Function In Adult Life Research Articles

Alcohol and fetal risk: a property of the drink or the drinker?

Alcohol and fetal risk: a property of the drink or the drinker?

Programmed hypertension in rats treated with a NF-κB inhibitor during nephrogenesis: renal mechanisms

Suppression of the renin-angiotensin system (RAS) during murine lactation causes progressive renal injury, indicating a physiological action of angiotensin II on nephrogenesis. The nuclear factor NF-κB system is one of the main intracellular mediators of angiotensin II. We investigated whether inhibition of this system with pyrrolidine dithiocarbamate (PDTC) during rat nephrogenesis would lead to similar hypertension and renal injury as observed with RAS suppressors. Immediately after delivery, 32 Munich-Wistar dams, each nursing 6 male pups, were divided into 2 groups: C, untreated, and PDTC, receiving PDTC, 280 mg kg(-1) day(-1) orally, during 21 days. After weaning, the offspring were followed until 10 months of age without treatment. Adult rats that received neonatal PDTC exhibited stable hypertension and myocardial injury, without albuminuria. To gain additional insight into this process, the renal expression of RAS components and sodium transporters were determined by quantitative real-time PCR (qRT-PCR) at 3 and 10 months of life. Renal renin and angiotensinogen were upregulated at 3 and downregulated at 10 months of age, suggesting a role for early local RAS activation. Likewise, there was early upregulation of the proximal sodium/glucose and sodium/bicarbonate transporters, which abated later in life, suggesting that additional factors sustained hypertension in the long run. The conclusions drawn from the findings were as follows: (1) an intact NF-κB system during nephrogenesis may be essential to normal renal and cardiovascular function in adult life; (2) neonatal PDTC represents a new model of hypertension, lacking overt structural injury or functional impairment of the kidneys; and (3) hypertension in this model seems associated with early temporary activation of renal RAS and sodium transporters.

Improvisational International Research: Seeking to Help Children in Ukrainian Orphanages Sooner than Later

Throughout the past decades tumultuous sociopolitical transitions in Ukraine, the number of orphaned children increased dramatically. Ukrainian orphanages commonly provide care for children without parents. While much data exist demonstrating the negative impact of institutional living on child development and functioning in adult life, more limited data reflects the mental status of children while institutionalized. Ascertaining the mental health needs of children in orphanages would inform practitioners and policymakers regarding programmatic interventions needed to mitigate social and emotional challenges in this population. Strategies could then be developed to increase social and emotional skills required for adjustment and adaptation into the larger community upon leaving institutional life. Support for such research and planned interventions seems an appropriate social work endeavor.

Prenatal environmental exposures that may influence β-cell function or insulin sensitivity in middle age.

The associations between fetal environment and diabetes risk are likely mediated by the offspring's diminished pancreatic β-cell function or reduced insulin sensitivity. Our ability to distinguish between these mechanisms is impeded by the lack of markers describing an individual's gestational environment. Fingerprints, however, are permanently fixed in the first half of gestation, and increased values of a dermatoglyphic marker that contrasts fingerprint ridge counts between the thumbs and fifth fingers (Md15) have been linked to type 2 diabetes. Among 763 adults without known diabetes from the Dutch Hunger Winter Families Study, we tested the associations of Md15 with homeostatic assessment indices of β-cell function (HOMA-b) and insulin sensitivity (QUICKI). For either outcome index, linear regression models included terms for Md15 tertiles and for maternal history of diabetes as reported by each participant. All models were corrected for sibling pairs and adjusted for age, sex and famine exposures. Increased Md15 was associated with decreased HOMA-b (P = 0.03 for Md15 tertile 3 v. 1) but not with QUICKI. In contrast, maternal history of diabetes was associated with decreased QUICKI (P < 0.001) but not with HOMA-b. Birth weight (available for 520 participants) was positively associated with increased QUICKI (P = 0.04 for birth weight tertile 3 v. 1) but not with HOMA-b. Fingerprint Md15, maternal history of diabetes and birth weight may help to identify specific defects in the control of adult glucose metabolism. Research into the environment associated with Md15 variation may suggest prenatal strategies for optimizing β-cell function in adult life.

