Добірка наукової літератури з теми "Cognition – Foetus"

Introduction: Corpus callosum (CC) is the largest commissural white fibres interconnecting cerebral hemispheres. The corpus callosum is responsible for interhemispheric transfer of information which is essential for cognitive function. The foetal corpus callosum serves as sensitive indicator for normal brain development and maturation. As the corpus callosum is a part of the highest order latest maturing mental network of the brain, its measurements are important to assess normal brain development and to locate structural changes. A comprehensive evaluation of normal human foetal corpus callosal development is essential to detect and understand the congenital anomalies of the brain. Thus, the prenatal diagnosis of partial or complete agenesis of the corpus callosum is important for predicting the normal development of the foetus. Foetal neural anomalies that are suspected on prenatal ultrasonography (USG) can be detected in early stage using foetal MRI. This imaging technique is highly useful for detailed visualization of normal neural development. Certain conditions like colpocephaly and widening of interhemispheric fissure can be clearly visualized using foetal MRI when compared to prenatal ultrasonography. Aim and objective: Was to establish the normal reference values for the measurement of foetal corpus callosum. The length and thickness of the foetal CC was measured corresponding to gestational age (GA) between 18-36weeks. Materials and methods: A retrospective MRI study was carried out in Radiology department of Sri Ramachandra Hospital. The study was conducted on 50 pregnant women with GA of 18-32 weeks and morphology of foetal corpus callosum was measured using MRI. The corpus callosum was visualized in a mid-sagittal plane as an anechoic structure, delimited by two echogenic lines superiorly by sulcus of the corpus callosum and inferiorly by the septum pellucidum. The length of corpus callosum was measured from the anterior most aspect of genu to the posterior most aspect of the splenium and the width of individual parts were measured and correlated with gestational age. The values obtained from the study were statistically calculated using regression coefficient method. Results: In the present study following parameters were observed such as length and width of diverse parts of Corpus callosum. The length of foetal CC ranged from 25.96 to 47.2 mm in 18 to 32 weeks of gestational age. The range of width of rostrum, genu, body and splenium were 1.2 to 2.2 mm, 1.2-2.8mm, 1.3-3.1mm and 1.36-3.2mm respectively. Conclusion: The periodic development of nervous system can be calculated more effectively with the morphometric measurement of foetal CC and its correlation with BPD. It is considered to be accurate than using BPD measurement of head circumference in USG. Hence, with the normative data of foetal CC measurements correlated with gestational age would give us accurate details of neuronal growth rather than measuring biparietal diameter (BPD) alone using USG. This knowledge will be highly helpful for the gynaecologists to predict the abnormal development of the foetus and it is advised to include foetal CC parameters as a one of the tools for early detection of CNS anomalies.

The foetal environment is filled with a variety of noises. Among the manifold sounds of the maternal respiratory, gastrointestinal and cardiovascular systems, the intonation properties of the maternal language are well perceived by the foetus, whose hearing system is already functioning during the last trimester of gestation. These intonation (melodic) features, reflecting native-language prosody, have been found to shape vocal learning. Having had ample opportunity to become familiar with their mother’s language in the womb, newborns have been found to exhibit salient pitch-based elements in their own cry melodies. An interesting issue is whether an intrauterine exposure to a maternal pitch accent language, such as Swedish, in which emphatic syllables are pronounced typically on a higher pitch relative to other syllables will affect newborns’ cry melody (fundamental frequency contour). The present study aimed to answer this question by quantitatively analysing and comparing the melody structure in 52 Swedish compared with 79 German newborns. In accordance with previous approaches, cry melody structure was analysed by calculating a melody complexity index (MCI) expressing the share of cries exhibiting two or more (well-defined) arc-like substructures uttered during the recording sessions. A low MCI reflects a dominance of cries with a ‘simple’, i.e. single-arc melody. A significantly higher MCI was found in the Swedish infant group, which further corroborates the assumption that the well-known foetal sensitivity for musical (melodic) stimuli seems to shape infants’ cry melody.

