Maternal obesity has significant consequences on the lifelong health of the developing child and rising global incidences make it one of the most common comorbidities during pregnancy. Offspring of obese mothers are at an increased risk of hospitalization for respiratory infections throughout childhood, which predispose these children to non-communicable respiratory diseases in later life. Animal models of maternal high fat diet (mHFD) feeding have observed common inflammatory outcomes with obesogenic models, but the effect on offspring varies with timing of the nutritional challenge and diet composition across studies. These studies demonstrate significant alterations to circulating and lung specific immune cells but the sequence of events that link maternal diet to these fetal outcomes are unclear, nor have they been tested in the context of a bacterial respiratory infection. Streptococcus pneumonaie is the most common causative pathogen of bacterial pneumonia and meningitis, making it of high clinical relevance. We aimed to investigate the effect of a mHFD (45% kcal from fat) during gestation and lactation, on offspring outcome and recovery from Streptococcus pneumoniae infection. Immunophenotyping, both before and after infection, revealed a hypo-inflammatory phenotype in circulating monocytes of the mHFD offspring with a decreased capacity to both initiate and terminate inflammatory responses. These offspring had significantly higher bacterial counts in lung tissues during infection and sustained cellular inflammation in survivors. In this thesis, we present foundational work on the detrimental influence of excess maternal nutrition on offspring immune function and infection outcomes, which may be involved in susceptibility to inflammatory and chronic disease in later life. A better understanding of this deep and lasting influence of the maternal environment will allow us to target preconception health as a form of harm reduction, informing stake holders and institutions to direct efforts towards DOHaD knowledge translation. / Thesis / Master of Science (MSc)

Background: A wealth of quantitative literature exists exploring the impact of parental alcohol misuse on adult and child offspring. It is often proposed that children of alcoholics are at risk of experiencing a host of negative outcomes, many of which are said to persist into adulthood. Confusing and contradictory results have led researchers to identify a subset of offspring deemed to be resilient. Little remains known about the factors that influence who becomes negatively affected and who becomes resilient, or how these factors are experienced by individuals. The recent up rise of qualitative methodologies also suggest this divide is not clear, with offspring of alcoholics demonstrating a range of functioning. Aim: With this in mind, the current study aims to explore the lived experience of adult children of alcoholics to gather a richer understanding of how these individuals develop into the people they are today. Method: Semi-structured interviews were conducted with six individuals who grew up with at least one alcoholic parent. Interpretative Phenomenological Analysis was used to analyse verbatim transcripts. Results: The analysis produced four master themes. These were: ‘Dealing with the loss of connection to parents’, ‘Feeling hopeless and helpless’, Struggling to stay sane’ and ‘I know who I want to be more than I know who I am’. The master themes and corresponding subordinate themes are discussed in relation to the relevant literature. Clinical implications, methodological considerations and directions for future research are also presented. Conclusions: This study provided insight into the lived experience of being an adult child of an alcoholic. It highlighted the challenges and struggles they faced in childhood and the ways in which they battled to overcome the difficulties they experienced to forge a preferred identity in adulthood. It also emphasised the importance of perceived parental rejection as the pathway to causing distress and the desire to be better than their parents as a pathway to resiliency.

