[Negative symptoms of schizophrenia: historical aspects]. / Les symptômes négatifs de la schizophrénie: aspects historiques.

The history of negative symptoms of schizophrenia rises early days of medicine in clinical and pathophysiological differences between positive and negative and their complex joint. Forming a set of typical core of symptoms, and some feature of a syndrome belonging to a specific pathophysiological mechanism, negative symptoms of schizophrenia emerge from old descriptions of clinical pictures, related to the overall look of madness, the heart of alienation, a central sign of early dementia, gradually more precisely describing the strange nature of the autistic withdrawal and schizophrenic apragmatism. At therapeutic era, negative symptoms have taken over the positive symptoms to establish an operational criteria whose importance lies in the progressive severity of this clinical type and in their contribution to therapeutic resistance. Despite the efforts of modern typological classifications, this work rehabilitates the old concept of "unitary psychosis" by defining a common symptomatic core to multiple clinical forms of psychosis, combining deficit of emotional expression and avolition, meaning a native psychopathology and a pathophysiology possibly in a common final way, and calling the arrival of new treatment strategies.

[Comorbidity of affective disorders and alcohol use disorder]. / Troubles affectifs et comorbidités éthyliques.

The comorbidity of affective disorders with alcohol use disorder remains insufficiently taken into account. In spite of the well-known frequency of the addict comorbidity in most psychiatric disorders, the level of association between affective disorders and alcohol is still underestimated and poorly understood. The label of "double diagnosis" relates to a simple addition of two independent pathologies. It is suggested to consider a "dual psychopathology" combining the effects of one disorder on the other. Interactions between the two disorders commit a complex state calling a new clinical reading, an adapted therapeutic strategy through a necessary integration of care. Association of alcohol use disorder and affective disorder, particularly in bipolar disorders, is correlated with severity, unstable course, treatment resistance and a greater risk of suicide. Alcohol aggravates depression and hampers therapeutics. Alcohol and mania remain a dreaded danger. The mechanism of the comorbid association does not only refer to a behavioral strategy of compensation but seems strongly based on a shared and crossed vulnerability, related to the genetics of the 5HT carrier and gene Clock. Therapeutic limitations do suggest the implementation of an "integrated" device which supposes a new organization of care and facilitation of collaborations between Addiction and Psychiatry.

[Mixed states: evolution of classifications]. / États mixtes. Évolution des classifications.

The nosological position of mixed states has followed the course of classifying methods in psychiatry, the steps of the invention of the clinic, progress in the organization of care, including the discoveries of psychopharmacology. The clinical observation of a mixture of symptoms emerging from usually opposite clinical conditions is classical. In the 70s, a syndromic specification fixed the main symptom combinations but that incongruous assortment failed to stabilize the nosological concept. Then stricter criteriology was proposed. To be too restrictive, a consensus operates a dimensional opening that attempts to meet the pragmatic requirements of nosology validating the usefulness of the class system. This alternation between rigor of categorization and return to a more flexible criteriological option reflects the search for the right balance between nosology and diagnosis. The definition of mixed states is best determined by their clinical and prognostic severity, related to the risk of suicide, their lower therapeutic response, the importance of their psychiatric comorbidities, anxiety, emotional lability, alcohol abuse. Trying to compensate for the lack of categorical definitions and better reflecting the clinical field problems, new definitions complement criteriology with dimensional aspects, particularly taking into account temperaments.

[Endophenotypes of the biorhythms and the sleep in depression]. / Endophénotypes des rythmes biologiques et du sommeil dans la dépression.

Chronobiological markers of depression display a biological desynchronization which participates in the pathogenesis of depression. Mood disorders and clock genes have shown significant associations suggesting a possible pathogenetic link between them, providing a privileged base for exploring biorhythmic endophenotypes. They would be useful indicators of vulnerability mechanisms, giving rise to new therapies and prevention programs. Two ways of research are of interest: the study of the genetic determinants of cholinergic hypersensitivity generating REM sleep pressure in depression, and the analysis of clinical response to sleep deprivation suggesting an exploration of links between genomic function of arousal and mood regulation. To date, the empirical principle of behavioral stimulus control reaches the level of the available eco-instrumental synchronization procedures.

Plasma carnitine is associated with fatigue in chronic hepatitis C but not in the irritable bowel syndrome.

