Marsha Kaitz

BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions

BACKGROUND A key protein in maintaining neuronal integrity throughout the life span is brain-derived neurotrophic factor (BDNF). The BDNF gene is characterized by a functional polymorphism, which has been associated with stress-related disorders such as anxiety-related syndromes and depression, prompting us to examine individual responses by Genotype and Sex to a standardized social stress paradigm. Gender differences in BDNFxstress responses were posited because estrogen induces synthesis of BDNF in several brain regions. METHODS 97 university students (51 females and 46 males) participated in a social stress procedure (Trier Social Stress Test, TSST). Indices of stress were derived from repeated measurement of cortisol, blood pressure, and heart rate during the TSST. All subjects were genotyped for the Val66Met polymorphism. RESULTS Tests of within-subject effects showed a significant three-way interaction (SPSS GLM repeated measures: Time (eight levels)xBDNF (val/val, val/met)xSex: p=0.0002), which reflects gender differences in the pattern of cortisol rise and decline during the social challenge. In male subjects, val/val homozygotes showed a greater rise in salivary cortisol than val/met heterozygotes. In female subjects, there was a trend for the opposite response, which is significant when area under the curve increase (AUCi) was calculated for the val/val homozygotes to show the lowest rise. Overall, the same pattern of results was observed for blood pressure and heart rate. CONCLUSIONS These results indicate that a common, functionally significant polymorphism in the BDNF gene modulates HPA axis reactivity and regulation during the TSST differently in men and women. Findings may be related to gender differences in reactivity and vulnerability to social stress.

Parturient women can recognize their infants by touch.

This article shows that parturient women can identify their newborns by tactile cues alone and that the discriminative features are learned, without intent, during routine mother-infant interactions. To test for touch recognition, mothers were instructed to stroke the hand (dorsal surface) of 3 newborns, 1 of which was her own. She then guessed which of the 3 was her own infant. The results showed that the majority of women were successful at the task if they has been with their infant for 1 hr or more since childbirth. Control experiments showed that the discrimination was not based on olfactory or other nontactile cues. It was concluded that during routine mother-infant contact, mothers learn the unique tactile features of their infants skin and use these cues for individual recognition

Epigenetic and Genetic Factors Predict Women's Salivary Cortisol following a Threat to the Social Self

Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis (HPAA) is modulated by both genetic and environmental variables. Of special interest are the underlying molecular mechanisms driving gender differences to psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal candidates for mediating the effects of signals on the HPAA. In the current study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and female university students who participated in the Trier Social Stress Test (TSST). A linear regression model was used to ascertain the effects of sex, CpG methylation and genes on stress response. Total cortisol output (area under the curve, AUC) was significantly predicted by glucocorticoid receptor (NR3C1) exon 1F methylation (averaged across 39 CpG sites) solely in female subjects. A single CpG site located in the exon 1F noncanonical nerve growth factor-inducible protein A (NGFI-A) transcription factor was a highly significant predictor of AUC in female subjects. Additionally, variations in the estrogen receptor alpha (ESR1) and the serotonin transporter promoter (5-HTTLPR) genes were independent additive predictors of AUC. The full model accounted for half of the variance (50.06%) in total cortisol output. Notably, this is the first demonstration that epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These findings have important implications for understanding the molecular mechanisms underlying gender differences in stress-related disorders and underscore the unique value of modeling both epigenetic and genetic information in conferring vulnerability to stress.

Vasopressin needs an audience: Neuropeptide elicited stress responses are contingent upon perceived social evaluative threats

The nonapeptide arginine vasopressin (AVP) plays an important role in hypothalamus-pituitary-adrenal axis regulation and also functions as a social hormone in a wide variety of species, from voles to humans. In the current report we use a variety of stress inducing tasks, including the Trier Social Stress Test (TSST) and intranasal administration of AVP to show that intranasal administration of this neuropeptide leads to a significant increase in salivary cortisol and pulse rate, specifically in conditions where subjects perform tasks in the presence of a social evaluative threat (task performance could be negatively judged by others). In contrast, in conditions without a social evaluative threat (no task condition, modified TSST without audience and bike ergometry), subjects receiving AVP did not differ from subjects receiving placebo. Thus exogenous AVPs influence is contingent upon a circumscribed set of initial conditions that constitute a direct threat to the maintenance of our social selves. Stress evoked by social threat is an integral part of social life and is related to self-esteem and in extreme forms, to poor mental health (e.g., social phobia). Our findings suggest that AVP is a key component in the circuit that interlaces stress and social threat and findings offer inroads to our understanding of individual differences in sociability and in stress response elicited in threatening social situations.

