[Add-on value of plasma assays during prescription of antipsychotics]. / Intérêt des dosages plasmatiques lors de la prescription des antipsychotiques.

The plasma dosage of antipsychotics is justified in many clinical situations, such as the existence of surprising side effects depending on the dose of administered antipsychotic or, in the event of a lack of therapeutic efficacy. This method allows the clinician to get out of the pure empiricism, trial and error, of his/her supposed beliefs concerning patient compliance and, above all, to base his/her decisions on objective elements in the psychopharmacological field. However, it is clear that this inexpensive and easily accessible technology is not used very often. In the event of a result of the plasma dosage higher or lower than the normal values, it will first be necessary to exclude a phenomenon of drug interactions. Then, the calculation of the metabolic ratio will make it possible to suspect the existence of a particular genetic polymorphism of metabolism (poor metabolizer? ultra-rapid metabolizer?) of the concerned cytochrome, which can then be confirmed by genotyping oriented towards this cytochrome.

Le dosage plasmatique des antipsychotiques est justifié dans de nombreuses situations cliniques, comme l'existence d'effets secondaires surprenants en fonction de la dose d'antipsychotique administrée, ou encore, en cas de manque d'efficacité thérapeutique. Cette méthode permet au clinicien de sortir de l'empirisme pur, essai-erreur, de ses supposées croyances concernant l'observance du patient et, surtout, de baser ses décisions sur les éléments objectifs dans le domaine psychopharmacologique. Pourtant, force est de constater que cette technologie peu coûteuse et facilement accessible n'est que trop peu souvent utilisée. En cas de résultat du dosage plasmatique supérieur ou inférieur à la norme, il conviendra, tout d'abord, d'exclure un phénomène d'interactions médicamenteuses. Ensuite, le calcul du ratio métabolique permettra de soupçonner éventuellement l'existence d'un polymorphisme génétique de métabolisation particulier (métaboliseur lent ? métaboliseur ultra-rapide ?) du cytochrome concerné, qui pourra alors être confirmé par un génotypage orienté vers ce cytochrome.

Treatment-Resistant Depression in Real-World Clinical Practice: A Systematic Literature Review of Data from 2012 to 2022.

OBJECTIVE: Real-world evidence in treatment-resistant depression (TRD; commonly defined as non-response to ≥ 2 consecutive treatments at adequate dosage and duration) is lacking. A systematic literature review was conducted to understand disease burden and treatment outcomes for patients with TRD, studied in a real-world setting over the last decade. DATA SOURCES: A literature search was conducted in May 2022 in MEDLINE, Embase, The Cochrane Libraries and PsycINFO, comprising studies published from 2012 to 2022. Bibliographies of all relevant identified systematic reviews and relevant conference proceedings from 2020 to 2022 were manually hand-searched. STUDY SELECTION: Real-world studies, including cohort, cross-sectional, case-control, chart review and registry studies, published in English and reporting outcomes in adults with TRD, were included. DATA EXTRACTION: Extracted data included study and baseline disease characteristics, treatment type, treatment response, clinical outcomes and health-related quality of life. RESULTS: Twenty studies were included. Criteria for TRD varied, but patients typically experienced long-lasting depression (range 1.4 to 16.5 years). Across studies, mean disease severity scores demonstrated moderate to severe depression, reflecting a high burden of disease at baseline. Remission rates were typically low but generally increased with longer follow-up durations. However, the heterogeneity of interventions, follow-up durations (range 2 weeks to 9.4 years) and assessment tools precluded their quantitative synthesis. Studies were frequently limited by low sample size (range 14 to 411 patients) and health-related quality of life was infrequently assessed. CONCLUSIONS: There is a lack of clinical consensus regarding the definition, assessment and monitoring of TRD in real-world practice. Nevertheless, TRD carries a high burden of illness and there is an unmet need for faster and more effective treatments. To better understand the personal burden of affected patients, future studies would benefit from standardisation of severity assessment and measures of treatment effectiveness, as well as greater consideration of health-related quality of life.

