Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients.

OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. METHODS: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. CONCLUSION: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

Indirect effect of impulsivity on suicide risk through self-esteem and depressive symptoms in a population with treatment-resistant depression: A FACE-DR study.

INTRODUCTION: Suicide is a major health issue. Its prevalence is particularly high in subjects presenting major depression disorder (MDD), making this a key suicide-related risk factor. Suicide attempts in severe forms of MDD were assumed to be linked to impulsivity and loss of control. Nevertheless, we failed to find data specifically investigating the link between impulsivity and suicide risk in treatment-resistant depression (TRD). This study seeks to review this relationship. METHOD: Patients were recruited for a prospective cohort. Suicide risk and impulsivity were assessed using the International Neuropsychiatric Interview and Barratt Impulsiveness Scale, Version 10, respectively, while the severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale, anxiety with the State-Trait Anxiety Inventory and childhood maltreatment using the Childhood Trauma Questionnaire. RESULTS: 220 TRD patients were enrolled in the study. The impulsivity score was correlated with self-esteem, marital status, professional status and anxiety. There was no direct link to suicide risk. However, impulsivity was associated with self-esteem (coefficient: -0.24; p value 0.043) and depressive symptom severity (coefficient: 0.; p value 0.045). The suicide risk was significantly correlated with depressive symptom severity (coefficient = 0.38, p < 0.001) and self-esteem (coefficient = -0.34, p = 0.01). Considering these correlations, we postulated that the effect of impulsivity on suicide risk could be mediated by self-esteem in terms of depressive symptom severity and we finally found a relevant mediation model within impulsivity having an indirect effect on suicide risk by impacting self-esteem and depressive symptoms with anxiety also playing a significant role as a covariable. CONCLUSION: We found that impulsivity could play an indirect role with the involvement of self-esteem and depressive symptoms and the contributing role of anxiety.

Evolution of Cognitive Impairments in Treatment-Resistant Depression: Results from the Longitudinal French Centers of Expertise for Treatment-Resistant Depression (FACE-DR) Cohort.

Previous studies set out profound cognitive impairments in subjects with treatment-resistant depression (TRD). However, little is known about the course of such alterations depending on levels of improvement in those patients followed longitudinally. The main objective of this study was to describe the course of cognitive impairments in responder versus non-responder TRD patients at one-year follow-up. The second aim was to evaluate the predictive aspect of cognitive impairments to treatment resistance in patients suffering from TRD. We included 131 patients from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centers. They undertook comprehensive sociodemographic, clinical, global functioning, and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16) at baseline (V0) and one-year follow-up (V1). Most patients (n = 83; 63.36%) did not respond (47 women, 49.47 ± 12.64 years old), while one-third of patients responded (n = 48, 30 women, 54.06 ± 12.03 years old). We compared the cognitive performances of participants to average theoretical performances in the general population. In addition, we compared the cognitive performances of patients between V1 and V0 and responder versus non-responder patients at V1. We observed cognitive impairments during the episode and after a therapeutic response. Overall, each of them tended to show an increase in their cognitive scores. Improvement was more prominent in responders at V1 compared to their non-responder counterparts. They experienced a more marked improvement in code, digit span, arithmetic, similarities, and D2 tasks. Patients suffering from TRD have significant cognitive impairments that persist but alleviate after therapeutic response. Cognitive remediation should be proposed after therapeutic response to improve efficiency and increase the daily functioning.

Long-term benzodiazepine prescription in treatment-resistant depression: A national FACE-TRD prospective study.