Epidemiology of the Origins of Airflow Limitation in Asthma

There is now conclusive evidence that, as a group, subjects with asthma have lower levels of lung function as compared with their peers and that a significant proportion of subjects with persistent asthma are at risk of developing non-fully reversible airflow limitation, the clinical hallmark of chronic obstructive pulmonary disease. Although at the population level the most conspicuous form of airflow limitation in asthma seems to be that of subjects who wheeze during the first years of life and whose symptoms persist into adult life, asthma-related lung deficits can be related to both acquired deficits in growth of lung function in childhood and steeper decline of lung function in adult life. These trajectories of lung function are likely to differ across subgroups of individuals with asthma, suggesting that different windows of opportunity may exist to modify the natural course of the disease before irreversible deficits are established. These observations indicate the importance of identifying biomarkers that can be used to target children and adults with asthma at increased risk for airflow limitation and determining whether pharmacological interventions can protect these patients from the development of chronic obstructive pulmonary disease.

Visual Function in Working-Age Adults: Early Life Influences and Associations with Health and Social Outcomes

To investigate how visual function in mid-adult life is associated with health and social outcomes and, using life-course epidemiology, whether it is influenced by early life biological and social factors. Population-based cohort study. Nine thousand three hundred thirty members of the 1958 British birth cohort at age 44 or 45 years. Distance, near, and stereo vision were assessed as part of a broader biomedical examination. Logistic, multinomial, and proportional odds ordinal logistic regression were used, as appropriate, to assess the association between these vision functions and both key early life influences and health and social outcomes in mid-adult life. Distance, near, and stereo acuities and health and social outcomes. In mid-adult life, vision function (across the full spectrum of both type and level of function) is associated with unemployment resulting from permanent sickness, lower socioeconomic status, and poorer general health (for example, for blindness; odds ratios were 2.5, 2.6, and 1.2, respectively). Also, impaired visual functions in mid-adult life are associated with a low birthweight, being small for gestational age, maternal smoking in pregnancy, and markers of socioeconomic deprivation in childhood (for example, for impaired distance acuity; odds ratios were 1.4, 1.3, 1.02, and 1.1, respectively). Although relatively uncommon in working-age adults, impaired vision can have important adverse consequences, which highlights the value of investigating visual function in the broader context of health and social functioning. In addition, visual function in adult life may be influenced directly by key prenatal and childhood biological and social determinants of general health. Thus, application of life-course epidemiology to complex chronic ophthalmic diseases of adult life such as glaucoma or macular degeneration is likely to prove valuable in elucidating whether and how biological, social, and lifestyle factors contribute to the cause.

Asma e função pulmonar aos 6-7 anos de idade em uma coorte de nascimentos no Sul do Brasil

Asthma and respiratory symptoms are common in children, and many studies have shown associations between childhood symptoms and impaired lung function in adult life. The aim of the present study was to investigate the association of various respiratory symptoms with wheezing patterns (persistent, early, and late-onset) and lung function, as well as to determine whether lung function was associated with atopy or with demographic, socioeconomic, environmental, and gestational factors, in a birth cohort at 6-7 years of age. The target population consisted of children aged 6-7 years from a birth cohort of 5,304 children born in southern Brazil in 1993. For this follow-up evaluation, 532 of those children were randomly selected, and a sub-sample was submitted to spirometry and skin prick tests. A questionnaire was administered to the parent(s) or legal guardian(s) of each child. Spirometric values were lower in the children with respiratory symptoms or asthma. Mean forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC ratio) was lower in children with any of the following: current wheezing and asthma; asthma ever; four or more episodes of wheezing within the preceding 12 months; sleep disturbance due to wheezing; and exercise-induced wheezing. Persistent wheezing was associated with lower FEV1/FVC ratio. After multiple linear regression, exercise-induced wheezing was also associated with reduced FEV1/FVC ratio. Nonwhite skin color and wheezing severe enough to limit speech were associated with lower FEV1. Children with persistent wheezing and symptoms of severe asthma have impaired lung function at 6-7 years of age.