Many people continue to experience depression even after trying two or more medications. This is called treatment-resistant depression (TRD). Most of the information we have on TRD comes from clinical trials, which take place under tightly-controlled conditions. It is important to understand the effects of TRD and TRD treatments on people in their day-to-day lives. Researchers studying people's day-to-day lives call this researching in a "real-world setting". We searched for studies carried out in real-world settings in the last 10 years. We found 20 relevant studies. As these studies were in real-world settings, there were many differences between them, including differences in how TRD was diagnosed, the treatments used, how long people were monitored and how results were measured. This made it difficult to compare how successful different treatments were. Most studies included a small number of people and monitored them for a relatively short time. We found people with TRD had usually lived with it for many years and their symptoms were moderate or severe. Only two studies asked people how TRD affected their lives. These two studies found health-related quality of life and work productivity was low. Most studies found lots of people still had symptoms of depression after treatment. However, symptoms typically improved more when studies monitored people for a longer time. To improve our knowledge of TRD, future studies should monitor more people for longer and use the same ways of measuring results. They should also ask how TRD affects people's daily lives.

Bioderived 4D Printable Terpene Photopolymers from Limonene and ß-Myrcene.

Green manufacturing and reducing our cultural dependency on petrochemicals have been topics of growing interest in the past decade, particularly for three-dimensional (3D) printable photopolymers where often toxic solvents and reagents have been required. Here, a simple solvent-free, free-radical polymerization is utilized to homo- and copolymerize limonene and ß-myrcene monomers to produce oligomeric photopolymers (Mn < 11 kDa) displaying Newtonian, low viscosities (∼10 Pa × s) suitable for thiol-ene photo-cross-linking, yielding photoset materials in a digital light processing (DLP)-type 3D printer. The resulting photosets display tunable thermomechanical properties (poly(limonene) displays elastic moduli exceeding 1 GPa) compared with previous works focusing on monomeric terpenes as well as four-dimensional (4D) shape memory behavior. The utility of such photopolymers for biomedical applications is briefly considered on the premise of the hydrophilic nature (measured by contact angle) as well as their cytocompatibility upon seeding films with macrophages. These terpene-derived, green 4D photopolymers are shown to have promising physical behaviors suitable for an array of manufacturing and 3D printing applications.

Movement, mood and cognition: Preliminary insights into the therapeutic effects of electroconvulsive therapy for depression through a resting-state connectivity analysis.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but how it achieves its clinical effects remains unclear. METHODS: We set out to study the brain's response to ECT from a large-scale brain-network perspective. Using a voxelwise analysis, we looked at resting-state functional connectivity before and after a course of ECT at the whole-brain and the between- and within-network levels in 17 patients with a depressive episode. Using a group-independent component analysis approach, we focused on four networks known to be affected in depression: the salience network (SN), the default mode network (DMN), the cognitive executive network (CEN), and a subcortical network (SCN). Our clinical measures included mood, cognition, and psychomotor symptoms. RESULTS: We found ECT to have increased the connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus as well as its within-network connectivity. Both the right CEN and the SCN showed increased connectivity with the precuneus and the anterior DMN with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity. LIMITATIONS: The limitations of our study include its small sample size and the lack of a control dataset to confirm our findings. CONCLUSION: Our voxelwise data demonstrate that ECT induces a significant increase of connectivity across the whole brain and at the within-network level. Furthermore, we provide the first evidence on the association between an increase of within-posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression.

Shape Memory Poly(ß-hydroxythioether) Foams for Oil Remediation in Aquatic Environments.

