The pattern of cortical thickness associated with executive dysfunction in MCI and SCC: The MEMENTO cohort.

BACKGROUND: The association between the pattern of cortical thickness (CT) and executive dysfunction (ED) in mild cognitive impairment (MCI) and subjective cognitive complaints (SCC) is still poorly understood. We aimed to investigate the association between CT and ED in a large French cohort (MEMENTO) of 2323 participants with MCI or SCC. METHODS: All participants with available CT and executive function data (verbal fluency and Trail Making Test [TMT]) were selected (n=1924). Linear regressions were performed to determine relationships between executive performance and the brain parenchymal fraction (BPF) and CT using FreeSurfer. RESULTS: The global executive function score was related to the BPF (sß: 0.091, P<0.001) and CT in the right supramarginal (sß: 0.060, P=0.041) and right isthmus cingulate (sß: 0.062, P=0.011) regions. Literal verbal fluency was related to the BPF (sß: 0.125, P<0.001) and CT in the left parsorbitalis region (sß: 0.045, P=0.045). Semantic verbal fluency was related to the BPF (sß: 0.101, P<0.001) and CT in the right supramarginal region (sß: 0.061, P=0.042). The time difference between the TMT parts B and A was related to the BPF (sß: 0.048, P=0.045) and CT in the right precuneus (sß: 0.073, P=0.019) and right isthmus cingulate region (sß: 0.054, P=0.032). CONCLUSIONS: In a large clinically based cohort of participants presenting with either MCI or SCC (a potential early stage of Alzheimer's disease [AD]), ED was related to the BPF and CT in the left pars orbitalis, right precuneus, right supramarginal, and right isthmus cingulate regions. This pattern of lesions adds knowledge to the conventional anatomy of ED and could contribute to the early diagnosis of AD.

French guidelines for the diagnosis and management of Tourette syndrome.

The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.

High prevalence of psychiatric disorders in patients with skin-restricted lupus: a case-control study.

BACKGROUND: Psychiatric disorders have been extensively documented in patients with systemic lupus erythematosus (SLE). However, the prevalence of psychiatric disorders in patients with skin-restricted lupus (SRL) remains unknown, although SRL is more common than SLE. OBJECTIVES: To assess current and lifetime prevalence of Axis I psychiatric disorders among outpatients with SRL and to examine the factors associated with psychiatric disorders among such patients. METHODS: A multicentre case-control study involving outpatients with SRL and controls matched for sex, age and education level. The Mini International Neuropsychiatric Interview was used for psychiatric evaluation. RESULTS: We evaluated 75 patients and 150 controls. Of these, 49% of patients vs. 13% of controls fulfilled the criteria for at least one current psychiatric disorder (P < 0·001). The following disorders were significantly more frequent among patients than controls: current and lifetime major depressive disorder (9% vs. 0%, P < 0·001 and 44% vs. 26%, P = 0·01), generalized anxiety disorder (23% vs. 3%, P < 0·001 and 35% vs. 19%, P = 0·03), panic disorder (7% vs. 0%, P = 0·004 and 21% vs. 3%, P < 0·001), current suicide risk (24% vs. 7%, P = 0·003), alcohol dependence (7% vs. 0%, P = 0·004) and lifetime agoraphobia (20% vs. 9%, P = 0·01). Lupus duration and lupus past treatment by thalidomide were significantly higher among patients with current psychiatric disorders. CONCLUSIONS: This study demonstrates a high prevalence of several psychiatric disorders (anxiety, depression, suicide risk, alcohol dependence) in patients with SRL.

[Psychiatrists' decision making and monitoring of antipsychotic prescription for elderly schizophrenia patients]. / Prescription et surveillance d'antipsychotiques chez les patients âgés souffrant de schizophrénie: pratiques des psychiatres et leurs déterminants.

