitting models invariably assumed sex-limited genetic effects and unique environmental influences only. Broad heritability ranged from 19% (father overprotection) to 39% (mother care). These results are interpreted in the broader perspective of gene-culture theory.

Adult↗
PubMed1994

Genetic, phenotypic, and behavioral variation in North American sylvatic isolates of Trichinella.

Two restriction endonucleases (Cla I and Hpa II) produced polymorphic repetitive DNA profiles which were used in a clustering analysis to quantify the level of genetic variation among 14 North American sylvatic isolates of T5 Trichinella. Differences in genetic profiles reflected phenotypic differences in parasite reproductive success as measured by an isolate's reproductive capacity index in natural hosts. Two genetically distinct isolates of the T5 genotype and T. spiralis were used to infect white-footed mice Peromyscus leucopus for a behavioral analysis. Three behavioral characteristics were tabulated from videotapes: time to emerge from cage, time spent inside cage, and number of rears (index of exploratory activity). Mice infected with 400 T. spiralis larvae showed a significant decrease in exploratory activity and significant increases in time to emerge and time spent inside cage, whereas mice infected with 200 larvae displayed no differences in behavior. Mice infected with a T5 isolate from a raccoon (R9) also displayed decreased exploratory activity. In contrast, mice infected with the other T5 isolate from a coyote (C26) showed relatively constant rearing levels but spent less time inside their cages during the late period of the infection. Results suggest that different genetic strains of Trichinella induce varied types of behavioral modifications upon their hosts.

Animals↗
PubMed2000

The in vitro ethanol sensitivity of hippocampal synaptic gamma-aminobutyric acid(A) responses differs in lines of mice and rats genetically selected for behavioral sensitivity or insensitivity to ethanol.

Previous work has demonstrated that in the hippocampal CA1 region of Sprague-Dawley rats, there are ethanol-sensitive and ethanol-insensitive populations of GABAergic synapses on pyramidal neurons. The present experiments characterized the ethanol sensitivity of these pathways in lines of rats and mice genetically selected for sensitivity or insensitivity to the behavioral effects of ethanol. In ethanol-sensitive inbred long sleep mice, GABA(A) IPSCs induced by stimulation of proximal (probably somatic) synapses were enhanced by 80 mM ethanol, whereas the distal (i.e., dendritic) pathway was unaffected. Thus, the relative sensitivity of these pathways (proximal > distal) is the same in both Sprague-Dawley rats and in inbred long sleep mice. However, in the ethanol-insensitive inbred short sleep mice, neither proximal nor distal IPSCs were affected by 80 mM ethanol. The ethanol sensitivity of the proximal pathway was also examined in replicate lines of rats selected for either high ethanol sensitivity or low ethanol sensitivity. GABA(A) IPSCs in the high ethanol sensitivity lines were significantly enhanced by 80 mM ethanol, whereas IPSCs in the low ethanol sensitivity lines were unaffected. Thus, IPSCs evoked via the proximal pathway were enhanced by ethanol in all the sensitive mouse and rat lines, and unaffected in all the insensitive lines. These experiments demonstrate that GABA(A) synapses in brain differ in their sensitivity to enhancement by ethanol, and the sensitivity to such enhancement is under the control of genes that can be selected for using classical genetic selective breeding based on a behavioral phenotype.

Animals↗
PubMed2000

Specific genetic interference with behavioral rhythms in Drosophila by expression of inverted repeats.

We describe a new experimental technique that allows for a tissue-specific reduction of gene activity in the Drosophila nervous system. On the basis of the observation that certain gene functions can be ubiquitously blocked by injecting double-stranded RNA into Drosophila embryos, we employed a method to interfere with an individual gene function permanently in a predetermined cell type. This was achieved by the formation of an inverted-repeat RNA sequence in the tissue of interest under control of the GAL4/UAS binary expression system. As an example, we show that inverted-repeat-mediated interference with the period gene produces a hypomorphic period phenotype. A selective decrease of period RNA appears to be a component of the cellular response.

Animals↗