Shape memory poly(ß-hydroxythioether) foams were produced using organobase catalyzed reactions between epoxide and thiol monomers, allowing for the rapid formation of porous media within approximately 5 min, confirmed using both rheology and physical foam blowing. The porous materials possess ultralow densities (0.022 g × cm-3) and gel fractions of approximately 93%. Thermomechanical characterizations of the materials revealed glass transition temperatures tunable from approximately 50 to 100 °C, elastic moduli of approximately 2 kPa, and complete strain recovery upon heating of the sample above its glass transition temperature. The foams were characterized for their ability to take up oil from an aqueous multilayered ideal environment, revealing more than 2000% mass of oil (relative to the foam mass) could be collected. Importantly, while post-fabrication functionalization was possible with isocyanate chemistry followed by addition of hexadecanethiol or 3,3-bis(hexadecylthio)propan-1-ol, the oil collection efficiency of the system was not significantly enhanced, indicating that these materials, as porous media, possess unique attributes that make them appealing for environmental remediation without the need for costly modifications or manipulations.

Inflammatory Markers May Inform the Effects of Electroconvulsive Therapy on Cognition in Patients with Depression.

INTRODUCTION: The neurobiological mechanisms underlying the acute cognitive effects of electroconvulsive therapy (ECT) remain poorly understood. Prior research has shown that proinflammatory cytokines such as IL-6, TNF-α, IL1-ß, and IL-10 may interfere with cognitive functioning. Interestingly, immunomodulation is one of the proposed modes of action of ECT. This study investigates whether changes of peripheral levels of IL-6, TNF-α, IL1-ß, and IL-10 are related to changes in cognitive functioning following ECT. METHODS: In the week before and 1 week after an acute course of ECT, 62 patients suffering from depression underwent a neuropsychological evaluation to assess their processing speed using the Symbol Digit Substitution Test (SDST), verbal episodic memory using the Hopkins Verbal Learning Test-Revised (HVLT-R), and their retrospective autobiographic memory using the Autobiographical Memory Interview (AMI) with the peripheral inflammatory markers being measured at the same 2 time points. RESULTS: Patients improved drastically following ECT, while their main performance on both the HVLT-R and AMI declined and their SDST scores remained stable. The levels of IL-6 and IL1-ß had both decreased, where the decrease in IL-6 was related to the decrease in HVLT-R scores. Higher baseline IL-10 levels were associated with a more limited decrease of the HVLT-R scores. CONCLUSION: Our findings tentatively suggest that the effects of ECT on verbal episodic memory may be related to the treatment's immunomodulatory properties, most notably due to decreased IL-6 levels. Moreover, baseline IL-10 appears to be a potential biomarker to predict the effects of ECT on verbal episodic memory. Whilst compelling, the results of this study should be interpreted with caution as, due to its exploratory nature, no correction for multiple comparisons was made. Further, a replication in larger cohorts is warranted.

Improvement of psychomotor retardation after electroconvulsive therapy is related to decreased IL-6 levels.

BACKGROUND: Prior studies suggest that IL-6 may be involved in the pathophysiology of psychomotor symptoms in depression. Electroconvulsive therapy (ECT), as yet the most effective biological treatment of severe depression, is known to improve psychomotor functioning, while recent studies have shown a decrease in the elevated IL-6 levels of depressed patients following ECT. OBJECTIVES: This study investigates whether the improvement in psychomotor functions in patients with depression after ECT is related to changes in IL-6 levels. METHODS: Peripheral IL-6 was quantified and the severity of psychomotor agitation and retardation determined using the CORE assessment of psychomotor symptoms in 62 patients with a (unipolar or bipolar) depressive episode within one week before and within one week after their course of ECT. RESULTS: IL-6 levels had decreased significantly following ECT and both psychomotor retardation and agitation had improved. The decrease in IL-6 levels was related to the improvement of psychomotor retardation, with post-hoc analysis revealing that higher baseline IL-6 levels positively correlated with higher psychomotor retardation scores. CONCLUSION: With this study, we provide the first evidence that the improvement of psychomotor retardation after ECT for depression is related to the immunomodulatory properties of the treatment, most specifically the decrease in IL-6 levels.

