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Biomedical subjects

C Grillon

Publications and source records attributed to C Grillon.

At least 37 records · Page 2Linked to original sources
PubMed1998

Fear-potentiated startle in adolescent offspring of parents with anxiety disorders.

BACKGROUND: The startle reflex and its potentiation by aversive states was used as a possible vulnerability marker for anxiety disorders in adolescent offspring of parents with this condition. METHODS: The participants were 39 low-risk adolescents (16 male/23 female) with a parental history of no psychiatric disorder and 35 high-risk adolescents (18 male/17 female) with a parental history of anxiety disorders. The magnitude of startle was examined at baseline and during anticipation of an aversive stimulus (fear-potentiated startle). RESULTS: Startle was found to discriminate between children at high and low risk for anxiety disorders; however, different abnormalities for high-risk male and female subjects were observed. Startle levels, overall, were elevated among high-risk female subjects, whereas high-risk male subjects exhibited greater magnitude of startle potentiation during aversive anticipation. CONCLUSIONS: Startle reactivity may serve as a vulnerability marker for the development of anxiety disorders. With its basic grounding in animal and human behavioral research, startle may enhance our understanding of the underlying neurobiological bases of human anxiety states.

Adolescent↗
PubMed1998

Regulation of arousal and attention in preschool children exposed to cocaine prenatally.

Four lines of evidence suggest a plausible link between prenatal cocaine exposure (CE) and specific effects on the mechanisms subserving arousal and attention regulation in infants and preschool-aged children. These are (1) the association of prenatal CE with alterations in monoaminergic system ontogeny; (2) neurobehavioral effects of prenatal CE in animals consistent with an enduring increased level of activity in response to novelty and inhibited exploration and altered responses to stress, suggesting overarousal in the face of novel/stressful situations and disrupted attention and exploration; (3) altered norepinephrine system function in cocaine-exposed human infants; and (4) neurobehavioral findings in infants and preschool-aged children suggestive of disrupted arousal regulation in the face of novelty, increased distractibility, and consequent impaired attention to novel, structured tasks. This paper summarizes findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool-aged children followed longitudinally since birth. Arousal regulation in the face of novel challenges is operationalized behaviorally as state and emotional reactivity and neurophysiologically as the startle response and heart rate variability. Across different ages and tasks, behavioral and neurophysiological findings suggest that prenatally cocaine-exposed children are more likely to exhibit disrupted arousal regulation. Because the regulation of arousal serves as a gating mechanism to optimize orientation and attention, arousal regulation has important implications for ongoing information processing, learning, and memory. Furthermore, impaired arousal regulation predisposes children to a lower threshold for activation of "stress circuits" and may increase their vulnerability to the developmentally detrimental effects of stressful conditions particularly when such children are also exposed to the chaotic environmental conditions often characterizing substance-abusing families.

Adult↗
PubMed1998

The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Goralatide) protects from doxorubicin-induced toxicity: improvement in mice survival and protection of bone marrow stem cells and progenitors.

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP or Goralatide), a physiological regulator of hematopoiesis, inhibits the entry into the S-phase of murine and human hematopoietic stem cells. It has been shown to reduce the damage to specific compartments in the bone marrow resulting from treatment with chemotherapeutic agents, ionizing radiations, hyperthermy, or phototherapy. The present study was performed to assess the therapeutic potential of AcSDKP in vivo in reducing both the toxicity and the hematopoietic damage induced by fractionated administration of doxorubicin (DOX), a widely used anticancer drug. Here we showed that AcSDKP could reduce DOX-induced mortality in mice and could protect particularly the long-term reconstituting cells (LTRCs) in addition to colony forming units-spleen, high proliferative potential colony-forming cells, and colony-forming units-granulocyte-macrophage (CFU-GM) from DOX toxicity. The protection against DOX-induced mortality in mice was improved when AcSDKP was administered for 3 days, at a dose of 2.4 micrograms/d, by continuous subcutaneous (SC) infusion or fractionated s.c. injections starting 48 hours before DOX treatment. Moreover, the recovery of the CFU-GM population in the AcSDKP-DOX-treated mice was optimized by the subsequent administration of granulocyte colony-stimulating factor (G-CSF). The coadministration of AcSDKP with DOX may improve its therapeutic index by reducing both acute hematotoxicity on late stem cells and progenitors and long-term toxicity on LTRCs. Optimization of these treatments combined with G-CSF may provide an additional approach to facilitate hematopoietic recovery after cancer chemotherapy.

