Human maternal responsiveness is a complex repertoire of infant-related behaviours and attitudes, which vary between and within mothers. Environmental and socioeconomic factors undoubtedly influence maternal care, but less is known about how genetic variation associates with maternal responsiveness. Where genetic variation has been examined in relation to mothering, the moderating effects of early life experiences in the mother have not been explored. Additionally, studies tend to focus on maternal sensitivity, neglecting to explore other dimensions of maternal responsiveness. The purpose of the present thesis was to explore genetic variation in three gene families – dopamine (DA), serotonin (5-HT), and oxytocin (OXT) – in relation to differences in maternal care in a Caucasian sample of new mothers recruited in early pregnancy from Hamilton, Ontario (N=187). Furthermore, interactions between early experiences in the mothers’ lives and their genetic polymorphic variants were examined. Early experience was a combined measure of the Parental Bonding Instrument and the Childhood Trauma Questionnaire. Maternal behaviour during mother-infant interaction was assessed at 6 months postpartum and derived from a video-recorded 30-minute mother-infant interaction. The behavioural outcomes of interest maternal sensitivity (assessed using the Ainsworth Maternal Care Scales) and maternal behaviors (vocalizing, orienting away from infant, instrumental caregiving). We also assessed maternal attitudes about parenting the infant at 6 months postpartum. Multiple polymorphisms on DA receptors D1 (rs686, rs4532, rs265981, rs265976, rs5326) and D2 (rs6277, rs1799732, rs1799978, rs1800497) associated with maternal vocalizing and orienting away from the infant, respectively. The OXT polymorphisms rs2740210 and rs4813627 associated with infant-directed vocalizing. A major polymorphism on the 5-HT transporter (5HTTLPR and a related rs25531 polymorphism) associated significantly with maternal sensitivity. There were gene-environment interactions between this 5-HT polymorphism and early adversity in association with maternal orienting away and maternal attitudes. Gene-environment interactions were also found between the OXT polymorphisms rs2740210 and rs4813627 and instrumental care of the infant. These results suggest that variations in genes encoding major brain neurotransmitters and neurohormones are related to observed maternal behaviour and self-reported maternal attitudes. These results showcase the importance of exploring multiple dimensions of complex behavioural phenotypes like mothering.

Human maternal responsiveness is a complex repertoire of infant-related behaviours and attitudes, which vary between and within mothers. Environmental and socioeconomic factors undoubtedly influence maternal care, but less is known about how genetic variation associates with maternal responsiveness. Where genetic variation has been examined in relation to mothering, the moderating effects of early life experiences in the mother have not been explored. Additionally, studies tend to focus on maternal sensitivity, neglecting to explore other dimensions of maternal responsiveness. The purpose of the present thesis was to explore genetic variation in three gene families – dopamine (DA), serotonin (5-HT), and oxytocin (OXT) – in relation to differences in maternal care in a Caucasian sample of new mothers recruited in early pregnancy from Hamilton, Ontario (N=187). Furthermore, interactions between early experiences in the mothers’ lives and their genetic polymorphic variants were examined. Early experience was a combined measure of the Parental Bonding Instrument and the Childhood Trauma Questionnaire. Maternal behaviour during mother-infant interaction was assessed at 6 months postpartum and derived from a video-recorded 30-minute mother-infant interaction. The behavioural outcomes of interest maternal sensitivity (assessed using the Ainsworth Maternal Care Scales) and maternal behaviors (vocalizing, orienting away from infant, instrumental caregiving). We also assessed maternal attitudes about parenting the infant at 6 months postpartum. Multiple polymorphisms on DA receptors D1 (rs686, rs4532, rs265981, rs265976, rs5326) and D2 (rs6277, rs1799732, rs1799978, rs1800497) associated with maternal vocalizing and orienting away from the infant, respectively. The OXT polymorphisms rs2740210 and rs4813627 associated with infant-directed vocalizing. A major polymorphism on the 5-HT transporter (5HTTLPR and a related rs25531 polymorphism) associated significantly with maternal sensitivity. There were gene-environment interactions between this 5-HT polymorphism and early adversity in association with maternal orienting away and maternal attitudes. Gene-environment interactions were also found between the OXT polymorphisms rs2740210 and rs4813627 and instrumental care of the infant. These results suggest that variations in genes encoding major brain neurotransmitters and neurohormones are related to observed maternal behaviour and self-reported maternal attitudes. These results showcase the importance of exploring multiple dimensions of complex behavioural phenotypes like mothering.