Inter-individual variability of social perception and social knowledge impairments among patients with schizophrenia.

Deficits in social perception and knowledge and their negative impact on social functioning, have been repeatedly reported among patients with schizophrenia. However, earlier studies have focused on an overall assessment of social perception and social knowledge, without exploring their sub-components nor the interindividual variation of the deficit. This study aims to refine the exploration of this deficit and to assess its interindividual variation. Twenty-nine patients with schizophrenia and 24 healthy controls, matched for age and gender, completed a validated and integrated social perception and knowledge task (i.e. the PerSo test). Patients with schizophrenia had reduced performance in all PerSo subtests, namely contextual fluency, interpretation and social convention. However, these deficits were not correlated with the severity of clinical symptoms, and individual profiles analyses showed a marked heterogeneity among patients on their abilities. Our study confirms the existence of deficits in social perception and knowledge and underlines their considerable heterogeneity. Therefore, it is necessary to test and rehabilitate individually social perception and knowledge.

Inflammation, Hippocampal Volume, and Therapeutic Outcome following Electroconvulsive Therapy in Depressive Patients: A Pilot Study.

INTRODUCTION: Electroconvulsive therapy (ECT) influences the concentration of peripheral inflammatory markers, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In which way this immune effect contributes to the impact of ECT on the central nervous system in depression remains unknown. OBJECTIVE: The aim of this study was to examine whether the hippocampal volumetric increase in depressed patients treated with ECT is related to changes in peripheral IL-6 and TNF-α levels. METHODS: IL-6 and TNF-α plasma levels were measured in 62 patients 1 week before and after an acute course of ECT. Hippocampal volumes were analyzed in a magnetic resonance imaging (MRI) subsample of 13 patients at the same time points. RESULTS: A significant decrease in IL-6 levels was observed in the total sample and a significant increase in hippocampal volume in the MRI subsample. The reduction of peripheral IL-6 correlated with an increase in total hippocampal volume. A more limited decrease of TNF-α correlated with a more limited increase of both the total and left hippocampus volumes. CONCLUSION: This pilot study is the first to highlight the link between peripheral immune changes and hippocampal volume increase following ECT. Further research is required to conclude whether ECT indeed exerts its central effect on the brain via changes of peripheral inflammatory markers.

The basal ganglia: A central hub for the psychomotor effects of electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective biological treatment for depression. Aside the well-known therapeutic effect on mood symptoms, it has also a unique positive impact on psychomotor agitation and retardation, which are core symptoms of depression. The neurobiology behind these effects, however, remains unclear. The basal ganglia are proposed to be important regions in the pathogenesis of psychomotor symptoms in depression. Since ECT can trigger neuroplasticity in these subcortical nuclei, we speculate that ECT-induced volumetric changes of the basal ganglia will positively influence psychomotor symptoms. METHODS: Psychomotor symptoms were analyzed in 17 patients with severe depression before and after an acute ECT course using a CORE assessment of the retardation, agitation, and non-interaction domains. The volumes of the caudate, putamen, pallidum, and accumbens regions were determined using magnetic resonance imaging one week before and after ECT. RESULTS: Psychomotor functions had improved significantly after ECT and significant volume increases were found for the accumbens region, the putamen, and pallidum. The volume increase of the nucleus accumbens correlated with an improvement of psychomotor retardation, while the volume increase of the pallidum correlated negatively with an improvement of the agitation subscore. CONCLUSION: Our findings support the notion of an association between the impact of ECT on depression-related psychomotor symptoms and volume increases of the accumbens region and pallidum, pointing to the importance of the basal ganglia in the therapeutic effect of ECT on psychomotor functioning.

Do patients from the Democratic Republic of Congo with schizophrenia have facial emotion recognition deficits?

