Prognostic value of the combination of volume, massiveness and fragmentation parameters measured on baseline FDG pet in high-burden follicular lymphoma.

The prognostic value of radiomic quantitative features measured on pre-treatment 18F-FDG PET/CT was investigated in patients with follicular lymphoma (FL). We conducted a retrospective study of 126 FL patients (grade 1-3a) diagnosed between 2006 and 2020. A dozen of PET/CT-derived features were extracted via a software (Oncometer3D) from baseline 18F-FDG PET/CT images. The receiver operating characteristic (ROC) curve, Kaplan-Meier method and Cox analysis were used to assess the prognostic factors for progression of disease within 24 months (POD24) and progression-free survival at 24 months. Four different clusters were identified among the twelve PET parameters analyzed: activity, tumor burden, fragmentation-massiveness and dispersion. On ROC analyses, TMTV, the total metabolic tumor volume, had the highest AUC (0.734) followed by medPCD, the median distance between the centroid of the tumors and their periphery (AUC: 0.733). Patients with high TMTV (HR = 4.341; p < 0.001), high Tumor Volume Surface Ratio (TVSR) (HR = 3.204; p < 0.003) and high medPCD (HR = 4.507; p < 0.001) had significantly worse prognosis in both Kaplan-Meier and Cox univariate analyses. Furthermore, a synergistic effect was observed in Kaplan-Meier and Cox analyses combining these three PET/CT-derived parameters (HR = 12.562; p < 0.001). Having two or three high parameters among TMTV, TVSR and medPCD was able to predict POD24 status with a specificity of 68% and a sensitivity of 75%. TMTV, TVSR and baseline medPCD are strong prognostic factors in FL and their combination better predicts disease prognosis.

[Health professionals facing the coronavirus disease 2019 (COVID-19) pandemic: What are the mental health risks?] / Les professionnels de santé face à la pandémie de la maladie à coronavirus (COVID-19) : quels risques pour leur santé mentale ?

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic. METHODS: Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms. RESULTS: The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications. CONCLUSIONS: In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.

Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

[Klinefelter'syndrome: A predisposition to sexual crime?] / Le syndrome de Klinefelter : une prédisposition au crime sexuel ?

BACKGROUND: Several studies have reported over-representation of psychiatric disorders among patients with Klinefelter' Syndrome (KS), with forensic complications. OBJECTIVE: Consider determinants of sexual assault in patient with KS. REVIEW: In this work, we present the case of Jules, 23 years old, with KS, benefiting from steroid replacement therapy, convicted of rape of a minor and evaluated in this context. We question here the role of his genetic pathology and of his hormonal treatment in this sexual assault. FINDINGS: According to evidence from the literature, it is not possible to determine with certainty the fair value of each factor and their impact on the occurrence of the sexual criminal act. Indeed, although the crime rate among KS subjects is higher than in the general population, the majority of them have never been in trouble with the law; moreover, these subjects were no more likely to commit violent sexual acts than were criminals without KS. As for hormonal treatment, it seems that testosterone is better viewed as a facilitator of initiating an aggressive response than as a primary inductor. CONCLUSION: In conclusion, the onset of sexual violence that accompanied the introduction of hormonal treatment into a patient with KS suggests an effective involvement of steroid replacement therapy, even small, in the criminal act. This must incite clinicians to extreme prudence and to take account of multidisciplinary expertise (psychiatrist, endocrinologist) in order to reconsider the continuation of the treatment in this particular forensic context. Finally, we discuss other factors that can precipitate such a violent act.

[French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression]. / Prise en charge des troubles dépressifs résistants : recommandations françaises formalisées par des experts de l'AFPBN et de la fondation FondaMental.

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22)(p24;q11).

BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24) that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U) showing a t(9;22)(p24;q11), which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most reported JAK2 fusions cases reveal an aggressive clinical course and long-term remissions have only been achieved after allogeneic stem cell transplantation (ASCT). To the best of our knowledge, this is the thirteenth case reported worldwide to describe a BCR-JAK2 fusion transcript in MPN-U. The present report revealed a sustained complete clinical, hematologic, and cytogenetic remission 35 months after diagnosis and ~24 months after ASCT. Regarding BCR-ABL1 negative MPN patients this case report provides strong support for a role of JAK2 activation in the oncogenesis and suggests a possible diagnostic and therapeutic target that should be investigated.