General practitioners’ understanding of depression in young people: qualitative study

BackgroundDepression in young people is not necessarily self-limiting, and is frequently associated with affective disorders and impaired psychosocial functioning in adult life. Early recognition of and response to depression in teenagers could be an important task for general practitioners (GPs), but there are multiple obstacles to achieving this.ObjectivesTo explore GPs perceptions of the opportunities and difficulties of working with teenagers, and of specifically recognizing and responding to depression.Setting and participantsNine GPs who had taken part in a developmental project on diagnosing and treating depression in young people. All worked in an Inner London Medical Centre.MethodsSemi-structured interviews transcribed and analysed thematically.FindingsTwo over-arching themes that emerged from the interviews were that teenagers were perceived as being qualitatively different from adults in the ways they used general practice, and that GPs were uncomfortable with making a diagnosis of depression in young people. Within the first theme, we identified sub-themes, including failure of teenagers to engage with services, parental involvement, complex presentations and lack of time. Within the second theme, the sub-themes were surprise, normalization of depressed mood and challenge to the validity of psychiatric diagnosis in this age group.ConclusionsProfessional development in general practice that addresses this topic needs to modify two perceptions; that depressed mood is in some sense ‘normal’ in this age group, and that teenagers are so different in their use of services that the management of depression (if it is recognized at all) is problematic.

Prenatal Programming of Renal Function: The Estimated Glomerular Filtration Rate is Influenced by Size at Birth in Apparently Healthy Children

Prenatal growth is known to affect glomerular function in adult life. It is unknown, however, whether this association is also present in children. In a cross-sectional study, we examined whether birth weight (BW) is associated with serum creatinine (measured by an improved Jaffe method) and GFR (estimated by the Haycock-Schwartz formula; eGFR) in 73 apparently healthy school-age children (35 boys and 38 girls; age 9.5 +/- 0.4 yr). All children were born after singleton term pregnancies (gestational age 39.6 +/- 0.2 wk) with normal BW (3.2 +/- 0.04 kg). A significant decrease in serum creatinine and increase in the eGFR was evident by tertiles of BW-SD score (SDS) (p = 0.001 and p < 0.0001). eGFR was correlated with BW-SDS (r = 0.45; p < 0.0001), so that each unit increase in BW-SDS was associated with an increase in eGFR of 10 (95% CI 5-14) ml/min per 1.73 m. In summary, estimates of glomerular function are in apparently healthy school-age children influenced by size at birth. These findings suggest early effects for the prenatal programming of renal function in humans.

Effects of fetal and neonatal exposure to nicotine on blood pressure and perivascular adipose tissue function in adult life

In Wistar rats, maternal exposure to nicotine was shown to impair the inhibitory function of perivascular adipose tissue on vascular contractility in the aorta of the offspring. It is not known whether an impairment of perivascular adipose tissue function occurs in smaller arteries, and whether the control of blood pressure is affected. Here we studied the blood pressure effects and the alteration of perivascular adipose tissue function in mesenteric arteries of the offspring born to Wistar–Kyoto rat (WKY) dams exposed to nicotine. Nulliparous female WKY rats were given either nicotine bitartrate (1 mg/kg/day) or saline (vehicle) by subcutaneous injection 2 weeks prior to mating, during pregnancy and until weaning. Blood pressure of the offspring and functional studies with mesenteric arteries were conducted. Tissue samples (thoracic aorta, mesenteric arteries, and kidneys) were collected for morphological and immunohistochemical examinations. Blood pressure increased from 14 weeks of age onwards in the offspring born to nicotine-exposed dams. Nicotine-exposed offspring showed a significant increase in the number of brown adipocytes in aortic perivascular adipose tissue relative to control offspring. In mesenteric arteries from control offspring, contractile responses induced by phenylephrine, serotonin, and 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F 2alpha (U44619) were significantly attenuated in the presence of perivascular adipose tissue, an effect not observed in the nicotine-exposed tissues. Endothelium-dependent relaxation responses to carbachol, kidney weight, the total number of nephrons and glomerulus' size were comparable in nicotine and saline groups. We conclude that fetal and neonatal exposure to nicotine caused blood pressure elevation. Alterations in perivascular adipose tissue composition and modulatory function are some of the mechanisms associated with this blood pressure increase.