BACKGROUND: Benzodiazepine long-term use (BLTU) is a public health challenge. We lack data on the consequences of LBTU on the trajectory of treatment-resistant depression (TRD). OBJECTIVE: To determine the prevalence of BLTU in a nationwide non-selected population of patients with TRD, to determine the rate of patients succeeding at withdrawing benzodiazepines at one year and to determine if persistent BLTU is associated with poorer mental health outcomes. METHOD: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at one year. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at one year. RESULTS: At baseline, 45.2% of the patients were classified in the BLTU group. In multivariate analysis, compared to patients without BLTU, patients with BLTU were more frequently classified in the "low physical activity" group (adjusted odds ratio (aOR) = 1.885, p = 0.036), and had higher primary healthcare consumption (B = 0.158, p = 0.031) independently of age, sex and antipsychotic consumption. We found no significant difference for personality traits, suicidal ideation, impulsivity, childhood trauma exposure, earlier age at first major depressive episode, anxiety and sleep disorders (all p > 0.05). Despite recommendations for withdrawal, <5% of BLTU patients withdraw benzodiazepines during the one-year follow-up. Persistent BLTU at one-year was associated with higher depression severity (B = 0.189, p = 0.029), higher clinical global severity (B = 0.210, p = 0.016), higher state-anxiety (B = 0.266, p = 0.003), impaired sleep quality (B = 0.249, p = 0.008), increased peripheral inflammation (B = 0.241, p = 0.027), lower functioning level (B = -0.240, p = 0.006), decreased processing speed (B = -0.195, p = 0.020) and verbal episodic memory (B = -0.178, p = 0.048), higher absenteeism and productivity loss (B = 0.595, p = 0.016) and lower subjective global health status (B = -0.198, p = 0.028). CONCLUSION: Benzodiazepines are over-prescribed in TRD (in almost a half of the patients). Despite recommendations for withdrawal and psychiatric follow-up, <5% of patients successfully stopped taking benzodiazepines at one-year. Maintaining BLTU may contribute to the worsening of clinical and cognitive symptoms and of daily functioning in TRD patients. Progressive and planed withdrawal of benzodiazepines seems therefore strongly recommended in TRD patients with BLTU. Pharmacological and non-pharmacological alternatives should be promoted when possible.

Diurnal symptoms of sleepiness and dysfunction predict future suicidal ideation in a French cohort of outpatients (FACE-DR) with treatment resistant depression: A 1-year prospective study about sleep markers.

BACKGROUND: Patients suffering from treatment-resistant depression (TRD) are at risk of suicide. Sleep and circadian rhythm alterations are widely recognized as core symptoms of major depressive disorder and are associated with suicidal ideation. Thus, sleep and circadian rhythm alterations may be targeted to prevent suicide. METHODS: Patients were recruited from a prospective cohort of the French network of TRD expert centers. Mood, sleep and circadian rhythms were assessed at baseline; suicidal risk was assessed both at baseline and during a one-year follow-up with standardized subjective questionnaires. RESULTS: Excessive daytime sleepiness (adjusted odds ratio aOR = 1.7(1-3.3), p = 0.04) and daytime dysfunction (aOR = 1.81(1.16-2.81), p = 0.0085) increased the risk of suicidal thoughts over the one-year follow-up period in patients with TRD after adjustment on age, gender, depression, trauma, anxiety, impulsivity, current daily tobacco smoking and body mass index. Hypnotics intake is associated with a reduced risk of suicidal ideation at one-year follow-up after the same adjustments (OR = 0.73(0.56-0.95), p = 0.019). Other associations between sleep quality or circadian rhythms and suicidal ideations at either baseline or one year did not remain significant in multivariate analyses after the same adjustments. LIMITATIONS: Sleep assessments were based on self-reported questionnaires rather than objective measures. CONCLUSIONS: Daytime sleepiness and dysfunction are predictors of suicidal ideations, whereas hypnotics intake is associated with a reduced risk of suicidal ideations. Diurnal symptoms of sleep disturbances are therefore red flags to target for preventing suicide in depressed patients, and hypnotics seem efficient in preventing suicide for patients with TRD.