The brown trout, Salmo trutta L., displays one of the most variable and polymorphic life-history strategies of all the salmonids. In some populations, individuals spend their whole life-cycle in the river (freshwater-resident) whereas in others, a varying proportion migrates to sea for variable amounts of time to better feeding conditions before returning to spawn (anadromous). The ‘decision’ if an individual will migrate or not will be determined by the balance of the costs and benefits of following a particular life-history strategy. The balance of these, which do not affect males and females equally, will determine the future success (measured by fitness) of each strategy. This research addresses the influences of parental contribution, mainly maternal effect, of anadromous and freshwater-resident brown trout on offspring performance and subsequent life-history. A partial migratory population of brown trout was studied in the Tadnoll Brook, one of the seven major tributaries on the River Frome. The tributary is classified as a circum-neutral chalk stream, 9.9 km long with a catchment approximately 50 km2. Carbon and nitrogen stable isotope analysis (SIA) was used to quantify maternal reproductive contribution of anadromous and freshwater-resident brown trout to offspring and determine the future success (measured by fitness) in terms of size and time of emergence. A panel of 12 microsatellite loci was used to assign parentage to 0+ parr. Using field data collected over 1.5 years on individual fish, this study tested parental influence on offspring performance in terms of size and growth rate and calculate the reproductive contribution of maternal/paternal anadromous and freshwater-residents. Adult life-history strategy was identified using a combination of results from SIA, PIT tag data and ecological data (body size, temperature). Parr life-history strategy (1+) was inferred using PIT tag detection data. The results of the SIA indicated fry of anadromous females emerged earlier and at a larger size than fry of freshwater-resident females. Parentage assignment of parr was low (28 %), with 8 parr assigned to both parents and 43 assigned to only a single parent. There was no detectable effect of parental life-history on parr size and growth rate, however the raw data may suggest offspring of anadromous parents have an early size advantage but a slower growth compared to offspring of freshwater-resident parents during the first year of the parr stage. Twenty-four percent of the offspring were identified as putative smolts at 2+ and both forms interbred and could produce offspring of each life-history. Estimates of reproductive contribution (SIA and growth) show a higher proportion of anadromous females and males (growth only) contributed to offspring production. The results of this research indicate that the maternal anadromous contribution is higher in the Tadnoll Brook population, affording fitness benefits to their offspring during early ontogeny such as size advantages and emerging at a more profitable time to establish feeding territories. Adult life-history does not appear to influence juvenile (0+ parr) life-history but may have an effect on offspring performance. The presence of both forms in the population suggests the anadromous fitness benefits to offspring may only have an affect during ontogeny and early stages of growth. Then after juveniles reach a size threshold environmental factors influence offspring life-history, resulting in the largest parr with the fastest growth adopting an anadromous life-history.

The presence of competitors and predators as well as plant quality affect which plants an insect feed from. These factors affect food choice through the entire insect life cycle, and is especially important when it comes to nurturing larvae. Females oviposition choice sets the initial stage for larval growth and survival, and it is therefore predicted that there is a strong selection pressure to make them oviposit on the best plants possible. This study looks into the behavior of nutrient driven ovipositing and food choice in the beetles Phratora vitellinae and Lochmaea caprea by offering individuals ten leaves of Salix viminalis, one treated with extra nitrogen in order to increase the nutritional value, and four treated with extra carbon, which should lower the nutritional value. During the choice experiment, only two females of Phratora vitellinae oviposited, making it impossible to draw any conclusion regarding nutrient driven oviposition choice. However, data showed a preference for nitrogen treated leaves and an avoidance of untreated control leaves in almost every case when looking into the largest loss of area for leaves of each treatment. When analyzing the number of leaves of each treatment that is eaten per individual there was a slight preference for nitrogen treated leaves, even though the probability of nitrogen being ranked as most preferred in this case was almost zero. Carbon treated leaves and acetone treated control leaves were equally avoided. For Lochmaea caprea, females fed from a significantly larger numer of leaves than males did (t-test, t=1.86, p=0.0003). An ANOVA showed no significant difference in C:N ratio among leaf treatments (ANOVA, F=9.28E-07, p=0.99). Since plant C:N ratio most likely will increase continuously due to CO2 emissions, the effects an increased carbon concentration in plant tissues has on oviposition and food choice in herbivorous insects is something to look further into. More studies on this subject are therefore needed.