OBJECTIVE: Advancing age entails specific treatment modalities for patients with schizophrenia. The choice of appropriate antipsychotic therapy (AP) and the monitoring of treatment is a major challenge. However, little is known about the real-world prescribing practices of psychiatrists for elderly schizophrenia patients. The aim of this study was to assess prescribing practices and treatment monitoring in elderly schizophrenia patients and whether socio-professional psychiatrists' characteristics are related to their practices. METHODS: We contacted by mail 190 psychiatrists to take part in an observational survey of their AP prescribing practices for elderly (aged over 65) schizophrenia patients. RESULTS: The response rate was 44.2%, and of the psychiatrists who replied 75% were treating elderly schizophrenia patients. A second-generation AP (SGAP) was prescribed as first-line of treatment by 87.7% of the psychiatrists. The most frequently used SGAPs were risperidone and olanzapine (respectively preferred by 54.4% and 19.3% of the psychiatrists taking part). At the beginning of treatment, 91.1% of the psychiatrists prescribed a lower dose than for middle-aged patients. Of the psychiatrists taking part, 64.9% prescribed monotherapy; and among these psychiatrists, 65% cited insufficient control of the disease as the reason for their choice, while 48.7% of those who elected not to prescribe combined AP did so in order to limit the side-effects. Of the psychiatrists taking part, 54.4% prescribed long-acting injectable AP (LAAP); better therapeutic compliance and alliance was the main argument in the choice of LAAP given by the psychiatrists taking part who prescribed the drug, whereas the absence of indications and problems of tolerance were arguments against for those who did not. "Personal experience" emerged as the governing factor in the choice of AP. The AP side-effect profile was the main criterion of choice of the AP agent for 3.5% of the psychiatrists taking part, and the most frequently chosen secondary criterion (29.8%). Monitoring of treatment was partly performed according to professional recommendations: pre-treatment and post-prescription assessments of waist circumference and ophthalmological monitoring were very infrequent (8.8 to 18.5%) as were pre-treatment and early post-prescription assessments of prolactinaemia (14.8 to 20.4%); long-term cardiac monitoring was infrequent (43.9%). The psychiatrists taking part whose first-line drug was SGAP were more familiar with professional recommendations than those who prescribed first generation antipsychotic (FGA) drugs (72% as against 14.3%, P=0.006). Of the psychiatrists taking part in the study, 64.9% reported they commonly use professional recommendations. Psychiatrists who declared they commonly use professional recommendations measured pulse rate and blood pressure significantly more often over the long-term than those who did not (74.3% as against 41.2%, P=0.0315). They also measured waist circumference over the long-term significantly more often than psychiatrists who did not commonly use professional recommendations (22.9% as against 0%, P=0.0420). Psychiatrists treating more than ten of these patients yearly measured significantly more often over the long-term pulse rate and blood pressure than those treating fewer patients (80% as against 50%, P=0.0399). Over the long-term monitoring, psychiatrists with a larger number of elderly schizophrenia patients in their care also performed more often fasting blood glucose test, lipid profile and referral for cardiac consultation with ECG (respectively, 95.5% as against 70.8%, P=0.0489; 90.9% as against 58.3%, P=0.0182; 81.8% as against 29.2%, P<0.0001). CONCLUSIONS: The results of this survey need to be confirmed in a larger population sample. The antipsychotic prescribing practices were broadly in agreement with current recommendations except for the tolerance profile which was not the first element taken into account in the choice of the AP agent. Some clinical and paraclinical medical examinations were carried out infrequently, in particular cardiac monitoring over the long-term, which is essential in this elderly patient population. One important element to emerge from our results was that common use of professional recommendations is associated with better monitoring.

[Health-related quality of life evaluation of elderly aged 65 years and over living at home]. / Évaluation de la qualité de vie liée à la santé de sujets âgés de 65ans et plus vivant à domicile en région Auvergne.

BACKGROUND: To assess health-related quality of life in French adults aged 65 years and over, living at home, with a specific self-administered questionnaire, the LEIPAD, cross-culturally adapted in French. METHODS: Elderly completed socio-demographic and medical questionnaires, a questionnaire about negative life events during the last 12 months and the LEIPAD. RESULTS: Data of 195 subjects (mean age: 72.6 years, men: 56.5%) were analyzed. The response rates to the LEIPAD scales were superior to 90%. Elderly reported on the whole a good health-related quality of life. Age had a negative effect on quality on life, which deteriorates over years. Age was correlated to the scales "Physical function", "Self-care", "Cognitive functioning" and "Sexual functioning". Elderly hospitalized in the last year had worse quality of life with a significant difference for "Physical function" scale. The number of health problems was positively correlated to "Physical function" scale. Elderly declaring at least one health problem had worse quality of life for this scale. Problems in couple, materials and financial problems had also negative effects on health-related quality of life. CONCLUSION: Our study highlights a good health-related quality of life for the majority of these adults aged 65 years and over, as well as the negative effect of age, health, couple, materials and financial problems on their quality of life.