BACKGROUND: Fatigue is an important determinant of altered quality of life in patients affected by chronic hepatitis C or the irritable bowel syndrome (IBS). AIM: In this study, we aimed at determining the contributory role of plasma levels of leptin and carnitine on fatigue in chronic hepatitis C and IBS. METHODS: We enrolled 81 patients with chronic hepatitis C, 42 with IBS and 44 healthy subjects. Fatigue was evaluated using the Fatigue Impact Scale questionnaire. Body composition was assessed through impedance analysis. Plasma carnitine and leptin were measured. RESULTS: Fatigue scores were significantly more elevated in patients with chronic hepatitis C and IBS than in healthy subjects. Patients with chronic hepatitis C but not IBS, had significant lower plasma levels of total and free carnitine adjusted for fat mass compared with healthy subjects. In patients with chronic hepatitis C and not with IBS, fatigue scores were negatively correlated with plasma levels of carnitine. Levels of free carnitine were significantly and independently associated with the severity of fatigue in patients with chronic hepatitis C [OR=2.019, P=0.02, CI 95% (1.01-1.23)]. CONCLUSIONS: In patients with chronic hepatitis C, the severity of fatigue is associated with a low level of carnitine, suggesting that an oral supplementation may be effective to relieve fatigue in chronic hepatitis C. The underlying mechanism of fatigue in IBS does not seem to involve carnitine.

[Treatment of a first depressive episode in bipolar disorder]. / Traitement d'un premier épisode dépressif dans le cadre du trouble bipolaire.

The first episode of bipolar depression needs a combined psychopharmacological, psychobehavioural and social treatment strategy but because of the pathological severity of the mood episode itself, it specifically requires to achieve total symptomatic remission and therefore appropriate treatment of the index episode. International recommendations which derive primarily from Anglo-Saxon regulations formally restrict the use of antidepressants in view of the risk of mania, suggesting that serotoninergic agents be used in preference and recommending the prescription of mood regulators or even antipsychotic agents and various stepwise associations based on the relative potencies of the pharmacological tools available and treatment stages deployed optimally to obtain complete remission. Finally, treatment of the episode includes prophylaxis as its initial episode is the first presentation of a chronic disease.

[Affective disorders: News in chronobiological models]. / Troubles affectifs : actualité des modèles chronobiologiques.

Good news on chronobiological models of affective disorders are coming from a therapeutic innovation in the field of antidepressive action. Coming back to fundamentals by reconsidering the importance of the role of biological rhythms impairment in dysthymic pathology, a new interest bored on studies exploring short periodicities, so-called "ultradian" ones, on the basis of pharmacodynamics in the concept of therapeutic "window" of administration. The priority of circadian rhythms due to the major external biological desynchronization in depression, as well as the importance of sleep and alertness pathology, the spectacular relief of the depressive mood upon sleep deprivation, and the strong reduction of sleep need in mania, delayed exploration of ultradian exaltation of harmonic circadian components, marking a "buzz" of rhythmic structure and calling a "chronobiotic compound" which would be able to apply a "reset" to the temporal organisation. Another return to the origin leads to the experimental genomics, informing nor the "depressivity" but manic pathogenesis, in a mouse gene model which queries on the share of addictive and affective disorders.

[Ontogenesis of circadian rhythm in the human]. / Ontogenèse des rythmes circadiens chez l'humain.

Ontogenesis of circadian rhythms in human beings, the history of the development of synchronisation of the daily rhythm describes the deployment of an adaptive capacity providing vital biological linkage to the environment. Methods for dating the stages in this temporal organisation have advanced and the genetics approach to the circadian cycle is dominated by studies of the maturation of the awake-asleep cycle. Disease involves the functional regression to one of the different stages of genesis or alternatively will involve a pathological lesion. Circadian dysfunction is characterised by loss of amplitude and multi-day fragmentation, correction of which requires control of multi-day pressure and within-day stabilisation.

Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome.