Following decades of research on stress and its impact on behaviour, it is now widely accepted that selective psycho-pathologies, in particular clinical depression are more prevalent in humans with prior history of life-stress events. Interest in stress has led to questions about how it might affect the physiology and behaviour of animals exposed indirectly during gestational development. Not unexpectedly gestational stress has been shown to affect the offspring in several ways: endocrine responses to stress are elevated, fear, arousal and affective disturbances are all subject to vary if the pregnant animal is subjected to periods of aversive stimulation. Beginning in 1997, Michael Meaney of McGill University produced a series of publications suggesting that peri-natal events influence offspring and infant development, not via physical discomfort or physiological disturbance, but does so through modifications of maternal behaviour. Highly nurturant mothers (those who engage in active arched-back nursing (ABN), and spend more time licking and grooming (L/G) their pups), programme their offspring with improved cognitive abilities, decreased anxiety and fear, and reduced HPA axis hormone secretion. Low-nurturant mothers, who engage in less ABN and less L/G, tend to programme the opposite responses in their offspring. Our initial foray into this field was to investigate if gestational stress might also produce responses in the offspring via changes in maternal behaviour, and indeed ABN and L/G were reduced in dams which were subjected to gestational stress. We queried why stressed Dams would be less maternal towards their infants, and tested gestationally-stressed Dams in the Porsolt test for depressive-like behaviour. Our results suggested that these stressed Dams were actually depressed and this resulted in less maternal behaviour. Human mothers with depression are also less maternal and have been shown to divest themselves of infant care much like our prenatally-stressed Dams. On this basis we have proposed that gestational stress induced decrements in maternal behaviour represent a novel rat model for postnatal depression with face and construct validities. In the present work we have attempted to replicate the findings of Smythe's group (Smith et al., 2004), and have investigated the potential for antidepressants to alter the influence of gestational stress on maternal behaviours and depressive-like response, and whether or not the offspring are modified by maternal treatment with ant-depressants. Approximately 140 time-mated, lister hooded rats were generated in house, and subjected to gestational stress on days 10-20 (1hr restraint/day) or remained undisturbed in their home cages. Following birth, cohorts of control and stressed Dams were administered vehicle or an antidepressant (imipramine 15mg/kg; or sertraline 10mg/kg) once daily until postnatal day 10. We assessed maternal Porsolt activity, nurturance (ABN, L/G, nest building) and anxiety-like behaviour in the elevated plus maze (EPM). Representative offspring of each Dam's treatment conditions were maintained post weaning and assessed in the Porsolt and EPM to determine if any changes in maternal behaviour elicited by the antidepressants altered their behavioural programming. Our findings confirm that Dams show depressive-like symptoms following gestational stress, and that administration of antidepressants to the Dams reduces depressive-like behaviour and increased maternal care. We propose that rat gestational stress is a putative model for human postnatal depression. Prenatal stress effects on maternal behaviour in the rat Dam represent a novel, and innovative model for human postnatal depression.

