Natural variation in learning ability in "Drosophila melanogaster"

Learning is the ability of an organism to adapt to the changes of its environment in response to its past experience. It is a widespread ability in the animal kingdom, but its evolutionary aspects are poorly known. Learning ability is supposedly advantageous under some conditions, when environmental conditions are not too stable - because in this case there is no need to learn to predict any event in the environment - and not changing too fast - otherwise environmental cues cannot be used because they are not reliable. Nevertheless, learning ability is also known to be costly in terms of energy needed for neuronal synthesis, memory formation, initial mistakes. During my PhD, I focused on the study of genetic variability of learning ability in natural populations. Genetic variability is the basis on which natural selection and genetic drift can act. How does learning ability vary in nature? What are the roles of additive genetic variation or maternal effects in this variation? Is it involved in evolutionary trade-offs with other fitness-related traits?¦I investigated a natural population of fruit fly, Drosophila melanogaster, as a model organism. Its learning ability is easy to measure with associative memory tests. I used two research tools: multiple inbred and isofemale lines derived from a natural population as a representative sample. My work was divided into three parts.¦First, I investigated the effects of inbreeding on aversive learning (avoidance of an odor previously associated with mechanical shock). While the inbred lines consistently showed reduced egg-to-adult viability by 28 %, the effects of inbreeding on learning performance was 18 % and varied among assays, with a trend to be most pronounced for intermediate conditioning intensity. Variation among inbred lines indicates that ample genetic variance for learning was segregating in the base population, and suggests that the inbreeding depression observed in learning performance was mostly due to dominance rather than overdominance. Across the inbred lines, learning performance was positively correlated with the egg-to-adult viability. This positive genetic correlation contradicts previous studies which observed a trade-off between learning ability and lifespan or larval competitive ability. It suggests that much of the genetic variation for learning is due to pleiotropic effects of genes affecting other functions related to survival. Together with the overall mild effects of inbreeding on learning performance, this suggests that genetic variation specifically affecting learning is either very low, or is due to alleles with mostly additive (semi-dominant) effects. It also suggests that alleles reducing learning performance are on average partially recessive, because their effect does not appear in the outbred base population. Moreover, overdominance seems unlikely as major cause of the inbreeding depression, because even if the overall mean of the inbred line is smaller than the outbred base population, some of the inbred lines show the same learning score as the outbred base population. If overdominance played an important part in inbreeding depression, then all the homozygous lines should show lower learning ability than¦outbred base population.¦In the second part of my project, I sampled the same natural population again and derived isofemale lines (F=0.25) which are less adapted to laboratory conditions and therefore are more representative of the variance of the natural population. They also showed some genetic variability for learning, and for three other fitness-related traits possibly related with learning: resistance to bacterial infection, egg-to-adult viability and developmental time. Nevertheless, the genetic variance of learning ability did not appear to be smaller than the variance of the other traits. The positive correlation previously observed between learning ability and egg- to-adult viability did not appear in isofemale lines (nor a negative correlation). It suggests that there was still genetic variability within isofemale lines and that they did not fix the highly deleterious pleiotropic alleles possibly responsible for the previous correlation.¦In order to investigate the relative amount of nuclear (additive and non-additive effects) and extra-nuclear (maternal and paternal effect) components of variance in learning ability and other fitness-related traits among the inbred lines tested in part one, I performed a diallel cross between them. The nuclear additive genetic variance was higher than other components for learning ability and survival to learning ability, but in contrast, maternal effects were more variable than other effects for developmental traits. This suggests that maternal effects, which reflects effects from mitochondrial DNA, epigenetic effects, or the amount of nutrients that are invested by the mother in the egg, are more important in the early stage of life, and less at the adult stage. There was no additive genetic correlation between learning ability and other traits, indicating that the correlation between learning ability and egg-to-adult viability observed in the first pat of my project was mostly due to recessive genes.¦Finally, my results showed that learning ability is genetically variable. The diallel experiment showed additive genetic variance was the most important component of the total variance. Moreover, every inbred or isofemale line showed some learning ability. This suggested that alleles impairing learning ability are eliminated by selection, and therefore that learning ability is under strong selection in natural populations of Drosophila. My results cannot alone explain the maintenance of the observed genetic variation. Even if I cannot eliminate the hypothesis of pleiotropy between learning ability and the other fitness-related traits I measured, there is no evidence for any trade-off between these traits and learning ability. This contradicts what has been observed between learning ability and other traits like lifespan and larval competitivity.