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Biomedical subjects

Curt A Sandman

Publications and source records attributed to Curt A Sandman.

14 recordsLinked to original sources

Alpha EEG predicts visual reaction time.

Studies have suggested that consciousness is encoded discretely in time and synchronously in space of the brain. The present study was to model the alpha EEG as a brain clock to carry out the functions and to test whether the quality and rate of the oscillation could predict behavioral timing. Results showed that the alpha peak frequency was correlated with the conflict reaction time, and the selectivity was associated with the simple reaction time. These findings are consistent with previous reports and support the hypothesis that alpha EEG represents excitability cycles and may serves as a brain clock for spatial synchronization.

Adult↗

Male violence, stress, and neuroendocrine parameters in pregnancy: a pilot study.

Stress during pregnancy has been associated with a number of adverse outcomes. This study compared and correlated neuroendocrine parameters in women (n=8) who self-reported battering during their pregnancy to those in women who did not (n=8). Women who identified themselves as having a violent relationship with an intimate partner were recruited from a rural midwestern community. They were matched on age, self-reported ethnicity, parity, gestational age, and personal and family income with nonbattered controls. Midgestational measures of self-reported stress levels showed that battered women reported markedly higher levels of anxiety and depression. Neuroendocrine levels were not different between groups (battered vs. nonbattered); however, the relationships among hormones were different between groups. In nonbattered women, adrenocorticotropic hormone (ACTH) and cortisol levels were correlated but not in battered women. Beta endorphin and ACTH levels in battered women showed a significant linear relationship but not in nonbattered women. These results suggest that the maternal experience of stress alters the relationship of hypothalamic-pituitary-adrenal-placental axis hormones despite the lack of absolute differences in blood levels.

Adrenocorticotropic Hormone↗

Elevated maternal cortisol early in pregnancy predicts third trimester levels of placental corticotropin releasing hormone (CRH): priming the placental clock.

The purposes of this study were to determine the intervals when placental corticotrophic-releasing hormone (CRH) was most responsive to maternal cortisol. A sample of 203 women each were evaluated at 15, 19, 25 and 31 weeks gestation and followed to term. Placental CRH and maternal adrenocorticotropin hormone (ACTH), B-endorphin and cortisol were determined from plasma. CRH levels increased faster and were higher in women who delivered preterm compared with women who delivered at term (F3,603 = 5.73, p < .001). Simple effects indicated that CRH levels only at 31 weeks predicted preterm birth (F1,201 = 5.53, p = .02). Levels of cortisol were higher in women who delivered preterm at 15 weeks gestation (F1,201 = 4.45, p = .03) with a similar trend at 19 weeks gestation. Hierarchical regression suggested that the influence on birth outcome of maternal cortisol early in pregnancy was mediated by its influence on placental CRH at 31 weeks. Elevated cortisol at 15 weeks predicted the surge in placental CRH at 31 weeks (R = .49, d.f. = 1,199, Fchange = 61.78, p < .0001). Every unit of change in cortisol (microg/dl) at 15 weeks was associated with a 34 unit change of CRH (pg/ml) at 31 weeks. These findings suggested that early detection of stress signals by the placenta stimulated the subsequent release of CRH and resulted in increased risk for preterm delivery.

Adrenocorticotropic Hormone↗

Corticotropin-releasing hormone during pregnancy is associated with infant temperament.

During pregnancy corticotropin-releasing hormone (CRH) is released into maternal and fetal circulation from the placenta. Elevated concentrations of placental CRH are associated with spontaneous preterm birth, but the consequences for infant development, independent of birth outcome, are unknown. In this study, the effects of placental CRH on infant temperament were examined in a sample of 248 full-term infants. Maternal blood samples were collected at 19, 25 and 31 weeks of gestation for CRH analysis. Infant temperament was assessed with measures of fear and distress at 2 months of age. Infants of mothers with low CRH at 25 weeks of gestation scored lower in fear and distress at 2 months. CRH at 19 and 31 weeks' gestation was not significantly associated with measures of infant temperament, suggesting the possibility that there is a sensitive period for its effects. These data suggest that prenatal exposure to CRH may exert influences that persist into the postnatal period.

