[Barriers to access to care evaluation scale (bace-3) psychometric properties of the french version in a naturalistic ambulatory psychiatric community setting]. / Les barrières à l'accès aux soins : validation de la BACE-3 française.

OBJECTIVES: To translate into French and validate the BACE-3 scale (Barriers to Care Evaluation) and describe the barriers to access to care in mental health settings. METHODS: The instrument was translated into French with its author's authorisation and her supervision. Three outpatient consultation centres and two day hospitals in the same geographical region were involved. We included patients aged between 18 and 6years under regular follow-up with psychiatrists and diagnosed with a psychotic disorder, a bipolar disorder, a mood disorder, a personality disorder, an anxiety disorder or a somatoform disorder, all according to ICD-10 criteria. To be included subjects further had to have sought some health care support in the last twelve months or be be regularly treated in a continuous way at the time of inclusion. RESULTS: One hundred twenty-one patients were successively included during a regular consultation. The exploratory factor analysis of the 30-item BACE-3 yielded to a method factor (items that could only be answered by patients with a family and/or at work were recoded) and two clinically meaningful factors were named, Stigmatisation and Cognitive Bias and Denial. We found that the first factor was nicely in line with the factors we had extracted from the Internalized Stigma Mental Illness (ISMI) scale in the same sample. This provided an external validation of the BACE but it was difficult to conclude any further given the limited size of our sample. CONCLUSIONS: Barriers to care need to be addressed by clinicians. Internal and external validity properties of the BACE-3 scale show it can be used in French-speaking populations of outpatients suffering from mental health problems.

Tyrosine kinases regulate chondrocyte hypertrophy: promising drug targets for Osteoarthritis.

Osteoarthritis (OA) is a major health problem worldwide that affects the joints and causes severe disability. It is characterized by pain and low-grade inflammation. However, the exact pathogenesis remains unknown and the therapeutic options are limited. In OA articular chondrocytes undergo a phenotypic transition becoming hypertrophic, which leads to cartilage damage, aggravating the disease. Therefore, a therapeutic agent inhibiting hypertrophy would be a promising disease-modifying drug. The therapeutic use of tyrosine kinase inhibitors has been mainly focused on oncology, but the Food and Drug Administration (FDA) approval of the Janus kinase inhibitor Tofacitinib in Rheumatoid Arthritis has broadened the applicability of these compounds to other diseases. Interestingly, tyrosine kinases have been associated with chondrocyte hypertrophy. In this review, we discuss the experimental evidence that implicates specific tyrosine kinases in signaling pathways promoting chondrocyte hypertrophy, highlighting their potential as therapeutic targets for OA.

Early mandibular morphological differences in patients with FGFR2 and FGFR3-related syndromic craniosynostoses: A 3D comparative study.

Syndromic craniosynostoses are defined by the premature fusion of one or more cranial and facial sutures, leading to skull vault deformation, and midfacial retrusion. More recently, mandibular shape modifications have been described in FGFR-related craniosynostoses, which represent almost 75% of the syndromic craniosynostoses. Here, further characterisation of the mandibular phenotype in FGFR-related craniosynostoses is provided in order to confirm mandibular shape modifications, as this could contribute to a better understanding of the involvement of the FGFR pathway in craniofacial development. The aim of our study was to analyse early mandibular morphology in a cohort of patients with FGFR2- (Crouzon and Apert) and FGFR3- (Muenke and Crouzonodermoskeletal) related syndromic craniosynostoses. We used a comparative geometric morphometric approach based on 3D imaging. Thirty-one anatomical landmarks and eleven curves with sliding semi-landmarks were defined to model the shape of the mandible. In total, 40 patients (12 with Crouzon, 12 with Apert, 12 with Muenke and 4 with Crouzonodermoskeletal syndromes) and 40 age and sex-matched controls were included (mean age: 13.7 months ±11.9). Mandibular shape differed significantly between controls and each patient group based on geometric morphometrics. Mandibular shape in FGFR2-craniosynostoses was characterized by open gonial angle, short ramus height, and high and prominent symphysis. Short ramus height appeared more pronounced in Apert than in Crouzon syndrome. Additionally, narrow inter-condylar and inter-gonial distances were observed in Crouzon syndrome. Mandibular shape in FGFR3-craniosynostoses was characterized by high and prominent symphysis and narrow inter-gonial distance. In addition, narrow condylar processes affected patients with Crouzonodermoskeletal syndrome. Statistical analysis of variance showed significant clustering of Apert and Crouzon, Crouzon and Muenke, and Apert and Muenke patients (p < 0.05). Our results confirm distinct mandibular shapes at early ages in FGFR2- (Crouzon and Apert syndromes) and FGFR3-related syndromic craniosynostoses (Muenke and Crouzonodermoskeletal syndromes) and reinforce the hypothesis of genotype-phenotype correspondence concerning mandibular morphology.