Cross-cultural evaluation of the French version of the LEIPAD, a health-related quality of life instrument for use in the elderly living at home.

PURPOSE: To cross-culturally adapt a French version of the LEIPAD, a self-administered questionnaire assessing the health-related quality of life (HRQoL) in adults aged 65 years and over living at home, and to evaluate its psychometric properties. METHODS: After having translated LEIPAD in accordance with guidelines, we studied psychometric properties: reliability and construct validity-factor analysis, relationships between items and scales, internal consistency, concurrent validity with the Medical Outcome Study Short-Form 36 and known-groups validity. RESULTS: The results obtained in a sample of 195 elderly from the general population showed very good acceptability, with response rates superior to 93 %. Exploratory factor analysis extracted eight factors providing a multidimensionality structure with five misclassifications of items in the seven theoretical scales. Good internal consistency (Cronbach's alpha ranging from 0.73 and 0.86) and strong test-retest reliability (ICCs higher than 0.80 for six scales and 0.70 for one) were demonstrated. Concurrent validity with the SF-36 showed small to strong expected correlations. CONCLUSION: This first evaluation of the French version of LEIPAD's psychometric properties provides evidence in construct validity and reliability. It would allow HRQoL assessment in clinical and common practice, and investigators would be able to take part in national and international research projects.

[Emotional valence of words in schizophrenia]. / Valence émotionnelle des mots dans la schizophrénie.

AIM OF THE STUDY: Emotion recognition is a domain in which deficits have been reported in schizophrenia. A number of emotion classification studies have indicated that emotion processing deficits in schizophrenia are more pronounced for negative affects. Given the difficulty of developing material suitable for the study of these emotional deficits, it would be interesting to examine whether patients suffering from schizophrenia are responsive to positively and negatively charged emotion-related words that could be used within the context of remediation strategies. The emotional perception of words was examined in a clinical experiment involving schizophrenia patients. This emotional perception was expressed by the patients in terms of the valence associated with the words. In the present study, we investigated whether schizophrenia patients would assign the same negative and positive valences to words as healthy individuals. METHODS: Twenty volunteer, clinically stable, outpatients from the Psychiatric Service of the University Hospital of Clermont-Ferrand were recruited. Diagnoses were based on DSM-IV criteria. Global psychiatric symptoms were assessed using the Positive and Negative Symptoms Scale (PANSS). The patients had to evaluate the emotional valence of a set of 300 words on a 5-point scale ranging from "very unpleasant" to "very pleasant". RESULTS: . The collected results were compared with those obtained by Bonin et al. (2003) [13] from 97 University students. Correlational analyses of the two studies revealed that the emotional valences were highly correlated, i.e. the schizophrenia patients estimated very similar emotional valences. More precisely, it was possible to examine three separate sets of 100 words each (positive words, neutral words and negative words). The positive words that were evaluated were the more positive words from the norms collected by Bonin et al. (2003) [13], and the negative words were the more negative examples taken from these norms. The neutral words reflected the more neutral emotional valences collected. The results suggested that the emotional valences for the negative words were significantly greater in the patients than is observed in the collected norms (P<0.001). Moreover, the emotional valence associated with positive words was significantly lower in the patients than in the collected norms (P<0.001). Nevertheless, only 16 words differed significantly in terms of evaluated emotional valence between patients and young adults. CONCLUSIONS: Despite their overall emotional impairments, the patients with schizophrenia had a very similar perception of word valence as controls. This result suggests that the emotional perception of most emotional words is preserved. This research provides data important to consider during rehabilitation. Moreover, this study will make it possible to select stimuli for use in future studies of emotion in patients.

[Therapeutic efficacy and safety of repetitive Transcranial Magnetic Stimulation in depressions of the elderly: a review]. / Efficacité et tolérance de la stimulation magnétique transcrânienne (SMTr) dans le traitement des dépressions chez le sujet âgé: revue de la littérature.