Early Feminizing Genitoplasty: Sexual Function in Adult Life

PURPOSE To evaluate the sensitivity of external genitalia and to assess sexual function and orgasm in a group of adult patients submitted to early feminizing genitoplasty during childhood. MATERIAL AND METHODS We included patients affected by congenital adrenal hyperplasia, who were surgically treated in their infancy, now aged 18 years or more and requiring a complete sexual life. Thermal and vibratory sensibility of clitoris, vagina and labia minora were analyzed using the Genito-Sensory Analayzer (GSA), a device aimed at determining temperature and vibratory measurements, with a feedback patient-response switch. Psychosexual outcome was assessed with validated questionnaires. RESULTS Fifteen patients entered the stdy. At GSA evaluation thermal sensibility appeared decreased both at the clitoris and vagina, whereas vibratory sensibility was decreased at the clitoris but within normal limits at the vagina in all cases. Questionnaires showed slight depression in 3 patients; slight anxiety in all patients; active sexual desire, good arousal, adequate lubrification and presence of orgasm in all patients. Eight patients described stable satisfactory heterosexual relationship, 3 patients reported stable unsatisfactory heterosexual relationship without penetration, 3 patients refused the test, and 1 patient described a satisfactory homosexual relationship. CONCLUSIONS Our study suggests that vaginal vibratory sensibility was conserved in all patients, whereas clitoral vibratory sensibility, vaginal thermal sensibility and clitoral thermal sensibility were altered. It was not possible to verify if these results have to be attributed to the surgical technique, to the age at surgery, or to the original malformation of the external genitalia. All patients reported orgasm even in absence of penetration.

Growth hormone (GH)-releasing hormone and GH secretagogues in normal aging: Fountain of Youth or Pool of Tantalus?

Although growth hormone (GH) is primarily associated with linear growth in childhood, it continues to have important metabolic functions in adult life. Adult GH deficiency (AGHD) is a distinct clinical entity, and GH replacement in AGHD can improve body composition, strength, aerobic capacity, and mood, and may reduce vascular disease risk. While there are some hormone-related side effects, the balance of benefits and risks is generally favorable, and several countries have approved GH for clinical use in AGHD. GH secretion declines progressively and markedly with aging, and many age-related changes resemble those of partial AGHD. This suggests that replacing GH, or stimulating GH with GH-releasing hormone or a GH secretagogue could confer benefits in normal aging similar to those observed in AGHD--in particular, could reduce the loss of muscle mass, strength, and exercise capacity leading to frailty, thereby prolonging the ability to live independently. However, while most GH studies have shown body composition effects similar to those in AGHD, functional changes have been much less inconsistent, and older adults are more sensitive to GH side effects. Preliminary reports of improved cognition are encouraging, but the overall balance of benefits and risks of GH supplementation in normal aging remains uncertain.

Glia-like Stem Cells Sustain Physiologic Neurogenesis in the Adult Mammalian Carotid Body

Neurogenesis is known to occur in the specific niches of the adult mammalian brain, but whether germinal centers exist in the neural-crest-derived peripheral nervous system is unknown. We have discovered stem cells in the adult carotid body (CB), an oxygen-sensing organ of the sympathoadrenal lineage that grows in chronic hypoxemia. Production of new neuron-like CB glomus cells depends on a population of stem cells, which form multipotent and self-renewing colonies in vitro. Cell fate mapping experiments indicate that, unexpectedly, CB stem cells are the glia-like sustentacular cells and can be identified using glial markers. Remarkably, stem cell-derived glomus cells have the same complex chemosensory properties as mature in situ glomus cells. They are highly dopaminergic and produce glial cell line-derived neurotrophic factor. Thus, the mammalian CB is a neurogenic center with a recognizable physiological function in adult life. CB stem cells could be potentially useful for antiparkinsonian cell therapy.

Zinc deficiency during growth: Influence on renal function and morphology

This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n = 12) or a control diet (zinc: 30 mg/kg, n = 12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex. Zinc-deficient rats showed a decrease in glomerular filtration rate and no changes in sodium and potassium urinary excretion. Zinc deficiency decreased NADPH diaphorase activity in glomeruli and tubular segment of nephrons, and reduced activity of nitric oxide synthase in the renal medulla and cortex, showing that zinc plays an important role in preservation of the renal nitric oxide system. A reduction in nephron number, glomerular capillary area and number of glomerular nuclei in cortical and juxtamedullary areas was observed in zinc deficient kidneys. Sirius red staining and immunostaining for 〈alpha〉-smooth muscle-actin and collagen III showed no signs of fibrosis in the renal cortex and medulla. An increase in the number of apoptotic cells in distal tubules and cortical collecting ducts neighboring glomeruli and, to a lesser extent, in the glomeruli was observed in zinc deficient rats. The major finding of our study is the emergence of moderate zinc deficiency during growth as a potential nutritional factor related to abnormalities in renal morphology and function that facilitates the development of cardiovascular and renal diseases in adult life.