¦L'apprentissage représente la capacité d'un organisme à s'adapter aux changement de son environnement au cours de sa vie, en réponse à son expérience passée. C'est une capacité très répandue dans le règne animal, y compris pour les animaux les plus petits et les plus simples, mais les aspects évolutifs de l'apprentissage sont encore mal connus. L'apprentissage est supposé avantageux dans certaines conditions, quand l'environnement n'est ni trop stable - dans ce cas, il n'y a rien à apprendre - ni trop variable - dans ce cas, les indices sur lesquels se reposer changent trop vite pour apprendre. D'un autre côté, l'apprentissage a aussi des coûts, en terme de synthèse neuronale, pour la formation de la mémoire, ou de coûts d'erreur initiale d'apprentissage. Pendant ma thèse, j'ai étudié la variabilité génétique naturelle des capacités d'apprentissage. Comment varient les capacités d'apprentissage dans la nature ? Quelle est la part de variation additive, l'impact des effets maternel ? Est-ce que l'apprentissage est impliqué dans des interactions, de type compromis évolutifs, avec d'autres traits liés à la fitness ?¦Afin de répondre à ces questions, je me suis intéressée à la mouche du vinaigre, ou drosophile, un organisme modèle. Ses capacités d'apprentissage sont facile à étudier avec un test de mémoire reposant sur l'association entre un choc mécanique et une odeur. Pour étudier ses capacités naturelles, j'ai dérivé de types de lignées d'une population naturelle: des lignées consanguines et des lignées isofemelles.¦Dans une première partie, je me suis intéressée aux effets de la consanguinité sur les capacités d'apprentissage, qui sont peu connues. Alors que les lignées consanguines ont montré une réduction de 28% de leur viabilité (proportion d'adultes émergeants d'un nombre d'oeufs donnés), leurs capacités d'apprentissage n'ont été réduites que de 18%, la plus forte diminution étant obtenue pour un conditionnement modéré. En outre, j'ai également observé que les capacités d'apprentissage était positivement corrélée à la viabilité entre les lignées. Cette corrélation est surprenante car elle est en contradiction avec les résultats obtenus par d'autres études, qui montrent l'existence de compromis évolutifs entre les capacités d'apprentissage et d'autres traits comme le vieillissement ou la compétitivité larvaire. Elle suggère que la variation génétique des capacités d'apprentissage est due aux effets pleiotropes de gènes récessifs affectant d'autres fonctions liées à la survie. Ces résultats indiquent que la variation pour les capacités d'apprentissage est réduite comparée à celle d'autres traits ou est due à des allèles principalement récessifs. L'hypothèse de superdominance semble peu vraisemblable, car certaines des lignées consanguines ont obtenu des scores d'apprentissage égaux à ceux de la population non consanguine, alors qu'en cas de superdominance, elles auraient toutes dû obtenir des scores inférieurs.¦Dans la deuxième partie de mon projet, j'ai mesuré les capacités d'apprentissage de lignées isofemelles issues de la même population initiale que les lignées consanguines. Ces lignées sont issues chacune d'un seul couple, ce qui leur donne un taux d'hétérozygosité supérieur et évite l'élimination de lignées par fixation d'allèles délétères rares. Elles sont ainsi plus représentatives de la variabilité naturelle. Leur variabilité génétique est significative pour les capacités d'apprentissage, et trois traits liés à la fois à la fitness et à l'apprentissage: la viabilité, la résistance à l'infection bactérienne et la vitesse de développement. Cependant, la variabilité des capacités d'apprentissage n'apparaît cette fois pas inférieure à celle des autres traits et aucune corrélation n'est constatée entre les capacité d'apprentissage et les autres traits. Ceci suggère que la corrélation observée auparavant était surtout due à la fixation d'allèles récessifs délétères également responsables de la dépression de consanguinité.¦Durant la troisième partie de mon projet, je me suis penchée sur la décomposition de la variance observée entre les lignées consanguines observée en partie 1. Quatre composants ont été examinés: la variance due à des effets nucléaires (additifs et non additifs), et due à des effets parentaux (maternels et paternels). J'ai réalisé un croisement diallèle de toutes les lignées. La variance additive nucléaire s'est révélée supérieure aux autres composants pour les capacités d'apprentissage et la résistance à l'infection bactérienne. Par contre, les effets maternels étaient plus importants que les autres composants pour les traits développementaux (viabilité et vitesse de développement). Ceci suggère que les effets maternels, dus à G ADN mitochondrial, à l'épistasie ou à la quantité de nutriments investis dans l'oeuf par la mère, sont plus importants dans les premiers stades de développement et que leur effet s'estompe à l'âge adulte. Il n'y a en revanche pas de corrélation statistiquement significative entre les effets additifs des capacités d'apprentissage et des autres traits, ce qui indique encore une fois que la corrélation observée entre les capacités d'apprentissage et la viabilité dans la première partie du projet était due à des effets d'allèles partiellement récessifs.¦Au, final, mes résultats montrent bien l'existence d'une variabilité génétique pour les capacités d'apprentissage, et l'expérience du diallèle montre que la variance additive de cette capacité est importante, ce qui permet une réponse à la sélection naturelle. Toutes les lignées, consanguines ou isofemelles, ont obtenu des scores d'apprentissage supérieurs à zéro. Ceci suggère que les allèles supprimant les capacités d'apprentissage sont fortement contre-sélectionnés dans la nature Néanmoins, mes résultats ne peuvent pas expliquer le maintien de cette variabilité génétique par eux-même. Même si l'hypothèse de pléiotropie entre les capacités d'apprentissage et l'un des traits liés à la fitness que j'ai mesuré ne peut être éliminée, il n'y a aucune preuve d'un compromis évolutif pouvant contribuer au maintien de la variabilité.

