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Biomedical subjects

C Grillon

Publications and source records attributed to C Grillon.

At least 19 recordsLinked to original sources

Lack of startle modulation by smoking cues in smokers.

RATIONALE: The startle reflex methodology has been used to study the effects of nicotine in humans and the motivational effects of smoking cues in smokers. However, no other studies investigate startle modulation by smoking cues in smokers compared to non-smokers. In the other studies, smoking deprivation was manipulated in smokers or smokers were not compared directly to non-smokers. OBJECTIVE: The goal of this study was to examine the temporal course of information processing following the presentation of a smoking-related cue using the startle probe methodology in smokers compared to non-smokers. METHODS: Thirty-four smokers were selected on the basis of nicotinic dependence according to the DSM-IV, and compared to 34 non-smokers. During testing, subjects viewed neutral pictures and smoking related pictures displayed on a computer screen. Acoustic startle stimuli were delivered at various times after picture onset (60, 120 or 5000 ms) to examine inhibition by lead stimulus and the affective modulation of startle. RESULTS: The magnitude of startle reflex inhibition increased in smokers compared to non-smokers, at 60 and 120 ms. In all, there was no PicturexGroup interaction effect. CONCLUSION: We showed that smoking cues have no impact on the startle reflex of either group, even if, in line with previous results, prepulse inhibition was higher in smokers than non-smokers. These results suggest that smoking cues have no effect on the positive reinforcement of nicotine consumption, and that cognitive factors play a primary role in the development and maintenance of tobacco dependence.

Adult↗

A new case of a severe clinical phenotype of the cat-eye syndrome.

A new case of severe clinical phenotype of the cat-eye syndrome: We report on a female infant with severe clinical phenotype of Cat-Eye Syndrome (CES). At birth, she had respiratory distress and marked hypotonia. Physical examination showed major craniofacial anomalies including microcephaly, bilateral total absence of the external ears, hypertelorism, bilateral ocular coloboma of iris and micrognathia. In addition, she had anal stenosis, a patent ductus arteriosus and intra- and extra- hepatic biliary atresia. She deteriorated with the development of bradycardia. She died at age one month of cardiac failure. Cytogenetic analysis of the proband showed an extra de novo small bisatelllited marker chromosome in all cells examined. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) identified the marker as a CES chromosome. Thus, the patient's karyotype was: 47, XX, +idic(22)(pter-->q11.2 ::q11.2-->pter). The duplication breakpoints giving rise to the CES chromosome were distal to the DiGeorge Syndrome (DGS) locus 22q11.2. The marker could be classed as a type 11 symmetrical (10). According to a recent review of CES literature (1) only 41 % of the CES patients have the combination of iris coloboma, anal anomalies and preauricular anomalies. Almost 60% are hard to recognize by their phenotype alone. Only twelve patients showed a severe clinical phenotype leading to the death of the child. This phenotypic variability increases the difficulties of genetic counseling.

Anal Canal↗

[Postnatal growth delay in 27 to 33 week premature infants: frequency and risk factors. Retrospective study of 161 cases].

UNLABELLED: The optimization of the nutrition of very low birth weight premature neonates has become a major concern given the improvement in survival for these children. The goal of the recommended nutritional intakes is to reach a quantitative and qualitative growth similar to the in utero growth. The objectives of this study were to analyze the anthropometric data at birth and near term in a cohort of premature neonates with birth weight appropriate for gestational age and to try to determine risk factors of postnatal hypotrophy. POPULATION AND METHODS: We conducted a retrospective study over three years (1998-2001) in the neonatology unit of the Armand Trousseau Children's Hospital, Paris, France. The inclusion criteria was a gestational age under 33 weeks with birth weight appropriate for gestational age. Data were collected at admission, during hospitalisation and at discharge and a standardised form was filled for each child. We defined postnatal hypotrophy (PNH) as an hypotrophy at discharge (weight < 10(th) centile according to the Audipog reference curve) in neonates with birth weight appropriate for gestational age. RESULTS: One hundred and sixty one neonates were included. Eighty two had PNH. In univariate analysis, factors significantly associated with PNH were: birth weight, gestational age, length of hospitalisation, the occurrence of nosocomial infection, of enteropathy, preeclampsia, neonatal asphyxia and antenatal corticoid treatment. In multivariate analysis, risk factors of PNH were: low birth weight, low gestational age and the occurrence of nosocomial infection. CONCLUSION: Our study shows that half of the appropriate for gestational age premature neonates were hypotrophic near term. The causes may be various: nutrition is not optimal and intercurrent factors may play a major role such as nosocomial infection.