Corticotropin-Releasing Hormone↗

Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: a prospective investigation.

OBJECTIVES: Recent advances in the physiology of human pregnancy have implicated placental corticotropin-releasing hormone (CRH) as one of the primary endocrine mediators of parturition and possibly also of fetal development. The aim of this study was (1) to prospectively assess the relationship of maternal plasma concentrations of CRH in the early third trimester of gestation with two prematurity-related outcomes-spontaneous preterm birth (PTB), and small-for-gestational age birth (SGA), and (2) to determine whether the effects of CRH on each of these outcomes are independent from those of other established obstetric risk factors. STUDY DESIGN: In a sample of 232 women with a singleton, intrauterine pregnancy, maternal plasma was collected at 33 weeks' gestation and CRH concentrations were determined by radioimmunoassay. Each pregnancy was dated on the basis of last menstrual period and early ultrasonography. Parity, obstetric risk conditions for prematurity, mode of delivery, and birth outcomes were abstracted from the medical record. RESULTS: After adjusting for the effects of established obstetric risk factors, elevated CRH levels at 33 weeks' gestation were significantly associated with a 3.3-fold increase in the adjusted relative risk (RR) for spontaneous preterm birth and with a 3.6-fold increase in the adjusted relative risk for fetal growth restriction. Women who delivered postterm had significantly lower CRH levels in the early third trimester than those who delivered at term. When outcomes were stratified by gestational length and birth weight, the lowest CRH levels at 33 weeks' gestation were associated with the term non-SGA births, intermediate and approximately equal CRH levels were associated with the preterm non-SGA and term SGA births, and the highest CRH levels were associated with the preterm SGA births. CONCLUSION: For deliveries occurring after 33 weeks' gestation (the time of CRH sampling in this study), our findings support the notion that in humans placental CRH may play an impending, direct role in not only the physiology of parturition but also in processes related to fetal growth and maturation. Our results also support the notion that the timing of onset of parturition may be determined or influenced by events occurring earlier in gestation rather than those close to the time of actual onset of labor (ie, the notion of a "placental clock").

Adolescent↗

Pregnancy affects appraisal of negative life events.

OBJECTIVE: It has been demonstrated that physiological responses to stress are diminished late in pregnancy. This study investigates whether emotional responding is diminished as well by measuring affective responses to specific life events during pregnancy. METHODS: A total of 292 pregnant women reported the occurrence of and affective responses to a range of major life events during gestation. Two analyses were conducted (across events and within events) on these responses to determine whether life events occurring in the first trimester were rated as more stressful than those that occurred in the third trimester. RESULTS: Both within-event and across-events analyses of responses to life events demonstrated that events occurring early in pregnancy were perceived as more stressful than events occurring later in pregnancy. CONCLUSION: Responses to stress and affective state are progressively altered in pregnant women, suggesting that timing of stress exposure during gestation may be critical in determining its impact.

Adult↗

Quantifying temporal distributions of self-injurious behavior: defining bouts versus discrete events.

An objective method is presented to group discrete self-injurious behavior (SIB) events into bouts. Survival analysis was used to determine how long after an SIB the probability of observing a subsequent SIB remained elevated. This estimated bout length criterion time point was determined individually for 19 subjects with developmental disorders and severe SIB. Bout length criterion estimates ranged from.6 to 15.5 seconds. When participants' SIBs were grouped into bouts using the bout length criterion estimate, the rate of bouts and the average number of SIBs in each bout were found to be more stable than the rate of individual SIBs. This approach may facilitate research on factors that initiate and maintain SIB.

Adolescent↗

Sequential analysis reveals a unique structure for self-injurious behavior.

