Early effects of mood stabilizers on the Akt/GSK-3β signaling pathway and on cell survival and proliferation

Rationale: Lithium, some of the anticonvulsants, and several second-generation antipsychotic drugs are common medications widely prescribed to treat bipolar disorder. Molecular targets and cellular events that mediate their effects have been described for these drugs but are only partially unraveled. Few comparative studies have been performed. Objectives: We evaluated seven mood stabilizers (MS) in the same in vitro system and found several differences and similarities in their cellular mechanisms (proliferation and cell survival). As some MS were previously shown to activate the Akt/GSK-3β axis, this pathway was explored for other drugs. Materials and methods: The SH-SY5Y cells were cultured in RPMI-1640 medium. Effects of MS drugs on serum-induced cell proliferation and on slowing of cell death were analyzed. Phosphorylation and expression of Akt-1 and GSK-3β mRNA and protein were assessed for the seven drugs as well. Results: Lithium, Valproate, Olanzapine, and Clozapine enhance proliferation and protect cells against serum withdrawal-induced injury. These drugs also activate Akt-1 and GSK-3β phosphorylation. Interestingly, gene expression of Akt-1 mRNA and protein, but not GSK-3β, was increased. The other drugs Lamotrigine, Haloperidol, and Carbamazepine did not affect cellular events nor activate Akt/GSK-3β axis. Conclusion: Valproate and atypical antipsychotics (Olanzapine and Clozapine) regulate SH-SY5Y cell proliferation and survival, activate the Akt/GSK-3β axis, and stimulate gene expression of Akt-1 mRNA and protein, as does Lithium. The other medications have no effect. The study shows the importance of the Akt/GSK-3 axis in MS actions but also pinpoints a different dependence of these drugs on this signaling axi

CBT/DBT SKILLS TRAINING FOR ADULTS WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD)

Background: Attention deficit hyperactivity disorder (ADHD) is associated with marked impairments in familial, social, and professional functioning. Although stimulant treatments can be effective in adult ADHD, some patients will respond poorly or not at all to medication. Previous studies demonstrated that cognitive behavioural therapy- (CBT) and dialectical behavior therapy- (DBT) oriented interventions are effective in reducing the burden of the disease, which is mainly marked by depression, interpersonal difficulties, low self-esteem, and low quality of life. In order to determine the effectiveness of this intervention, we assessed the benefits of a CBT/DBT programme to reduce residual symptoms and help patients improve their quality of life. Subjects and methods: 49 ADHD-patients, poor responders to medication, were enrolled in a one-year programme where they received individual therapy, associated with weekly sessions of group therapy with different modules: Mindfulness, Emotion Regulation, Interpersonal Effectiveness and Distress Tolerance, Impulsivity/Hyperactivity and Attention. Each subject was assessed at baseline, at months 3 and 6, and at the end of the treatment for ADHD severity (ASRS v1.1), depression severity (BDI-II), hopelessness (BHS), mindfulness skills (KIMS), anger expression and control (STAXI), impulsivity (BIS-11), quality of life (WHOQOL-BREF), and social functioning (QFS). The 49 ADHD patients were compared with 13 ADHD subjects on a waiting list. Linear mixed models were used to measure response to treatment. Results: Overall, the psychotherapeutic treatment was associated with significant improvements in almost all dimensions. The most significant changes were observed for BDI-II (b=-0.30; p<0.0001), ASRS total score (b=-0.16; p<0.0001), and KIMS AwA (b=0.21; p<0.0001), with moderate to large effect sizes. Compared with the waiting list controls, ADHD patients showed a better, albeit non-significant, pattern of response. Conclusions: Individual and structured psycho-educational DBT/CBT groups support existing data suggesting that a structured psychotherapeutic approach is useful for patients who respond partially or not at all to drug therapy

New dating of the «mask» of La Roche-Cotard (Langeais, Indre-et-Loire, France)