INTRODUCTION: During the past 15 years, therapeutic effects of repetitive Transcranial Magnetic Stimulation (rTMS) have been studied in psychiatric diseases, particularly in the treatment of depressive disorders. There are more and more data suggesting its efficacy in the treatment of depression in older patients. Thus, the authors found it useful to conduct an up-to-date review of studies that examined the efficacy and safety of rTMS to treat depressive disorders in the aged. METHOD: After an exhaustive consultation of databases (Medline/PubMed and the Avery-George-Holtzheimer Database of rTMS Depression Studies), supplemented by a manual research, the authors retained studies evaluating the therapeutic efficacy of rTMS on depressive disorders in the aged. RESULTS: Fifteen studies were retained. Four open studies using high frequency rTMS, applied to the left dorsolateral prefrontal cortex (DLPFC), demonstrated a decrease in the mean Hamilton Depression Rating Scale (HDRS) scores; however, only a quarter of the aged patients studied experienced a significant remission of depression. Five parallel arm double-blind versus placebo studies concluded in contradicting results: two studies confirmed a significantly greater efficacy of rTMS compared to placebo, whereas three studies did not; but the sham procedure (positioning coil at 90 degrees from the scalp) was disputable in most studies. One study concluded in therapeutic efficacy by inhibiting the right DLPFC. Three controlled parallel arm studies compared rTMS and electroconvulsive-therapy (ECT); one study concluded in greater efficacy of ECT at end of treatment, but the number of ECT treatments depended on the patients' response, whereas a 15-day course of rTMS was systematically administered; additionally HDRS scores were similar in two groups of patients (rTMS and ECT) at 6 months. Lastly, three studies focused on aged patients with cerebrovascular disease. They showed the efficacy of rTMS, although older age and smaller frontal gray mater volumes were associated with a poorer response to rTMS. DISCUSSION: Thus, although some studies concluded contradicting results, literature data globally sustain an efficacy of rTMS for depression in the elderly. Several parameters might be associated with greater antidepressant efficacy (higher intensity pulses of rTMS of the left DLPFC; higher number of stimulations or higher number of rTMS sessions). Poorer responsiveness to rTMS may be related to several patients' factors including older age and smaller frontal gray matter volumes; lesions of the white matter pathways connecting the left DLPFC and the left anterior cingulate cortex might explain a poor response to rTMS. Literature data globally confirm that rTMS is safe and does not produce cognitive deficits, even among highly vulnerable patients with clinical evidence of cerebrovascular disease. CONCLUSION: Many questions remain concerning the optimal stimulation parameters, administration protocol, and privileged indications. Thus, the next rTMS studies should be carefully designed to clarify these questions.

[Recurrences of bipolar disorders - comparative study of bipolar disorders, recurring depressions and single depressions in a cohort of patients aged over 65 years]. / Récurrences dans les troubles bipolaires - Etude comparative à partir d'une population âgée de 65 ans et plus entre troubles bipolaires, troubles dépressifs récurrents et épisodes dépressifs simples.

BACKGROUND: Bipolar mood disorders, after starting at adulthood, may remain active throughout life, but bipolar disorders may only be revealed in later life. Indeed, Yet few data on bipolar disorders in the elderly have been reported in the litterature. The influence of normal aging on the outcome of the disease as well as the specific prognosis of bipolar disorders in the elderly has occasionally been studied. Eventually Finally, and contrasting with adults, few studies comparing the various subtypes of mood disorders were have been performed in the elderly. OBJECTIVES: We therefore developed a study in patients aged 65 or above, in order to evaluate the course (recurrences) of bipolar disorders, compared to recurring depressions and single depressions, and to determine the influence of recurrences on the outcome of bipolar disorders. METHOD: Patients aged over 65 years were inpatients admitted to the department of psychiatry in 2000 for one of the three previously mentioned diagnoses according to DSM IV. Retrospective data were collected from medical reports. Prospectively, data were collected from the general practitioner of each patient (relying on telephone calls), before statistical analysis was performed. RESULTS: Our study demonstrates a more severe outcome for bipolar disorders compared to recurring depressions and single depressions. Patients with bipolar disorders have a higher prevalence of psychiatric recurrences. Furthermore, the greater the number of previous relapses (or the longer the duration and intensity of the disease), the higher the risk of future new future recurrences both in bipolar disorders and recurring depressions. An age of onset of bipolar disorders before 60 years and more than 5 in-hospital admissions increase the risk of recurrences. CONCLUSION: We originally compare the outcome of bipolar disorders in the elderly, to recurring depressions and single depressions. We confirm the fatal outcome of recurrences in bipolar disorders in old age. Bipolar disorders in the elderly should be considered as a real public health care problem: strategies to minimize the number of episodes experienced by patients with bipolar illness must be pursued aggressively throughout life.