Risk factors for treatment resistance in unipolar depression: a systematic review.

BACKGROUND: Treatment resistant depression is a complex disorder and an important source of morbidity and mortality. Identification of risk factors of resistance may be useful to improve early recognition as well as treatment selection and prediction of outcome in patients with depression. METHODS: The aim of this paper was to review the current status of knowledge regarding risk factors of treatment resistance in unipolar depression, in patients who failed to respond to at least two successive and adequate antidepressant treatments. RESULTS: Systematic literature search yielded 8 publications exploring clinical and biological factors. Specific psychiatric comorbidities, psychosocial factors, clinical characteristics of the depressive episode and biological markers emerge as possible risk factor for treatment resistant depression. LIMITATIONS: Due to the lack of objective definition and diagnostic criteria for treatment resistant depression, and the paucity of reports on risk factors, our review only summarized a small number of studies. CONCLUSION: Future investigations of risk factors should help to improve the understanding of the mechanisms underlying resistance in mood disorders and contribute to improve their therapeutic management.

Exploratory study toward development of the French version of the questionnaire on personality traits (QPT/VKP-4) in an elderly population in comparison to young adults.

This research is an exploratory study toward development of the French version of the Questionnaire on Personality Traits (QPT/VKP-4). The goal was to assess its association with the Big Five Inventory (BIG-5) and to explore the personality characteristics of the elderly compared to young adults. The 241 participants included 83 elderly people and 158 young adults. Borderline and anxious personality disorders were less frequent in elderly women than in young women, and depressive personality disorder was less frequent in elderly men. Dimension scores were higher for Conscientiousness in the elderly, Agreeableness in elderly women, and Extraversion in elderly men. Statistically significant correlations were found between personality dimension scores using the VKP-4 and the BIG-5.

Neuroinflammation and ß amyloid deposition in Alzheimer's disease: in vivo quantification with molecular imaging.

BACKGROUND/AIMS: Neuroinflammation plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Its relationship with underlying ß amyloid deposition remains unclear. In vivo visualization of microglial activation has become possible with the development of molecular imaging ligands when used with positron emission tomography (PET). The translocator protein (TSPO) is upregulated during neuroinflammation. Consequently, targeting TSPO with radiolabeled ligands for PET is an attractive biomarker for neuroinflammation. METHODS: A review of the research literature on PET imaging which studied in vivo neuroinflammation in AD subjects and its relationship with amyloid load was performed, including papers published between 2001 and 2012. RESULTS: Six studies were included using either [(11)C]PK-11195 or another non-TSPO radioligand that binds to the monoaminooxidase B. All the studies evaluated amyloid load with [(11)C]PIB. Microglial activation and astrocytosis are potentially early phenomena in AD. However, the individual levels of amyloid deposition and microglial activation were not correlated. CONCLUSION: Noninvasive in vivo molecular imaging to visualize neuroinflammation in AD may contribute to our understanding of the kinetics of neuroinflammation and its relationship to the hallmarks of the disease. Both are important for the development of future therapeutic modalities and for quantifying the efficacy of future disease-modifying treatments.

Adjustment disorder with anxiety in old age: comparing prevalence and clinical management in primary care and mental health care.

PURPOSE: Adjustment disorder with anxiety (AjD-A) is a common cause of severe anxiety symptoms, but little is known about its prevalence in old age. METHODS: This cross-sectional study examined the prevalence of AjD-A in outpatients over the age of 60 who consecutively consulted 34 general practitioners and 22 psychiatrists during a 2-week period. The diagnosis of AjD-A was obtained using the optional module for diagnostic of adjustment disorder of the Mini International Neuropsychiatric Interview (MINI). The study procedure also explored comorbid psychiatric conditions and documented recent past stressful life events, as well as social disability and current pharmacological and non-pharmacological management. RESULTS: Overall, 3651 consecutive subjects were screened (2937 in primary care and 714 in mental health care). The prevalence rate of AjD-A was 3.7% (n=136). Up to 39% (n=53) of AjD-A subjects had a comorbid psychiatric condition, mostly of the anxious type. The most frequently stressful life event reported to be associated with the onset of AjD-A was personal illness or health problem (29%). More than 50% of the AjD-A patients were markedly to extremely disabled by their symptoms. Compared to patients who consulted psychiatrists, patients who were seen by primary care physicians were older, had obtained lower scores at the Hamilton Anxiety Rating Scale, benefited less frequently from non-pharmacological management and received benzodiazepines more frequently. CONCLUSIONS: AjD-A appears to be a significantly disabling cause of anxiety symptoms in community dwelling elderly persons, in particular those presenting personal health related problems. Improvement of early diagnosis and non-pharmacological management of AjD-A would contribute to limit risks of benzodiazepine overuse, particularly in primary care settings.