Foetal Alcohol Spectrum Disorders (FASD) develop when unborn children are exposed to alcohol prenatally. As a result of this exposure, children with FASD exhibit a range of social, behavioural, cognitive and even physical deficits that can impede their life-long development. These deficits can be influenced by maltreatment and the instability resulting from being placed into out-of-home care, and/or multiple foster-care placement breakdowns. The aim of this article is to increase awareness amongst child welfare professionals of how prenatal alcohol exposure impacts on children's social development. Social deficits include problems with social cognition and social information processing, which result in issues in social problem solving, processing social cues, social judgement, and developing and maintaining relationships. These deficits leave children with a FASD vulnerable to victimisation, exploitation, peer pressure and, as a result, interaction with the criminal justice system. Deficits are life-long and become more pronounced with age, although early detection and intervention appears to improve social skills deficits. Such interventions need to be explored further as they could potentially mitigate some of these deficits by capitalising on the neuroplasticity of a child's developing brain and pave a more positive trajectory for these children's future.

Prenatal nutrient exposures can impact on brain development and disease susceptibility across the lifespan. It is well established that maternal macronutrient intake during pregnancy influences foetal and infant development. Therefore, we hypothesise that macronutrient intakes during pregnancy are correlated with cognitive development during early childhood. The current study aimed to investigate the relationship between maternal macronutrient intake during pregnancy and child cognitive and behavioural outcomes at age 4 years. We analysed prospective data from a cohort of 64 Australian mother–child dyads. Maternal macronutrient intake was assessed using a validated 74-item food frequency questionnaire at 2 timepoints during pregnancy. Child cognition and behaviour were measured at age 4 years using the validated Wechsler Preschool and Primary Scale of Intelligence, 3rd version (WPPSI-III) and the Child Behaviour Checklist (CBC). Linear regression models were used to quantify statistical relationships and were adjusted for maternal age, education, pre-pregnancy BMI, breastfeeding duration and birthweight. Child Performance IQ was inversely associated with maternal starch intake (b = −11.02, p = 0.03). However, no other associations were found. Further research is needed to explore the association between different types of starch consumed during pregnancy and child cognitive development.

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (>17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (<7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.

Background: Alcohol exposure impairs brain development and leads to a range of behavioural and cognitive dysfunctions, termed as foetal alcohol spectrum disorders. Although different mechanisms have been proposed to participate in foetal alcohol spectrum disorders, the molecular insights of such effects are still uncertain. Using a mouse model of foetal alcohol spectrum disorder, we have previously shown that maternal binge-like alcohol drinking causes persistent effects on motor, cognitive and emotional-related behaviours associated with neuroimmune dysfunctions. Aims: In this study, we sought to evaluate whether the long-term behavioural alterations found in offspring with early exposure to alcohol are associated with epigenetic changes in the hippocampus and prefrontal cortex. Methods: Pregnant C57BL/6 female mice underwent a model procedure for binge alcohol drinking throughout both the gestation and lactation periods. Subsequently, adult offspring were assessed for their cognitive function in a reversal learning task and brain areas were extracted for epigenetic analyses. Results: The results demonstrated that early binge alcohol exposure induces long-term behavioural effects along with alterations in histone acetylation (histone H4 lysine 5 and histone H4 lysine 12) in the hippocampus and prefrontal cortex. The epigenetic effects were linked with an imbalance in histone acetyltransferase activity that was found to be increased in the prefrontal cortex of mice exposed to alcohol. Conclusions: In conclusion, our results reveal that maternal binge-like alcohol consumption induces persistent epigenetic modifications, effects that might be associated with the long-term cognitive and behavioural impairments observed in foetal alcohol spectrum disorder models.