Inflammatory biomarkers associated with depression, anxiety, and/or fatigue in primary Sjögren's syndrome – a systematic review

Background and objectivesFatigue, depression, and anxiety are common burdens present in primary Sjögren's syndrome patients. Those symptoms have all been linked to inflammatory dysregulations. To explore the link between inflammatory biomarkers and fatigue, depression, and anxiety in pSS patients, we aim to do a systematic literature review.MethodsThe systematic review protocol and data extraction forms were designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our protocol has been registered on Prospero (ID CRD42020161952). The Cochrane Library, PubMed, Scopus, and PsycInfo were used, from inception to December 2019.ResultsThe literature search initially identified 445 articles. Finally, 12 articles were included in this systematic review. The population in studies was quite similar with mainly middle-aged women. Dates of publication extended from 2008 to 2019. Different scales were used to measure fatigue, depression, and/or anxiety. Measured inflammatory biomarkers were very diverse across studies. In consequence, results in the different included studies were disparate. Only one study explored the link between depression/anxiety and inflammatory markers: patients with depression and/or anxiety were compared to pSS patients.ConclusionEven if the association between fatigue, depression, and/or anxiety with inflammatory markers in pSS is of interest, there are a lot of discrepancies. Sickness behavior and IFN pathways seem to be important in the inflammatory physiopathology of fatigue in pSS, and interest in depression. It also appears crucial to standardize clinical scales, inflammatory blood, and CSF tests in pSS patients to allow better generalization. (AU)

Recommendations of the treatment-resistant depression expert center network for promoting tobacco smoking cessation based on the results from the real-world FACE-TRD national cohort.

BACKGROUND: Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. OBJECTIVE: To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. METHOD: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. RESULTS: 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. INTERPRETATION: Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed.

Occurrence of Side Effects in Treatment-Resistant Depression: Role of Clinical, Socio-Demographic and Environmental Characteristics.

Introduction: Treatment-resistant depression (TRD) is a disabling psychiatric condition characterized by the failure of two antidepressants (ADs). Since the occurrence of side effects (SEs) appears to be one of the main determinants of early discontinuation of pharmacological treatments contributing to a pseudo-resistance, the purpose of this study was to determine the parameters associated with the occurrence of SEs under ADs in a cohort of patients with TRD. Methods: An observational, cross-sectional, multicentre study was carried out using data from the French network of Expert Centers for TRD. For the 108 patients enrolled in the study, the statistical analyses focused on the overall occurrence and on the profile of the SEs (9 categories, 32 items). Results: SEs were influenced by age and sex and were positively associated with the intensity of anxious, depressive and suicidal symptoms, a history of childhood trauma (sexual abuse, emotional abuse and neglect), and negatively associated with self-esteem, and assessment of overall functioning. Conclusion: Using variables accessible in common practice, these results fall within the dynamic of a more tailored approach to medicine that could allow, through integrated pharmacological management, the continuation of antidepressant treatments, and therefore limit the risk of therapeutic failure.

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population.

INTRODUCTION: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample. METHODS: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres. RESULTS: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0-30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (ß = 0.274; p = 0.07) and QIDS-SR (ß = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (ß = 0.304; p = 0.03) and QIDS-SR (ß = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly's Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect. CONCLUSION: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.

Childhood Trauma increases suicidal behaviour in a treatment-resistant depression population: a FACE-DR report.