O presente estudo investigou o perfil comportamental de ovinos entre o parto e a primeira mamada dos neonatos e sua influência sobre a sobrevivência e peso ao desmame dos cordeiros. O experimento foi conduzido em uma criação comercial de sistema intensivo, ao longo de três estações de parição, entre junho e novembro de 2006. Foram acompanhadas 216 ovelhas gestantes da raça Santa Inês e os 306 cordeiros nascidos. As observações comportamentais de ovelhas e cordeiros foram realizadas em períodos de 12 horas, através do método direto e em amostragem focal a cada 5 minutos. Para as mães, foram analisadas as variáveis postura (PTM), atividade (ATM) e tempo para tocar a cria (TTC). Os comportamentos avaliados nos cordeiros foram postura (PTC), atividade (ATC), tempo para ficar em pé (TEP) e tempo para mamar (TPM). Foi também estudada a influência do tipo (simples, duplo ou triplo) e duração do parto (TP e DP) sobre a manifestação dos comportamentos materno-filiais e desempenho dos cordeiros. As análises foram conduzidas através do pacote estatístico SAS®. O modelo adotado para avaliar a relação entre as variáveis foi o General Linear Model, através do procedimento GLM. As ovelhas recém-paridas despendem seu tempo principalmente com comportamentos voltados à formação de um vínculo exclusivo com a cria e com cuidados importantes para a sobrevivência imediata do cordeiro. Já os cordeiros, após aptos a se levantarem e se locomoverem, priorizaram a ingestão do colostro. A rapidez das ovelhas em iniciar os cuidados maternais (TTC=1,4863±8,3587 segundos), a baixa ocorrência de comportamentos antagônicos à cria e a agilidade dos cordeiros para se levantar (TEP=20,8797±17,6991 minutos) e mamar (TPM=46,0726±27,7284 minutos) são indícios da adaptação comportamental da raça Santa Inês a condições extensivas de criação. Os cuidados maternais realizados entre o nascimento e a primeira mamada do cordeiro influenciaram em sua agilidade, medida através do tempo para ficar em pé (P<0,01) e para mamar (P<0,01). A atividade da mãe interferiu no peso do cordeiro ao desmame (P<0,05), tendo os que receberam cuidados mais adequados apresentado um melhor desempenho. Sob as condições deste estudo, a agilidade do neonato não interferiu no peso ao desmame. Também não foram verificados efeitos do comportamento materno ou neonatal sobre a sobrevivência dos cordeiros até o desmame. Cordeiros nascidos de partos múltiplos ou longos apresentaram menor agilidade neonatal (P<0,05). O peso ao nascer sofreu forte influência do tipo de parto (P<0,01), sendo maior para filhotes nascidos de partos simples. Da mesma forma, o tipo do parto influenciou também o peso ao desmame dos cordeiros (P<0,01). / The present study investigated sheep maternal-offspring behavior from birth to first suck and its influence on lamb survival and weight at weaning. The experiment was conducted on a commercial intensive system flock, from June to November, 2006. Data were collected on 216 Santa Inês ewes and their 306 newly-born lambs. Focal animal observations were carried out every 5 minutes, in 12-hour periods. For the ewes, the variables analyzed consisted on posture (PTM), activity (ATM) and time to touch the lamb (TTC). The behaviors analyzed for the lambs were posture (PTC), time to stand up (TEP) and time to suck (TPM). The influence of birth type (simple, double or triple) and labor length, litter size and weight at weaning were also considered. The analyses were conducted through the SAS® statistical package. The model adopted to evaluate the relation between variables was the General Linear Model through the GLM procedure. Immediately after parturition, ewes spent their time mostly with behaviors directed to bonding with the neonates. Newly-born lambs, soon after succeeding in standing up and walking, prioritized colostrum ingestion. The short time required to start maternal care (TTC=1.4863±8.3587 seconds), the low incidence of negative behaviors against the lambs and the neonatal agility to stand (TEP=20.8797±17.6991 minutes) and suck (TPM=46.0726±27.7284 minutes) are indicatives of behavioral adaptations to extensive conditions. Maternal behaviors influenced neonatal agility, measured through time to stand (P<0.01) and to suck (P<0.01). Maternal activity influenced lamb weight at weaning (P<0.05), so lambs that received more adequate care were heavier. Under this study conditions, neonatal agility did not interfere on lamb weight at weaning. Effects of maternal and neonatal posture or activity on lamb survival up to weaning were not verified either. Lambs born from multiple or long births showed less neonatal agility (P<0.05). Lamb birth weights were influenced by the litter size, being singles born heavier (P<0.01). Labor conditions also influenced lamb weight at weaning (P<0.01).