Foetal development has dictated by maternal gestational diet and intrinsic factors, physical activity, and environmental stimulations. Many studies provided evidence for metabolic disorders in adult life who underwent under nutrition during their foetal life. This review is an effort to use the published data to know the effect of the intrauterine environment on chronic metabolic disorders. Here, we discuss the impact of foetal under nutrition on the development of chronic metabolic diseases. Intrauterine under nutrition negatively influences health after birth. In adults, under-nutrition in utero results in metabolic impairments and cognitive impairments. Under nutrition during foetal/embryonic development influences human physiology and has a lifelong effect, often called foetal programming. This review concludes that the intrauterine environment and foetal nutrition play a significant role in developing chronic metabolic disorders. Therefore, this study provides the necessary insight into target timely interventions in the earliest possible time to prevent offspring from developing chronic diseases in adult life.

Cette étude s'intéresse au devenir de l'expérience vécue in utero après la naissance et sa fonction dans l'économie psychique infantile. Il s'agit de réfléchir au phénomène d'humanisation de l'être nouveau : comment le bébé se détourne-t-il du mode d'être fœtal qu'il a connu, pour s'orienter vers le mode d'être social qui lui est promis ? La réflexion se fait en deux temps et dans l'ordre chronologique. La première partie se consacre au prénatal. Après avoir fait un tour d'horizon des perspectives actuelles autour de cet objet d'étude, nous proposons une phénoménologie de la vie fœtale. La deuxième partie se situe dans le postnatal pour y étudier le devenir des traces du prénatal. Dans notre hypothèse, la disparition du milieu intra-utérin à la naissance laisserait des traces en creux chez le nouveau-né. Ces empreintes de la vie fœtale permettraient d'orienter le bébé vers des formes sensorielles complémentaires de contenance et de rythmes dans les soins maternels. Chez le bébé autiste, cette recherche se ferait de façon auto-sensuelle, sans passer par l'autre. Elle perdurerait dans le temps sans aboutir à la formation d'une peau psychique
This research aims to study the remnants of prenatal experience after birth and their clinical expression in early development and in autistic symptoms. The thesis is divided in two parts following a chronological order. The first part is a literature review of the prenatal experience. We also present new theoretical considerations about in utero life, in line with the perspective of phenomenology. In the second part, we discuss the role of its remnants in the early onset of infantile psychological development. According to our hypothesis, imprints of the prenatal experience are created at birth. These imprints guide the newborn baby in finding complementary forms of foetal experiences in the postnatal world. While a healthy baby will search for those extensions through its mother's care, an autistic baby will create sensorial substitutes of the prenatal life by itself. Finally, we explore three situations of adults with autism, who display a clinical form of regression to a foetal state of existence

Les humains peuvent ressentir leurs muscles. Ils peuvent également reconnaître leur environnement et les objets qui s'y trouvent. Enfin, ils sont capables de se situer dans cet environnement et d'y atteindre des objets. Comment ces capacités sont acquises et interagissent les unes avec les autres au cours du développement ? Cette question demeure ouverte en biologie. Notre objectif est donc d’aider les biologistes à mieux comprendre comment un humain est capable de construire sa carte cognitive et d’effectuer des mouvements dirigés vers un objectif. Sur le plan développemental, l’acquisition des capacités sensorimotrices humaines débute avec le fœtus. Nous présentons ici un modèle théorique du développement de la carte cognitive d’un fœtus humain à partir de son système sensorimoteur. Le modèle intègre les proprioceptions des membres du corps et les perceptions de l’environnement et comment celles-ci coopèrent pour construire une carte cognitive. Cette carte est essentielle afin d'effectuer des mouvements dirigés vers un objectif et atteindre différents objets au sein de l’environnement. Nous proposons un nouvel algorithme de clustering appelé “Frequency-based-means”, qui est utilisé pour obtenir les proprioceptions et les perceptions qui constituant la carte d’association. Des modèles de Markov cachés sont utilisés pour modéliser l’apprentissage et la production de mouvements
Humans can internally sense their muscles. They can also recognize their environment with its objects and are able to navigate through it easily to reach them. How these abilities are gained and interact each other is still an open question in biology. Our aim is to help biologists to understand how a human is able to build his cognitive map and make goal-directed movements. The origin of human capabilities goes back to the fetus stage. We present a theoretical model of the development of the cognitive map of a fetus human from his sensorimotor system. The model integrates the proprioceptions of body limbs and perceptions from the environment and how these cooperate to build a cognitive map, which in turn, is essential for making goal-directed movements to reach different objects in the surrounding environment. We propose a new clustering algorithm called “Frequency-based-means”; which is used to get the proprioceptions and the perceptions that form the association map. Hidden Markov Models are used to model movement learning and production