Dépression, suicide assisté et vieillissement: cas clinique et commentaires = Depression, assisted suicide and ageing: case report and comments

L'hôpital de jour de psychiatrie de l'âge avancé du centre hospitalier universitaire Vaudois (CHUV), en Suisse, prend en charge ambulatoirement les personnes âgées souffrant de troubles psychiatriques. Cet article relate la première expérience de notre équipe d'une patiente qui est décédée à domicile via l'assistance au suicide alors qu'elle était suivie dans notre service pour un épisode dépressif sévère, de probables troubles cognitifs et un trouble de la personnalité émotionnellement labile de type borderline. Cette pratique d'assistance au suicide, autorisée par la loi suisse sous certaines conditions, est reprécisée et quelques directives médicoéthiques professionnelles sont présentées, avec un accent sur la capacité de discernement. © 2010 Elsevier Masson SAS. Tous droits réservés. The old age psychiatric daycare hospital of the Vaud University Hospital (CHUV), in Switzerland, follows up on elderly ambulatory patients with psychiatric disease. This article relates our team's first time experience with a patient who, while she was being treated in our unit for severe depression, cognitive symptoms and a borderline personality disorder, died at home via a suicide organization. Assisted suicide, allowed by the Swiss law, is also discussed in this article and, in addition, a few professional medico-ethics directives, with an emphasis on decision-making capacity are presented. © 2010 Elsevier Masson SAS. All rights reserved.

Correlates of insomnia in patients with social phobia: role of depression and anxiety.

The severity of insomnia and the relationships between social fear, anxiety, depression and insomnia were examined in 179 patients with social phobia. Two-thirds of our sample had insomnia. Depression, anxiety, social anxiety, and insomnia were positively correlated. General and social anxiety contributed to insomnia when accounting for depression.

The neuroanatomical model of post-stroke depression: towards a change of focus?

One third of all stroke survivors develop post-stroke depression (PSD). Depressive symptoms adversely affect rehabilitation and significantly increase risk of death in the post-stroke period. One of the theoretical views on the determinants of PSD focuses on psychosocial factors like disability and social support. Others emphasize biologic mechanisms such as disruption of biogenic amine neurotransmission and release of proinflammatory cytokines. The "lesion location" perspective attempts to establish a relationship between localization of stroke and occurrence of depression, but empirical results remain contradictory. These divergences are partly related to the fact that neuroimaging methods, unlike neuropathology, are not able to assess precisely the full extent of stroke-affected areas and do not specify the different types of vascular lesions. We provide here an overview of the known phenomenological profile and current pathogenic hypotheses of PSD and present neuropathological data challenging the classic "single-stroke"-based neuroanatomical model of PSD. We suggest that vascular burden due to the chronic accumulation of small macrovascular and microvascular lesions may be a crucial determinant of the development and evolution of PSD.

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors.

Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (MIF gene deletion) and pharmacological (treatment with the MIF antagonist Iso-1) approaches. Behaviorally, genetic deletion of MIF resulted in increased anxiety- and depression-like behaviors, as well as of impaired hippocampus-dependent memory. Together, our studies provide evidence supporting a pivotal function for MIF in both basal and antidepressant-stimulated adult hippocampal cell proliferation. Moreover, loss of MIF results in a behavioral phenotype that, to a large extent, corresponds with alterations predicted to arise from reduced hippocampal neurogenesis. These findings underscore MIF as a potentially relevant molecular target for the development of treatments linked to deficits in neurogenesis, as well as to problems related to anxiety, depression, and cognition.