Glucocorticoid “Programming” and PTSD Risk

Epidemiological data have linked an adverse fetal environment with increased risks of cardiovascular, metabolic, neuroendocrine, and psychiatric disorders in adulthood. Prenatal stress and/or glucocorticoid excess might underlie this link. In animal models, prenatal stress, glucocorticoid exposure or inhibition/knockout of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD-2), the feto-placental barrier to maternal glucocorticoids, reduces birth weight and causes permanent hypertension, hyperglycemia, increased hypothalamic-pituitary-adrenal (HPA) axis activity and behavior resembling of anxiety. In humans, 11 beta-HSD-2 gene mutations cause low birth weight and placental 11 beta-HSD-2 activity correlates directly with birth weight and inversely with infant blood pressure. Low birth weight babies have higher plasma cortisol levels throughout adult life, indicating HPA programming. In human pregnancy, severe maternal stress affects the offspring HPA axis and associates with neuropsychiatric disorders. Posttraumatic stress disorder (PTSD) appears to be a variable in the effects. Intriguingly, some of these effects appear to be 'inherited' into a further generation, itself unexposed to exogenous glucocorticoids at any point in the lifespan from fertilization, implying epigenetic marks persist into subsequent generation(s). Overall, the data suggest that prenatal exposure to excess glucocorticoids programs peripheral and CNS functions in adult life, predisposing to some pathologies, perhaps protecting from others, and these may be transmitted perhaps to one or two subsequent generations.

Neurogenetic interactions and aberrant behavioral co-morbidity of attention deficit hyperactivity disorder (ADHD): dispelling myths

BackgroundAttention Deficit Hyperactivity Disorder, commonly referred to as ADHD, is a common, complex, predominately genetic but highly treatable disorder, which in its more severe form has such a profound effect on brain function that every aspect of the life of an affected individual may be permanently compromised. Despite the broad base of scientific investigation over the past 50 years supporting this statement, there are still many misconceptions about ADHD. These include believing the disorder does not exist, that all children have symptoms of ADHD, that if it does exist it is grossly over-diagnosed and over-treated, and that the treatment is dangerous and leads to a propensity to drug addiction. Since most misconceptions contain elements of truth, where does the reality lie?ResultsWe have reviewed the literature to evaluate some of the claims and counter-claims. The evidence suggests that ADHD is primarily a polygenic disorder involving at least 50 genes, including those encoding enzymes of neurotransmitter metabolism, neurotransmitter transporters and receptors. Because of its polygenic nature, ADHD is often accompanied by other behavioral abnormalities. It is present in adults as well as children, but in itself it does not necessarily impair function in adult life; associated disorders, however, may do so. A range of treatment options is reviewed and the mechanisms responsible for the efficacy of standard drug treatments are considered.ConclusionThe genes so far implicated in ADHD account for only part of the total picture. Identification of the remaining genes and characterization of their interactions is likely to establish ADHD firmly as a biological disorder and to lead to better methods of diagnosis and treatment.

Recombinant Cell-Based Bioluminescence Assay for Androgen Bioactivity Determination in Clinical Samples