Maternal alcohol binge drinking during pregnancy can be deleterious for the developing foetus, leading to a wide range of long-lasting morphological and neurobehavioural disabilities known as foetal alcohol spectrum disorders, associated with a higher risk of developing substance use disorders later in life. We sought to assess the effects of prenatal and postnatal alcohol exposure on cognitive, emotional, motor and addictive behaviour in mice and its underlying molecular mechanisms. Pregnant C57BL/6 female mice underwent a procedure to model alcohol binge drinking either during gestation or throughout both the gestation and lactation periods. Then, male offspring were assessed for their behaviour at adulthood. Binge alcohol exposure during early brain development induces cognitive deficits, increased anxiety-like behaviour, motor coordination impairments, and age-dependent locomotor activity alterations. Behavioural effects are associated with an upregulation of pro-inflammatory signalling, gliosis, neuronal death, myelin impairments and epigenetic modifications in the prefrontal cortex and hippocampus. Furthermore, early alcohol exposed mice show alterations in brain network connectivity. Curcumin treatment ameliorates anxiety and cognitive dysfunctions, and rescues alcohol-induced neuroinflammation. In addition, mice exposed to alcohol in utero and postnatally show increased susceptibility to later alcohol and cocaine intake compared with their counterparts. Molecular analyses of the prefrontal cortex and striatum of these animals suggest alterations in the glutamatergic excitability within the mesocorticolimbic reward system following cocaine-induced reinstatement. Altogether, our results reveal that maternal binge-like alcohol consumption induces molecular alterations in offspring’s brain that may underlie the long-lasting impairments in offspring’s behaviour.
El consum maternal d’alcohol en afartament durant l’embaràs pot resultar perjudicial per al fetus en desenvolupament, donant lloc a una àmplia gamma de discapacitats físiques i mentals conegudes com a trastorns de l’espectre alcohòlic fetal que persisteixen al llarg de la vida i estan associades a un major risc de desenvolupar trastorns d’ús de substàncies en el futur. En aquesta tesi hem tractat d’avaluar els efectes de l’exposició prenatal i postnatal a l’alcohol en la conducta cognitiva, emocional, motora i addictiva en ratolins i els mecanismes moleculars subjacents a aquests. Les femelles de ratolins C57BL/6 embarassades van ser sotmeses a un procediment per modelar el consum d’alcohol en afartament durant la gestació o bé, al llarg dels períodes de gestació i lactància. A continuació es va avaluar el comportament de la descendència masculina a l’edat adulta. S’ha observat que l’exposició d’alcohol en afartament durant el desenvolupament cerebral indueix dèficits cognitius, augment de l’ansietat, alteracions de coordinació motora i de l’activitat locomotora en funció de l’edat. Els efectes del comportament estan associats a un increment de la senyalització proinflamatòria, gliosi, mort neuronal, deteriorament de la mielina i modificacions epigenètiques en el còrtex prefrontal i l’hipocamp, així com també alteracions en la connectivitat de la xarxa neuronal. El tractament de curcumina alleuja l’ansietat i les disfuncions cognitives, i restableix la neuroinflamació induïda per l’alcohol. A més, els ratolins exposats a l’alcohol durant la gestació i la lactància mostren una major susceptibilitat a la ingesta posterior d’alcohol i cocaïna en comparació amb els seus homòlegs. Els anàlisis moleculars de l’escorça prefrontal i de l’estriat d’aquests animals suggereixen la presència d’alteracions en l’excitabilitat glutamatèrgica en el sistema de recompensa mesocorticolimbic després de la recaiguda induïda per cocaïna. En conjunt, els nostres resultats indiquen que el consum maternal d’alcohol en afartament provoca alteracions moleculars en el cervell de la descendència com a mecanisme subjacent a les alteracions relatives al comportament persistents.