Analysis of Variance↗

A double dissociation in the affective modulation of startle in humans: effects of unilateral temporal lobectomy.

In the present study we report a double dissociation between right and left medial temporal lobe damage in the modulation of fear responses to different types of stimuli. We found that right unilateral temporal lobectomy (RTL) patients, in contrast to control subjects and left temporal lobectomy (LTL) patients, failed to show potentiated startle while viewing negative pictures. However, the opposite pattern of impairment was observed during a stimulus that patients had been told signaled the possibility of shock. Control subjects and RTL patients showed potentiated startle while LTL patients failed to show potentiated startle. We hypothesize that the right medial temporal lobe modulates fear responses while viewing emotional pictures, which involves exposure to (emotional) visual information and is consistent with the emotional processing traditionally ascribed to the right hemisphere. In contrast, the left medial temporal lobe modulates fear responses when those responses are the result of a linguistic/cognitive representation acquired through language, which, like other verbally mediated material, generally involves the left hemisphere. Additional evidence from case studies suggests that, within the medial temporal lobe, the amygdala is responsible for this modulation.

Adult↗

Synthesis and biological evaluation of analogues of the tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of primitive haematopoietic cell proliferation.

The tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of haematopoietic stem cell proliferation, reduces in vivo and in vitro the damage to the stem cell compartment resulting from treatment with chemotherapeutic agents or ionizing radiations. In order to provide new molecules likely to improve the myeloprotection displayed by this tetrapeptide, we have prepared a set of analogues of AcSDKP. These compounds are derived from the parent peptide by substitution or modification of the N- or of the C-terminus, or substitution of side chains. We report here that almost all investigated analogues retain the antiproliferative activity reducing in vitro the proportion of murine Colony-Forming Units Granulocyte, Macrophage (CFU-GM) in S-phase and inhibiting the entry into cycle of High Proliferative Potential Colony-Forming Cells (HPP-CFC). This shows that the polar groups of Ser, Asp or Lys are critical for the expression of biological activity, but that the modification of the N- or C-terminus mostly yielded compounds still retaining antiproliferative activity and devoid of toxicity. The efficacy of AcSDKP analogues in preventing in vitro the primitive haematopoietic cells from entering into cycle makes these molecules new candidates for further in vivo investigations.

Animals↗

Gender and activation level in smokers.

Studies on the enhancing effects of nicotine on performance are usually pharmacological challenges using deprived male smokers. However, gender may be a factor that influences nicotine/smoking effects upon information processing. We investigated gender differences in contingent negative variation (CNV) amplitude in non-deprived dependent smokers performing a go-no go reaction time paradigm. Female smokers did not differ from female non-smokers in both early and late CNV, whereas male smokers presented greater early and late CNV compared to male non-smokers and an alteration in inhibiting processes responsible for CNV development in the no go condition. Consistent with the evidence of gender differences in nicotine/smoking sensitivity, these preliminary results emphasize the need for taking into account gender in psychophysiological research of nicotine/smoking effects.

Arousal↗

Activation of the left amygdala to a cognitive representation of fear.

We examined the neural substrates involved when subjects encountered an event linked verbally, but not experientially, to an aversive outcome. This instructed fear task models a primary way humans learn about the emotional nature of events. Subjects were told that one stimulus (threat) represents an aversive event (a shock may be given), whereas another (safe) represents safety (no shock will be given). Using functional magnetic resonance imaging (fMRI), activation of the left amygdala was observed in response to threat versus safe conditions, which correlated with the expression of the fear response as measured by skin conductance. Additional activation observed in the insular cortex is proposed to be involved in conveying a cortical representation of fear to the amygdala. These results suggest that the neural substrates that support conditioned fear across species have a similar but somewhat different role in more abstract representations of fear in humans.

Amygdala↗

Contextual fear-potentiated startle conditioning in humans: replication and extension.

Contextual fear conditioning was examined using the startle reflex in two groups of participants over two sessions separated by 1/2 h. The conditioned stimulus (CS) was paired (paired group) or not (unpaired group) with an unpleasant shock during conditioning. The paired group showed conditioning to the CS that was well retained over the retention interval. Session I intertrial interval startles--a measure of contextual conditioning--were greater in the unpaired compared to the paired group. Context conditioning was retained in Session 2 and was present before the shock electrodes were attached. Self-rating of state anxiety, arousal, and pleasure indicated differential changes in mood from Session 1 to Session 2 in the two groups, with the unpaired group showing relatively greater negative affects compared to the paired group. These results indicate that unpredictable shocks lead to greater context conditioning as measured by startle and self-reports.

Adolescent↗

Conditioned inhibition of fear-potentiated startle and skin conductance in humans.

