Critical Period Of Susceptibility Research Articles

Not Just a Mood Disorder─Is Depression a Neurodevelopmental, Cognitive Disorder? Focus on Prefronto-Thalamic Circuits.

Depression is one of the most burdensome psychiatric disorders, affecting hundreds of millions of people worldwide. The disease is characterized not only by severe emotional and affective impairments, but also by disturbed vegetative and cognitive functions. Although many candidate mechanisms have been proposed to cause the disease, the pathophysiology of cognitive impairments in depression remains unclear. In this article, we aim to assess the link between cognitive alterations in depression and possible developmental changes in neuronal circuit wiring during critical periods of susceptibility. We review the existing literature and propose a role of serotonin signaling during development in shaping the functional states of prefrontal neuronal circuits and prefronto-thalamic loops. We discuss how early life insults affecting the serotonergic system could be important in the alterations of these local and long-range circuits, thus favoring the emergence of neurodevelopmental disorders, such as depression.

Developmental Sensitivity to the Induction of Great Vessel Malformations by N-(2-Aminoethyl)ethanolamine

N-(2-Aminoethyl)ethanolamine (AEEA) induced malformations of the great vessels in the offspring of rats treated during gestation and early lactation (Schneider et al., 2012. Birth Defects Res B Dev Reprod Toxicol [in press]). The aim of this study was to determine if in utero exposure alone was sufficient to induce these malformations or whether a peri-postnatal exposure or physiological component was required. Three groups of five time-mated female Wistar Han rats were administered AEEA (250 mg/kg/day) by gavage from gestation day (GD) 6 to GD 19 (groups 1 and 2) or from GD 6 to postnatal day 3 (group 3). Animals were euthanized on GD 21 (group 1) or postnatal day 4 (groups 2 and 3), and the hearts of the offspring were examined for changes to the great vessels. The incidence of malformations in group 1 was 91.1%, and primarily consisted of high aortic arch and abnormal carotid course. One fetus had an aortic aneurysm. All fetuses in groups 2 and 3 were malformed, primarily exhibiting abnormal carotid course and aneurysms, which mainly affected the aorta, ductus arteriosus, and pulmonary trunk. The incidence of high aortic arch was lower relative to group 1. Aneurysms were more prevalent in group 3 compared to group 2. These findings indicate that exposure to AEEA during gestation alone was sufficient to induce malformations of the great vessels and aneurysms, which may be triggered by physiological changes that occur during or after birth, but that the critical period of susceptibility to AEEA-induced aneurysms in the rat extends beyond gestation into the early postnatal period.

The Impact of Environmental and Occupational Exposures on Reproductive Health

Environmental exposures during critical periods of susceptibility in utero may result in lifelong or intergenerational adverse health effects. Most chemicals in commercial use in the United States have not been tested for possible developmental toxicity to fetuses, infants, and children. Environmental and occupational exposures can result in adverse effects on female and male reproduction. Nurses can identify at-risk patients, provide education about the impact of chemical toxicants, and empower women to take precautionary action.

The Critical Period for Susceptibility of Human Stereopsis

Purpose To define the critical period for susceptibility of human stereopsis to an anomalous binocular visual experience. Methods Random dot stereoacuity was measured in 152 children with a history of onset of either infantile or accommodative strabismus before 5 years of age. In each of these populations and in the combined population, the critical periods for susceptibility of stereopsis are described using four-parameter developmental weighting functions. Results In children with infantile strabismus, the critical period for susceptibility of stereopsis begins at 2.4 months and peaks at 4.3 months. In children with accommodative esotropia, the critical period for susceptibility of stereopsis begins at 10.8 months and peaks at 20 months. When the data are combined across the two populations, the critical period begins soon after birth and peaks sharply at 3.5 months but shows continued susceptibility to at least 4.6 years. Conclusions An anomalous binocular visual experience during early infancy severely disrupts stereopsis, yet the critical period for susceptibility of stereopsis extends through late infancy and early childhood and continues to at least 4.6 years of age.

Childhood socioeconomic circumstances and cause-specific mortality in adulthood: systematic review and interpretation.

There is convincing evidence that exposures acting across the life course influence adult health outcomes (1–3). Lifecourse epidemiology examines a range of potential processes through which exposures acting at different stages of life can, singly or in combination, influence disease risk (table 1) (4). In the critical period model, an exposure acting at a specific time has long-lasting effects on the structure or function of the body. The fetal origins hypothesis, in its original formulation, took this approach (5). Other examples of processes where outcomes appear to depend upon the time window during which an exposure acts are limb development (in relation to maternal thalidomide use); infection with hepatitis B and risk of adulthood liver cancer (with very early postnatal infection being most implicated); and environmental lead exposure, which results in serious neurodevelopmental deficits only if occurring in infancy and childhood (3). However, the influence of exposures acting during critical periods of susceptibility may be modified by later life exposures. This is the case for the associations of birth weight with coronary heart disease, high blood pressure, and insulin resistance, where associations are stronger (or only evident) among those who become obese during adolescence or adulthood (6–8).