Dans une perspective de médecine régénératrice, les cellules souches nerveuses et progénitrices fœtales humaines constituent indéniablement un des outils les plus adaptés au traitement des lésions du SNC et des maladies neurodégénératives. Jusqu'à présent, leur utilisation en thérapie cellulaire a eu recours à des populations hétérogènes composées à la fois de cellules immatures, de cellules en voie de différenciation et de cellules pleinement différenciées. Or des études récentes ont révélé l'intérêt de disposer de populations enrichies en un type cellulaire donné afin d'améliorer l'efficacité des greffes. Pour homogénéiser les populations et mieux cibler les pathologies, nous avons donc mis en œuvre deux stratégies. La première consiste à surexprimer, dans les cellules en culture, les gènes proneuraux à motif bHLH Ngn1, Ngn2, Ngn3 et Mash1 au travers de vecteurs lentiviraux dits « de différenciation ». Cette surexpression a permis d'orienter la différenciation des cellules majoritairement vers le lignage neuronal et également de spécifier des sous-types neuronaux. La seconde méthode utilise des vecteurs lentiviraux traceurs pour exprimer une protéine rapportrice sous le contrôle de promoteurs spécifiques des différents lignages du SNC en vue de leur sélection par tri cellulaire. Nous avons ainsi utilisé le promoteur Nestine pour les cellules immatures, le promoteur Synapsine pour les cellules neuronales et le promoteur GFAP pour les cellules astrocytaires. Si les promoteurs Synapsine et GFAP ont révélé une spécificité contestable, le promoteur Nestine, quant à lui, a permis de sélectionner une population enrichie à 81% en cellules nestine+. Ce travail s'inscrit dans un projet de plus grande envergure, qui a pour but d'évaluer les bénéfices de greffes de ces populations homogénéisées.

Le terme Foetal Alcohol Spectrum Disorder (FASD) définit l’ensemble des perturbations observées dans la descendance de femme consommant de l’alcool durant leur grossesse. La variabilité des phénotypes du FASD suppose des mécanismes complexes de l’effet tératogène de l’alcool, et leur compréhension nécessite l'emploi d'une multiplicité de modèles animaux. A la lumière de ces modèles, quatre grands effets de l’alcoolisation d’un cerveau immature sont observés au niveau comportemental, avec des modifications de : (i) l’attention et la locomotion ; (ii) l’apprentissage et la mémoire ; (iii) du niveau de stress, d’anxiété et de dépression ; (iv) la sensibilité aux drogues. Le travail de cette thèse a porté à la fois sur les conséquences psycho-comportementales de l’alcoolisation fœtale et sur la possibilité de modulation de ces effets par des approches pharmacologique et/ou comportementale. Nous avons pour cela travaillé à partir de deux modèles murins d’alcoolisation précoce, le premier issu d’un protocole d’alcoolisation pré- et post-natale et le second correspondant à un protocole d’alcoolisation néonatale. Ce travail nous a permis tout d'abord d’établir que les rats pubères, précédemment alcoolisés en période pré- et post-natale, développaient un trouble hyperactif combiné à un déficit attentionnel. Dans un deuxième temps, nous avons observé qu’un traitement par un agoniste des Peroxisome Proliferator-Activated Receptors contrecarrait l’apparition de ces troubles de l’activité locomotrice et des capacités attentionnelles. Enfin dans un troisième temps, nous avons tenté d’accentuer ces effets de l’alcoolisation d’un cerveau immature. Ainsi l’apparition d’un trouble mnésique n’a pu être observée que consécutivement à l’application successive, soit d’un protocole d’alcoolisation pré- et post-natale et d’un traitement amphétaminique à l’adolescence, soit d’un protocole d’alcoolisation néonatale et d’un protocole de perturbation de la rythmicité circadienne à l’âge adulte. Les deux principales conclusions de ce travail portent sur : (i) la modélisation, chez le rat, de certains symptômes décrits dans le FASD et (ii) la modulation des effets de l’alcoolisation précoce qui peuvent être contrecarrés ou aggravés
The term Foetal Alcohol Spectrum Disorder (FASD) defines the set of foetal alcohol-induced alterations. The variability of FASD phenotypes may be due to the complex teratogenic effects of alcohol, and implies the use of multiple animal models to study them. In light of these models, the effects of alcohol on an immature brain have been shown to induce four major behavioural alterations: (i) attention and locomotion, (ii) learning and memory, (iii) Stress, anxiety and depression, (iv) drug sensitivity. Our work has focused on the consequences of foetal alcoholization to induce psycho-behavioural effects and their modulation. Using two rodent models of early alcohol exposure (by pre- and post-natal or neonatal alcoholization) we modulated the effects of alcohol by pharmacological or behavioural approaches. First, this work has allowed us to observe that early (pre-and post-natal) alcohol-exposed rats have a hyperactivity disorder combined with an attention deficit during puberty. Secondly we observed an improvement in those disorders treated by a peroxisome proliferator-activated receptors agonist. Thirdly, we tried to accentuate the effects of alcohol on an immature brain. We showed that the use of an amphetamine treatment during puberty on rats under a pre-and post-natal alcoholic treatment, as well as disruption of the circadian rhythm in adulthood on rats under a neonatal alcoholic treatment, induced a memory disorder. The two main conclusions of this work are: (i) the ability to model some FASD symptoms in the rat; (ii) the modulation of these early alcohol effects that can be reversed or aggravated