What happens when feminist body theory and reductionist theories of biological sex difference are brought together? In this work I take as my starting point the increasing ubiquity of appeals to biology as an explanation for ‘human’ and ‘woman’s’ nature on the one hand, and the reactive and reflexive distancing of biology within feminist body theory on the other, to begin to question the middle ground. I aim to constructively dissent from taking up either of these positions in order to confront the question: what if the reductionists prove to be, even partially, right? In acknowledging that possibility, I am interested in whether/where there is potential for feminist theory to be more relaxed about biologically sex differentiated attributes. I position myself as a women’s studies scholar taking a walk across the campus to see what evidence is being produced by ‘the opposition’. To place my walk in context, I first briefly explore various feminist approaches to the problem of biological sex differences, and the continuing difficulties surrounding binaries and binary thinking. Next, in the main part of the thesis, I review the historical and contemporary reasoning and claims made within three areas of reductionist science that are aligning at this time, and which have been reproached for promoting a return to a more biologically determinist social environment. I then take a brief excursion off campus to demonstrate the dangerous aspects of these scientific enterprises when their interpretation into popular culture is not carefully monitored. Finally, I return again to my own side of the campus to look at some of the ways feminists have already begun the work of overturning outworn and contested conventional theories about biology and human nature in conversation with reductionist theory. Having done this, was it worth the walk? My assessment is that while, in some cases, feminism’s defensive antiessentialism is warranted, there is work being undertaken within these reductionist sciences that is less rigid and reactionary than some critical interpretation would suggest. I conclude that there is a certain futility in feminist body theory’s oppositional stance to biology, and that its utility is put at risk by a continued investment in one side of a binary. Further, my walk across the campus leads me to believe that, while perhaps not imminent, there is every reason to expect that the scientific pursuit of an unequivocal genetic basis for specific sex differentiated behaviours will succeed. That being so, there are spaces where the insights of both sides might be productively brought together so as to avoid the worst excesses of biological determinism and, at the same time, loosen the grip of binary thinking on approaches to biology and the body.

<p dir="ltr">This dissertation sought to contribute a pair of genetically informed studies strategically designed to make potentially causal inferences about potential co-developing processes of internalizing symptoms, body mass index (BMI) and relative pubertal timing during adolescence. Paper 1 used the Early Growth and Development Study (EGDS; N=561), a prospective adopted-at-birth design which primarily accounts for passive gene environment correlation by virtue of youth having been adopted at birth and placed in non-relative adoptive families. Paper 2 used the discordant sibling design from a subsample of siblings from the Adolescent Brain Cognitive Development (ABCD) Study (N=3792), which by design accounts for all confounding of the effects of a risk factor with all shared familial influences that siblings share and all environmental differences that exist between families. The hypothesized associations were further examined in subsamples of twins and MZ twins to make increasingly strict, potentially causal inferences. Across the two studies, I hypothesized that higher internalizing symptoms and higher BMI would positively co-develop at the within person and within family level, respectively for each paper. I hypothesized that there would be unidirectional within person effects of relatively earlier pubertal development on higher internalizing symptoms, across both studies. Finally, I hypothesized that there would be positive co-development of higher BMI and earlier relative pubertal timing early on in both studies, but that only higher BMI would continue to unidirectionally predict earlier relative pubertal timing across the two studies’ ends. In paper 1, specific hypotheses were completely unsupported. In Paper 2, hypotheses were partially supported for two of out three pairs of phenotypes. Specifically, there was evidence of one within family cross-lagged effect between higher discordance in internalizing symptoms at age 10 and higher discordance in BMI at age 11. There was also evidence of one within family cross-lagged effect between higher discordance in relative pubertal timing at age 12 and higher discordance in internalizing symptoms at 13. Findings from both papers indicated that the association between BMI and relative pubertal timing is likely largely confounded by common stable between person, stable discordance, and stable family average factors. Implications and limitations are discussed.</p>