Longevity of augmented phagocytic activity of heterophils in neonatal chickens following administration of Salmonella enteritidis-immune lymphokines to chickens

Previously, our laboratory reported an existing relationship between ontogenesis of heterophil activity and susceptibility to Salmonella enteritidis infection in poultry during the first week post-hatch. The prophylactic administration of S. enteritidis-immune lymphokines has been shown to enhance heterophil function in vitro and reduce S. enteritidis organ invasion in 1-day-old chicks. However, how long the heterophils remain activated is currently unknown. The objective of this research was to evaluate the duration of enhanced heterophil phagocytosis of S. enteritidis following the prophylactic administration of a single injection of S. enteritidis-immune lymphokines to neonatal chicks. Administration of S. enteritidis-immune lymphokines on the day of hatch resulted in a significant increase in heterophil phagocytic activity (P < 0.05) through day 5 post-hatch. No significant differences in phagocytic activities of heterophils from control and S. enteritidis-immune lymphokinetreated chicks was demonstrated from day 6 to 14 post-hatch. These data suggest that the administration of S. enteritidis-immune lymphokines on day of hatch potentiates heterophil phagocytic activity during a critical period of susceptibility to Salmonella infection in neonatal chicks. The immune lymphokine-induced enhancement of heterophil activity subsides by day 5 as the chick's natural defenses mature and are able to resist infections without exogenous augmentation.

Do seasonal priming effects in the first months of life influence development of middle ear disease?

A history of acute otitis media (AOM) often precedes development of otitis media with effusion (OME); where that history pre-dates the first birthday an increased risk has been demonstrated previously. The possibility of establishing a critical period of susceptibility to the priming attack of AOM is explored using a large national database. The complete GP histories of 7510 children born in the year beginning October 1989 and followed until their fifth year of life, within practices representative of England and Wales, permit examination of the following risk factors: history of asthma, eczema and hayfever; type and timing of all middle-ear-related conditions; upper respiratory tract infections; reported snoring; sex. The following risk factors were confirmed: sex, atopy (in particular hayfever), nose, chest and throat infections (particularly chest), and reported snoring. Age of first attack of AOM was the strongest indicator of subsequent OME. Risk decreased with increased age. Different age groups were examined in 3-month bands and a critical period could be detected covering the first 9 months of life. Risk of subsequent OME varied slightly by season of first AOM, particularly within the critical period. Children born in spring appeared to be at highest risk.

Critical periods during development as assessed by thallium-induced inhibition of growth of embryonic chick tibiae in vitro.

In ovo application of thallium sulfate has been shown to produce a characteristic shortening and angulation of the tibia of the embryonic chick. The critical period for susceptibility to thallium-induced inhibition of tibial growth ends at 8 2/3 days of incubation, a time when the growth rate of the embryo declines by 55%. The aim of the present study was to expose tibiae to thallium in vitro to determine whether this response was intrinsic to the tibia. A 4-hour exposure to 400 micrograms thallium was found to be most effective. Growth of tibiae from 8-day-old embryos was inhibited, growth of tibiae from 9-day-old embryos was not, and the response of tibiae isolated from embryos of 8 2/3 days of incubation was intermediate. Therefore, the response of the tibia to thallium represents an intrinsic property and is not secondary to inhibited nerve growth as has been suggested. The critical period and its termination is also an intrinsic property of the tibia. Tibiae were exposed to thallium for 4 hours at various times after the tibiae had been established in vitro. Susceptibility to growth inhibition was shown to decline as tibiae developed beyond the critical period, a decline that could be correlated with a declining growth rate. Emphasis is placed upon critical events during development as a more useful concept than critical periods for explaining susceptibility to teratogens.

Critical periods in development for susceptibility to the effects of stroboscopic rearing in the rabbit visual cortex.

Previous studies have shown that rearing rabbits in a stroboscopically illuminated environment results in a decrease in orientation and direction selectivity and an increase in responsivity to stroboscopic stimuli among neurons in area 17. In the present study, the critical period for susceptibility to these effects was studied by varying the time of onset of the deprivation. Groups of Dutch belted rabbits were reared normally and then placed in a stroboscopically illuminated environment at ages 1, 2 or 3 months, and response characteristics of visual cortical neurons were compared with those obtained from normal rabbits and from rabbits reared in a stroboscopic environment from birth. Results show that the different effects of strobe rearing have different critical periods. Increased responsivity to stroboscopic stimuli was seen only in rabbits deprived from birth. The effects of strobe rearing on both direction and orientation selectivity decreased with increasing age at the time of onset of the deprivation. However, only direction selectivity was modified by deprivation beginning at 3 months of age.