OBJECTIVE: In addition to heredity, exposure to early-life adversity is an important predisposing risk factor of suicidal behaviour. Although the association between Childhood Trauma (CT) and suicide risk is well documented, interactions between CT and suicidal behaviour in Treatment-Resistant Depression (TRD) populations have received little coverage. This study aimed to evaluate i) association between CT and suicidal behaviour in a TRD population, and ii) the role of personality traits and impulsiveness as potential factors of mediation in these associations. METHODS: Patients were recruited from a cohort of the French network of TRD expert centers. Depressive symptom severity, CT, suicidal behaviour, personality traits, and impulsiveness were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Childhood Trauma Questionnaire (CTQ), the Columbia Suicide Severity Rating Scale (CSSRS), the Structured Clinical Interview for DSM-IV, the Big Five Inventory, and the Barratt Impulsivness Scale (BIS) respectively. RESULTS: Among the 256 patients with a baseline CTQ, in relation to suicide risk for the current depressive episode, we found an association with the total CTQ scores mediated by the intensity of the current episode in a model adjusted for age and sex (total effect: ß = 0.171; p = 0.011, direct effect: ß = 0.135; p = 0.043; indirect effect: ß = 0.036; p = 0.048). Focusing on CT subtypes, we detected an association between suicide risk and physical neglect in a model adjusted for age and sex (ß = 0.301; p = 0.002), without any mediation by the intensity of the current episode. There was no mediation effect from personality traits nor impulsiveness. With regards to CSSRS to assess suicidal ideation, we did not find any association with the total CTQ score and CT subtype scores. CONCLUSION: We report a strong association between suicidal behaviour and CT (in particular childhood physical neglect) in a TRD population.

Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study.

BACKGROUND: As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention. METHODS: For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion. RESULTS: Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment. CONCLUSIONS: The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.

Treatment-Resistant Depression in a Real-World Setting: First Interim Analysis of Characteristics, Healthcare Resource Use, and Utility Values of the FondaMental Cohort.

BACKGROUND: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes. METHODS: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery-Åsberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status. RESULTS: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, p < 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states. CONCLUSION: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.

Childhood maltreatment and clinical severity of treatment-resistant depression in a French cohort of outpatients (FACE-DR): One-year follow-up.

BACKGROUND: Childhood maltreatment is associated with major depressive disorder (MDD). It not only increases the risk of lifetime MDD, but it also aggravates its course. Among depressed patients, 20-30% of them experience treatment-resistance depression (TRD). We aimed to assess the association between childhood maltreatment, severity of depression in a unipolar TRD sample, and patient outcomes after one-year of follow-up. METHODS: Patients were recruited for a prospective cohort from the French network of TRD expert centers. Depressive symptom severity was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology self-report (QIDS-SR). Childhood maltreatment was evaluated with the Childhood Trauma Questionnaire (CTQ). RESULTS: In total, 256 patients filled in the CTQ at baseline between 2012 and 2019. At baseline, the MADRS score was associated with CTQ score (ß = .185; p = .004). QIDS was also associated with CTQ scores (ß = .27; p < .001). Regarding the different subtypes of childhood maltreatment, MADRS was associated with physical (ß = .21; p = .005) and sexual abuse (ß = .22; p = .002), while QIDS with physical abuse (ß = .304; p < .001) and physical neglect (ß = .254; p < .001). However, we did not find any significant association focusing on the other types of traumas. During a 1-year follow-up focusing on remission, CTQ scores (baseline) were less important in remittent patients [n = 38; CTQ score = 39.26 (9.68)] than in nonremittent ones [n = 92; CTQ score = 46.02 (17.53)] (p = .027). There was no significant difference among remitters and nonremitters based on trauma subtypes. At baseline, CTQ scores had a significant influence on remission at 1 year (χ2 (1) = 5.57; p < .05). We lost this influence adding MADRS scores at baseline in the model (p = .063). CONCLUSION: We highlighted a significant association between the severity of depressive disorders and childhood maltreatment in the TRD population. Information about a history of childhood maltreatment helps in identifying individuals who could be less likely to go into remission after treatment.

Prevalence of Metabolic Syndrome and Associated Factors in a Cohort of Individuals With Treatment-Resistant Depression: Results From the FACE-DR Study.