Animal models of craniosynostosis.

BACKGROUND: Various animal models mimicking craniosynostosis have been developed, using mutant zebrafish and mouse. The aim of this paper is to review the different animal models for syndromic craniosynostosis and analyze what insights they have provided in our understanding of the pathophysiology of these conditions. MATERIAL AND METHODS: The relevant literature for animal models of craniosynostosis was reviewed. RESULTS: Although few studies on craniosynostosis using zebrafish were published, this model appears useful in studying the suture formation mechanisms conserved across vertebrates. Conversely, several mouse models have been generated for the most common syndromic craniosynostoses, associated with mutations in FGFR1, FGFR2, FGFR3 and TWIST genes and also in MSX2, EFFNA, GLI3, FREM1, FGF3/4 genes. The mouse models have also been used to test pharmacological treatments to restore craniofacial growth. CONCLUSIONS: Several zebrafish and mouse models have been developed in recent decades. These animal models have been helpful for our understanding of normal and pathological craniofacial growth. Mouse models mimicking craniosynostoses can be easily used for the screening of drugs as therapeutic candidates.

Oxidative and nitrosative stress markers in obsessive-compulsive disorder: a systematic review and meta-analysis.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic, prevalent, and highly impairing psychiatric illness. Although the pathophysiology of OCD remains unknown, pathways involved in oxidative and nitrosative stress (O&NS) have been implicated. The present study aims to systematically review the literature for quantitative evidence that patients with OCD have altered measures of blood O&NS markers. METHODS: Independent random-effects meta-analyses using standardized mean differences were conducted to assess each marker separately. Additionally, data from multiple markers were pooled together in a meta-analysis for measures of oxidant activity and another for measures of antioxidant activity. RESULTS: Thirteen studies met inclusion criteria, involving 433 OCD patients and 459 controls. Eleven blood O&NS markers were eligible for independent quantitative analyses. We found that, in OCD patients, the oxidant markers 8-hydroxydeoxyguanosine and malondialdehyde, and the antioxidants glutathione peroxidase and superoxide dismutase, were significantly increased while total antioxidant status, vitamin C, and vitamin E were significantly decreased, when comparing with controls. Regarding pooled meta-analyses, we found a statistically significant increase in oxidant markers, but non-significant results regarding antioxidant markers. CONCLUSIONS: Our meta-analysis suggests that OCD patients have a systemic oxidative imbalance that is not adequately buffered by the antioxidant system. Additional studies are needed in order to support this association.

Crazy'App: A web survey on representations and attitudes toward mental disorders using video testimonies.

