Establishing a therapeutic relationship: An initial stake in psychotherapy with young psychotic adults.

Although psychosis and psychoanalysis have been closely linked since the earliest Freudian theories, the psychoanalytic treatment of psychotic states still presents major difficulties. The establishment of a therapeutic situation allowing the deployment of psychic work is still uncertain. The resumption of the work of S. Freud and DW. Winnicott associated with the development of the theorization of a metapsychology of the process of symbolization by the French school (Green, Roussillon) allows a revival of the reflection on the stakes of the establishment of the therapeutic situation. This theorization of representative processes makes it possible to consider the psychotherapeutic approach to psychoses from the angle of a "psychopathology of the psychic apparatus" and thus to model the psychic dynamics involved in psychotic problems which initially appear in a chaotic form. The apparent failure of the psychic processes, in their linking and transforming activity with which the psychotic states are confronted, can then be thought of as the seat of a particular psychic work that can provide essential support to the therapeutic work. Two cases studies illustrate these processes.

Longitudinal Assessment of Remnant Foveal Cone Structure in a Case Series of Early Macular Telangiectasia Type 2.

Purpose: To determine the extent of remnant cone structure within early foveal ellipsoid zone (EZ) lesions in macular telangiectasia type 2 longitudinally using both confocal and split detector adaptive optics scanning light ophthalmoscopy (AOSLO). Methods: Spectral domain optical coherence tomography (SDOCT), confocal and split detector AOSLO were acquired from seven patients (10 eyes) with small (early) EZ lesions on SDOCT secondary to macular telangiectasia type 2 at baseline, 6 months, and 12 months. The presence of cone structure on AOSLO in areas of EZ loss as well as cones at 1° eccentricity, and their change over time were quantified. Results: By split detector AOSLO, remnant cone structure was identified within and on the borders of all foveal EZ lesions. Within the extent of these lesions, cone spacing ranged from 4.97 to 9.95 µm at baseline, 5.30 to 6.10 µm at 6 months, and 4.99 to 7.12 µm at 12 months. Four eyes with significantly smaller EZ lesions showed evidence of recovery of EZ reflectivity on SDOCT B-scans. Remnant cone structure was identified in some areas where EZ reflectivity recovered at the following time point. Eyes that showed recovery of EZ reflectivity had a continuous external limiting membrane. Conclusions: Remnant cone structure can persist within small SDOCT-defined EZ lesions, which can wax and wane in appearance over time. AOSLO can help to inform the interpretation of SDOCT imaging. Translational Relevance: The absence of EZ in early macular telangiectasia type 2 and other retinal conditions needs careful interpretation because it does not always indicate an absence of underlying cone structure. The integrity of the external limiting membrane may better predict the presence of remnant cone structure and recovery of EZ reflectivity.

International Health Practices: A Multidisciplinary Approach to Therapeutic Mediations With an Artistic Medium Based on the Model of Play.

This article, corresponding to a part of the restitution of a financed international research project between France, Brazil, Canada, Italy and Belgium, aims to offer a modelisation and qualitative evaluation of mediation care settings based on an original methodological tool that involves identifying the typical games at the foundations of creativity, following a multidisciplinary perspective. Therapeutic mediations are settings or devices organized around a "pliable medium," often artistic, like painting, modeling, writing and theater, which are very widespread in institutional practices, both in France and abroad. The scientific objectives of this research consist in a multi-disciplinary exploration (anthropology, criminology, neuroscience, clinical psychology) of the process of creative symbolization understood as a process of transformation involving play. According to this orientation, play can be defined as a psychic process whereby a subjective experience can be explored with pleasure, and consequently symbolized and appropriated. Our fundamental and original hypothesis is that play is at the source of the creative process, conceived as a work of metabolization by the psyche of playful experiences during the different stages of life. The review of the understanding of play in psychoanalysis, anthropology, criminology and neuroscience emphasizes the richness of this model and the importance of reflecting on the typical games in the field of psychic care. A clinical example of treatment in a pictorial therapeutic mediation setting of a child with psychotic disorders makes it possible to identify a number of typical games as well as the modalities of interpretation of the therapists through play. These multidisciplinary studies lead to the presentation of a general table of typical games, and these first results highlight the richness of identifying typical games in clinical settings. Ultimately, the multidisciplinary approach shows the interest of the model of play in the evaluation of therapeutic mediation settings, with a convergence of the different disciplines emphasizing the pertinence of this model. The scientific impact of this research overlaps with its societal impact, through the development of innovative tools for evaluating therapeutic mediations, in order to take account of the evolution of the different forms of social expression of psychic suffering.

High-Resolution In Vivo Fundus Angiography using a Nonadaptive Optics Imaging System.

PURPOSE: We provide a proof of concept for the detailed characterization of retinal capillary features and surrounding photoreceptor mosaic using a customized nonadaptive optics angiography imaging system. METHODS: High-resolution fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA) images were obtained using a modified Heidelberg retina angiograph (HRA2) device with a reduced scan angle enabling 3° field of view. Colocalized images of the photoreceptor mosaic also were captured in vivo using the same instrument. Visibility of vascular subbranches were compared between high-resolution images and conventional fundus angiography (FA) with a 30° field of view. RESULTS: High-resolution angiographic and infrared images (3° × 3° field of view, a 10-fold magnification) were obtained in 10 participants. These included seven patients with various retinal diseases, including myopic degeneration, diabetic retinopathy, macular telangiectasia, and central serous chorioretinopathy, as well as three healthy controls. Images of the retinal vasculature down to the capillary level were obtained on angiography with the ability to visualize a mean 1.2 levels more subbranches compared to conventional FA. In addition, imaging of the photoreceptor cone mosaic, to a sufficient resolution to calculate cone density, was possible. Movement of blood cells within the vasculature also was discernible on infrared videography. CONCLUSIONS: This exploratory study demonstrates that fast high-resolution angiography and cone visualization is feasible using a commercially available imaging system. TRANSLATIONAL RELEVANCE: This offers potential to better understand the relationship between the retinal neurovascular system in health and disease and the timing of therapeutic interventions in disease states.