Patients with schizophrenia can have difficulty recognizing emotion, and the impact of this difficulty on social functioning has been widely reported. However, earlier studies did not thoroughly explore how this deficit may vary according to emotion intensity, or how it may differ among individuals and across cultures. In the present study, our aim was to identify possible deficits in facial emotion recognition across a wide range of emotions of different intensities among patients with schizophrenia from the Democratic Republic of Congo (DRC). Thirty stable patients with schizophrenia and 30 healthy controls matched for age and level of education were evaluated using a validated and integrative facial emotion recognition test (TREF). A total recognition score and an intensity threshold were obtained for each emotion. Patients with schizophrenia had emotion recognition deficits, particularly for negative emotions. These deficits were correlated to the severity of negative symptoms. Patients showed no threshold deficit at the group level, but analysis of individual profiles showed marked heterogeneity across patients for the intensity of the emotion decoding deficit. Our study confirms the existence of deficits in emotion recognition for negative emotions in patients with schizophrenia, generalizes it to DRC patients, and underlines considerable heterogeneity among patients.

Imbalance between abstract and concrete repetitive thinking modes in schizophrenia.

OBJECTIVE: Repetitive thoughts can be divided in two modes: abstract/analytic (decontextualized and dysfunctional) and concrete/experiential (problem-focused and adaptive). They constitute a transdiagnostic process involved in many psychopathological states but have received little attention in schizophrenia, as earlier studies only indexed increased ruminations (related to dysfunctional repetitive thoughts) without jointly exploring both modes. This study explored the two repetitive thinking modes, beyond ruminations, to determine their imbalance in schizophrenia. METHODS: Thirty stabilized patients with schizophrenia and 30 matched controls completed the Repetitive Response Scale and the Mini Cambridge-Exeter Repetitive Thought Scale, both measuring repetitive thinking modes. Complementary measures related to schizophrenic symptomatology, depression and anxiety were also conducted. RESULTS: Compared to controls, patients with schizophrenia presented an imbalance between repetitive thinking modes, with increased abstract/analytic and reduced concrete/experiential thoughts, even after controlling for comorbidities. Schizophrenia is associated with stronger dysfunctional repetitive thoughts (i.e. abstract thinking) and impaired ability to efficiently use repetitive thinking for current problem-solving (i.e. concrete thinking). CONCLUSION: This imbalance confirms the double-faced nature of repetitive thinking modes, whose influence on schizophrenia's symptomatology should be further investigated. The present results also claim for evaluating these processes in clinical settings and for rehabilitating the balance between opposite repetitive thinking modes.

Facial decoding in schizophrenia is underpinned by basic visual processing impairments.

Schizophrenia is associated with a strong deficit in the decoding of emotional facial expression (EFE). Nevertheless, it is still unclear whether this deficit is specific for emotions or due to a more general impairment for any type of facial processing. This study was designed to clarify this issue. Thirty patients suffering from schizophrenia and 30 matched healthy controls performed several tasks evaluating the recognition of both changeable (i.e. eyes orientation and emotions) and stable (i.e. gender, age) facial characteristics. Accuracy and reaction times were recorded. Schizophrenic patients presented a performance deficit (accuracy and reaction times) in the perception of both changeable and stable aspects of faces, without any specific deficit for emotional decoding. Our results demonstrate a generalized face recognition deficit in schizophrenic patients, probably caused by a perceptual deficit in basic visual processing. It seems that the deficit in the decoding of emotional facial expression (EFE) is not a specific deficit of emotion processing, but is at least partly related to a generalized perceptual deficit in lower-level perceptual processing, occurring before the stage of emotion processing, and underlying more complex cognitive dysfunctions. These findings should encourage future investigations to explore the neurophysiologic background of these generalized perceptual deficits, and stimulate a clinical approach focusing on more basic visual processing.

Attentional impairments in Huntington's disease: A specific deficit for the executive conflict.