Le trouble bipolaire (TB) est un trouble psychiatrique qui toucherait au minimum 1% à 2% de la population adulte. Si l'étiologie de ce trouble reste complexe et multifactorielle, le poids des facteurs génétiques est conséquent avec une héritabilité estimée entre 70% et 80%. Le fait d'avoir un parent bipolaire apparaît comme le premier facteur de risque de développer soi-même un trouble bipolaire. Egalement, ces enfants présentent un très haut risque d’avoir des psychopathologies. Un marqueur intéressant chez ces enfants pour identifier ce risque est le profil de dysrégulation obtenu au CBCL-DP. Ainsi, l'accès à des programmes de prévention ciblés, avant même l’apparition des troubles de ces enfants « à risque » (enfants de parents bipolaires ayant des symptômes sub-cliniques et un profil au CBCL-DP élevé) est une démarche prometteuse. Les programmes centrés sur la famille (Family Focused Therapy, FFT) dont l'efficacité est établie dans le TB à début précoce pourraient servir de base à des actions de prévention. En France, à ce jour aucune étude ne s’est intéressée à ces enfants.Méthode : Ce protocole exploratoire a été écrit dans le cadre d’une collaboration entre le service de pédopsychiatrie et le Centre Expert Bipolaire au sein du CHU de Montpellier. Nous proposons de faire participer 17 enfants « à risque » (moyenne age = 9,6 ans) à un programme de TCC multifamilles centré sur la gestion émotionnelle et la résolution de problèmes afin de voir si la dimension de dysrégulation est améliorée en fin de groupe. Au terme de ce groupe et à 12 mois, une réévaluation est proposée afin d’en mesurer les éventuels bénéfices par rapport à l’évaluation initiale.Résultats : Une amélioration significative est montrée sur la dimension de dysrégulation à la fin du groupe (p = 0,007) et en phase de suivi (p = <.001). Toutefois, compte tenu des limites méthodologiques de notre étude et en l’absence de groupe contrôle, il faut être prudent quant aux conclusions et répliquer cette étude avec un groupe contrôle. / Bipolar disorder (BD) is a psychiatric disorder that affects about 1% to 2% of adults. Its aetiology is complex and multifactorial but the genetic factors play an important role, with an estimated heritability between 70% and 80%. Having a bipolar parent appears to be the first risk factor for self-development of BD. Also, these children present a very high risk of having disorders.In this context, a high score in the Child Behavior Check-List-Dysregualtion Profile (CBCL-DP) is constantly reported as a reliable screener. Offering the identified children targeted prevention programs, in order to provide them strategies to face the developing symptoms, is a promising approach. The Family Focused Therapy (FFT) is a multifamily, parents-children CBT program. Its effectiveness was proved in early-onset BD and it is now considered as a possible preventive action for BD offsprings. In France, no study have been conducted on this population Method : The aim of our research is to test the efficacy of a FFT program on a French sample of 17 parents and BD offsprings (mean age = 9,6 years). The protocol was written in the context of a collaboration between the Child and Adolescent Mental Health Service (CAMHS) St Eloi and the Bipolar Expert Centre, within the University Hospital of Montpellier. Families were involved in a CBT program that focuses on emotion and problem solving strategies. Assessment was conducted at the end of this group and after 12 months, in order to measure the benefits compared to the first evaluation. Results: A significant decrease is shown on the dysregulation dimension at the end of the group (p = 0,007) and in the follow-up phase (p = <.001). However, given the methodological limitations of our study and in the absence of a control group, one should be cautious when considering caution should be exercised in making the findings. A replication of this first exploratory study, including a control group, is now necesary.