In the international context of efforts to combat the stigmatization of people with mental health problems, representations and attitudes about these illnesses have not to date been widely investigated in France. However, new technologies offer an unprecedented opportunity to collect such information on a large scale and to deploy more efficient action against stigma. OBJECTIVES: The Crazy'App survey was designed as an instrument for studying potentially stigmatizing representations and attitudes towards mental disorders. It asks respondents to react, rather than to standard diagnostic labels or case vignettes, to video testimonies by people with different mental disorders talking about their experiences. METHODS: The web survey was made available on smartphone or computer and advertised on various media and during a French exhibition about mental disorders, mental health and well-being ("Mental Désordre", Cité des sciences, Paris, 2016). It consisted of short (<2min) video testimonials by four people presenting respectively anorexia, bipolar disorder, obsessive-compulsive disorder and addiction to alcohol. Each testimony was immediately followed by series of questions to which participants were to respond using visual analog scales. The questionnaires investigated different domains, such as the causes of each of these mental disorders, the possible treatments and the respondent's personal attitudes in hypothetical situations (e.g. working with the person seen in the video). After having completed the survey, respondents were offered an opportunity to compare their own responses to those of the other respondents, and watch expert psychiatrists interviews delivering clinical and scientific knowledge and sharing their own attitudes. RESULTS: The respondents (n=2600) were young, mostly women, educated and concerned about the subject. They exhibited good knowledge of the disorders. They reported a multi-causal view of the etiologies, where psychological causes were rated higher than neurobiological causes (although less so for respondents reporting having had a mental disorder themselves), while other types of causes (environmental, spiritual, and nutritional) received much lower ratings. Respondents also expressed high potential social proximity, but this result varied according to the type of disorder, in particular, the social distance and the perception of dangerousness were greater for addiction and bipolar disorder. CONCLUSIONS: Crazy'App operationalizes emerging strategies in the efforts to combat stigma, implementing what is known as a "contact based intervention" in English-speaking countries. While it does not erase the differences in attitudes observed from one pathology to another, this type of survey-intervention based on video testimonies could help to reduce the desire for social distancing from people with mental disorders, even in a particularly sensitized and informed population. Multimedia technologies are an efficient way to offer rich, potentially interactive content better able to embody people and their actual experiences than clinical descriptions or even life narratives. However the use of videos could put the focus on the individual characteristics (physical, gestural, verbal, nonverbal…), and this should be cautiously taken into account according to the anti-stigma objectives. Connected technologies also make it possible to enhance the more classic de-stigmatization actions focused on the deconstruction of preconceived ideas, making the action more participatory, while simultaneously assessing their efficacy. By mediating contact with individuals and behaviors perceived as deviant, the aim would be to develop psycho-social skills and concrete abilities for action in the general population, to include people with mental disorders in the community.

[Mindfulness-based interventions in obsessive-compulsive disorder: Mechanisms of action and presentation of a pilot study]. / Les interventions basées sur la pleine conscience dans le trouble obsessionnel compulsif : mécanismes d'action et présentation d'une étude pilote.

Obsessive-compulsive disorder (OCD) is a frequent and severe disease, potentially inducing a major impairment for the patient and burden for their family. Recent research in psychiatry and neuroscience have led to better comprehension of the disease's mechanisms and helped to improve its treatment. However, a large proportion of patients have refractory symptoms, including for traditional cognitive and behavioral therapy by exposure and response prevention (ERP), leading clinicians to look for new treatments. Mindfulness-based interventions (MBI) are a new type of approach, initially based on Buddhist meditation, which aims to provide better consciousness of the present moment. It has been successfully developed in some psychiatric diseases and other general medical conditions such as chronic pain. The two main programs using mindfulness meditation, Mindfulness-based stress reduction (MBSR) and Mindfulness-based cognitive therapy (MBCT), have shown effectiveness for the reduction of depressive and anxiety symptoms and relapses of depressive episodes in unipolar depression. It has no side effects and is well tolerated by patients. Its action relies on the specific correction of cognitive deficits in attention, emotion regulation and executive functions which are shared by OCD, GAD and depression. For OCD, we make the hypothesis that Mindfulness-Based Interventions could reduce the cognitive bias specifically existing in this pathology, such as dysfunctional beliefs, and therefore improve the symptoms. This article first reviews the existing literature on clinical trials involving Mindfulness-Based Interventions in OCD which comprises a small number of clinical studies based on very different types of protocols. At this time, and due to the lack of gold-standard studies with a large number of patients, no proof of the efficiency of mindfulness-based interventions in OCD has been shown. In a second section, following our hypothesis on the mechanisms of specific and non-specific action of this therapy in OCD, we propose a cognitive model of mindfulness-based therapy action in OCD involving the correction of OCD's cognitive bias. In this model, mindfulness-based therapy is supposed to treat specifically the cognitive aspects of the disease, while ERP is focused on its behavioral part. Then we present a clinical study aiming to prove the feasibility and the interest of the use of mindfulness in OCD, carried out in two different clinical centers. One of them used MBCT while the second used MBSR. Its results show the feasibility of mindfulness-based therapy in OCD patients and tend to prove that it could be more effective in young patients suffering from less severe forms of OCD. In parallel, attention tests and fMRI scans were done at the beginning and at the end of the therapy. Their results will be published separately. We also discuss the putative role of a specific form of MBCT adapted for OCD, specifically for its benefits in psychoeducation, which could reduce the dysfunctional beliefs present in OCD patients. Finally, we propose a therapeutic strategy in which the MBCT could complement the classical ERP therapy, as a "maintenance" treatment, aiming to extend the relapse of OCD symptoms. This article is a step further in the use of mindfulness-based therapy for OCD which could be added to the existing treatments reducing the patient's symptoms and improving their quality of life.