Lamb mortality remains a significant welfare and economic issue for sheep production. Two significant causes of mortality are dystocia and low lamb vigour; both requiring high levels of human care to ensure lamb survival. Genetic solutions to reduce lamb mortality and its main causes (dystocia and low vigour lambs) are desirable, with at least two possible solutions available: (i) use of suitable breeds or strains and (ii) intrabreed selection. Approach (i) requires the existence of breed/strain differences in the desired traits and approach (ii) needs sufficient intrabreed genetic variance. Reproductive and behavioural traits are, however, difficult to quantify and measure on farm. On dedicated research farms, lamb vigour has been measured using latencies to perform specific behaviours (e.g. standing and sucking) but this methodology is difficult to transfer to a commercial setting - timed behavioural traits are not as easy to measure on farm when compared with categorical indicator traits. Therefore, proxy methods (categorical scoring systems) are needed to measure behaviour traits in a manner that allows for collection of sufficient data to enable genetic analysis. The main purpose of this thesis was to develop such proxy methods, to estimate the heritability of lamb traits, and thus to investigate whether it is possible to improve the welfare of lambs through selection of parents with superior vigour and lambing ease characteristics. Scoring systems were developed for quantifying neonatal lamb fitness and behaviour traits. Detailed historical behaviour data were analysed to develop criteria for three scores: birth assistance (BA), lamb vigour (LV) and sucking assistance (SA). These scoring systems were then validated in a separate flock by simultaneously recording scores and the latency to perform certain landmark behaviours. The results obtained indicated that the scoring systems developed were a practical, reliable and sensitive indicator of lamb fitness traits. To determine whether neonatal lamb vigour traits were heritable, scores from the scoring systems previously developed and validated were recorded in an experimental flock of pure-bred Texel sheep for the purpose of estimating genetics parameters for each trait. Results indicated that heritabilities for all traits range from low-moderate, BA 0.43 (s.e. 0.063), LV 0.15 (s.e. 0.059), SA (0.27 (s.e. 0.045), suggesting there is sufficient variation present within this Texel sub-population to allow for selection for improved neonatal fitness traits. Thus far, we have determined that neonatal traits are heritable and can be measured using proxy scoring systems. The next step was to establish whether the proxy scores developed were feasible, in a commercial setting, for the mass data collection needed for estimation of genetic parameters and to determine the relationship between neonatal traits and later production traits, with the aim of integrating this data into breeding programmes. A total of 11,092 lambs with complete neonatal records, from 290 flocks belonging to the Industrial Partner, the Suffolk Sheep Society (UK), were analysed to report the genetic variance present within the UK population of registered pure-bred Suffolk sheep. The results from this analysis show that heritabilities were moderate for BA, 0.26 (s.e. 0.03), LV, 0.40 (s.e. 0.04) and SA, 0.32 (s.e. 0.03) with genetic correlations between neonatal traits all moderate to high and positive. This demonstrates that neonatal fitness traits can have heritabilities comparable to those of production traits. The analysis also shows that neonatal survival traits of birth assistance and sucking assistance are moderately heritable, when treated as a lamb trait rather than a sire or ewe trait, indicating the selection should target the lambs in order to successfully, and efficiently, improve survival. A possible alternative method for improving dystocia and lamb vigour would be to introgress genes for improved lambing ease and lamb vigour from the New Zealand strain of Suffolk sheep into the British Suffolk strains. However, there has been no published record of how much ‘NZ genetics’ would improve (or compare to) British Suffolk’s under standard UK management practises. Therefore, the objectives of this study were to examine possible differences in neonatal behavioural traits (birth assistance, lamb vigour and sucking assistance) between NZ and UK Suffolks when used as terminal sires on commercial cross-bred ewes. Thus, neonatal scores from cross-bred lambs sired by rams from one of the three main Suffolk strains currently used in the UK were compared. The analysis indicated there was no significant effect of sire strain on any of the neonatal traits, and that individual sire variation was greater than the variation between the strains. In conclusion, the work contained within this thesis shows that neonatal lamb behaviour traits can be measured accurately and easily using well-realised and biologically relevant scoring systems. Furthermore, these scoring systems are a feasible and practical method of measuring neonatal lamb vigour which may be used to evaluate management systems and to improve selection criteria for neonatal traits.