This article focuses on musically relevant psychological aspects of prenatal development: the development of perception, cognition, and emotion; the relationships between them; and the musical and musicological implications of those relationships. It begins by surveying relevant foetal sensory abilities: hearing, the vestibular sense of balance and acceleration, and the proprioceptive sense of body orientation and movement. All those senses are relevant for musical development, since in all known cultures music is inseparable from bodily movement and gesture, whether real or implied. The article then considers what sounds and other stimuli are available to the foetus: what patterns are the earliest to be perceptually learnt? It examines psychological and philosophical issues of foetal attention, ‘consciousness’, learning, and memory. The article closes with speculations about the possible role of prenatal development in the phylogeny of musical behaviours.

Developmental brain disorders, such as developmental dyslexia, specific language impairment (SLI), autism spectrum of disorders (ASD), and oral clefts, include perceptual-cognitive deficits of language, audition, attention, and memory. It is important to detect these dysfunctions in early childhood in order to determine how the development of perception and cognition differs from the typical course and to design interventions supporting development. The MMN, being elicited from the foetal stage onwards, is a promising tool for this purpose. It has illuminated low-level perceptual-cognitive dysfunctions in these disorders and shows promise as an early neural marker of future language-related dysfunction.

The challenge of sustaining democracy is complicated by the fact that political engagement exposes citizens to a cognitive and social dynamical force known as belief polarization that leads us to over-ascribe malicious motives, irrational ideas, and extreme commitments to those who we perceive to be political opponents. As we politically interact with our fellow partisans, we come to see those who do not share our political identity as untrustworthy, incompetent, and threatening. This gives rise to the democrat’s dilemma. However, belief polarization also infects our alliances, turning groups of like-minded people into increasingly homogeneous and conformist units that ultimately are internally hierarchical and unstable. The reason we have to sustain democracy with our foes is that unless we do so, we will not be able to sustain democracy among our allies.