EFFECT OF DARK ADAPTATION AND BLEACHING ON BLUE LIGHT REFLECTANCE IMAGING IN MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: In patients with macular telangiectasia Type 2, blue light reflectance imaging reveals an oval, parafoveal area in the macula that has increased reflectance compared with its surrounding. Here, we examine how dark adaptation and photobleaching can affect the blue light reflectance imaging pattern. METHODS: Prospective study of patients with macular telangiectasia enrolled in the MacTel Natural History Observation Study. After dark adaptation, a sequence of images was obtained with a confocal scanning laser ophthalmoscope at 488 nm. Change of reflectance patterns was analyzed over time. RESULTS: Eighteen eyes from 16 patients were analyzed. Initially, increased reflectivity in the parafoveal area resulted in higher gray values compared with the paramacular surrounding on blue light reflectance imaging. The difference between parafoveal and paramacular reflectance intensity decreased steadily during imaging, from 17.7 gray-value units (95% confidence interval: 12.1-23.2) down to 2.8 (95% confidence interval: -0.8 to 6.5) after around 30 seconds, and recovered after 5 minutes of dark adaptation. CONCLUSION: A bleaching effect was evident in our study. Understanding these changes is important for both diagnosis and assessment of blue light reflectance phenotype in patients with macular telangiectasia and could also provide further insights into the pathophysiology of this disease.

Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1.

The hemagglutinin-tagged human trace amine-associated receptor1 (TAAR1) was stably coexpressed with rat Galpha(s) in the AV12-664 cell line, and receptor activation was measured as the stimulation of cAMP formation. After blockade of endogenously expressed alpha2- and beta-adrenoceptors with 2-[2-(2-methoxy-1,4-benzodioxanyl)]-imidazoline hydrochloride (2-methoxyidazoxan, RX821002) and alprenolol, respectively, the resulting pharmacology was consistent with that of a unique receptor subtype. beta-Phenylethylamine (beta-PEA), the putative endogenous ligand, gave an EC50 of 106 +/- 5 nM in the assay. For a series of beta-PEA analogs used to explore the pharmacophore, small substituents at ring positions 3 and/or 4 generally resulted in compounds having lower potency than beta-PEA, although several were as potent as beta-PEA. However, small substituents at ring position 2 resulted in a number of compounds having potencies as good as or better than beta-PEA. A number of nonselective antagonists known to share affinity for multiple monoaminergic receptors were evaluated for their ability to inhibit beta-PEA stimulation of the human TAAR1. None had an IC50 <10 microM. For comparison, the rat TAAR1 receptor was expressed in the AV12-664 cell line. A number of agonist compounds had significantly different relative potencies between the rat and human TAAR1, demonstrating a significant species difference between the rat and human TAAR1. The TAAR1 receptor exhibits a pharmacologic profile uniquely different from those of classic monoaminergic receptors, consistent with the structural information that places them in a distinct family of receptors. This unique pharmacologic profile suggests the potential for development of TAAR-selective agonists and antagonists to study their physiologic roles.

Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 5.

A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT1A receptor antagonism and serotonin reuptake inhibition was discovered. 1-(1H-Indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols exhibited selective and high affinities at the 5-HT1A receptor and serotonin reuptake site in vitro. In vivo evaluation of this series of compounds demonstrated elevated extracellular serotonin levels from the basal and quick recovery of neuron firing that was presumably suppressed by the initial acute activation of 5-HT1A somatodendritic autoreceptors.

Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 4.

A series of 1-(1H-indol-4-yloxy)-3-(4-arylpiperidinyl)propan-2-ols possessing potent dual 5-HT(1A) receptor antagonism and serotonin reuptake inhibition was discovered. The fused aryl ring moiety contributed to the robust dual activities irrespective of the regiochemistry associated with its connectivity to the piperidine central ring.

Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 3.

A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT(1A) receptor antagonism and serotonin reuptake inhibition was discovered. Modification of potential metabolic sites of 1-(1H-indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols further improved the in vitro binding affinities and functional antagonism.

Advances Toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT(1A) receptor antagonism/SSRI activities. Part 2.

Potent 5-HT1A/SSRIs at low nanomolar and subnanomolar concentrations were identified in a series of 1-(1H-indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols. Incorporation of an alpha-Me group in the piperidine ring with its specific stereochemistry enhanced binding affinity at the 5-HT reuptake site and in vitro 5-HT(1A) antagonist functional activity.

Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 1.

A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT(1A) receptor antagonism and serotonin reuptake inhibition was discovered. 1-(1H-Indol-4-yloxy)-3-(4-benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols exhibited selective and high affinity at the 5-HT(1A) receptor and serotonin reuptake inhibition at nanomolar concentrations for dual activities.