Animals↗
PubMed1998

Effects of threat of shock, shock electrode placement and darkness on startle.

Fear can be elicited by physically-presented explicit threat stimuli or by more static contextual stimuli that are not an immediate source of danger. Research in both humans and animals suggest that fear produced by these two types of stimuli represents separate processes mediated by different brain structures. The present study used the startle reflex methodology to examine affective responses elicited by an explicit threat cue signalling a period of shock anticipation and by two types of contextual stimuli; darkness and attaching the shock electrodes. As expected, shock anticipation potentiated startle (fear-potentiated startle). Startle was also facilitated by darkness and by the placement of shock electrodes. Further, darkness increased fear-potentiated startle to an explicit threat cue, but did not affect the facilitation of startle produced by attaching the shock electrodes. It is suggested that affective responses to contextual stimuli should be considered when investigating both normal and pathological fear.

Adult↗
PubMed1998

Effect of darkness on acoustic startle in Vietnam veterans with PTSD.

OBJECTIVE: Exaggerated startle is a symptom of posttraumatic stress disorder (PTSD), but empirical studies have not consistently documented elevated baseline startle in PTSD. The authors proposed in a previous study that Vietnam veterans with PTSD exhibit exaggerated startle only under stressful conditions. They reported that darkness facilitated startle in humans, suggesting that the startle reflex is sensitive to the aversive nature of darkness. In the present study they tested the hypothesis that the magnitude of facilitation of startle by darkness would be greater in Vietnam veterans with PTSD than in comparison groups of subjects without PTSD. Prepulse inhibition was also investigated. METHOD: The magnitude of startle and prepulse inhibition were assessed in alternating periods of darkness and light in 19 nonmedicated Vietnam veterans with PTSD, 13 Vietnam veterans without PTSD, and 20 civilians without PTSD. RESULTS: The overall startle level was higher in the veterans with PTSD than in either of the two groups of subjects without PTSD. Startle was facilitated by darkness, and the magnitude of this facilitation was greater in the veterans with PTSD than in the civilians without PTSD, but it was not greater in the veterans without PTSD. Prepulse inhibition was not affected by darkness and did not significantly differ among groups. CONCLUSIONS: Contrary to the hypothesis, elevated sensitivity to darkness was specific to individuals with combat experience, not to individuals with PTSD, perhaps because veterans had become aversively conditioned to darkness during their combat experiences. The more general increase in startle reactivity in the veterans with PTSD is consistent with clinical observations and descriptions of symptoms in DSM-IV.

Acoustic Stimulation↗
PubMed1997

Darkness facilitates the acoustic startle reflex in humans.

The effects of darkness on startle reactivity and prepulse inhibition were investigated in two studies with 25 subjects participating in each study. Acoustic startle stimuli that were or were not preceded by an acoustic prepulse were delivered in alternating periods of complete darkness or light. In both studies, darkness significantly increased the magnitude of startle but did not affect prepulse inhibition (PPI). The PPI results suggest that darkness did not increase attention to the auditory modality, so that the startle facilitation in the dark probably did not result from an attentional process. The increased startle in the dark was significantly correlated with the intensity of subjects' fear of the dark as children based on retrospective rating scales. It is hypothesized that the startle facilitation in the dark results from a change in affect rather than from a change in attention.

Acoustic Stimulation↗
PubMed1997

Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-chlorophenylpiperazine (mCPP).