Made available in DSpace on 2017-07-21T14:35:55Z (GMT). No. of bitstreams: 1 Joao Lucas Paula Xavier.pdf: 2302678 bytes, checksum: a0e9c597df36bf49fdcaa1d1a19eee7b (MD5) Previous issue date: 2016-03-04 / Metabolic programming is a phenomenon triggered by nutritional and/ or hormonal changes that occur at critical stages of development, such as lactation and may promote metabolic and functional changes that determine the greater predisposition to pathological conditions in adulthood, as obesity and DM2. The work aims to characterize the effect of reducing the number of offspring pups on the biometric parameters, metabolic and histological maternal and offspring at different stages of lactation.On the 3rd day after birth the number of offspring pups was adjusted Normal Litter (NL), and 9 puppies Reduced Litter (RL), 3 puppies. Mothers and Mothers-NL-RL and the puppies and puppies-NL-RL were studied after 7, 14 and 21 day lactation evaluating the metabolic profile, body composition and histological aspects. The results demonstrated decreased food intake Mother-RL in 3 stages of lactation, higher stock of retroperitoneal fat and increased thermogenic activation in brown adipose tissue (BAT). The mammary gland presented a lower degree of alveolar development with increased adiposity, resulting in milk with higher calorie content. Mothers-RL also show a reduction in the size of pancreatic islets, liver weight reduction with increased blood glucose levels. Puppies-RL had higher body weight, obesity, accompanied by increase in BAT and indications of lower thermogenic activity in this sector. Additionally these animals showed less brain and adrenal weight during the progression of lactation. Puppies-RL also have elevated blood glucose and serum protein. Thus, the study confirms that litter reduction during the lactation period promotes maternal morphophysiological changes with effects on body weight and metabolism of offspring, events that can be programming markers and its complications throughout life. / A programação metabólica é um fenômeno desencadeado por alterações nutricionais e/ou hormonais que ocorrem em fases críticas do desenvolvimento, como a lactação, podendo promover mudanças metabólicas e funcionais que determinam a maior predisposição a estados patológicos na vida adulta. O trabalho teve como objetivo caracterizar o efeito da manipulação do número de filhotes da ninhada sobre os parâmetros biométricos, metabólicos e histológicos maternos e sua repercussão sobre a prole em diferentes fases da lactação. No 3º dia após o nascimento o número de filhotes da prole foi ajustado em Ninhada Normal (NN), 9 filhotes e Ninhada Reduzida (NR), 3 filhotes. As Mães-NN e Mães-NR, bem como, os Filhotes-NN e Filhotes-NR foram estudados ao 7º, 14º e 21º dia de lactação avaliando o perfil metabólico, composição corporal e aspectos histológicos. Os resultados demonstraram diminuição de consumo alimentar das Mães-NR, maior estoque de gordura retroperitoneal e menor depósito de gordura no tecido adiposo marrom (TAM). A glândula mamária apresentou menor grau de desenvolvimento alveolar, com aumento da adiposidade, resultando em leite com maior teor calórico. Mães-NR também apresentaram redução no tamanho de ilhotas pancreáticas, redução de peso do fígado, com aumento da glicemia. Filhotes-NR apresentaram maior peso corporal, obesidade, acompanhada de aumento do TAM e indícios de menor atividade termogênica. Adicionalmente estes animais apresentaram menor peso cerebral e adrenal durante a progressão da lactação. Filhotes-NR também apresentaram elevação da glicemia e proteinemia.Deste modo, o estudo confirmou que a redução de ninhada durante o período lactacional promove alterações morfofisiológicas materna com repercussões sobre o peso corporal e metabolismo da prole, eventos que podem ser marcadores de programação e suas complicações ao longo da vida.

Les maladies métaboliques sont en pleine expansion dans nos sociétés actuelles et constituent un enjeu de santé publique majeur. Les antécédents familiaux, l'environnement et les habitudes de vie de l'individu vont jouer un rôle dans la susceptibilité à certains de ces désordres métaboliques. Sur la base de données épidémiologiques, un lien a été établi entre environnement durant les premières phases de la vie et survenue de pathologies à l'âge adulte conduisant au concept de DOHaD. L'objectif de ce travail était d'étudier, à partir d'un modèle murin, les conséquences de l'exercice physique quotidien de la mère pendant la gestation ou la lactation sur la composition corporelle, la fonction pancréatique et la gestion des substrats énergétiques de la descendance à plus ou moins long terme. L'entraînement maternel avant et pendant la gestation est associé à des modifications de la structure et de la fonction du pancréas de la descendance et semble modifier sa gestion des substrats énergétiques à tous les âges. L'exercice de la mère est également associé à une moindre prise de poids de la descendance et limite sa prise de masse grasse lorsqu'elle est soumise à un régime gras et sucré. L'exercice physique de la mère durant la lactation va modifier la composition du lait et la