Le «masque» de la Roche-Cotard a été découvert au sein d’une couche contenant une industrie lithique de technologie et typologie caractéristiques du Paléolithique moyen. Après une première datation de la couche, supérieure à 32 ka BP et deux autres datations par le 14C attribuant à la couche un âge supérieur à 40 ka, une datation sur quartz par la méthode de la luminescence (OSL) donne un âge de 75,6 ± 5,8 ka au dépôt alluvial qui contient le «masque». Ce nouveau résultat confirme que les datations 14C par Spectrométrie de Masse par Accélérateur (AMS) obtenues sur des fragments osseux de cette même couche sont au-delà de la limite de la validité de la méthode de datation par le radiocarbone. Nous exposons, en annexe, le principe de la méthode des datations OSL qui doivent être retenues pour dater l’occupation néandertalienne de La Roche Cotard II d’où provient le masque, et leurs implications.The "mask" of La Roche-Cotard was discovered in a layer containing a characteristic Middle Paleolithic lithic industry. After a first 14C result of 32 ka BP, two further 14C dates now assign the layer to more than 40 ka, but above all an OSL date obtained on quartz attributes to the layer containing the «mask» an age of 75.6 ± 5.8 ka. This new result confirms that 14C dates with Accelerator Mass Spectrometry, obtained on bones of that layer are beyond the limit of validity of the radiocarbon dating method. We present the principle of the method of luminescence dating that should be retained for the Neanderthal occupation of the Roche Cotard II level 7 and its implications.info:eu-repo/semantics/publishedVersio

Treatment of Blunt Aortic Isthmus Rupture: 19-Years Single Center Experience

peer reviewe

Principales matières premières lithiques disponibles au Paléolithique entre le Bassin parisien et l'Auvergne: partie 2 - Loir-et-Cher, Indre-et-Loire. Le cas du Turonien inférieur et supérieur.

Dans le sud du Bass in parisien, les silex du Turonien inférieur - dits silex blonds - et supérieur - dits silex du Grand-Pressigny - constituent des ressources de première importance au Paléolithique supérieur. Leur exploitation préhistorique est reconnue dans tout le Berry, la Touraine, le Poitou et l'Auvergne. Ils se retrouvent également en petite quantité dans les séries lithiques du Paléolithique supérieur du Bassin parisien, de la vallée du Rhône, de l' Aquitaine et des Charentes. Ces ressources, malgré leur importance, n'avaient jusqu'alors pas fait l'objet d'une description pétrographique détaillée et ont été parfois confondues avec des silicifications cénozoïques localisées dans l'est et le sud du Massif central. Nous présentons une synthèse de nos observations sur plus de 700 échantillons issus de 104 gîtes différents et sur plusieurs milliers d'artefacts lithiques, étayée par une revue bibliographique des publications, cartes géologiques et mémoires universitaires ayant trait au sujet. En conclusion, rapport massif de silex du Turonien et notamment du Turonien inférieur comme élément structurant des assemblages lithiques du Paléolithique supérieur se cantonne pour l'essentiel dans un espace contraint au sud par le seuil du Poitou et les Combrailles creusoises au nord et à l'est par la Loire. Leur circulation sur plusieurs centaines de kilomètres n'est plus un rait anecdotique mais un élément structurant du fonctionnement des sociétés préhistoriques.info:eu-repo/semantics/publishedVersio

Affective Temperaments in Alcohol and Opiate Addictions

Temperament is considered as a biological disposition reflected by relatively stable features related to mood and reactivity to external and internal stimuli, including variability in emotional reactions. The aim of the present study is to test the hypothesis that affective temperaments might differ according to co-occurring mood disorders among patients with alcohol and/or opiate dependence; to explore the relationship between temperaments and dual substance use disorders (SUDs, alcohol and other drugs). Ninety-two patients attending an alcohol addiction treatment facility and 47 patients in an opiate addiction treatment facility were assessed for SUDs, mood disorders and affective temperaments using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego 39-item auto-questionnaire. Comparison of patients with bipolar disorder, depressive unipolar disorder and no (or substance-induced) mood disorder revealed significant differences for the cyclothymic subscale, with highest scores among patients with bipolar disorder. No difference was observed for the depressive, irritable, hyperthymic and anxious subscales. After adjustment for age, gender and bipolar disorder, irritable temperament was a significant risk factor for past or present history of drug use disorders in patients treated for alcohol addiction (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.05-1.93). Anxious temperament was a significant risk factor for history of alcohol use disorders in patients treated for opiate addiction (OR 3.30, 95% CI 1.36-7.99), whereas the hyperthymic subscale appeared as a significant protective factor (OR 0.65, 95% CI 0.42-0.99). The results highlight the need to consider temperamental aspects in further research to improve the long-term outcome of patient with addictive disorders, who often present complex comorbidity pattern