Preclinical studies suggest that acoustic startle amplitude is increased during ethanol withdrawal. The current study evaluated the effects of intravenous infusion of the alpha 2-adrenergic antagonist, yohimbine (0.4 mg/kg), the serotonin partial agonist m-chlorophenylpiperazine (mCPP, 0.1 mg/kg), and placebo administered to 22 male patients meeting DSM-III-R criteria for alcohol dependence and 13 male healthy subjects. Patients and healthy subjects completed 3 test days under double-blind conditions in a randomized order. Patients were sober for 12-26 days prior to testing. On each test day, participants completed startle testing 80 min following drug infusion. Stimuli with varying intensities (90, 96, 102, 108, 114 dB) were presented in a randomized order balanced across four blocks. Stimuli consisted of 40-ms bursts of white noise administered every 45-60 s for 15-20 min through headphones. Analyses indicated that patients exhibited elevated acoustic startle magnitudes on the placebo day relative to healthy subjects. In patients, the magnitude of startle amplitudes elicited at 90 dB, but not 114 dB, correlated significantly with the number of previous alcohol detoxifications. Yohimbine increased startle magnitudes and reduced startle latencies relative to placebo and mCPP in both patients and healthy subjects. mCPP did not alter startle magnitude in either group. Yohimbine also increased the probability that a 90-dB stimulus produced a startle response in healthy subjects, but not in patients. Blunting of yohimbine effects on startle probability may reflect the baseline elevations in startle probability levels in patients, but may also be consistent with other evidence of reduced postsynaptic, but not presynaptic, noradrenergic function in these same patients. These data replicate and extend previous reports indicating that yohimbine facilitates the acoustic startle response in humans. They also further implicate the number of episodes of ethanol withdrawal as a factor influencing subsequent neurobiological responsivity in chronic alcoholic patients. Based on the current data, future research should explore whether measurement of the acoustic startle response provides an objective quantitative severity measure of ethanol withdrawal.

Acoustic Stimulation↗
PubMed1997

Startle modulation in children at risk for anxiety disorders and/or alcoholism.

OBJECTIVE: To examine the startle reflex as a possible vulnerability marker among offspring of parents with anxiety disorders and/or alcoholism. METHOD: The subjects were 66 male and female offspring (aged 10 to 17 years) of proband who participated in a family study of comorbidity of alcoholism and anxiety disorders. Testing consisted of examining the startle reflex and its modulation by prepulse stimuli (prepulse facilitation and prepulse inhibition). RESULTS: Different components of the startle discriminated among children of parents with anxiety disorders, children of alcoholics, and children of normal controls. Specifically startle magnitude was elevated in children with a parental history of an anxiety disorder, whereas startle habituation and prepulse inhibition were impaired in children with a parental history of alcoholism. CONCLUSION: These findings suggest that individual differences in the startle reflex may serve as a vulnerability marker for the development of anxiety disorders and alcohol problems.

Adolescent↗
PubMed1997

Effects of stress and shock anticipation on prepulse inhibition of the startle reflex.

The effects of shock anticipation and attention to external stimuli on prepulse inhibition (PPI) were compared. In the threat-of-shock experiment, acoustic startle stimuli were presented with and without prepulses when aversive shocks were or were not anticipated. In the control experiment, startle and prepulse stimuli were delivered during periods with attended or ignored external stimuli. In the threat-of-shock experiment, startle was potentiated (fear-potentiated startle) and PPI was increased by shock anticipation. A gradual reduction in the overall PPI throughout the experiment was also found. In the control experiment, only PPI was increased in the attend condition. The PPI level remained constant throughout the experiment. The increase in PPI in the threat and attend conditions may have resulted from an increase in the general level of alertness that facilitated the processing of the prepulse. The gradual decrease in PPI in the threat experiment was hypothesized to result from a progressive deficit in sensory functioning due to the stressful nature of repeated shock anticipation.

Acoustic Stimulation↗
PubMed1997

Fear-potentiated startle conditioning in humans: explicit and contextual cue conditioning following paired versus unpaired training.

Conditioned fear in response to explicit and contextual cues was examined using the startle reflex in three groups of participants over two sessions separated by 4-5 days. The conditioned stimulus (CS) was paired with an aversive unconditioned stimulus (US) (shock) during conditioning in the paired but not in the unpaired group. In the reaction time (RT) group, the US was a nonaversive visual signal for an RT task. In the paired group, the CS potentiated startle in the postconditioning phase. This conditioned response was fully retained over the retention interval. There was no substantial change in baseline startle (startle delivered in the absence of CS). By contrast, startle was not potentiated by the CS in the unpaired group, but baseline startle was increased from Session 1 to Session 2. In the RT group, startle was not affected by the CS, and baseline startle was reduced from Session 1 to Session 2. These results suggest that paired presentations of a CS and an aversive US result in conditioned fear in response to the CS but little contextual fear, whereas unpaired presentations of a CS and US leads to poor explicit cue conditioning but substantial contextual fear.