[Obsessive-compulsive disorder as seen by those who are confronted with it: A survey of patients, relatives and clinicians]. / Le trouble obsessionnel compulsif vu par ceux qui y sont confrontés : enquête auprès de patients, de proches et de cliniciens.

INTRODUCTION: Obsessive compulsive disorder (OCD) is one of the most disabling mental health disorders due to its negative impact on the patient's quality of life as well on that of her living caregivers. This disorder generates an additional burden for relatives, which may in turn affect the family dynamics and impair the evolution of the disease. Along with medications, cognitive behavioral therapy (CBT) represents a well-validated first line of treatment for OCD. However, therapeutic responses across patients are uneven with often residual symptoms and limited quality of life improvements. In total, OCD is a severely debilitating disease with repercussions on both personal, social and professional lives of patients and their relatives even after clinically-delivered treatments. The mutual identification of points of convergence and divergence in social representations is a factor that contributes to satisfactory interpersonal relationships. In the care relationship in general and particularly in the field of mental health, taking account of these different representations and expectations is essential for improving the care process: upstream of the care in the choice the therapeutic strategy and in strengthening the therapeutic alliance. Although less studied, the relationship with relatives of patients also depends on representations of each which have a significant impact on clinical outcomes and experience of the disease. OBJECTIVE: To carry out the first study of cross-representations of OCD in three groups of people affected by it: those who suffer, their families and clinicians. HYPOTHESIS: Considering the experiences and knowledge of patients, relatives and clinicians, we assumed that their representations related to OCD would partially overlap. Specifically, we assumed that the positioning of each population compared to the other two would differ depending on the investigated dimensions: nosology, etiology, therapy and psychiatric disability. METHODS: From 2010 to 2011 we conducted an online survey among self-declared OCD-patients (n=86), OCD-patients' relatives (n=38) and clinicians (n=79). The questionnaire included both closed questions regarding the nosology, etiology, therapy and psychiatric disabilities and open questions probing the representations of the disorder and its evolution, its impact on personal, social and professional domains, and on the quality of life. In particular, we investigated how each population conceived the role and involvement of the relatives in the care process and how they dealt daily with the disorder. RESULTS: Confirming our hypothesis, our results showed that representations of OCD converge on the DSM-based definition of the disorder conveyed by patient associations and mass media. The three populations also recognize the burden and the handicap associated with OCD considerably restrict their daily functioning. However, patients and relatives differ from clinicians in their view of the etiology and their expectations of the therapeutic process. Unexpectedly, patients do not report frequent stigmatization although this may reflect their attempt to hide their disorder as a form of self-stigmatization. Patients focus on care modalities (alternative therapies) motivated by quality of life improvement rather than symptom reduction put forward by clinicians. Relatives ask for being involved in the care process. CONCLUSION: Our study emphasizes the importance for health professionals to take into account the expectations of patients and their relatives in order to maximize the therapeutic alliance and efficiency of treatment.