Treatment of tardive dyskinesia: A systematic review (1997-2011)

Background and Objectives: Tardive dyskinesia (TD) is a frequent and incapacitating side effect of first-generation antipsychotics. Although second-generation antipsychotics (SGAs) seem to be associated with a decreased risk of TD, it remains a severe, unresolved iatrogenic condition. Moreover, there is no commonly accepted effective treatment for TD. We conducted a systematic review of the literature to assess evidence regarding the effectiveness of different therapeutic interventions for TD. Methods: We performed a systematic review focussing exclusively on randomised controlled trials (RCTs). We searched the MEDLINE database (1997 to 2011) using the keyword "tardive dyskinesia" within the "title" search field. Twenty-six RCTs were included. Based on the evidence from RCTs, we built a decision tree that healthcare professionals can use to choose an effective therapeutic intervention for TD. Results: Four therapeutic interventions were found to be effective in TD (vitamin B6, ginkgo biloba, branched-chain amino acids, and piracetam). Conclusions: Patients with TD could benefit from the therapeutic interventions supported by the data accumulated from RCTs (AU)

[Current status and management of patients with bipolar disorder in France: the MONTRA survey]. / Caractéristiques et modalités de prise en charge des patients présentant un trouble bipolaire en France : enquête MONTRA.

OBJECTIVES: The objectives were to assess the characteristics of patients with bipolar disorder (BD) and to evaluate the prescribing practices. METHODS: MONTRA is a quantitative survey conducted between December 2010 and February 2011. Data were extracted by the psychiatrists from the medical files of BD patients seen on four consecutive days of consulting. RESULTS: Four hundred and thirty-nine psychiatrists included 2529 patients (inpatients, n=319; outpatients from mental clinics, n=1090; outpatients consulting in private practice, n=1020). In the total patient population (mean age: 47 years; women, 58%), BD was distributed as follows: BD type I, 56%; BD type II, 40%; other types of BD, 4%; rapid cyclers, 10%. The prevalence of psychiatric comorbidities was high (anxiety disorders, 48%; abuse and dependence on toxic substances, 17 and 10% respectively), 36% of the patients had a history of suicide attempt and the risk of suicide, when assessed, was 6%. In about half the patients (48%), the polarity of the initial bipolar episode was of the depressive type (versus 39% for the manic/hypomanic type). Outpatients were globally independent and did not require assistance in the management of their disease or its treatment whereas the social and professional lives of inpatients were negatively affected by their condition. Based on the psychiatrist's declarations, 39 to 50% of the outpatients were symptom-free, 36 to 40% were in the intercurrent phase with residual symptoms, 11 to 17% presented either a manic or depressive acute BP episode, and 3 to 4% were in a mixed state; among inpatients, 52% presented an acute episode either manic or depressive, 38% were in the intercurrent phase and 9% were in a mixed state. In the symptomatic patients from the total population (61%), the most prevalent symptoms were depressive and corresponded to acute symptoms (patients with a depressive episode, 14%) or residual symptoms (patients in the intercurrent phase, 27%). The predominant depressive polarity was observed in both hospitalized and outpatients. The pharmacological treatment of BD included polytherapy in 73% of the patients. In the manic episodes (n=126), the patients were treated with a Mood Stabilizer (MS, 56%) or an atypical antipsychotic (AAP, 52%) in association. In the depressive episodes (n=342), the patients received an antidepressant drug associated with a MS or an AAP (70%). In symptom-free or symptomatic intercurrent periods (n=1943), the patients were treated with a MS (49-58%) or an AAP (37-49%), in association. CONCLUSION: BD patients evaluated in our survey were in majority diagnosed with BD type I, associated with considerable comorbidity. In the symptomatic patients, the most prevalent symptoms, either acute or residual, were of the depressive type. In the majority of the patients, whatever the clinical status, polytherapy was prescribed for the BD.

Progression of Alzheimer disease in Europe: data from the European ICTUS study.