Adolescent↗
PubMed1997

Startle reflex abnormalities in women with sexual assault-related posttraumatic stress disorder.

OBJECTIVE: This investigation was designed to assess the acoustic startle response in treatment-seeking women with sexual assault-related posttraumatic stress disorder (PTSD). METHOD: Thirteen patients with sexual assault-related PTSD and 16 healthy female comparison subjects were recruited for participation in the study. Each patient met the full criteria for PTSD according to the Structured Clinical Interview for DSM-III-R. All subjects in the study were right-handed. The acoustic stimuli were bursts of white noise (92 dB and 102 dB) with a nearly instantaneous onset delivered binaurally through headphones. RESULTS: The magnitude of the startle response (eye blink) to the first stimulus was asymmetrically distributed in the PTSD patients but not in the comparison subjects: it was greater for the left eye than the right eye in the PTSD patients only. There was a differential asymmetry of startle response in the two subgroups of patients (recent PTSD and long-standing PTSD): the startle reflex was larger for the left eye than the right in the subgroup with recent PTSD but not in the group with long-standing PTSD. CONCLUSIONS: This study provides the first objective evidence of startle abnormalities in women with PTSD. The significantly greater startle responses for the left eye compared with the right in the PTSD subjects suggest a laterality effect. As suggested by the preclinical model of shock sensitization, it is possible that in a subgroup of individuals with PTSD, trauma may sensitize the startle reflex. This model may hold true in humans and is supported by the findings of greater startle response in the patients with recent-onset PTSD.

Acoustic Stimulation↗
PubMed1996

Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder.

Although an exaggerated startle response is a symptom of posttraumatic stress disorder (PTSD), empirical support for elevated baseline startle in PTSD has been weak. The present study investigated the eyeblink component of the acoustic startle reflex and prepulse inhibition (PPI) in 21 unmedicated Vietnam veterans with PTSD and in 17 civilian and 10 combat veteran comparison subjects. Patients with PTSD exhibited normal acoustic startle amplitude, but showed a significant reduction in PPI relative to the civilian subjects. There was only a trend toward a reduction in PPI in the PTSD group compared with the combat control group. The study does not support the hypothesis of exaggerated baseline startle in Vietnam veterans with PTSD but suggests abnormal startle modulation by a prepulse (i.e., PPI). Discrepancies between studies concerning the amplitude of startle in PTSD are discussed.

Acoustic Stimulation↗
PubMed1996

The antiproliferative activity of the tetrapeptide Acetyl-N-SerAspLysPro, an inhibitor of haematopoietic stem cell proliferation, is not mediated by a thymosin beta 4-like effect on actin assembly.

Acetyl-N-SerAspLysPro (AcSDKP), known as a negative regulator of haematopoiesis, has been principally reported as an inhibitor of haematopoietic pluripotent stem cell proliferation. The tetrapeptide sequence is identical to the N-terminus of thymosin beta 4 (T beta 4), from which it has been suggested that it may be derived. Recently, evidence was shown that T beta 4 plays a role as a negative regulator of actin polymerization leading to the sequestration of its monomeric form. The structural similarity between the N-terminus of T beta 4 and AcSDKP has raised the possibility that AcSDKP may also participate in intracellular events leading to actin sequestration. The effect of T beta 4 on the proliferation of haematopoietic cells was compared to that of AcSDKP. The results revealed that T beta 4, like AcSDKP, exerts an inhibitory effect on the entry of murine primitive bone marrow cells into cell cycle in vitro. Qualitative electrophoretic analysis and quantitative polymerization assays were used to investigate the role of AcSDKP in actin polymerization. AcSDKP does not affect actin assembly at concentrations up to 50 microM, and does not compete with T beta 4 for binding to G-actin. These results suggest that AcSDKP is not involved in cell cycle regulation via an effect on the process of actin polymerization.

Actin Cytoskeleton↗
PubMed1996

Exaggerated acoustic startle reflex in Gulf War veterans with posttraumatic stress disorder.