[Can the efficacy of behavioral and cognitive therapy for obsessive compulsive disorder be augmented by innovative computerized adjuvant?] / Peut-on augmenter l'efficacité de la thérapie cognitive et comportementale pour le trouble obsessionnel compulsif par un adjuvant informatique innovant ?

AIM: Cognitive behavioral therapy (CBT) is recognized as an effective treatment for obsessive-compulsive disorder (OCD). To maximize its effectiveness, we designed an "experimental" CBT defined by the addition of a computerized psychoeducative tool. METHOD: In a participative process involving patients through meetings of the French OCD association (AFTOC) and therapists through methodological workshops, we built a therapeutic tool from an experimental checking task. This task, which had been published in an earlier work, was adapted for its psychoeducative dimension. We here report on a randomized double-blind trial which included 35 patients with a moderate to severe OCD (Yale-Brown obsessive-compulsive scale, YBOCS between 16 and 25) predominant checking symptoms, no comorbidities, and 2-month stabilized or no treatment. Patients were randomly assigned to either "standard" versus "experimental" CBT. Both therapies were conducted by four CBT-experienced therapists specialized in OCD through weekly individualized sessions over 3 months. Therapy sessions of the experimental CBT were conducted as the standard CBT except for a short exercise with the computerized psychoeducative tool performed by the patient and debriefed with the therapist at the end of the sessions. Patients were assessed before, during, after therapy and again 6 months later using standard clinical tools and a neurobehavioral assessment based on an original symptom-provocation task with anxiety ratings including three types of photographs: neutral, generic inducing obsessions (e.g., doorknobs, electric wires…) and personalized (taken by the patients in their own environment). RESULTS: Clinically, "standard" and "experimental" CBT resulted in a significant but equivalent improvement (48% vs 45% reduction of the Y-BOCS score; P=0.36; d=0.12). Therapists were satisfied with the psychoeducative dimension of the computerized psychoeducative tool but reported variable acceptance across patients. Patients appreciated its usability. The clinical improvement was associated with a reduction of the task-induced anxiety (r=0.42, P<0.05), especially towards personalized items (-28,2% vs -20.41% for generic and -6.24% for neutral photographs, P<0.001). Mid-therapy response level was predictive of the final improvement (r=0.82, P<0.001). CONCLUSION: The computerized tool may provide a well-accepted therapeutic adjuvant even though it doesn't improve the therapeutic effect. Using a personalized symptom-provocation task reveals the parallel evolution of symptoms and neurobehavioral markers through CBT. Despite the difficulty of improving an evidence-based therapy, mid-therapy results call for investigating the possible adjustments of treatment strategies at an early stage.

Dynamics of psychotherapy-related cerebral haemodynamic changes in obsessive compulsive disorder using a personalized exposure task in functional magnetic resonance imaging.

BACKGROUND: Cognitive behavioural therapy (CBT) is a successful treatment of obsessive compulsive disorder (OCD). It is known to induce changes in cerebral metabolism; however, the dynamics of these changes and their relation to clinical change remain largely unknown, precluding the identification of individualized response biomarkers. METHOD: In order to study the dynamics of treatment response, we performed systematic clinical and functional magnetic resonance imaging (fMRI) evaluation of 35 OCD patients immediately before a 3-month course of CBT, halfway through and at its end, as well as 6 months after. To sensitize fMRI probing, we used an original exposure task using neutral, generic and personalized obsession-inducing images. RESULTS: As expected, CBT produced a significant improvement in OCD. This improvement was continuous over the course of the therapy; therefore, outcome could be predicted by response at mid-therapy (r 2 = 0.67, p < 0.001). Haemodynamic response to the task was located in the anterior cingulate and orbitofrontal cortices and was stronger during exposure to personalized obsession-inducing images. In addition, both the anxiety ratings and the haemodynamic response to the obsession-inducing images in the anterior cingulate and the left but not the right orbitofrontal clusters decreased with symptom improvement. Interestingly, haemodynamic activity continued to decrease after stabilization of clinical symptoms. CONCLUSIONS: Using an innovative and highly sensitive exposure paradigm in fMRI, we showed that clinical and haemodynamic phenotypes have similar time courses during CBT. Our results, which suggest that the initial CBT sessions are crucial, prompt us to investigate the anatomo-functional modifications underlying the very first weeks of the therapy.

