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Cuervo-Lombard C.,Center Hospitalier University Of Reims | Cuervo-Lombard C.,University of Toulouse II – Le Mirail | Lemogne C.,University of Paris Descartes | Lemogne C.,Hopitaux Universitaires Paris Ouest | And 9 more authors.
British Journal of Psychiatry | Year: 2012

Background: Autobiographical memory retrieval is impaired in schizophrenia. Aims: To determine the neural basis of this impairment. Method: Thirteen patients with schizophrenia and 14 healthy controls performed an autobiographical memory retrieval task based on cue words during functional magnetic resonance imaging. Patients were selected on the basis of their ability to perform the task and all participants received training. Results: Although patients and controls activated a similar brain network during autobiographical memory retrieval, patients displayed decreased activation in several of these regions, including the anterior cingulate cortex, left lateral prefrontal cortex, right cerebellum and ventral tegmental area (k≥10, P<0.001, uncorrected). In addition, activation of the caudate nuclei was negatively correlated with retrieval performance in controls but positively correlated with performance in patients. Conclusions: The autobiographical memory retrieval brain network is impaired in schizophrenia. Patients with schizophrenia display decreased activation of the cognitive control network during retrieval, possibly due to aberrant functioning of the dorsal striatum.

PubMed | RainDance Technologies, Hopitaux Universitaires Paris Ouest, University of Versailles, Reims University Hospital Center and 5 more.
Type: Journal Article | Journal: Clinical chemistry | Year: 2016

Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored.We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up.Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution.These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.

Le Port A.,University of Versailles | Gueguen A.,University of Versailles | Kesse-Guyot E.,French National Conservatory of Arts and Crafts | Melchior M.,University of Versailles | And 8 more authors.
PLoS ONE | Year: 2012

Background: Data on the association between dietary patterns and depression are scarce. The objective of this study was to examine the longitudinal association between dietary patterns and depressive symptoms assessed repeatedly over 10 years in the French occupational GAZEL cohort. Methods: A total of 9,272 men and 3,132 women, aged 45-60 years in 1998, completed a 35-item Food Frequency Questionnaire (FFQ) at baseline. Dietary patterns were derived by Principal Component Analysis. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression scale (CES-D) in 1999, 2002, 2005 and 2008. The main outcome measure was the repeated measures of CES-D. Longitudinal analyses were performed with logistic regression based on generalized estimating equations. Principal Findings: The highest quartile of low-fat, western, high snack and high fat-sweet diets in men and low-fat and high snack diets in women were associated with higher likelihood of depressive symptoms at the start of the follow-up compared to the lowest quartile (OR between 1.16 and 1.50). Conversely, the highest quartile of traditional diet (characterized by fish and fruit consumption) was associated with a lower likelihood of depressive symptoms in women compared to the lowest quartile, with OR = 0.63 [95%CI, 0.50 to 0.80], as the healthy pattern (characterized by vegetables consumption) with OR = 0.72 [95%CI, 0.63 to 0.83] and OR = 0.75 [95%CI, 0.61 to 0.93] in men and women, respectively. However, there was probably a reverse causality effect for the healthy pattern. Conclusion: This longitudinal study shows that several dietary patterns are associated with depressive symptoms and these associations track over time. © 2012 Le Port et al.

Lemogne C.,University of Paris Descartes | Lemogne C.,Hopitaux Universitaires Paris Ouest | Lemogne C.,French Institute of Health and Medical Research
Annales Medico-Psychologiques | Year: 2015