Alexithymia and depression in eating disorders.

We compared alexithymia and depression ratings for non-hospitalized women meeting DSM-IV criteria for anorexia nervosa (n=32) and bulimia nervosa (n=32) to ratings for healthy women (n=74). Alexithymia was evaluated by the Toronto Alexithymia Scale (TAS-20) and depression by the Hospital Anxiety and Depression Scale (HAD). TAS and HAD scores were significantly higher in anorexic compared to bulimic patients, although these two scales were significantly and positively correlated (r=0.53, P=0.001). After taking depression into account as a confounding variable, rates of alexithymia did not vary according to the type of eating disorder (anorexia or bulimia).

Stressful life events and neuroticism as predictors of late-life versus early-life depression.

BACKGROUND: The occurrence of depression in younger adults is related to the combination of long-standing factors such as personality traits (neuroticism) and more acute factors such as the subjective impact of stressful life events. Whether an increase in physical illnesses changes these associations in old age depression remains a matter of debate. METHODS: We compared 79 outpatients with major depression and 102 never-depressed controls; subjects included both young (mean age: 35 years) and older (mean age: 70 years) adults. Assessments included the Social Readjustment Rating Scale, NEO Personality Inventory and Cumulative Illness Rating Scale. Logistic regression models analyzed the association between depression and subjective impact of stressful life events while controlling for neuroticism and physical illness. RESULTS: Patients and controls experienced the same number of stressful life events in the past 12 months. However, in contrast to the controls, patients associated the events with a subjective negative emotional impact. Negative stress impact and levels of neuroticism, but not physical illness, significantly predicted depression in young age. In old age, negative stress impact was weakly associated with depression. In this age group, depressive illness was also determined by physical illness burden and neuroticism. CONCLUSIONS: Our data suggest that the subjective impact of life stressors, although rated as of the same magnitude, plays a less important role in accounting for depression in older age compared to young age. They also indicate an increasing weight of physical illness burden in the prediction of depression occurrence in old age.

Having a good relationship with their mother: a protective factor against sexual risk behavior among adolescent females?

STUDY OBJECTIVE: To assess whether having a good relationship with their mother was a protective factor against risky sexual behavior for female adolescents and whether it was independent of family structure. DESIGN: Cross-sectional survey of in-school adolescents aged 14-19 years. SETTING: Catalonia, in northeast Spain. PARTICIPANTS: A total of 3677 females divided according on whether they had a good (n=3335) or a bad (n=342) relationship with their mother. MAIN OUTCOME MEASURES: Rates of sexual activity and sexual behavior. RESULTS: Adolescents in the good relationship group were significantly younger, more likely to live in an intact family, to have a good relationship with their father and siblings, and to talk about sexuality and their partner with their mother. They were also less likely to have ever had sexual intercourse. Among those sexually experienced, they were significantly older at first intercourse and less likely to have multiple partners or a history of STI. After adjusting for potential confounders, females in the good relationship group were less likely to be sexually active and to have had multiple partners, independently of family structure. CONCLUSIONS: Having a good relationship with their mother is a protective factor against sexual intercourse and having multiple sexual partners independently of family structure. Communication between generations and having a good relationship with their father and siblings also play an important role.

Efficacy of an adjunctive brief psychodynamic psychotherapy to usual inpatient treatment of depression: rationale and design of a randomized controlled trial.