Cognitive behavior therapy versus supportive therapy in social phobia: a randomized controlled trial.

BACKGROUND: The efficacy of cognitive behaviour therapy (CBT) in social phobia has been demonstrated in several controlled trials and meta-analyses, but no comparison of CBT with supportive therapy (ST) can be found in the literature. METHOD: The aim of the trial was to study the effectiveness of CBT versus ST carried out 'as usual'. Sixty-seven DSM-4 social phobic patients (89% generalized subtype, most with avoidant personality) were randomly allocated into two groups. Group 1 (CBT) received 8 1-hour sessions of individual cognitive therapy (CT) for 6 weeks, followed by 6 2-hour sessions of social skills training (SST) in group weekly. Group 2 received ST for 12 weeks (6 half-hour sessions), then the patients were switched to CBT. All patients agreed not to take any medication during the whole trial. In group 1, 29 patients reached week 6, 27 reached week 12, and 24 weeks 36 and 60 (endpoint). In group 2, 29 patients reached week 6, 28 reached weeks 12 and 18, 26 week 24, and 23 reached weeks 48 and 72 (endpoint). RESULTS: At week 6, after CT, group 1 was better than group 2 on the main social phobia measure. At week 12, after SST, group 1 was better than group 2 on most of the measures and demonstrated a significantly higher rate of responders. This finding was replicated after switching group 2 to CBT. Sustained improvement was observed in both groups at follow-up. Compliance with abstinence from medication increased over time. CONCLUSIONS: CBT was more effective than ST and demonstrated long-lasting effects. This may suggest that social phobia management requires more than a simple and inexpensive psychological intervention.

[Social anxiety in patients with social phobia: validation of the Liebowitz social anxiety scale: the French version]. / L'anxiété sociale chez les phobiques sociaux: validation de l'échelle d'anxiété sociale de Liebowitz (version française).

The Liebowitz's Social Anxiety Scale (LSAS) (Liebowitz, 1987) is a rating scale of fear and avoidance in social interaction (12 items) and performance-oriented situations (12 items). This paper present the study of empirical and concurrent validation of the LSAS. Ninety-six patients suffering from social phobia according to DSM IV were included and compared with 64 non-clinical control subjects. Both patients and controls were divided into two sub-groups: the LSAS passation by hetero-evaluation or auto-evaluation. Social phobics had much higher scores on anxiety and avoidance of the LSAS than control subjects, whatever the method. There were no differencies between hetero and auto-evaluation in both groups of patients and non-clinical subjects, either on anxiety or on avoidance. The LSAS correlated better with social anxiety and negative cognition in social situations than with anxiety-depression in social phobics. The French version of the LSAS showed a good empirical and concurrent validity and the scale presents a good sensitivity to change after cognitive behavioral therapy in social phobics.

Plasma levels of 8-epiPGF2alpha, an in vivo marker of oxidative stress, are not affected by aging or Alzheimer's disease.

Free radicals are likely involved in the aging process and there is a growing body of evidence that free radical damage to cellular function is associated with a number of age-related diseases such as atherosclerosis, cancer, and neurologic disorders. The present study was designed to evaluate in a healthy population the evolution with age of 8-epiPGF2alpha plasma levels, a recently proposed marker of in vivo lipid peroxidation. Moreover we investigated this marker of oxidative stress in patients with Alzheimer's disease (AD), an age-related neurodegenerative disorder in the development of which free radicals have been involved. Our results show that in the healthy population studied, despite decreased antioxidant defenses with increasing age as monitored by antioxidant capacity measurement, plasma 8-epiPGF2alpha levels were not correlated with age. Moreover, we have demonstrated that AD patients presented no modification of plasma 8-epiPGF2alpha level and no major alteration of the antioxidant status. In conclusion, the measurement of plasma 8-epiPGF2alpha did not allow us to detect alterations in oxidative stress with aging or in AD.

Developmental distribution of astrocytic proteins in the rat cochlear nucleus.