OBJECTIVE: Huntington's disease (HD) is characterized by motor and cognitive impairments including memory, executive, and attentional functions. However, because earlier studies relied on multidetermined attentional tasks, uncertainty still abounds regarding the differential deficit across attentional subcomponents. Likewise, the evolution of these deficits during the successive stages of HD remains unclear. The present study simultaneously explored 3 distinct networks of attention (alerting, orienting, executive conflict) in preclinical and clinical HD. METHOD: Thirty-eight HD patients (18 preclinical) and 38 matched healthy controls completed the attention network test, an integrated and theoretically grounded task assessing the integrity of 3 attentional networks. RESULTS: Preclinical HD was not characterized by any attentional deficit compared to controls. Conversely, clinical HD was associated with a differential deficit across the 3 attentional networks under investigation, showing preserved performance for alerting and orienting networks but massive and specific impairment for the executive conflict network. This indexes an impaired use of executive control to resolve the conflict between task-relevant stimuli and interfering task-irrelevant ones. CONCLUSION: Clinical HD does not lead to a global attentional deficit but rather to a specific impairment for the executive control of attention. Moreover, the absence of attentional deficits in preclinical HD suggests that these deficits are absent at the initial stages of the disease. In view of their impact on everyday life, attentional deficits should be considered in clinical contexts. Therapeutic programs improving the executive control of attention by neuropsychology and neuromodulation should be promoted. (PsycINFO Database Record

Dissociating emotional and cognitive empathy in pre-clinical and clinical Huntington's disease.

Huntington's disease (HD) is centrally characterized by motor, neurocognitive and psychiatric symptoms, but impaired emotional decoding abilities have also been reported. However, more complex affective abilities are still to be explored, and particularly empathy, which is essential for social relations and is impaired in various psychiatric conditions. This study evaluates empathic abilities and social skills in pre-clinical and clinical HD, and explores the distinction between two empathy sub-components (emotional-cognitive). Thirty-six HD patients (17 pre-clinical) and 36 matched controls filled in the Empathy Quotient Scale, while controlling for psychopathological comorbidities. At the clinical stage of HD, no global empathy impairment was observed but rather a specific deficit for the cognitive sub-component, while emotional empathy was preserved. A deficit was also observed for social skills. Pre-clinical HD was not associated with any empathy deficit. Emotional deficits in clinical HD are thus not limited to basic emotion decoding but extend towards complex interpersonal abilities. The dissociation between impaired cognitive and preserved emotional empathy in clinical HD reinforces the proposal that empathy subtypes are sustained by distinct processes. Finally, these results underline the extent of distinct affective and social impairments in HD and the need to grasp them in clinical contexts.

A comparative study between cognitive impairments of adults with schizophrenia and children with psychotic spectrum disorders: a literature review.

BACKGROUND: Cognitive impairments have been extensively reported for patients suffering from schizophrenia but a lot of questions persist about these troubles. Several domains of cognitive functions are impaired which result in daily life difficulties. Many arguments tend to show that children suffering from psychotic spectrum disorders present cognitive impairments also but things are not clearly defined. The aim of this review is to compare the cognitive impairments of children suffering from psychotic symptoms and adults suffering from schizophrenia in order to improve the understanding of the two clinical affections. A better understanding of the disease is necessary to improve the health care which currently give poor results. SUBJECTS AND METHODS: Besides the Diagnostic and Statistical Manual (DSM-5) and the French reference books, the present research has been conducted using PubMed, Medline, PsycINFO, PsycARTICLES and ScienceDirect. Literature about cognitive impairments of adults with schizophrenia and children with psychotic spectrum disorders is assessed and results are compared. RESULTS: Both children and adults suffer from cognitive impairments: language, memories, executive and motor functions and IQ are impaired. An important heterogeneity in the troubles has been observed and a poor knowledge in terms of onset time, evolution, intensity, impact on everyday life and therapeutic interest has been reported. CONCLUSION: Adults with schizophrenia and children suffering from psychotic spectrum disorders have similar cognitive impairments in many domains of cognition. The similarities in term of cognitive impairments highlighted in the present work should support new studies in order to adapt to children the current cognitive therapies which are mostly provided to adults. As the cognitive impairments are heterogeneous, each patient should receive a tailored neurocognitive exam which takes into account its abilities and weaknesses.