BACKGROUND: A few recent studies have found indications of the effectiveness of inpatient psychotherapy for depression, usually of an extended duration. However, there is a lack of controlled studies in this area and to date no study of adequate quality on brief psychodynamic psychotherapy for depression during short inpatient stay exists. The present article describes the protocol of a study that will examine the relative efficacy, the cost-effectiveness and the cost-utility of adding an Inpatient Brief Psychodynamic Psychotherapy to pharmacotherapy and treatment-as-usual for inpatients with unipolar depression. METHODS/DESIGN: The study is a one-month randomized controlled trial with a two parallel group design and a 12-month naturalistic follow-up. A sample of 130 consecutive adult inpatients with unipolar depression and Montgomery-Asberg Depression Rating Scale score over 18 will be recruited. The study is carried out in the university hospital section for mood disorders in Lausanne, Switzerland. Patients are assessed upon admission, and at 1-, 3- and 12- month follow-ups. Inpatient therapy is a manualized brief intervention, combining the virtues of inpatient setting and of time-limited dynamic therapies (focal orientation, fixed duration, resource-oriented interventions). Treatment-as-usual represents the best level of practice for a minimal treatment condition usually proposed to inpatients. Final analyses will follow an intention-to-treat strategy. Depressive symptomatology is the primary outcome and secondary outcome includes measures of psychiatric symptomatology, psychosocial role functioning, and psychodynamic-emotional functioning. The mediating role of the therapeutic alliance is also examined. Allocation to treatment groups uses a stratified block randomization method with permuted block. To guarantee allocation concealment, randomization is done by an independent researcher. DISCUSSION: Despite the large number of studies on treatment of depression, there is a clear lack of controlled research in inpatient psychotherapy during the acute phase of a major depressive episode. Research on brief therapy is important to take into account current short lengths of stay in psychiatry. The current study has the potential to scientifically inform appropriate inpatient treatment. This study is the first to address the issue of the economic evaluation of inpatient psychotherapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ACTRN12612000909820).

Die Krankheit Depression kann jeden treffen [In Process Citation].

The survey "Datenerhebung zur Depression in der Allgemeinbevölkerung" was conducted from fall 2010 to spring 2011 on several online platforms. The results show that there is a considerable timespan between the appearance of initial symptoms of depression and the first diagnosis of a patient. Intervention at early stages of the disease can reduce a potentially long time of suffering and can lead to the successful treatment of depression. General practitioners play an important role as the link between patient and psychiatrist.

The Brief Psychiatric Rating Scale (version 4.0) factorial structure and its sensitivity in the treatment of outpatients with unipolar depression.

The 24-item Brief Psychiatric Rating Scale (BPRS, version 4.0) enables the rater to measure psychopathology severity. Still, little is known about the BPRS's reliability and validity outside of the psychosis spectrum. The aim of this study was to examine the factorial structure and sensitivity to change of the BPRS in patients with unipolar depression. Two hundred and forty outpatients with unipolar depression were administered the 24-item BPRS. Assessments were conducted at intake and at post-treatment in a Crisis Intervention Centre. An exploratory factor analysis of the 24-item BPRS produced a six-factor solution labelled "Mood disturbance", "Reality distortion", "Activation", "Apathy", "Disorganization", and "Somatization". The reduction of the total BPRS score and dimensional scores, except for "Activation", indicates that the 24-item BPRS is sensitive to change as shown in patients that appeared to have benefited from crisis treatment. The findings suggest that the 24-item BPRS could be a useful instrument to measure symptom severity and change in symptom status in outpatients presenting with unipolar depression.

Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids.

The prevalence of obesity has markedly increased over the past few decades. Exploration of how hunger and satiety signals influence the reward system can help us understand non-homeostatic feeding. Insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce long-term depression (LTD) of mouse excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high-fat meal, which elevates endogenous insulin, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior in mice and conditioned place preference for food in rats. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces anticipatory activity and preference for food-related cues.

Psychomotor retardation in depression: bradykinesia or paucity of movement?

Objectives: Psychomotor retardation is part of Major Depression (MD) diagnosis criteria and has been assimilated to bradykinesia, even though there is a clear lack of objective measurement of motor activity in MD. We conducted a study to evaluate bradykinesia, posture and gait parameters in MD patients with an ambulatory system, allowing continuous motor measurements. Methods: Patients with DSM-IV MD and healthy controls matched for age and sex were asked to carry on with their usual activities while being recorded for 6 hours by a wireless autonomous ambulatory system, containing miniature gyroscopes, data-logger, battery and flash memory. allowing continuous recording of upper limbs movements (speed, amplitude and activity (% of time with movement)), posture (% of time standing, walking, lying or sitting) and gait parameters (speed, cadence, stance, double support, stride). Results: Hands activity was significantly lower in depressed patients, as compared to controls (MD: 40%, controls: 60%; p<0.05). Speed of hand movements (p= 0.13) and their amplitude (p=0.71) were similar to controls. MD patients had a trend to spend more time lying or sitting than controls (p=0.06) but did not differ in terms of any gait parameters. Conclusion: Patients with MD displayed less hand movements than controls and tended to spend more time lying or sitting over 6 hours, but did not differ in terms of speed and amplitude of movement, nor in gait parameters. These results suggest that psychomotor retardation classically described in MD might be the expression of a paucity of movement rather than a bradykinesia as observed in parkinsonism and might involved different (nondopaminergic) mechanisms.