To investigate the developmental distribution of cochlear nucleus (CN) astrocytes, we used immunocytochemical localization of glial fibrillary acidic protein (GFAP) and S100beta in rats at 0, 5, 10, 15, 21, 30 postnatal days plus the adult. Differential developmental trends were observed for both proteins. The spatial distribution showed a progressive increase of the number of GFAP-immunoreactive (GFAP-IR) astrocytes during development. GFAP positive cells occurred first in the granule cell domain of the ventral CN and in the molecular cell layer of the dorsal CN, then followed an outside to inside pattern of progression. The GFAP-IR reached an adult distribution 1 month after birth. By contrast with GFAP, the apparition of S100beta-immunoreactivity (S100beta-IR) was abrupt (between 0 and 5 days) followed by a rapid stabilization of density and distribution of IR cells (between 15 and 21 days). The developmental distribution of S100beta-IR cells occurred from the posterodorsal region and progressed toward a rostroventral direction. With contrast to GFAP-IR astrocytes, S100beta-positive cells were mainly restricted to the central part of the CN, while only few IR astrocytes were observed in the granule cell domain of the ventral CN or in the molecular cell layer of the dorsal CN. This differential distribution suggests that both antigens were expressed by two different cell populations at least, it is obvious during the first postnatal week. The gradual expression of GFAP and S100beta is interpreted as reflecting the time course of astrocytic maturation. These data suggest that the maturation of CN astrocytes may be linked to the final maturation of CN neurons.

Age-related changes in GFAP-immunoreactive astrocytes in the rat ventral cochlear nucleus.

The age-related changes in the ventral cochlear nucleus (VCN) as revealed by glial fibrillary acid protein (GFAP) immunoreactivity were analyzed in the following age groups: 3-, 6-, 12-, 18-, and 24-month-old Sprague-Dawley rats. A cartographic and a quantitative analysis showed a significant increase in the number of GFAP positive astrocytes during the first year of life and a significant decrease in older rats. We also observed an age-induced modification in the spatial distribution of GFAP positive astrocyte. In the anterior part of the VCN of the 3- and 6-month-old rats, we observed a significant decrease in the rostro-caudal as well in the dorso-ventral axes. In the posterior part of the VCN, a significant decrease in the dorso-ventral axis could be also observed, but no significant difference in the spatial distribution was obtained in the rostro-caudal axis. In older rats, the distribution appeared homogeneous throughout the nucleus. Additionally, aging was associated with a significant increase in GFAP positive astrocyte sizes, except for immunolabelled astrocytes in the granule cell layer. The different levels of GFAP expression occurring in the VCN during normal aging could reflect a progressive decline of cellular activity in the VCN, without severe cell degeneration or synaptic loss.

Neurotrophin receptor immunostaining in the rat ventral cochlear nucleus.

By virtue of its known segregated distribution of cell types, their known neurotransmitters and neurophysiologic properties, the cochlear nucleus is an excellent model and provides the opportunity to study the relation between neurotrophins and their receptors along with the functional properties of the adult cochlear nucleus. To investigate the potential role of neurotrophins in the mature cochlear nucleus, we determined the expression of the three major neurotrophin tyrosine kinase receptors (Trk) in the adult rat ventral cochlear nucleus, as revealed by antibodies against the full-Trk proteins. A qualitative and a cartographic analysis showed a widespread distribution of the three Trk receptors throughout the nucleus. Immunostaining was mainly restricted to neurons as shown by the lack of double immunostaining with specific markers for glial cells. However, we observed variability in immunostaining for given receptors. Three classes of cells were distinguished by their specificity for Trk receptors. The first one was a cell population that stained for TrkA or TrkB. This population characterizes the majority of small and small round neurons and fusiform cells. The second group consists of TrkC-immunolabeled cells and comprises the majority of spherical, globular, granule and small multipolar cells. The third group consists of cells that seem to be immunopositive for all three Trk receptors. This group includes in part multipolar, giant and octopus cells. A possible correlation between Trk expression and cell functional properties is suggested: TrkA- and TrkB-immunoreactive cells could include inhibitory neurons while cells stained for TrkC could include excitatory neurons. The abundant and widespread neuronal distribution of signal-transducing forms of TrkA, TrkB and TrkC predicts that their cognate ligands may exert significant effects on a large proportion of neurons within the mature ventral cochlear nucleus.