<p>Tolerance is a diagnostic criterion for alcohol use disorder (AUD) and dependence and is often measured metabolically or behaviorally by comparing blood ethanol concentrations (BEC) or locomotor performance to an ethanol (EtOH) challenge before and after a drinking history, respectively. To explore another aspect of chronic behavioral tolerance in a family history positive (FH+) model of AUD, crossed High Alcohol Preferring (cHAP) mice were allowed to respond instrumentally for an EtOH reinforcer after either a five-week history of continuous home cage two-bottle choice (2BC) drinking or a concurrent five-week water-drinking period. Additionally, some of these animals were placed back into the operant box after home cage drinking histories to respond in extinction, allowing for the quantification of alcohol-motivated seeking alone in the absence of EtOH taking and its intoxicating effects. The results demonstrate that an alcohol history does not lead to a subsequent increase in active lever responding or inactive lever responding when compared to water-drinking controls. However, female cHAP mice with an EtOH-drinking history respond more on the inactive lever in extinction compared to water controls, suggesting that home cage EtOH history potentiates variation in responding in extinction. Overall, female mice responded more on the active lever and drank more alcohol in the reinforced condition, but again, there was not an effect of drinking history on this sex-specific effect. Together these results suggest that while female cHAPs, regardless of drinking history, are more motivated to work to drink EtOH, reinforced and non-reinforced instrumental responding are not reliable readouts for tolerance in cHAP mice compared to other endpoints such as drinking in the dark (DID) assays.</p>

<p dir="ltr">Juvenile stress (JS) is a known risk factor for the development of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD), both of which frequently occur together, suggesting common genetic influences on vulnerability toward these disorders. The present study investigated the impact of JS on contextual fear learning and extinction, as well as corticosterone (CORT) responses before and after JS, before and after contextual fear conditioning (CFC), and after fear extinction in male and female high-alcohol-preferring (HAP2) and low-alcohol-preferring (LAP2) mice. We also measured unconditioned anxiety-related behavior in the light-dark-transition test. No line differences were seen in fear acquisition, however, HAP2 mice showed faster fear extinction compared to LAP2 mice. No effects of JS were seen in HAP2 mice, whereas in LAP2 mice, JS reduced fear acquisition in males and facilitated fear extinction in females. Females showed greater fear relative to males, regardless of subgroup. Anxiety-related behavior, assessed by the light-dark transition test, did not correspond with fear-related behavior, as LAP2 females demonstrated more anxiolytic-like responses than LAP2 males, while HAP2 males demonstrated more anxiolytic-like responses than LAP2 males. There were no line differences in CORT during the juvenile stage; however, adult LAP2 mice showed greater CORT levels than HAP2 mice at baseline and after CFC and extinction testing. These findings provide new information regarding fear learning and extinction in these unique mouse lines that model mechanisms theorized to contribute to co-morbid AUD and PTSD.</p>