Conditioned inhibition of classical conditioning was investigated with the startle reflex and the skin conductance response (SCR) in humans using a serial presentation of the conditioned inhibitor (X) and of the conditioned stimulus (CS). The unconditioned stimulus (US) was a shock. During conditioning, participants were presented with two different reinforced CS (A, B) and with X preceding A (noted X-->A). During X-->A, A was not reinforced with the US. During the summation test, B, X-->B, and Y-->B were presented (Y was a new stimulus that tested the specificity of the inhibitory properties of X). B was not reinforced during the summation test. A, B, X, and Y were lights of different colors. Participants were divided into a low and a high anxious group based on the TPQ (C.R. Cloninger, 1987). In the low anxious group, conditioned startle potentiation and SCR responses to A were inhibited when X preceded A (noted A(XA)). This differential responding to A and A(XA) emerged earlier with the SCR than with startle. During the summation test, the inhibitory properties of X did not transfer to B. In the high anxious group, there was only a differential SCR to A and A(XA). X did not inhibit startle potentiation to A.

Adolescent↗

Effects of alcohol on baseline startle and prepulse inhibition in young men at risk for alcoholism and/or anxiety disorders.

OBJECTIVE: This study examined the hypothesis that a decreased reaction to alcohol and a deficit in prepulse inhibition (PPI) of the startle reflex are characteristics of male offspring of alcoholics without comorbid anxiety disorder. METHOD: Male offspring (N = 51) with a parental history of (1) alcoholism only, (2) anxiety disorder only, (3) alcoholism and anxiety disorder, and (4) no psychiatric disorder participated in an experiment examining the effects of alcohol on the acoustic startle reflex and on PPI. The experiment was carried out in two sessions in which subjects received an alcoholic beverage and placebo beverage on alternate days. RESULTS: The magnitude of startle was reduced by alcohol in each group. However, the degree of reduction was less in the offspring of alcoholics only compared to the other groups. In addition, PPI was reduced in the offspring of alcoholics only compared to the offspring of parents with no psychiatric disorder. CONCLUSIONS: A reduced reactivity to the effect of alcohol and a deficit in PPI might constitute vulnerability markers for alcoholism, but only in offspring of alcoholics without comorbid anxiety disorder.

Adult↗

Vulnerability factors among children at risk for anxiety disorders.

BACKGROUND: The high-risk strategy is one of the most powerful approaches for identifying premorbid risk factors and reducing etiologic and phenotypic heterogeneity characteristic of the major psychiatric disorders. METHODS: This paper reviews the methods of high-risk research and findings from previous high-risk studies of anxiety. The preliminary results of the 6-8 year follow-up of a high-risk study of 192 offspring of probands with anxiety disorders, substance abuse, and unaffected controls are presented. The key study measures include comprehensive diagnostic interviews, symptom ratings, indirect measures of brain functioning (neuropsychologic, neurologic and psychophysiologic function), developmental measures, and family functioning measures. RESULTS: The major findings reveal that there is specificity of familial aggregation of anxiety disorders among parents and children; children at high risk for anxiety have increased startle reflex, autonomic reactivity, and stress reactivity, higher verbal IQ, and deficits in paired associative learning as compared to other children. CONCLUSIONS: The finding that family environment and parenting do not differ between children at risk for anxiety disorders and other children, when taken together with the strong degree of specificity of transmission of anxiety disorders, suggests that there may be temperamental vulnerability factors for anxiety disorders in general that may already manifest in children prior to puberty.

Adolescent↗

Abnormal mismatch negativity in women with sexual assault-related posttraumatic stress disorder.

BACKGROUND: Disturbances in sensory processing have been hypothesized in individuals with posttraumatic stress disorder (PTSD). The authors investigated this possibility by using mismatch negativity (MMN), an event-related potential (ERP) that reflects the operation of a preconscious cortical detector of stimulus change. METHODS: Thirteen medication-free women with sexual assault-related PTSD were compared with 16 age-matched, healthy comparison women without PTSD. ERPs were elicited by regularly presented "standard" auditory stimuli and by infrequently occurring "deviant" auditory stimuli, which differed slightly in frequency. The MMN was identified in the subtraction waveforms as the difference between ERPs elicited by the deviant and standard stimuli. Group comparisons of P50, N1, P2, and N2 to the standard and to the deviant stimuli, and of the MMN in the subtraction waveform were performed. RESULTS: The amplitude of the MMN was significantly greater in the PTSD compared to the non-PTSD women. MMN was significantly correlated with the total Mississippi PTSD Symptom Scale score in the PTSD group. No significant group differences were noted in P50, N1, or P2 responding. Significant group differences in N2 were due to the increased MMN in PTSD subjects. CONCLUSIONS: The data provide evidence for abnormalities in preconscious auditory sensory memory in PTSD, whereas earlier studies have reported abnormalities in conscious processing. These data suggest an increased sensitivity to stimulus changes in PTSD and implicate the auditory cortex in the pathophysiology of the disorder.