A cohort study is one in which the outcome (usually disease status) is ascertained for groups of individuals defined on the basis of their exposure. At the time exposure status is determined, all must be free of the disease. All eligible participants are then followed up over time. Since exposure status is determined before the occurrence of the outcome, a cohort study can clarify the temporal sequence between exposure and outcome, with minimal information bias. The historical and the population cohort study (Box 9.1) are efficient variants of the classical cohort study described above, which nevertheless retain the essential components of the cohort study design. The exposure can be dichotomous [i.e. exposed (to obstetric complications at birth) vs. not exposed], or graded as degrees of exposure (e.g. no recent life events, one to two life events, three or more life events). The use of grades of exposure strengthens the results of a cohort study by supporting or refuting the hypothesis that the incidence of the disease increases with increasing exposure to the risk factor; a so-called dose–response relationship. The essential features of a cohort study are: ♦ participants are defined by their exposure status rather than by outcome (as in case–control design); ♦ it is a longitudinal design: exposure status must be ascertained before outcome is known. The classical cohort study In a classical cohort study participants are selected for study on the basis of a single exposure of interest. This might be exposure to a relatively rare occupational exposure, such as ionizing radiation (through working in the nuclear power industry). Care must be taken in selecting the unexposed cohort; perhaps those working in similar industries, but without any exposure to radiation. The outcome in this case might be leukaemia. All those in the exposed and unexposed cohorts would need to be free of leukaemia (hence ‘at risk’) on recruitment into the study. The two cohorts would then be followed up for (say) 10 years and rates at which they develop leukaemia compared directly. Classical cohort studies are rare in psychiatric epidemiology. This may be in part because this type of study is especially suited to occupational exposures, which have previously been relatively little studied as causes of mental illness. However, this may change as the high prevalence of mental disorders in the workplace and their negative impact upon productivity are increasingly recognized. The UK Gulf War Study could be taken as one rather unusual example of the genre (Unwin et al. 1999). Health outcomes, including mental health status, were compared between those who were deployed in the Persian Gulf War in 1990–91, those who were later deployed in Bosnia, and an ‘era control group’ who were serving at the time of the Gulf war but were not deployed. There are two main variations on this classical cohort study design: they are popular as they can, depending on circumstances, be more efficient than the classical cohort design. The population cohort study In the classical cohort study, participants are selected on the basis of exposure, and the hypothesis relates to the effect of this single exposure on a health outcome. However, a large cohort or panel of subjects are sometimes recruited and followed up, often over many years, to study multiple exposures and outcomes. No separate comparison group is required as the comparison group is generally an unexposed sub-group of the panel. Examples include the British Doctor's Study in which over 30,000 British doctors were followed up for over 20 years to study the effects of smoking and other exposures on health (Doll et al. 1994), and the Framingham Heart Study, in which residents of a town in Massachusetts, USA have been followed up for 50 years to study risk factors for coronary heart disease (Wolf et al. 1988). The Whitehall and Whitehall II studies in the UK (Fuhrer et al. 1999; Stansfeld et al. 2002) were based again on an occupationally defined cohort, and have led to important findings concerning workplace conditions and both physical and psychiatric morbidity. Birth cohort studies, in which everyone born within a certain chronological interval are recruited, are another example of this type of study. In birth cohorts, participants are commonly followed up at intervals of 5–10 years. Many recent panel studies in the UK and elsewhere have been funded on condition that investigators archive the data for public access, in order that the dataset might be more fully exploited by the wider academic community. Population cohort studies can test multiple hypotheses, and are far more common than any other type of cohort study. The scope of the study can readily be extended to include mental health outcomes. Thus, both the British Doctor's Study (Doll et al. 2000) and the Framingham Heart Study (Seshadri et al. 2002) have gone on to report on aetiological factors for dementia and Alzheimer's Disease as the cohorts passed into the age groups most at risk for these disorders. A variant of the population cohort study is one in which those who are prevalent cases of the outcome of interest at baseline are also followed up effectively as a separate cohort in order (a) to study the natural history of the disorder by