Excessive checking for non-anxiogenic stimuli in obsessive-compulsive disorder.

BACKGROUND: Repetitive checking in obsessive-compulsive disorder (OCD) would serve to relieve obsession-related anxiety and/or to compensate memory deficit, but experimental literature on this subject is inconsistent. The main objective is to test the influence of obsession-related anxiety and memory on repetitive checking in OCD. METHODS: Twenty-three OCD checkers, 17 OCD non-checkers and 41 controls performed a delayed-matching-to-sample task with an unrestricted checking option. Some stimuli were obsession-related in order to measure the influence of anxiety on checking. A version of the task without checking possibility was used to assess memory abilities. RESULTS: OCD checkers had similar memory performances but checked more than the other groups when presented with non-anxiogenic stimuli. Level of anxiety associated to the stimulus did not influence the number of checks. CONCLUSIONS: Increased checking in OCD checkers, being independent of memory abilities and primary obsession-related anxiety, would, therefore, be closer to an automated behaviour than a coping strategy.

[Obsessive-compulsive disorder, a new model of basal ganglia dysfunction? Elements from deep brain stimulation studies]. / Le trouble obsessionnel-compulsif, un nouveau modèle de dysfonction des noyaux gris centraux ? Apports de la stimulation cérébrale profonde.

Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology.

Six questions on the subthalamic nucleus: lessons from animal models and from stimulated patients.

Since the early 90s, the subthalamic nucleus (STN) has started to be the subject of an increasing interest not only in the community of the basal ganglia scientists but also for neurosurgeons and neurologists, thanks to the development of the surgical treatment for Parkinson's disease. The involvement of the STN in cognitive and motivational processes has been demonstrated since, and psychiatrists are now considering this small structure as a possible target for the treatment of various disorders. In this review, we will address six questions to highlight (1) How increased knowledge has led us from a strictly motor model to an integrative one. (2) How knowledge acquired in animal models can be similar or (3) different from the effects observed in human patients. (4) How clinical trials are sometimes ahead of fundamental research carried out in animals, showing effects that could not be predicted on the basis of animal studies, thus questioning the relevance of some animal models, especially for psychiatric disorders. We will also address the possible future orientations (5) and how the use, or precaution not to use, certain key words in animal research dedicated to STN functions can lead to the omission of a certain amount of available data in the literature (6).

Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

A multidisciplinary study of patients with early-onset PD with and without parkin mutations.

OBJECTIVE: To establish phenotype-genotype correlations in early-onset Parkinson disease (EOPD), we performed neurologic, neuropsychological, and psychiatric evaluations in a series of patients with and without parkin mutations. BACKGROUND: Parkin (PARK2) gene mutations are the major cause of autosomal recessive parkinsonism. The usual clinical features are early-onset typical PD with a slow clinical course, an excellent response to low doses of levodopa, frequent treatment-induced dyskinesias, and the absence of dementia. METHODS: A total of 44 patients with EOPD (21 with and 23 without parkin mutations) and 9 unaffected single heterozygous carriers of parkin mutations underwent extensive clinical, neuropsychological, and psychiatric examinations. RESULTS: The neurologic, neuropsychological, and psychiatric features were similar in all patients, except for significantly lower daily doses of dopaminergic treatment and greater delay in the development of levodopa-related fluctuations (p < 0.05) in parkin mutation carriers compared to noncarriers. There was no major difference between the two groups in terms of general cognitive efficiency. Psychiatric manifestations (depression) were more frequent in patients than in healthy single heterozygous parkin carriers but did not differ between the two groups of patients. CONCLUSION: Carriers of parkin mutations are clinically indistinguishable from other patients with young-onset Parkinson disease (PD) on an individual basis. Severe generalized loss of dopaminergic neurons in the substantia nigra pars compacta in these patients is associated with an excellent response to low doses of dopa-equivalent and delayed fluctuations, but cognitive impairment and special behavioral or psychiatric symptoms were not more severe than in other patients with early-onset PD.

