Les traitements actuels de la dépression présentent une efficacité partielle et nécessitent une administration pendant plusieurs semaines avant d’obtenir un effet thérapeutique. Il est donc urgent de trouver de nouvelles stratégies antidépressives. La vortioxetine (Lu AA21004) est un nouvel antidépresseur en cours de développement. À la différence des inhibiteurs sélectifs de recapture de la sérotonine (ISRS), il est multi-cibles. Il bloque non seulement le transporteur de la sérotonine (SERT) mais aussi les récepteurs 5-HT3. Afin de caractériser les effets de ce composé et d’évaluer l'implication du blocage des récepteurs 5-HT3 dans son mécanisme d’action, plusieurs marqueurs précliniques de la réponse antidépressive ont été évalués. Nous avons utilisé des approches électrophysiologiques, immunohistochimiques, comportementales et de microdialyse chez le rat. La vortioxetine augmente la prolifération cellulaire hippocampique et induit une désensibilisation des autorécepteurs 5-HT1A dès 3 jours contre 2 à 3 semaines pour les antidépresseurs classiques. Elle induit également une importante libération de sérotonine malgré une occupation partielle du SERT. Ces effets sont liés, au moins en partie, au blocage des récepteurs 5-HT3. Nous avons ensuite montré qu’un antagoniste des récepteurs 5-HT3, l’ondansetron, à très faible dose, potentialisait l’effet d’un ISRS, la paroxetine. L’ensemble de nos données in vivo et ex vivo prouvent que le blocage des récepteurs 5-HT3 participe à l’efficacité pseudo-antidépressive de la vortioxetine. Les récepteurs 5-HT3 sont donc une cible intéressante pour améliorer l’efficacité des antidépresseurs et raccourcir leur délai d’action / Therapeutic effects of current antidepressant drugs only appear after several weeks of treatment and a significant number of patients do not respond to any treatment. Thus, more effective treatments for major depression are still needed. Vortioxetine (Lu AA21004), a novel antidepressant in development, displays effective properties in human. To the difference of selective serotonin reuptake inhibitors (SSRIs), it is a multimodal serotoninergic agent. Not only does it block the 5-HT transporter but it is also a potent 5-HT3 receptor antagonist. This current study was undertaken to characterize the effects of this compound and the role of 5-HT3 blockade. Using electrophysiological, immunohistochemical, autoradiography and behavioral approaches in rats, several pre-clinical markers of antidepressant-like response were assessed. Vortioxetine increased hippocampal cell proliferation and desensitized 5-HT1A autoreceptors from 1-3 days versus 2-3 weeks for classical antidepressants. In contrast to SSRIs, it also increased 5-HT hippocampal release with an incomplete SERT occupancy. Later effects are at least partly due to 5-HT3 receptors blockade. In parallel, we also showed that the 5-HT3 receptor antagonist ondansetron potentiated the effect of the SSRI paroxetine. Taken together, our in and ex vivo findings highlight the crucial role of 5-HT3 receptor blockade in the antidepressant-like efficacy of vortioxetine. Thus, we propose that the 5-HT3 receptors are an interesting target to improve antidepressant efficacy and reduce the therapeutic delay

The present study explored factors affecting vulnerability to depression among gay men and lesbian women in metropolitan Gauteng, South Africa. Risk factors consistently cited in the literature on depression among gay men and lesbian women, namely self-esteem, social integration, hate speech, physical victimisation, fear of victimisation and alcohol and drug abuse, were examined to determine their ability to predict vulnerability to depression. Data was collected from 385 participants who self-identified as lesbian or gay, using a purposive quota sampling technique to ensure representation across age, gender, race and socio-economic status lines. Participants were selected through gay and lesbian organisations, support groups, counselling centres, the gay and lesbian Pride Parade, an online questionnaire, and via snowballing techniques. Multiple regression analysis indicated that self-esteem and hate speech were the only significant predictors of vulnerability to depression. The regression model accounted for 21.7% of the variance in vulnerability to depression scores. / Psychology / M. Sc. (Psychology)

The present study explored factors affecting vulnerability to depression among gay men and lesbian women in metropolitan Gauteng, South Africa. Risk factors consistently cited in the literature on depression among gay men and lesbian women, namely self-esteem, social integration, hate speech, physical victimisation, fear of victimisation and alcohol and drug abuse, were examined to determine their ability to predict vulnerability to depression. Data was collected from 385 participants who self-identified as lesbian or gay, using a purposive quota sampling technique to ensure representation across age, gender, race and socio-economic status lines. Participants were selected through gay and lesbian organisations, support groups, counselling centres, the gay and lesbian Pride Parade, an online questionnaire, and via snowballing techniques. Multiple regression analysis indicated that self-esteem and hate speech were the only significant predictors of vulnerability to depression. The regression model accounted for 21.7% of the variance in vulnerability to depression scores. / Psychology / M. Sc. (Psychology)