estimating its maintenance (or recovery) rate, and (b) studying risk factors for maintenance (non-recovery) over the follow-up period (Prince et al. 1998). Historical cohort studies In the classical cohort study outcome is ascertained prospectively. Thus, new cases are ascertained over a follow-up period, after the exposure status has been determined. However, it is possible to ascertain both outcome and exposure retrospectively. This variant is referred to as a historical cohort study (Fig. 9.1). A good example is the work of David Barker in testing his low birth weight hypothesis (Barker et al. 1990; Hales et al. 1991). Barker hypothesized that risk for midlife vascular and endocrine disorders would be determined to some extent by the ‘programming’ of the hypothalamo-pituitary axis through foetal growth in utero. Thus ‘small for dates’ babies would have higher blood pressure levels in adult life, and greater risk for type II diabetes (through insulin resistance). A prospective cohort study would have recruited participants at birth, when exposure (birth weight) would be recorded. They would then be followed up over four or five decades to examine the effect of birth weight on the development of hypertension and type II diabetes. Barker took the more elegant (and feasible) approach of identifying hospitals in the UK where several decades previously birth records were meticulously recorded. He then traced the babies as adults (where they still lived in the same area) and measured directly their status with respect to outcome. The ‘prospective’ element of such studies is that exposure was recorded well before outcome even though both were ascertained retrospectively with respect to the timing of the study. The historical cohort study has also proved useful in psychiatric epidemiology where it has been used in particular to test the neurodevelopmental hypothesis for schizophrenia (Jones et al. 1994; Isohanni et al. 2001). Jones et al. studied associations between adult-onset schizophrenia and childhood sociodemographic, neurodevelopmental, cognitive, and behavioural factors in the UK 1946 birth cohort; 5362 people born in the week 3–9 March 1946, and followed up intermittently since then. Subsequent onsets of schizophrenia were identified in three ways: (a) routine data: cohort members were linked to the register of the Mental Health Enquiry for England in which mental health service contacts between 1974 and 1986 were recorded; (b) cohort data: hospital and GP contacts (and the reasons for these contacts) were routinely reported at the intermittent resurveys of the cohort; (c) all cohort participants identified as possible cases of schizophrenia were given a detailed clinical interview (Present State examination) at age 36. Milestones of motor development were reached later in cases than in non-cases, particularly walking. Cases also had more speech problems than had noncases. Low educational test scores at ages 8,11, and 15 years were a risk factor. A preference for solitary play at ages 4 and 6 years predicted schizophrenia. A health visitor's rating of the mother as having below average mothering skills and understanding of her child at age 4 years was a predictor of schizophrenia in that child. Jones concluded ‘differences between children destined to develop schizophrenia as adults and the general population were found across a range of developmental domains. As with some other adult illnesses, the origins of schizophrenia may be found in early life’. Jones' findings were largely confirmed in a very similar historical cohort study in Finland (Isohanni et al. 2001); a 31 year follow-up of the 1966 North Finland birth cohort (n = 12,058). Onsets of schizophrenia were ascertained from a national hospital discharge register. The ages at learning to stand, walk and become potty-trained were each related to subsequent incidence of schizophrenia and other psychoses. Earlier milestones reduced, and later milestones increased, the risk in a linear manner. These developmental effects were not seen for non-psychotic outcomes. The findings support hypotheses regarding psychosis as having a developmental dimension with precursors apparent in early life. There are many conveniences to this approach for the contemporary investigator. ♦ The exposure data has already been collected for you. ♦ The follow-up period has already elapsed. ♦ The design maintains the essential feature of the cohort study, namely that information bias with respect to the assessment of the exposure should not be a problem. ♦ As with the Barker hypothesis example, historical cohort studies are particularly useful for investigating associations across the life course, when there is a long latency between hypothesized exposure and outcome. Despite these important advantages, such retrospective studies are often limited by reliance on historical data that was collected routinely for other purposes; often these data will be inaccurate or incomplete. Also information about possible confounders, such as smoking or diet, may be inadequate.

New data suggest that a high maternal prenatal body mass index (BMI) is associated with differences in functional connectivity in the foetal brain that might confer a risk of mental health and cognitive problems in childhood.