The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North, South, West) and investigated with biannual follow-up over 2 years. Primary outcomes were cognitive, functional and behavioral measures. Caregiver burden, hospital admission and admission to nursing home were also recorded. Participant cognitive function declined non-linearly over time (MMSE: -1.5 pts/first year, -2.5 pts/second year; ADAScog: + 3.5 pts/first year, + 4.8 pts/second year), while the progression of behavioral disturbances (NPI scale) was linear. Neither scale showed regional differences, and progression of the disease was similar across Europe despite different health care systems. Functional decline (ADL, IADL) tended to progress more rapidly in Southern Europe (p=0.09), while progression of caregiver burden (Zarit Burden Interview) was most rapid in Northern Europe (5.6 pts/y, p=0.04). Incidences of hospital admission (10.44, 95%CI: 8.13-12.75, p < 0.001) and admission to nursing home (2.97, 95%CI: 1.83-4.11, p < 0.001) were lowest in Southern Europe. In general cognitive and functional decline was slower than in former cohorts. European geographical location reflecting differences in culture and in health care system does not impact on the progression of AD but does influence the management of AD subjects and caregiver burden.

Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment.

PURPOSE: Positron emission tomography (PET) imaging of brain amyloid load has been suggested as a core biomarker for Alzheimer's disease (AD). The aim of this study was to test the feasibility of using PET imaging with (18)F-AV-45 (florbetapir) in a routine clinical environment to differentiate between patients with mild to moderate AD and mild cognitive impairment (MCI) from normal healthy controls (HC). METHODS: In this study, 46 subjects (20 men and 26 women, mean age of 69.0 ± 7.6 years), including 13 with AD, 12 with MCI and 21 HC subjects, were enrolled from three academic memory clinics. PET images were acquired over a 10-min period 50 min after injection of florbetapir (mean ± SD of radioactivity injected, 259 ± 57 MBq). PET images were assessed visually by two individuals blinded to any clinical information and quantitatively via the standard uptake value ratio (SUVr) in the specific regions of interest, which were defined in relation to the cerebellum as the reference region. RESULTS: The mean values of SUVr were higher in AD patients (median 1.20, Q1-Q3 1.16-1.30) than in HC subjects (median 1.05, Q1-Q3 1.04-1.08; p = 0.0001) in the overall cortex and all cortical regions (precuneus, anterior and posterior cingulate, and frontal median, temporal, parietal and occipital cortex). The MCI subjects also showed a higher uptake of florbetapir in the posterior cingulate cortex (median 1.06, Q1-Q3 0.97-1.28) compared with HC subjects (median 0.95, Q1-Q3 0.82-1.02; p = 0.03). Qualitative visual assessment of the PET scans showed a sensitivity of 84.6% (95% CI 0.55-0.98) and a specificity of 38.1% (95% CI 0.18-0.62) for discriminating AD patients from HC subjects; however, the quantitative assessment of the global cortex SUVr showed a sensitivity of 92.3% and specificity of 90.5% with a cut-off value of 1.122 (area under the curve 0.894). CONCLUSION: These preliminary results suggest that PET with florbetapir is a safe and suitable biomarker for AD that can be used routinely in a clinical environment. However, the low specificity of the visual PET scan assessment could be improved by the use of specific training and automatic or semiautomatic quantification tools.

[Cenesthopathies: a disorder of background emotions at the crossroads of the cognitive sciences and phenomenology]. / Les cénesthopathies : un trouble des émotions d'arrière plan. Regards croisés des sciences cognitives et de la phénoménologie.