Distribution of glial fibrillary acidic protein (GFAP) in the cochlear nucleus of adult and aged rats.

The age-related change in glial fibrillary acidic protein (GFAP) immunoreactivity was analyzed in young (3 months) and old (24 months) adult rat cochlear nuclei (CN). Quantitative analyses show a significant increase with age, in the number of GFAP positive astrocytes and processes in the old adult when compared with the young adult rat. There was also a differential distribution of GFAP immunoreactivity in the young adult CN where it predominates in the granular cell region, whereas in old rats, the GFAP immunoreactivity distribution was homogeneous in all parts of the nucleus. There was no change in the total number of neurons between these two stages in any part of the nucleus except for the antero-ventral CN, where a decrease in neuronal number was observed in the aged rats. The increase in GFAP immunoreactivity was related to an increase of both GFAP positive astrocyte number and processes. The increase of GFAP positive astrocytes may be due either to an alteration of auditory nerve fibers, changing the trophic interactions with post-synaptic cells, or to intrinsic alterations of CN neurons and local circuits reflecting aging of the CN.

[Pharmacologic approach to negative symptoms in schizophrenia]. / Approche psychopharmacologique des symptômes négatifs dans les schizophrénies.

Various pharmacologic agents have been reported to be effective in treating negative symptoms of schizophrenia. European schools of psychiatry and especially the French one assumed the opinion that part of negative symptoms of schizophrenia do respond to neuroleptics. In light of effects of reserpine and some phenothiazines on negative schizophrenia, various pharmacologic agents have been studied focusing on these properties. Various papers devoted to this question concluded that some drugs, particularly neuroleptics, can be considered as disinhibitors: phenothiazines (thiotixene, trifluoperazine, fluphenazine, pipotiazine), butyrophenones (trifluperidol, risperidone), diphenylbutylpiperidines (pimozide) and benzamides (sulpiride, amisulpiride). Major part of controlled studies concluded to the better efficacy of low doses of such drugs on negative symptoms, while high doses are almost inefficient. Some studies concluded in the activity of clozapine on negative symptoms of schizophrenic patients. To answer the question whether negative symptoms of schizophrenia are improved concomitantly or independently of improvement in positive symptoms or of decrease in extrapyramidal side effects and/or depressive symptoms, the authors prospectively followed up for 30 months, 13 DSM-IV resistant schizophrenics. Symptoms were assessed by means of 18 item Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale and Extrapyramidal Symptom Rating Scale (ESRS). Improvement in negative symptoms was significantly correlated to improvement in positive ones and to scores in ESRS. Many open studies concerning anti-depressants and other drugs have been published; however controlled studies are necessary to confirm these data.

[Clozapine and refractory schizophrenia. Long-term prospective study of 20 patients]. / Clozapine et schizophrénies résistantes. Etude prospective à long terme chez vingt patients.

Clozapine, a dibenzodiazepine derivative, has potent antipsychotic activity. But bone marrow suppression resulting in agranulocytosis has been associated with clozapine treatment; thus its clinical development has been delayed and the administration of this drug has been restricted to treatment-resistant schizophrenic patient. This report describes an open prospective study of the effects of clozapine on symptomatology of patients who are refractory to neuroleptics. Authors prospectively followed up until 36 months, 20 DSM III-R schizophrenic patients who had failed to respond to various neuroleptics (7.7 +/- 3.0). When clozapine treatment was initiated, the mean duration of the illness was 17 +/- 10 years. Various scales were used for evaluation: total BPRS, BPRS "positive symptoms", BPRS "negative symptoms", PANSS positive and PANSS negative were realized at days 0 and 15, months 1, 2 and 3 and then every 3 months. Significative improvements in total BPRS, BPRS positive symptoms and PANSS positive were noted at day 15 (p < 0.005, p < 0.026, p < 0.02, respectively); clozapine produced significant improvement on the BPRS negative symptoms and the PANSS negative at 1 month (p < 0.03 and p < 0.008, respectively). Side effects were studied: dry mouth was more prominent in the first month after wash-out (15%), while salivation was more and more prevalent (20% within the first month; 53% beyond). There was no agranulocytosis in this cohort; 2 cases (10%) of eosinophilia occurred during the first month; 20% of the patients experienced an increase in total white blood cell count (> 12.000/mm3). Weight gain (> 5 kg) affected 32% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)