A challenging task for assessment of checking behaviors in obsessive-compulsive disorder.

OBJECTIVE: The present study concerns the objective and quantitative measurement of checking activity, which represents the most frequently observed compulsions in obsessive-compulsive disorder (OCD). To address this issue, we developed an instrumental task producing repetitive checking in OCD subjects. METHOD: Fifty OCD subjects and 50 normal volunteers (NV) were administered a delayed matching-to-sample task that offered the unrestricted opportunity to verify the choice made. Response accuracy, number of verifications, and response time for choice taken to reflect the degree of uncertainty and doubt were recorded over 50 consecutive trials. RESULTS: Despite similar levels of performance, patients with OCD demonstrated a greater number of verifications and a longer response time for choice before checking than NV. Such behavioral patterns were more pronounced in OCD subjects currently experiencing checking compulsions. CONCLUSION: The present task might be of special relevance for the quantitative assessment of checking behaviors and for determining relationships with cognitive processes.

[Pseudo-dementia conversion and post-traumatic stress disorder]. / Pseudo-démence conversive et état de stress post-traumatique.

BACKGROUND: Post-traumatic stress disorder (PTSD) is often associated with other psychiatric syndromes. However, studies exploring conversion and PTSD comorbidity are scarce. CASE-REPORT: This paper reports the case of a 45 year-old patient without medical or psychiatric history. In 2003, he suddenly started suffering from amnesia and symptoms of delirium: he was at his office with a cup of coffee but he did not remember why. Aphasia, trembling, behavioural disorders appeared over the next hours and days. Numerous neurological examinations and laboratory tests (including cerebral imagery) were performed without evidence of any physical disease. Three psychiatric examinations were also negative, even if a possible psychogenic origin was hypothesized. Neurological or psychiatric diagnoses were discussed but without definitive conclusion. One year later, the symptoms were unchanged until the patient watched a movie ("Mystic River") that described the story of a man with sexual abuse in childhood. He suddenly remembered that he lived the same experience when he was 8 years old. At the end of the movie, his wife surprisingly noticed that he was walking and speaking normally. All the neurological symptoms disappeared. Unfortunately, symptoms of a severe PTSD appeared, as well as a major depressive disorder. The patient and his parents remembered that he had been more irritable, depressed and anxious at school and during the night, between 8 and 13 years of age, with a possible PTSD during this period. He always refused to talk with his parents about the traumatic event. When he was 13, the family moved house, the patient seemed to forget everything and the symptoms disappeared. About thirty years later, the symptoms were similar with the reexperien of the traumatic event through unwanted recollections, distressing images, nightmares, or flashbacks. He had also symptoms of hyperarousal with physiological manifestations, such as irritability, insomnia, impaired concentration, hypervigilance, and increased startle reactions. Hospitalisation became necessary because of a severe depressive disorder with suicidal ideation and suicidal attempt by hanging. After two failed treatments with SSRI antidepressants, the administration of clomipramine (200 mg/d) and a combined therapy with Eyes Movement Desensitization and Reprocessing (EMDR) led to a significant improvement of PTSD and depression symptoms. DISCUSSION: Even if PTSD and conversion may share common dissociative mechanisms, the links between both syndromes have not yet been sufficiently explored. Our clinical case raises specifically the question of the initial manifestations of pseudo-dementia (why this type of symptoms, and why at this particular moment of his life, without any targeting events). Moreover, the case of this patient is particularly interesting because of the very long amnesia period between the traumatic event and the onset of PTSD. CONCLUSION: The different phases of this case warrant more precise exploration of the links between PTSD and conversion, with clinical, epidemiological and cerebral imagery perspectives.