fonction pancréatique de la descendance. Cependant, il est associé à une augmentation du poids corporel de la descendance adulte mais semble la protéger contre l'insulino-résistance induite par la séparation maternelle. La pratique d'un exercice physique quotidien pendant la gestation et/ou la lactation semble donc modifier le développement et la maturation de certains organes (pancréas, tissu adipeux, foie, muscle squelettique) de la descendance ainsi que sa gestion des substrats énergétiques. Les conséquences de cet entraînement maternel sur la descendance vont être plus ou moins bénéfiques selon son âge et selon son environnement nutritionnel. Ce travail de thèse vient compléter les travaux menés dans le cadre des DOHaD et renforce l'idée que l'environnement lors des premières phases de la vie va avoir des conséquences à plus ou moins long terme sur la santé de l'individu. / Prevalence of metabolic diseases is growing up in our modern societies and constitutes a major public health concern. Family history, environment and lifestyle play a role in the susceptibility to several metabolic disorders. Based on epidemiological data, a link has been established between the environment during the first stages of life and diseases occurrence in adulthood leading to the concept of DOHaD. The aim of this work was to study, using a murine model, the effect of daily maternal exercise during gestation or lactation on offspring body composition, pancreatic function and energy substrates handling on a short- and a long-term basis. Maternal training before and during gestation is associated with changes in offspring pancreas structure and function and in energy substrates handling at all ages. Maternal exercise also decreases offspring body weight gain and fat mass gain when exposed to a high-fat/high sucrose diet. Maternal physical exercise during lactation modifies milk composition and offspring pancreatic function. However, it is associated to an increase in offspring body weight in adulthood but seems to protect against the insulin resistance induced by maternal separation. In conclusion, daily physical exercise during gestation and/or lactation modifies offspring organs development and maturation (such as pancreas, adipose tissue, liver, skeletal muscle) and its energy substrates handling. Maternal training consequences on offspring can be either beneficial or deleterious depending on its age and on its nutritional environment. This work is complementary to studies conducted in the framework of the DOHaD concept and strengthens the idea that the environment during the first stages of life will have short- to long-term impacts on the health of the individual.

Offspring of parents with bipolar disorder (BD) are at high risk for psychiatric disorders, but mechanisms conferring risk are not well understood. Identifying and understanding factors that increase offspring vulnerability may inform intervention efforts. Three studies examined the following risk factors: (1) obstetric complications (OCs); (2) family functioning; and (3) clinical characteristics of parental BD. Investigations included cross-sectional data from two Massachusetts General Hospital studies of 109 BD parents and 206 offspring. Study 1 examined associations between: (1) maternal lifetime comorbid anxiety and OCs in pregnancy/delivery; (2) OCs and development of offspring psychopathology. Associations emerged between maternal anxiety and OCs. OCs, particularly during delivery, also correlated with offspring anxiety disorders. Path analyses revealed that delivery complications mediated the relationship between maternal and offspring anxiety. Study 2 examined associations between family functioning (cohesion, expressiveness, conflict) and offspring psychopathology, and explored moderation by offspring age and sex. Higher conflict and lower cohesion correlated with offspring internalizing and externalizing symptoms. Lower cohesion correlated with offspring mood disorders. Moderation analyses indicated that the link between cohesion and internalizing symptoms was stronger for younger compared to older children. Also, conflict and mood disorder were associated in younger boys, but not in older boys or in girls. Study 3 classified parents according to BD course presentation using latent class analysis, and examined associations between parental class membership and offspring psychopathology. The best-fitting model yielded three parent groups that were based on 8 illness characteristics. Some notable patterns differentiated classes: Class 1 and 2 parents had earlier illness onset, whereas Class 3 parents had later onset; Class 2 consisted of parents with Bipolar-II Disorder, whereas Class 1 parents had Bipolar-I Disorder. Class differences emerged for offspring anxiety disorders, but only among females. Class 3 parents had girls with fewer anxiety disorders compared to the other classes, with girls of Class 2 parents at greatest risk. Altogether, these studies identify several specific environmental mechanisms that increase psychopathology risk in offspring of BD parents. Such findings have important implications for targeted prevention and intervention.