Conditional probability, calculated using sequential analysis techniques in four time conditions (2, 10, 30, and 60 seconds), provided evidence that successive episodes of self-injury were sequentially dependent. This unique distribution of sequential association for self-injurious behavior (SIB) was not related to frequency or rate of occurrence. Compared with other environmental and behavioral events, the best predictor of SIB was an earlier SIB episode, consistent with a contagious distribution. This study is one of the few in which sequential analysis techniques were applied to data derived from a large group of individuals with severe behavior disorders. It may be the first in which this analytic tool was used to investigate systematically successive occurrences of SIB as it takes place in vivo.

Adolescent↗

beta-Endorphin and ACTH are dissociated after self-injury in adults with developmental disabilities.

Relations between self-injuring behavior (SIB), the hypothalamic-pituitary-adrenal (HPA) stress axis, and response to an opiate antagonist were examined. Subjects were observed in their residential settings, while behavior was recorded. Blood was collected in the morning, evening, and immediately after SIB. Plasma beta-E was uncoupled from ACTH after SIB but not during the morning baseline. A significant number of the subjects (a) reduced their SIB at least 25% at all doses of naltrexone (NTX) and (b) reduced their SIB over 50% for at least one dose of NTX. The lowest dosage of NTX significantly reduced SIB in subjects with baseline levels of beta-E higher than after SIB. Results support previous reports that the HPA axis is disturbed among subjects exhibiting SIB.

Adolescent↗

Disregulation of proopiomelanocortin and contagious maladaptive behavior.

Self-injurious behavior (SIB) is an untreatable and often life-threatening problem among individuals with developmental disorders, especially those diagnosed with autism. Functioning, relationships and processing of the proopiomelanocortin (POMC) system are "uncoupled" in subgroups of self-injuring individuals resulting in different ratios of ACTH and opioids in the bloodstream, particularly under conditions of stress. In this study, relations between SIB and POMC were evaluated in a multi-year study of the largest prospective sample studied to date. Observations were collected on palmtop computers for 45 treatment-resistant patients who exhibited chronic SIB. Behavior of each subject was observed in natural settings without disruption or intrusion, for continuous, 2.5-h periods, two times a day (morning and afternoon), 4 days a week for two consecutive weeks, for a total of 40 h/subject. Blood was collected in the morning, late afternoon and immediately after an SIB episode on two separate occasions separated by at least 6 months. Levels of beta-endorphin (beta E) and ACTH were assayed by RIA. We discovered that the SIB was the best predictor of subsequent SIB. Moreover, the majority of subjects exhibited this contagious pattern of SIB. Levels of POMC fragments were reliable over a 6- to 9-month period. Subjects exhibiting POMC disregulation characterized by high morning levels of beta E had the highest transitional probabilities of SIB (i.e. contagious patterns; F=8.17, P<0.01). These findings suggest that subjects with "contagious" SIB may represent a behavioral phenotype associated with disregulated expression of the POMC gene.

Adrenocorticotropic Hormone↗

Behavioral perinatology: biobehavioral processes in human fetal development.

Behavioral perinatology is as an interdisciplinary area of research that involves conceptualization of theoretical models and conduct of empirical studies of the dynamic time-, place-, and context-dependent interplay between biological and behavioral processes in fetal, neonatal, and infant life using an epigenetic framework of development. The biobehavioral processes of particular interest to our research group relate to the effects of maternal pre- and perinatal stress and maternal-placental-fetal stress physiology. We propose that behavioral perinatology research may have important implications for a better understanding of the processes that underlie or contribute to the risk of three sets of outcomes: prematurity, adverse neurodevelopment, and chronic degenerative diseases in adulthood. Based on our understanding of the ontogeny of human fetal development and the physiology of pregnancy and fetal development, we have articulated a neurobiological model of pre- and perinatal stress. Our model proposes that chronic maternal stress may exert a significant influence on fetal developmental outcomes. Maternal stress may act via one or more of three major physiological pathways: neuroendocrine, immune/inflammatory, and vascular. We further suggest that placental corticotropin-releasing hormone (CRH) may play a central role in coordinating the effects of endocrine, immune/inflammatory, and vascular processes on fetal developmental outcomes. Finally, we hypothesize that the effects of maternal stress are modulated by the nature, duration, and timing of occurrence of stress during gestation. In this paper, we elaborate on the conceptual and empirical basis for this model, highlight some relevant issues and questions, and make recommendations for future research in this area.