<p>Adolescents are highly sensitive to peer influence and thus at higher risk of acquiring problematic behaviors through peer interactions. However, adolescents vary in the extent to which they are influenced by their peers. Resistance to peer influence (RPI), the tendency to refuse undesired peer norms and peer pressure, is one of the crucial explanations for this variation. Prior to designing effective interventive plans to improve RPI, it is important to elucidate the pathways of how RPI develops in childhood and adolescence. Therefore, the present study leverages an adopted-at-birth design and proposes a moderated mediation model to examine whether: 1) child phenotypic impulsivity mediates the association between birth parent impulsivity and adolescent RPI; 2) child phenotypic self-esteem mediates the association between birth parent self-esteem and adolescent RPI; 3) adoptive parent responsiveness buffers the impulsivity pathway; and 4) adoptive parent responsiveness strengthens the self-esteem pathway. The sample consists of 538 family triads, with adopted child, birth parents, and adoptive parents, drawn from a sample of 561 families recruited from 45 adoption agencies in the United States. Birth parents’ impulsivity and self-esteem were measured to index heritable factors for phenotypic impulsivity and self-esteem. Adoptive parents’ responsiveness was measured via home observations. Impulsivity and self-esteem of adopted adolescent were reported by their adoptive parents, whereas RPI was assessed via self-report. Covariates included adolescent sex, age, and the openness to adoption between birth parents and adoptive parents. Results of structural equation models revealed that none of the proposed mediating or moderating pathways reached statistically significant levels. Overall, girls reported higher RPI than boys. For future studies, researchers may want to consider more accurate proxies of genetic factors for impulsivity and self-esteem, and repeated measures designs.</p>

<p>The genetic basis for behavioural traits is largely unknown. The overall aim of this thesis was to find genes with importance for behavioural traits related to fear and anxiety. Microarray analysis was used to screen expression profiles of brain regions important for emotional behaviour in dogs, wolves, foxes and mice. In a first experiment, dogs and their wild ancestors the wolves were compared. Our results suggested that directed selection for behaviour might have resulted in expression changes in few genes acting on several brain functions, possibly affecting behaviour. However, the observed expressional differences were confounded with environmental effects. This was addressed in a second study on domesticated silver foxes. By correlating behaviour and brain gene expression in foxes selected for tameness to non-selected foxes raised in the same environment, we found large behavioural differences but only few genes with differential expression in the brain. Fifteen of the 40 genes showing evidence of expression difference were related to haem or haemoglobins. Further studies showed an additive genetic effect on brain gene expression, similar to the additive genetic inheritance of behaviour, indicating an involvement in domestication. Transcriptional profiling was also used for finding genes involved with the sleep disorder narcolepsy. Narcoleptic Doberman pinschers homozygous for the canarc-1 mutation were compared to their unaffected heterozygots revealing reduced expression of three genes, TAC1, PENK and SOCS2, with relevance to the narcoleptic phenotype. Finally gene expression was investigated in relation to anxiety-related traits in a mouse model. Surprisingly, as in the fox study, genes coding for haemoglobins indicated differential expression in the brain between animals with different anxiety levels. Our combined results suggest that genes like haemoglobins, best known for their function in oxygen transport in blood, may also participate in brain functions related to decreased anxiety in domestic animals. </p>

The genetic basis for behavioural traits is largely unknown. The overall aim of this thesis was to find genes with importance for behavioural traits related to fear and anxiety. Microarray analysis was used to screen expression profiles of brain regions important for emotional behaviour in dogs, wolves, foxes and mice. In a first experiment, dogs and their wild ancestors the wolves were compared. Our results suggested that directed selection for behaviour might have resulted in expression changes in few genes acting on several brain functions, possibly affecting behaviour. However, the observed expressional differences were confounded with environmental effects. This was addressed in a second study on domesticated silver foxes. By correlating behaviour and brain gene expression in foxes selected for tameness to non-selected foxes raised in the same environment, we found large behavioural differences but only few genes with differential expression in the brain. Fifteen of the 40 genes showing evidence of expression difference were related to haem or haemoglobins. Further studies showed an additive genetic effect on brain gene expression, similar to the additive genetic inheritance of behaviour, indicating an involvement in domestication. Transcriptional profiling was also used for finding genes involved with the sleep disorder narcolepsy. Narcoleptic Doberman pinschers homozygous for the canarc-1 mutation were compared to their unaffected heterozygots revealing reduced expression of three genes, TAC1, PENK and SOCS2, with relevance to the narcoleptic phenotype. Finally gene expression was investigated in relation to anxiety-related traits in a mouse model. Surprisingly, as in the fox study, genes coding for haemoglobins indicated differential expression in the brain between animals with different anxiety levels. Our combined results suggest that genes like haemoglobins, best known for their function in oxygen transport in blood, may also participate in brain functions related to decreased anxiety in domestic animals.