BACKGROUND: A subset of patients with irritable bowel syndrome (IBS) have an increased number of mast cells (MCs) in the colonic mucosa. Psychological factors are believed to contribute to the course of IBS. AIMS: To examine associations between fatigue, depression and MCs of the colonic mucosa in IBS. METHODS: Colonic biopsies were taken from 50 Rome II IBS patients, 21 healthy controls and 11 depressed/fatigued patients without IBS. The cellularity of the lamina propria was determined as the number of inflammatory cells per high power field (hpf) through a 400x microscope. The Fatigue Impact Scale (FIS) and the short form Beck Depression Inventory (BDI) evaluated the severity of fatigue and depression. RESULTS: IBS patients had a significant increase in the cellularity of the lamina propria compared with controls or with depressed patients (mean (SD) 94.5 (48-110) vs 68 (58-82) and 78 (87-90) cells per hpf, p = 0.005 and p = 0.05, respectively), in particular of MCs (9.3 (5.6-11.7) vs 4.0 (2.7-6.8) and 4.3 (2.8-7.8) cells per hpf, p = 0.001 and p = 0.005, respectively). Both the FIS and BDI scores were significantly higher in IBS or in depressed patients than in controls (p<0.001). In IBS, the FIS score correlated significantly with the cellularity of the lamina propria (r = 0.51, p<0.0001) and MCs (r = 0.64, p<0.0001). In IBS, the BDI score correlated significantly with MCs (r = 0.29, p = 0.03). CONCLUSIONS: Elevated MCs counts are a key feature of the low-grade inflammatory infiltrate in the caecal mucosa of IBS. Fatigue and depression are associated with mucosal cell counts, in particular MCs, suggesting that psychological factors are associated with the low-grade inflammatory infiltrate in IBS.

Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study.

BACKGROUND AND AIMS: There are no available effective therapies for fatigue associated with chronic hepatitis C (CHC). The serotonin antagonist ondansetron has been shown to be effective in the chronic fatigue syndrome. In this randomised, placebo controlled, double blind trial, we investigated the effect of orally administered ondansetron on fatigue in CHC. METHODS: Thirty six patients with CHC were included if fatigue was their predominant symptom and they scored more than 4 on a visual analogue scale (0-10). During the study, fatigue and depression were measured on days 0, 15, 30, and 60 using a validated self report questionnaire (fatigue impact scale and Beck depression inventory). Patients were randomised to receive ondansetron tablets 4 mg twice daily or placebo for one month followed by an additional four weeks of observation. RESULTS: Fatigue score was 85.4 (28.2) and 98.2 (26.9) in the ondansetron and placebo groups, respectively (NS). Ondansetron significantly reduced the fatigue score with more than 30% improvement on day 15 (57.1 (38.9); p<0.01), day 30 (54.5 (37.6); p<0.01), and day 60 (60.8 (37.3); p<0.01) whereas placebo did not. Overall, the reduction in fatigue was significantly higher with ondansetron compared with placebo (ANOVA for repeated measurements) for the whole follow up period (p = 0.03) or for the treatment period only (p = 0.04). Ondansetron also significantly reduced depression scores. CONCLUSIONS: The 5-hydroxytryptamine receptor type 3 antagonist ondansetron had a significant positive effect on fatigue in CHC. These observations support the concept that fatigue involves serotoninergic pathways and may encourage further evaluations of the efficacy of ondansetron on fatigue in chronic liver diseases.

[Sleep polygraphy: diagnostic value in depressive pseudo-dementia. Attempt to improve visual scoring by digital periodic analysis]. / La polygraphie du sommeil: outil diagnostique dans la pseudo-démence dépressive. Tentative d'amélioration de la méthode de lecture visuelle par l'analyse digitale de période.

ARGUMENT: Pseudo depressive dementia is a common pathology for elderly patients. Classically, it is said that depression is taking the mask of dementia, but very often deterioration and depression are present at the same time. Sleep EEG can help the clinician to differentiate dementia and depression in pseudo depressive dementia. Slow Wave Sleep (SWS) is a good indicator of deterioration process. We tried to improve the sleep recording and analysis and our ability to differentiate SWS in this indication. We use a portable digital recording material (Hypnotrace). The signal is analysed by the association of a visual standard method to Digital Periodic Analysis (DPA) which is very sensitive to SWS. The visual analysis gives informations about the macroarchitecture of the night. The Digital Periodic Analysis gives at any moment the value of the wave frequency and thus informations about the microarchitecture. Our hypothesis is that this association helps to better recognise SWS and thus improves sleep EEG as a diagnostic tool in this indication. METHODS: 23 inpatients meeting both the criteria for major depression and dementia (DSM IV) have been recorded during two nights after 15 days of wash out and before antidepressant treatment. The recordings are analysed with the visual standard method and with the help of DPA. The patients are evaluated every 15 days during two months in order to define three groups based on the clinical evolution. RESULTS: The scoring with DPA is more sensitive to Slow Wave Sleep, particularly for the patients with good clinical evolution (with the strongest depressive component). Thus, this method could be a good diagnostic tool to differentiate dementia and depression in pseudo depressive dementia.