Psychopathology is worthy of consideration to inform the application of functional neuroimaging to the study of mental disorders. By promoting an approach based on mental processes underlying disorders rather than an approached based on diagnostic categories, it offers the opportunity to identify biomarkers that could be used as nosological tools. Such biomarkers may eventually inform treatment strategies. However, the question of whether functional brain imaging can be used to learn something about psychopathology, that is understanding the nature and the relationships of mental processes that underlie psychiatric disorders, remains controversial. A potential advantage of functional brain imaging could be the examination of non-conscious mental processes that could be both non reportable by the subject and difficult to capture with behavioral measures. As an example, several studies found depression and anxiety to be associated with amygdala aberrant reactivity to masked emotional stimuli. This might be interpreted as signaling automatic cognitive biases such as those proposed by cognitive theory. But when trying to deduce the presence of a mental process M from a specific pattern of brain activity A, frequently referred to as reverse inference, one has to consider several issues, regardless of the nature of the mental process. These issues can be best formalized with a Bayesian approach where the probability of the presence of M according to A, P(. M|. A) depends on the a priori probability of M to be present, P(. M), as well as on conditional probabilities P(. R|. M) and P(R|M-). Obviously, P(. M) depends on the specificity of the experimental paradigm used. However, reverse inference usually takes place when A was unexpected (i.e. not supposed to be engaged by the experimental task). Conditional probabilities regarding the probability of A according to the presence or the absence of M, P(. A|. M) and P(A|M-) can be estimated using methods of data mining based on growing databases. The less A is specific to M, that is to say the higher P(A|M-) is, the less valid the reverse inference will be. This is even worse when the definition of R is loose. Despite these limitations, reverse inference is nevertheless a powerful heuristic tool when it comes to generate testable hypotheses about the nature of mental processes and their relationships. Combined with carefully designed experimental paradigms, functional brain imaging is thus likely to bring new knowledge to psychopathology. © 2015 Elsevier Masson SAS.

Limosin F.,Hopitaux Universitaires Paris Ouest | Limosin F.,University of Paris Descartes | Limosin F.,French Institute of Health and Medical Research
BMC Psychiatry | Year: 2014

The negative symptoms of schizophrenia, avolition, alogia, apathy and impaired or nonexistent social functioning, are strongly correlated with the progressive course and long-term prognosis of the disease, undermining the patient's ability to integrate socially, interpersonal skills and quality of life. At a time when new drug strategies are being developed, a better understanding of the etiology and pathogenesis underpinning the occurrence of negative symptoms constitutes an essential prerequisite for real therapeutic advances. Approaching this vulnerability from the neurodevelopmental perspective is especially pertinent with regard to the experimental studies conducted in animals. Several models have been put forward, involving a variety of topics such as the deleterious impact of a prenatal infection or of early maternal deprivation on brain development, or else the consequences of trauma and abuse suffered during childhood. These various models are based on biological abnormalities that could guide the identification of new therapeutic targets. They notably include the hyperreactivity of the hypothalamic-pituitary-adrenal axis and dysfunction of corticostriatal glutamatergic transmission. As such, in the traumagenic model, which associates neurodevelopmental and neurodegenerative processes, the dysfunction of corticostriatal glutamatergic transmission, by reducing the tonic dopamine release, could be the cause of an increase in the phasic dopamine release linked to stress. This excessive phasic response to stress may induce cerebral damage by increasing excitotoxicity and oxidative stress. © 2014 Limosin; licensee BioMed Central Ltd.

Alhenc-Gelas M.,Hopitaux Universitaires Paris Ouest | Plu-Bureau G.,University of Paris Descartes | Horellou M.H.,University of Paris Descartes | Rauch A.,Institute Dhematologie Transfusion | Suchon P.,Aix - Marseille University
Thrombosis and Haemostasis | Year: 2016