Behavior↗

Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia.

BACKGROUND: The neurotransmitters dopamine and glutamate have been implicated in the prefrontal dysfunction associated with schizophrenic illness. Studies suggest that the D1 subclass of dopamine receptor and the N-methyl-D-aspartate subclass of glutamate receptor are involved in this prefrontal dysfunction. These 2 receptors regulate, in opposing directions, the amount of phosphorylated activated DARPP-32, a potent inhibitor of protein phosphatase 1 that modulates the activity of several classes of receptors and ion channels. Thus, DARPP-32 occupies a key regulatory position, and may play an important role in the pathophysiological changes in dopamine and glutamate function reported in patients with schizophrenia. METHODS: The amounts of DARPP-32, synapsin I, and the alpha subunit of calcium/calmodulin-dependent protein kinase II were measured by immunoblotting in postmortem samples from 14 schizophrenic subjects and their age-, gender-, and autolysis time-matched control subjects. Possible confounding influences of neuroleptic treatment were analyzed by comparing subjects with Alzheimer disease who were and were not treated with neuroleptic agents. RESULTS: DARPP-32 was significantly reduced in the dorsolateral prefrontal cortex in more schizophrenic subjects relative to matched controls. The ratios of 2 other synaptic phosphoproteins, synapsin I and the alpha subunit of calcium/calmodulin-dependent protein kinase II, did not differ between schizophrenic and control subjects, nor between subjects with Alzheimer disease who were and were not treated with neuroleptic agents. CONCLUSIONS: Our findings are consistent with a selective reduction in DARPP-32 levels in schizophrenic subjects. This may be involved in the prefrontal dysfunction associated with schizophrenia.

Adult↗

Stressed-out, or in (utero)?

The molecular and cellular mechanisms by which plasticity is induced in the mature CNS (and, specifically, in the hippocampus) by environmental input are progressively being elucidated. However, the mechanisms - and even the existence - of functional and structural effects of environmental input (and, particularly, stress) early in life are incompletely understood. Here, we discuss recent evidence that stressful stimuli have a significant impact on neonatal (rat) and prenatal (human) hippocampal function and integrity. Stressful signals provoke expression and release of neuromodulators, including the peptide corticotropin-releasing hormone (CRH), leading to activation of CRH receptors on principal hippocampal neurons. Although physiological activation of these receptors promotes synaptic efficacy, pathological levels of CRH at hippocampal synapses contribute to neuronal death. Thus, early-life stress could constitute a 'double-edged sword': mild stress might promote hippocampal-dependent cognitive function, whereas severe stress might impair neuronal function and survival, both immediately and in the long-term. Importantly, these CRH-mediated processes could be targets of preventive and interventional strategies.

Aging↗

Maternal hypothalamic-pituitary-adrenal disregulation during the third trimester influences human fetal responses.

Maternal peptides from the hypothalamic-pituitary-adrenal (HPA) axis rise during human pregnancy. The effects of circulating maternal adrenocorticotropin (ACTH) and beta-endorphin (BE) on human fetal behavior was determined in 135 women during their 32nd week of gestation. Fetal behavior was measured by assessing heart rate habituation to a series of repeated vibroacoustic stimuli. Individual differences in habituation were determined by computing the number of consecutive responses above the standard deviation during a control period. There was no significant relation between levels of ACTH, BE and the rate of fetal heart rate habituation. However, an index of HPA disregulation (uncoupling of ACTH and BE) was related significantly to fetal behavior. Fetal exposure to high levels of maternal BE relative to ACTH was associated with significantly lower rates of habituation. Results indicate that maternal stress and stress-related peptides influence fetal response patterns. It is possible that this influence persists over the life span.

Acoustic Stimulation↗