OBJECTIVE: Exaggerated startle reflex is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD). The goal of this study was to assess the magnitude of the acoustic startle reflex in Gulf War veterans with PTSD. METHOD: The eye-blink component of the startle reflex was measured in response to six blocks of pseudorandomized 40-msec white noise bursts of varying intensities (90, 96, 102, 108, and 114 dB) in 10 Gulf War veterans with PTSD, seven Gulf War veterans without PTSD, and 15 civilian subjects without PTSD. RESULTS: The magnitude of the first startle response, as well as the magnitude of startle response averaged across blocks of testing, was significantly greater in Gulf War veterans with PTSD than in veteran and civilian comparison groups. CONCLUSIONS: Consistent with some clinical studies investigating the startle response in Vietnam veterans with PTSD, this investigation provides evidence for exaggerated startle response in this disorder. Preclinical studies of shock sensitization of the startle response suggest that the higher levels of startle response seen in the PTSD subjects may reflect a sensitization of the fear/alarm response created by the stress of combat trauma.

Acoustic Stimulation↗
PubMed1996

Preliminary evidence of an association between sensorimotor gating and distractibility in psychosis.

Impaired sensory gating and increased distractibility are key information-processing deficits in schizophrenia. This study evaluated the hypothesis that distractibility is related to reduced sensory gating. Performance on vigilance and distractibility tasks was compared to prepulse inhibition (PPI) of the acoustic startle reflex in 28 stable chronic psychotic patients. PPI significantly correlated with distractibility task score on a continuous performance test and lateralized attention on the Posner test. These results suggest that performance on tests of distractibility and lateralized attention are related to a measure of sensory gating.

Acoustic Stimulation↗
PubMed1996

The psychobiological basis of posttraumatic stress disorder.

Posttraumatic stress disorder is a disorder with an identifiable etiological factor (exposure to a traumatic event) and with a complex symptomatology (i.e. intrusive memories, avoidance, hyperarousal) that suggests dysfunction in multiple psychobiological systems. This review considers studies of the neurobiological consequences of acute and chronic stress showing that traumatic experiences can produce long-lasting alterations in multiple neurochemical systems. The role of the locus coeruleus noradrenergic system, prefrontal cortex dopaminergic system, endogenous opiates, hypothalamic-pituitary-adrenal axis, and cortico-releasing factors are reviewed. Several models of PTSD are highlighted, including fear conditioning, kindling, and sensitization. In particular, fear conditioning to explicit and contextual cues is proposed as a model for intrusive memories reactivated by trauma-related stimuli and hyperarousal, respectively. It is argued that the amygdala plays a crucial role in the encoding and retrieval of fear memories activated by specific stimuli that have been associated with aversive events. Association involving more complex environmental stimuli and aversive events may require the involvement of the hippocampus and the bed nucleus of the stria terminalis. Repeated activation of conditioned fear memories may produce a kindling-like process which results in spontaneous intrusive memories.

Humans↗
PubMed1995

Fear-potentiated startle in posttraumatic stress disorder.

Exaggerated startle is reputed to be one of the cardinal symptoms of posttraumatic stress disorder (PTSD); however, objective studies have given conflicting results as to whether or not startle is increased in PTSD. The present study investigated startle in PTSD during the threat of shock (fear-potentiated startle). The eyeblink component of the startle reflex was measured at various times preceding and following the anticipation of unpleasant electric shocks in 9 PTSD subjects and 10 age-matched, healthy controls. Startle amplitude was significantly greater during baseline and during shock anticipation in the PTSD subjects, compared to the controls. Habituation of the startle reflex was normal. Because other studies in the literature, as well as in our own laboratory, have failed to find exaggerated startle at baseline (i.e., absence of stress) in PTSD patients, it is unlikely that the present results reflect a chronic elevation of startle in this group. Instead, the higher levels of startle in the PTSD group probably resulted from a greater conditioned emotional response in this group, triggered by anticipation of electric shocks that generalized to the unfamiliar experimental context in which testing occurred. Hence, emotionally charged test procedures may be especially informative in distinguishing PTSD patients from other psychiatric diagnostic groups.

Adult↗