Inherited protein S deficiency (PSD) is an established risk factor for venous thromboembolism (VTE). However, data are conflicting concerning risk of VTE associated with decreased free PS level (FPS) and information on PROS1 genotype-phenotype relationship is sparse. In a retrospective cohort of 579 patients with inherited type I/III deficiency suspicion, PROS1 genotyping was performed and the effect of genotype on FPS and on VTE risk was investigated. We found 116 (including 65 novel) detrimental mutations (DM) in 222 (type I/III in 194, type II in 28), PS Heerlen in 74, possibly non DM in 38 and no mutation in 245 subjects. Among DMs, type I/IIIDMs only were found in subjects with FPS< 30 %. Prevalence of type I/III DM decreased with increasing FPS level. Risk of VT associated with FPS level and genotype was studied in the 467 subjects with personal or family history of thrombo sis. Only type I/IIIDM carriers presented with an increased risk of VTE [1.41 (95 %CI (1.05–1.89)] compared to subjects with no mutation. Among the group of type I/IIIDM heterozygotes and subjects with no mutation, the optimal FPS cut-off point for identifying subjects at increased VTE risk was searched for. We found that only subjects with FPS< 30 % and type I/IIIDM presented with an increased risk [1.48 (95 %CI 1.08–2.04)]. Our findings confirm the value of a cut-off FPS level for identifying subjects at increased VTE risk far below the lower limit of the normal range and suggest a place for PROS1 genotyping in PSD diagnosis strategy. © Schattauer 2016.

Lemogne C.,University of Paris Descartes | Lemogne C.,Hopitaux Universitaires Paris Ouest | Lemogne C.,French Institute of Health and Medical Research
Bulletin de l'Academie Nationale de Medecine | Year: 2015

Empathy may be defined as the ability to share and/or understand others' emotional state. It is a multi-faceted construct that relies on discrete psychological processes with specific neural correlates. These psychological processes might be impaired in some mental disorders, such as schizophrenia, autism spectrum disorders, borderline personality disorder or mood disorders. Among these disorders, psychopathy is mainly characterized by a lack of empathy for others' distress associated with amygdala hypo-reactivity. In the context of doctor-patient relationships, clinical empathy also encompasses the physician's ability to communicate his or her understanding of the emotional state of the patient. However, sharing the emotional states may elicit compassion fatigue and burnout symptoms among physicians and medical students and reduce their empathic capacities. A decline of these capacities is indeed observed during medical training. Perspective-taking may protect physicians from such negative effects while allowing them to show sustained empathic concern. Interventions to promote empathy among medical students should target both communication skills and humanist values: communication skils may depend on humanist values to grow.

PubMed | Hopitaux Universitaires Paris Ouest and University of Paris Descartes
Type: | Journal: Neuropsychologia | Year: 2015

Patients with anosmia are not able to detect volatile chemicals signaling the presence of infectious and non-infectious environmental hazards, which typically elicit disgust and fear, respectively. Social animals may compensate a loss of olfaction by taking advantage of signals of threat that are produced by their conspecifics. Among humans and other primates, body postures and facial expressions are powerful cues conveying emotional information, including fear and disgust. The aim of the present study was to examine whether humans with agenesis of the olfactory bulb, a rare disorder characterized by congenital anosmia, would be more accurate in recognizing facial expressions of fear and disgust. A total of 90 participants with no history of mental disorder or traumatic brain injury were recruited, including 17 patients with congenital anosmia (10 men, mean age standard deviation: 36.5 14.8 years), 34 patients with acquired anosmia (18 men, mean age standard deviation: 57.2 11.8 years) and 39 healthy subjects (22 men, mean age standard deviation: 36.7 13.2 years). For each patient with congenital anosmia, the agenesis of the olfactory bulb was ascertained through magnetic resonance imaging. Emotion recognition abilities were examined with a dynamic paradigm in which a morphing technique allowed displaying emotional facial expressions increasing in intensity over time. Adjusting for age, education, depression and anxiety, patients with congenital anosmia required similar levels of intensity to correctly recognize fear and disgust than healthy subjects while they displayed decreased error rates for both fear (mean difference [95% confidence interval] = -28.3% [-46.3%, -10.2%], P = 0.003) and disgust (mean difference [95% confidence interval] = -15.8% [-31.5%, -0.2%], P = 0.048). Furthermore, among patients with acquired anosmia, there was a negative correlation between duration of anosmia and the rate of errors for fearful (Spearmans = -0.531, P= 0.001) or disgust (Spearmans = -0.719, P < 0.001) faces recognition. No significant difference was observed for the other primary emotions. Overall, these results suggest that patients with congenital anosmia and long-lasting acquired anosmia may compensate their inability to detect environmental hazards through olfaction by an increased ability to detect fear or disgust as facially expressed by others.

