Do general practitioners and psychiatrists agree about defining cure from depression? The DEsCRIBE™ survey

BACKGROUND: This study aimed to document the outcome dimensions that physicians see as important in defining cure from depression. The study also aimed to analyse physicians' attitudes about depression and to find out whether they affect their prescribing practices and/or the outcome dimensions that they view as important in defining cure. METHODS: A 51-item questionnaire based on six validated scales was used to rate the importance of several depression outcome dimensions. Physicians' attitudes about depression were also assessed using the Depression Attitude Scale. Overall, 369 Belgian physicians (264 general practitioners [GPs]; 105 psychiatrists) participated in the DEsCRIBE survey. RESULTS: GPs and psychiatrists strongly agreed that functioning and depressive symptomatology were most important in defining cure; anxious and somatic symptomatology was least important. GPs and psychiatrists differed in their attitudes about depression (p <0.001). Logistic regression revealed that the attitudes of GPs - but not psychiatrists - were significantly associated with their rates of antidepressant prescription (p < 0.001) and that certain attitudes predicted which outcome dimensions were seen as important in defining cure. CONCLUSIONS: Belgian GPs and psychiatrists strongly agreed on which criteria were important in defining cure from depression but differed in their attitudes about depression. The outcome dimensions that were considered important in defining cure were influenced by physicians' attitudes - this was more pronounced in GPs than in psychiatrists

Social Modulation during Songbird Courtship Potentiates Midbrain Dopaminergic Neurons

Synaptic transmission onto dopaminergic neurons of the mammalian ventral tegmental area (VTA) can be potentiated by acute or chronic exposure to addictive drugs. Because rewarding behavior, such as social affiliation, can activate the same neural circuitry as addictive drugs, we tested whether the intense social interaction of songbird courtship may also potentiate VTA synaptic function. We recorded glutamatergic synaptic currents from VTA of male zebra finches who had experienced distinct social and behavioral conditions during the previous hour. The level of synaptic transmission to VTA neurons, as assayed by the ratio of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to N-methyl-D-aspartic acid (NMDA) glutamate receptor mediated synaptic currents, was increased after males sang to females, and also after they saw females without singing, but not after they sang while alone. Potentiation after female exposure alone did not appear to result from stress, as it was not blocked by inhibition of glucocorticoid receptors. This potentiation was restricted to synapses of dopaminergic projection neurons, and appeared to be expressed postsynaptically. This study supports a model in which VTA dopaminergic neurons are more strongly activated during singing used for courtship than during non-courtship singing, and thus can provide social context-dependent modulation to forebrain areas. More generally, these results demonstrate that an intense social encounter can trigger the same pathways of neuronal plasticity as addictive drugs

Dopamine Transporter and Reward Anticipation in a Dimensional Perspective : A Multimodal Brain Imaging Study

We would like to thank Christine Baron, Vincent Brulon, Stéphane LeHelleix, Stéphane Demphel, Claude Comtat, Frédéric Dollé, Philippe Gervais, and Renaud Maroy from the Service Hospitalier Frédéric Joliot for their efficient technical support and 11C radioligand preparation. They thank Marie Prat, Audrey Pepin, and Audrey Mabondo for their help in PET processing and Pr. Maria-Joao Santiago-Ribeiro and Dr Renaud de Beaurepaire for their involvement in the recruitment of participants.Peer reviewedPostprin

Disorders of compulsivity: a common bias towards learning habits.

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.This study was funded by the WT fellowship grant for VV (093705/Z/ 10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. YW is supported by the Fyssen Fondation and MRC Studentships. PD is supported by the Gatsby Charitable Foundation. JEG has received grants from the National Institute of Drug Abuse and the National Center for Responsible Gaming. TWR and BJS are supported on a WT Programme Grant (089589/Z/09/Z). The BCNI is supported by a WT and MRC grant.This is the final published version. It's also available from Molecular Psychiatry at http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201444a.html

Epigenetic management of major psychosis

Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychosis: (1) the role of epigenetic drugs in treating these disorders. At present, there are three categories of epigenetic drugs that are being actively investigated for their ability to treat psychosis: drugs inhibiting histone deacetylation; drugs decreasing DNA methylation; and drugs targeting microRNAs; and (2) the role of epigenetic mechanisms in electroconvulsive therapy in these disorders

Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

Iron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2hipp/hipp mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2hipp/hipp mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2hipp/hipp mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems

Novel animal models for studying complex brain disorders: BAC-driven miRNA-mediated in vivo silencing of gene expression

In schizophrenia, glutamic acid decarboxylase 1 (GAD1) disturbances are robust, consistently observed, cell-type specific and represent a core feature of the disease. In addition, neuropeptide Y (NPY), which is a phenotypic marker of a sub-population of GAD1-containing interneurons, has shown reduced expression in the prefrontal cortex in subjects with schizophrenia, suggesting that dysfunction of the NPY+ cortical interneuronal sub-population might be a core feature of this devastating disorder. However, modeling gene expression disturbances in schizophrenia in a cell type-specific manner has been extremely challenging. To more closely mimic these molecular and cellular human post-mortem findings, we generated a transgenic mouse in which we downregulated GAD1 mRNA expression specifically in NPY+ neurons. This novel, cell type-specific in vivo system for reducing gene expression uses a bacterial artificial chromosome (BAC) containing the NPY promoter-enhancer elements, the reporter molecule (eGFP) and a modified intron containing a synthetic microRNA (miRNA) targeted to GAD1. The animals of isogenic strains are generated rapidly, providing a new tool for better understanding the molecular disturbances in the GABAergic system observed in complex neuropsychiatric disorders such as schizophrenia. In the future, because of the small size of the silencing miRNAs combined with our BAC strategy, this method may be modified to allow generation of mice with simultaneous silencing of multiple genes in the same cells with a single construct, and production of splice-variant-specific knockdown animals

Neural Circuits Underlying Rodent Sociality: A Comparative Approach

All mammals begin life in social groups, but for some species, social relationships persist and develop throughout the course of an individual’s life. Research in multiple rodent species provides evidence of relatively conserved circuitry underlying social behaviors and processes such as social recognition and memory, social reward, and social approach/avoidance. Species exhibiting different complex social behaviors and social systems (such as social monogamy or familiarity preferences) can be characterized in part by when and how they display specific social behaviors. Prairie and meadow voles are closely related species that exhibit similarly selective peer preferences but different mating systems, aiding direct comparison of the mechanisms underlying affiliative behavior. This chapter draws on research in voles as well as other rodents to explore the mechanisms involved in individual social behavior processes, as well as specific complex social patterns. Contrasts between vole species exemplify how the laboratory study of diverse species improves our understanding of the mechanisms underlying social behavior. We identify several additional rodent species whose interesting social structures and available ecological and behavioral field data make them good candidates for study. New techniques and integration across laboratory and field settings will provide exciting opportunities for future mechanistic work in non-model species