Facial, vocal and musical emotion recognition is altered in paranoid schizophrenic patients.

Disturbed processing of emotional faces and voices is typically observed in schizophrenia. This deficit leads to impaired social cognition and interactions. In this study, we investigated whether impaired processing of emotions also affects musical stimuli, which are widely present in daily life and known for their emotional impact. Thirty schizophrenic patients and 30 matched healthy controls evaluated the emotional content of musical, vocal and facial stimuli. Schizophrenic patients are less accurate than healthy controls in recognizing emotion in music, voices and faces. Our results confirm impaired recognition of emotion in voice and face stimuli in schizophrenic patients and extend this observation to the recognition of emotion in musical stimuli.

What is important in being cured from: does discordance between physicians and patients matter? (2).

AIMS: The influence of discordance in what is important in being cured from depression on clinical outcome at 6 months, assessed with a divergence index. METHODS: 304 outpatients treated for depression by general practitioners or by psychiatrists and completing a 6-month treatment period: a divergence index (divergence between physician and patient view on what is important in being cured from depression) was calculated for each physician-patient pair. The relation between this index and outcome at 6 months was analyzed (including depressive, anxious and somatic symptom severity, positive effect, functional impairment and quality of life (psychological and social relations). RESULTS: Response rates (50% improvement) were 65.9% for depressive symptomatology and 46.2% for anxious symptomatology. The subgroup with a poor physician-patient agreement (highest quartile) on expectations had a worse clinical outcome than the subgroup with an excellent physician-patient agreement (lowest quartile): differences in response rate between these groups ranged from 9% to 27%; this difference reached statistical significance for 3 outcome variables (anxiety, positive effect and social relationships). CONCLUSIONS: The study shows that outcomes with standard antidepressant drugs are still suboptimal and that discordance between what patients׳ and physicians׳ consider important in the definition of cure from depression significantly influences clinical outcomes at 6 months.

What is important in being cured from depression? Discordance between physicians and patients (1).

AIMS: The comparison of what physicians and patients consider important in being cured from depression. METHODS: 426 outpatients (in primary care and in psychiatric care) with a clinical diagnosis of major depression were included: at the start of antidepressant treatment, the importance of a range of items for being cured from depression (depressive, anxious and somatic symptoms, positive affect, functional impairment, quality of life) was assessed in physicians and patients separately and a ranking was made; after 3 months of treatment, the importance of these items for being cured from depression was re-assessed in the patients. RESULTS: The items ranked top 10 by physicians mainly contain depressive symptoms while those ranked top 10 by patients mainly contain positive affect items and this attention to positive affect even increases at 3 months follow-up and is higher in patients with recurrent depression than in patients with a first episode of depression. Somatic symptoms consistently get the lowest ranking, as well in physicians as in patients. CONCLUSIONS: Physicians differ significantly from patients in what they consider important for 'being cured from depression': physicians mainly focus on alleviation of depressive symptoms while patients mainly focus on the restoration of positive affect.

Enhanced high harmonic generation driven by high-intensity laser in argon gas-filled hollow core waveguide.

We show that a significant enhancement of the photon flux produced by high harmonic generation can be obtained through guided configuration at high laser intensity largely above the saturation intensity. We identify two regimes. At low pressure, we observe an intense second plateau in the high harmonic spectrum in argon. At relatively high pressure, complex interplay between strongly time-dependent ionization processes and propagation effects leads to important spectral broadening without loss of spectral brightness. We show that the relevant parameter for this physical process is the product of laser peak power by gas pressure. We compare source performances with high harmonic generation using a gas jet in loose focusing geometry and conclude that the source developed is a good candidate for injection devices such as seeded soft x-ray lasers or free electron lasers in the soft x-ray range.