Androgens regulate several physiologic processes, such as normal prostate development and maintenance of male sexual function in adult life, and they are also involved in pathologic conditions, including prostate cancer, prepubertal gynecomastia, and premature pubarche. Androgens enter the target cell and bind to androgen receptor (AR), a ligand-dependent transcription factor in the nuclear receptor superfamily comprising receptors for vitamin D3 and thyroid and steroid hormones (1)(2). After binding of the hormone, AR enters the nucleus and binds to the regulatory region of the target gene as a homodimer. Recent findings suggest that some environmental chemicals disrupt the endocrine system and cause adverse effects such as cancers and sexual abnormalities in humans and wildlife (3). These endocrine-disrupting compounds include several xenoestrogens, androgens, and antiandrogens, which present a variety of chemical structures and mechanisms of action (4)(5). Conventional detection methods for androgenic and antiandrogenic compounds cannot evaluate hormonal bioactivity, which is important in a wide range of clinical conditions, and no alternative direct and simple methods for measurement of plasma androgen bioactivity are available. In addition, the increased use of androgenic substances as therapeutic drugs and their abuse to enhance athletic performance require sensitive and rapid screening tests. The very low amounts of single analytes in anabolic cocktails and nutritional supplements are difficult to detect with standard techniques such as gas chromatography–mass spectrometry. Thus, bioassays that reveal the overall androgen bioactivity of complex mixtures would be more appropriate tools with great implications in antidoping analysis (6)(7)(8). We developed and validated a yeast-based bioassay to measure androgen bioactivity in clinical samples, including human serum, for the detection of androgen-like and antiandrogenic compounds (9). The bioassay is based on recombinant Saccharomyces cerevisiae BMA64-1A strain genetically engineered with the introduction of 2 plasmids: an …

Retrospective review of L3 myelomeningocele in three age groups: should posterolateral iliopsoas transfer still be indicated to stabilize the hip?

The data from 58 hips in 29 myelodysplastic children with L3 paralysis has been reviewed retrospectively. Posterolateral transfer of the iliopsoas (Sharrard technique) was performed on all hips to correct muscle imbalance between 1975 and 1992. The average length of follow-up was 21 years. Preoperatively, 58.6% of the hips were either subluxated or dislocated (these were surgically reduced at the same stage). Radiological assessment revealed that 91.4% of the hips were stable at preschool age and 84.5% in adolescence. Of the patients 86% were functional walkers at preschool age and 75.8% in adolescence. Downward transitions in seven patients were related to the presence of scoliosis, spasticity and obesity. All patients who were community walkers in adolescence maintained their function in adult life at the time of the review. We conclude that the procedure has value in obtaining hip stability and walking ability in carefully selected patients with myelomeningocele.

Effects of Intrauterine Food Restriction and Long-Term Dietary Supplementation with l-Arginine on Age-Related Changes in Renal Function and Structure of Rats

We have previously demonstrated that restricting intrauterine food by 50% in 3-mo-old rats produced lower nephron numbers and early-onset hypertension, the latter being normalized by L-arginine administration. In 18-mo-old rats, such restriction increased glomerulosclerosis. In this study, we expanded our investigation, evaluating functional, morphologic, and immunohistochemical parameters in intrauterine-food-restricted 18-mo-old rats, either receiving L-arginine (RA18) or not (R18). Age-matched, non-food-restricted controls were assigned to similar groups with L-arginine (CA18) and without (C18). After weaning, L-arginine was given daily for 17 mo. No functional or morphologic changes were observed in C18 rats. The R18 rats developed early-onset hypertension, which persisted throughout the observation period, as well as significant proteinuria from 12 mo on. In RA18 rats, L-arginine decreased both blood pressure levels and proteinuria, and glomerular diameter was significantly smaller than in R18 rats (115.63 +/- 2.2 versus 134.8 +/- 1.0 mum, p < 0.05). However, in RA18 rats, glomerular filtration rate remained depressed. Although L-arginine prevented glomerulosclerosis (R18 = 14%, RA18 = 4%; p < 0.05), glomerular expression of fibronectin and desmin was still greater in RA18 rats than in controls. Our data show that, although L-arginine prevented hypertension and proteinuria, glomerular injury still occurred, suggesting that intrauterine food restriction may be one of the leading causes of impaired renal function in adult life.

A “deficient environment” in prenatal life may compromise systems important for cognitive function by affecting BDNF in the hippocampus

The intrauterine environment has the capacity to mold the prenatal nervous system. Particularly, recent findings show that an adverse prenatal environment produces structural defects of the hippocampus, a critical area sub-serving learning and memory functions. These structural changes are accompanied by a disruption in the normal expression pattern of brain-derived neurotrophic factor (BDNF) and its cognate tyrosine kinase B (TrkB) receptor. The important role that the BDNF system plays in neural modeling and learning and memory processes suggests that fetal exposure to unfavorable intrauterine conditions may compromise proper cognitive function in adult life. These findings have implications for disorders that involve a dysfunction in the BDNF system and are accompanied by cognitive deficits.