BACKGROUND: Cenesthesia and cenesthopathy have played a fundamental role in 19th and early 20th century French and German psychiatry. Cenesthesia refers to the internal, global, implicit and affective perception of one's own body. The concept of cenesthopathy was coined by Dupre and Camus in 1907 to describe a clinical entity characterized by abnormal and strange bodily sensations. AIMS: In this review, we examine the history of these concepts and the influence they have had on clinical, nosographical and phenomenological psychiatry and on cognitive neuropsychiatry. METHOD: We performed a narrative review of the published research literature. RESULTS: Classical French and German psychiatrists have written extensively on cenesthesia and cenesthopathy although these notions are no longer in the mainstream of contemporary psychiatry. However, they are still present in contemporary psychiatric nosography in the form of some controversial clinical entities clearly related to cenesthesia such as cenesthetic schizophrenia, hypochondriacal monothematic delusions, or the Capgras and the Cotard syndromes. These clinical entities are all associated with a state of depersonalization. We point out the similarities between Ey's description of the depersonalization syndrome, especially in psychosis, and the characteristics of cenesthesia. Philosophers like Sartre or Merleau-Ponty have developed the concept of cenesthesia, and in particular have added new concepts like "body schema". Similarly, phenomenological psychiatrists like Minkowski or Tellenbach have attempted to describe psychiatric disorders associated with cenesthesia and have also proposed new concepts (i.e. atmospheric sense) in order to understand them better. More recently, cognitive neuropsychiatry has tried to discover the mechanisms, which cause or contribute to the genesis of delusions. The majority of delusion theories developed in cognitive neuropsychiatry consider that the explanation of monothematic delusions involves one or two explanatory stages. The first stage corresponds to an abnormal experience (the experiential stage) while the second is related to abnormal reasoning (the inferential stage). This theoretical first stage has been considered to be the result of a highly unusual or bizarre perceptual experience. According to the authors, this experience refers to a phenomenon of depersonalization, a loss of cenesthesia, or a loss of a feeling of familiarity. For example, the neurocognitive models of the Capgras and Cotard syndromes have in common the belief that they are both based on various kinds of unusual experiences. These unusual experiences are thought to include affective or emotional experiences. Capgras' syndrome is possibly triggered by an abnormal affective experience in response to the sight of closed-person's face. Similarly, the Cotard syndrome may result from a general flattening of affective responses to external stimuli. The inferential stage can also differentiate between the two syndromes. Some empirical validation has already been obtained in Capgras' syndrome but not yet in Cotard's syndrome. CONCLUSION: This review illustrates that the historical descriptions of cenesthesia and cenesthopathy remain relevant in contemporary neurocognitive models and more generally suggests that the comprehension of quite complex phenomena like delusion requires a multidisciplinary approach.

Attitudes towards Alzheimer's disease as a risk factor for caregiver burden.

BACKGROUND: There is abundant literature on the determinants of caregiver burden in Alzheimer's disease (AD), but little is known about the possible implication of specific patterns of a caregiver's attitudes towards the disease that could increase their risk of--or protect them from--emotional distress and burden. The aim of this study was to test the hypothesis that negative attitudes towards AD are associated with an increased level of burden experienced by caregivers of AD patients. METHODS: Family caregivers of 51 patients with AD were asked to complete a questionnaire regarding their attitudes towards AD. In addition, we assessed the level of their quality of life, anxiety and depression as well as their perceived level of burden. In parallel, we documented the patients' characteristics: global cognitive efficiency (Mini-Mental State Examination), behavioral and affective symptoms (Neuropsychiatric Inventory) and functional level (Instrumental Activities of Daily Living). RESULTS: The score of caregiver burden was positively correlated with negative attitudes such as authoritarianism (r = 0.41, p < 0.01) and social restrictiveness (r = 0.49, p < 0.001) as well as emotional reactions of anxiety (r = 0.44, p < 0.01) and aggressiveness (r = 0.47, p < 0.001). In addition, scores of social restrictiveness, rejection and anxiety were significantly higher in women than in men. CONCLUSION: These results may have implications in terms of the prevention of caregiver burden. In particular, educational and support programs for caregivers should not be limited to developing their knowledge and skills but should also target attitudes towards the disease.

Review of cerebral microangiopathy and Alzheimer's disease: relation between white matter hyperintensities and microbleeds.

Although Alzheimer's disease (AD) is basically considered to be a neurodegenerative disorder, cerebrovascular disease is also involved. The role of vascular risk factors and vascular disease in the progression of AD remains incompletely understood. With the development of brain MRI, it is now possible to detect small-vessel disease, whose prevalence and severity increase with age. The first types of small-vessel disease to be described were white matter hyperintensities (WMHs). More recently, small areas of signal loss on T(2)*-weighted images, also called microbleeds (MBs), have been reported. Cerebral MBs are focal deposits of hemosiderin that indicate prior microhemorrhages around small vessels, related to either ruptured atherosclerotic microvessels or amyloid angiopathy. Consequently, using brain MRI for the detection of microangiopathy may prove useful to improve our understanding of the impact of the vascular burden in AD pathology. The relationship between microangiopathy and the clinical course of AD or the conversion of mild cognitive impairment to AD remains questionable in terms of cognitive or affective symptoms, particularly if we consider MBs.