PubMed | University of Versailles, Hopitaux Universitaires Paris Ouest, University of Paris Descartes, Aventino Medical Group and University Pierre and Marie Curie
Type: Journal Article | Journal: Health psychology : official journal of the Division of Health Psychology, American Psychological Association | Year: 2015

Evidence for an association between hostility and peptic ulcer mainly relies on cross-sectional studies. Prospective studies are rare and have not used a validated measure of hostility. This prospective study aimed to examine the association between hostility and peptic ulcer in the large-scale French GAZEL cohort.In 1993, 14,674 participants completed the Buss and Durkee Hostility Inventory. Participants were annually followed-up from 1994 to 2011. Diagnosis of peptic ulcer was self-reported. The association between hostility scores and ulcer incidence was measured by hazard ratios (HR) and 95% confidence intervals computed through Cox regression.Among 13,539 participants free of peptic ulcer history at baseline, 816 reported a peptic ulcer during a mean follow-up of 16.8 years. Adjusting for potential confounders, including smoking, occupational grade, and a proxy for nonsteroidal anti-inflammatory drug exposure, ulcer incidence was positively associated with total hostility (HR per SD: 1.23, confidence interval: 1.14-1.31), behavioral hostility (HR per SD: 1.13, confidence interval: 1.05-1.21), cognitive hostility (HR per SD: 1.26, confidence interval: 1.18-1.35), and irritability (HR per SD: 1.20, confidence interval: 1.12-1.29). The risk of peptic ulcer increased from the lowest to the highest quartile for all hostility measures (p for linear trend < .05).Hostility might be associated with an increased risk of peptic ulcer. Should these results be replicated, further studies would be needed to explore the underlying mechanisms.

PubMed | Hopitaux Universitaires Paris Est, Hopitaux Universitaires Paris Ouest and Groupe Hospitalier Diaconesses Croix Saint Simon
Type: Journal Article | Journal: Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland | Year: 2015

The clinicopathological and virological characteristics of anal superficially invasive squamous-cell carcinoma (SISCCA) were determined.Seventeen patients with a completely excised stage T1N0M0 anal squamous-cell carcinoma (SCC) were included in the study. The tumours were divided into superficially invasive and invasive. Patients with anal high-grade squamous intraepithelial dysplasia, which corresponded to anal intraepithelial neoplasia (AIN) Grades 2 or 3, were used as a control group. Clinicopathological and virological characteristics were investigated. Overall survival and cancer recurrence-free survival were also assessed.Of the 17 patients, 12 (70.5%) were men. Ten (58.8%) were human immunodeficiency virus positive. Seven (41%) patients met the same diagnostic criteria as those recently proposed for anal SISCCA. According to the results obtained using the polymerase chain reaction, human papillomavirus (HPV) 16 was the most commonly detected (94%) type of HPV. Twelve (70.6%) patients with an inadequate surgical margin around the tumour received adjuvant radiotherapy, including the two (11.7%) tumours that locally recurred, one of which was an anal SISCCA. Superficially invasive anal cancers differed from the other T1N0M0 anal carcinomas according to the clinical presentation and the absence of lymph-vascular invasion (LVI). There were no differences in cancer recurrence-free and overall survival rates between the superficially invasive and invasive groups.Anal SISCCAs have a low index of clinical suspicion, are associated with an absence of LVI and are linked to high-risk HPV. Prospective studies are needed to define the clinical behaviour of these anal tumours and to determine their best therapeutic strategy.

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