The effect of light on brightness perception in rats with retinal dystrophy

Abstract Rats of the Royal College of Surgeons (RCS) strain undergo retinal degeneration within their first postnatal months. In this study, brightness detection thresholds for white and colored stimuli were measured in RCS rats using the behavioral method of conditioned suppression . Despite their retinal degeneration, RCS rats reared in cyclic light showed only a small visual deficit. Dark reared RCS rats had thresholds equal to those of nondystrophic albino rats. When exposed to continuous illumination, however, RCS rats raised in cyclic light showed severe visual deficits not incurred by nondystrophic albinos exposed to the same conditions.

Performance of Early-Blind and Sighted Children on Olfactory Tasks

The goal of the study was to test whether children with congenital or early-onset blindness outperform sighted children on olfactory tasks. Measures of olfactory sensitivity, odour recognition, and odour labeling were obtained. The results show that the blind children were more proficient at correctly labeling 25 common odours than were matched sighted children. However, the blind were not more sensitive to a target odour, nor more proficient at choosing a correct odour label from a list of four. Together, the data point to a circumscribed advantage of blind children at self-generating and retrieving odour labels and, as such, to a limited, but still compensatory, cognitive function.

Differential Genetic Susceptibility to Child Risk at Birth in Predicting Observed Maternal Behavior

This study examined parenting as a function of child medical risks at birth and parental genotype (dopamine D4 receptor; DRD4). Our hypothesis was that the relation between child risks and later maternal sensitivity would depend on the presence/absence of a genetic variant in the mothers, thus revealing a gene by environment interaction (GXE). Risk at birth was defined by combining risk indices of childrens gestational age at birth, birth weight, and admission to the neonatal intensive care unit. The DRD4-III 7-repeat allele was chosen as a relevant genotype as it was recently shown to moderate the effect of environmental stress on parental sensitivity. Mothers of 104 twin pairs provided DNA samples and were observed with their children in a laboratory play session when the children were 3.5 years old. Results indicate that higher levels of risk at birth were associated with less sensitive parenting only among mothers carrying the 7-repeat allele, but not among mothers carrying shorter alleles. Moreover, mothers who are carriers of the 7-repeat allele and whose children scored low on the risk index were observed to have the highest levels of sensitivity. These findings provide evidence for the interactive effects of genes and environment (in this study, children born at higher risk) on parenting, and are consistent with a genetic differential susceptibility model of parenting by demonstrating that some parents are inherently more susceptible to environmental influences, both good and bad, than are others.

Action spectrum for light-induced retinal degeneration in dystrophic rats

Abstract Rats with an inherited retinal dystrophy were reared under red. green or blue lights and the time course of their retinal degeneration was followed electroretinographically. When light intensities were matched for total energy flux, the retinal degeneration in rats reared under red light was far slower than in those raised under the green and blue light conditions. When the colored lights were matched for equal energy absorbed by rhodopsin, the retinal degeneration of all rats followed an identical time course. The action spectrum for the damaging effect of light therefore follows the rhodopsin absorption curve.

Infant recognition by tactile cues

We previously showed that parturient women can recognize their newborn by stroking their infants hand. Control experiments showed that the discrimination was tactile. In this experiment, we asked whether the womens skill was generalizable to other parts of the infants body. Each subject was tested twice, once for touch recognition of her infants hand and once for recognition of her infants cheek. In both trials, the women were instructed to stroke the target area of 3 newborns and then to guess which of the infants was her own. Results show that the women succeeded at both recognition tasks. These data corroborate our previous findings and underscore mothers sensitivity to her infants unique tactile features. We propose that their talent at “knowing” their infant by touch is an adaptive skill, beneficial to both mother and infant.

Recognition of familiar individuals by touch

I have examined whether adults can recognize their boyfriends/husbands or girlfriends/wives by stroking either their partners hand or face. On both trials, subjects were asked to chose their mate from amongst two unfamiliar age- and gender-matched adult foils. During testing, the subjects eyes and nose were covered and auditory cues were masked by ambient noise. The results show that a significant proportion of the total sample succeeded on one or both of the touch-recognition tasks. However, while both women and men were successful at the face-touch-recognition task, only the women were successful at the hand-recognition task. I conclude that tactile cues afforded by stroking skin are sufficiently salient to allow for individual recognition. As for the gender-related difference, women may have an advantage at hand recognition because mens hands are more discriminable than womens hands.