Adult↗

In vitro effect of acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) analogs resistant to angiotensin I-converting enzyme on hematopoietic stem cell and progenitor cell proliferation.

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of hematopoietic stem cell proliferation, is known to reduce in vivo the damage resulting from treatment with chemotherapeutic agents or ionizing radiation on the stem cell compartment. Recently, AcSDKP has been shown to be a physiological substrate of the N-active site of angiotensin I-converting enzyme (ACE). Four analogs of the tetrapeptide expressing a high stability towards ACE degradation in vitro have been synthesized in order to provide new molecules likely to improve the myeloprotection displayed by AcSDKP. These analogs are three pseudopeptides with a modified peptidic bond, Ac-Serpsi(CH2-NH)Asp-Lys-Pro, Ac-Ser-Asppsi(CH2-NH)Lys-Pro, Ac-Ser-Asp-Lyspsi(CH2-N)Pro, and one C-terminus modified peptide (AcSDKP-NH2). We report here that these analogs reduce in vitro the proportion of murine colony-forming units-granulocyte/macrophage in S-phase and inhibit the entry into cycle of high proliferative potential colony-forming cells. The efficacy of AcSDKP analogs in preventing in vitro primitive hematopoietic stem cells from entering into cycle suggests that these molecules could be new candidates for the powerful inhibition of hematopoietic stem and progenitor cell proliferation in vivo.

Animals↗

Startle potentiation by threat of aversive stimuli and darkness in adolescents: a multi-site study.

In recent years, the startle reflex has become an exciting new tool to investigate affective responses to aversive stimuli in humans. The popularity of this methodology is largely based on the substantial amount of animal research available on this topic. Several procedures have been developed to examine startle potentiation in humans, but most studies have been carried out in adults and may not be appropriate for children or adolescents. The present study is a multi-site project (Yale University, Harvard University, and the University of Minnesota) investigating two new procedures to examine the potentiation of startle in adolescents. The subjects were 50 male and female aged 13-17 years old. One procedure examined fear-potentiated startle to the threat of an unpleasant airblast directed to the larynx. The second examined the facilitation of startle in darkness. Potentiation was found using each procedure and the degree of potentiation was similar across laboratories. These results suggest that both the threat of an airblast and darkness can reliably be used to examine startle potentiation in young subjects.

Adolescent↗

Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder.

Aversive conditioning to explicit and contextual cues was examined in Gulf War veterans with and without posttraumatic stress disorder (PTSD) by use of the startle reflex methodology. Veterans participated in a differential aversive conditioning experiment consisting of 2 sessions separated by 4 or 5 days. Each session comprised two startle habituation periods, a preconditioning phase, a conditioning phase, and a postconditioning extinction test. In contrast to the non-PTSD group, the PTSD group showed a lack of differential startle response in the presence of a conditioned stimulus with or without an unconditioned stimulus in Session 1 and an increase in the baseline startle response during Session 2. The PTSD group also exhibited normal differential conditioning following reconditioning in Session 2. These data suggest that individuals with PTSD tend to generalize fear across stimuli and are sensitized by stress.

Adult↗

Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder.

BACKGROUND: The hypothesis that exaggerated startle in Vietnam veterans with posttraumatic stress disorder (PTSD) reflects an anxiogenic response to stressful contexts was tested. METHODS: Thirty-four nonmedicated Vietnam veterans with PTSD, and 17 combat and 14 civilian non-PTSD controls participated in two testing sessions over separate days. Acoustic startle stimuli were delivered alone or in a test of prepulse inhibition. In the first session, startle was assessed without experimental stress. In the second session, startle was investigated during a stressful "threat of shock" experiment, when subjects anticipated the administration of shocks during threat periods and during safe periods when no shocks were anticipated. RESULTS: The magnitude of startle did not differ significantly among the three groups in the first session, but was increased throughout the threat of shock experiment in the PTSD veterans in the second session. The actual increase in startle in the threat compared to the safe condition did not significantly differ among the three groups. Prepulse inhibition was reduced in the PTSD veterans, compared to the non-PTSD civilians, but not compared to the non-PTSD veterans. CONCLUSION: Exaggerated startle in Vietnam veterans with PTSD reflects an anxiogenic response to an environment that is experienced as stressful.

Acoustic Stimulation↗