BACKGROUND: The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its components in a cohort of French patients with treatment-resistant depression (TRD) and to determine correlations with sociodemographic, clinical, and treatment-related factors. METHODS: From 2012 to 2018, 205 patients who met DSM-IV criteria for major depressive episode with moderate-to-severe symptoms (Montgomery-Asberg Depression Rating Scale score ≥ 20), and at least Stage II resistance according to Thase and Rush criteria were enrolled in the FondaMental Advanced Centers of Expertise in Resistant Depression (FACE-DR) cohort. Data on sociodemographic and clinical characteristics, lifestyle information, and treatment and comorbidities were collected, and a blood sample was drawn. MetS was defined according to the criteria of the International Diabetes Federation. RESULTS: Overall, 38% of individuals with TRD met criteria for MetS. The frequency of MetS was significantly higher in men than in women only for patients aged 40 years or older (46.3% vs 35.2%, P = .0427). Moreover, whereas the management for diabetes was good, less than one-third of the patients with high blood pressure or dyslipidemia were treated for these conditions. Multivariate analysis showed that individuals with abnormal plasma c-reactive protein levels had a 3-fold increased risk (95% CI, 1.5-5.2) of having MetS, independent of other potential confounders. CONCLUSION: The prevalence of MetS is higher in patients with TRD than in those with other psychiatric disorders and characterized by a considerable undertreatment of some components of MetS in this population. Diagnosis and treatment of the components of MetS should be systematically performed to prevent the occurrence of cardiovascular diseases in patients with TRD. These findings highlight the need for integrated care, with more interaction and coordination between psychiatrists and primary care providers.

Significant Need for a French Network of Expert Centers Enabling a Better Characterization and Management of Treatment-Resistant Depression (Fondation FondaMental).

BACKGROUND: Major depression is characterized by (i) a high lifetime prevalence of 16-17% in the general population; (ii) a high frequency of treatment resistance in around 20-30% of cases; (iii) a recurrent or chronic course; (iv) a negative impact on the general functioning and quality of life; and (v) a high level of comorbidity with various psychiatric and non-psychiatric disorders, high occurrence of completed suicide, significant burden along with the personal, societal, and economic costs. In this context, there is an important need for the development of a network of expert centers for treatment-resistant depression (TRD), as performed under the leadership of the Fondation FondaMental. METHODS: The principal mission of this national network is to establish a genuine prevention, screening, and diagnosis policy for TRD to offer a systematic, comprehensive, longitudinal, and multidimensional evaluation of cases. A shared electronic medical file is used referring to a common exhaustive and standardized set of assessment tools exploring psychiatric, non-psychiatric, metabolic, biological, and cognitive dimensions of TRD. This is paralleled by a medico-economic evaluation to examine the global economic burden of the disease and related health-care resource utilization. In addition, an integrated biobank has been built by the collection of serum and DNA samples for the measurement of several biomarkers that could further be associated with the treatment resistance in the recruited depressed patients. A French observational long-term follow-up cohort study is currently in progress enabling the extensive assessment of resistant depressed patients. In those unresponsive cases, each expert center proposes relevant therapeutic options that are classically aligned to the international guidelines referring to recognized scientific societies. DISCUSSION: This approach is expected to improve the overall clinical assessments and to provide evidence-based information to those clinicians most closely involved in the management of TRD thereby facilitating treatment decisions and choice in everyday clinical practice. This could contribute to significantly improve the poor prognosis, the relapsing course, daily functioning and heavy burden of TRD. Moreover, the newly created French network of expert centers for TRD will be particularly helpful for a better characterization of sociodemographic, clinical, neuropsychological, and biological markers of treatment resistance required for the further development of personalized therapeutic strategies in TRD.

[Acute and transient psychotic disorder at the onset of schizophrenia]. / La bouffée délirante aiguë au début de la schizophrénie.

Although the mode of onset of schizophrenia can be acute, it is important to remember that the disorder rarely starts as a "clap of thunder in a quiet sky", and that it is more often gradual and insidious, with negative and affective symptoms. Acute and transient psychotic disorder, on the other hand, is a short delusional episode forming suddenly and lasting a few days, sometimes a few hours. Schizophrenic evolution forms only part of the possible evolutions. It is therefore necessary to disassociate acute and transient psychotic disorder from schizophrenic disorders, which gives a wrong representation of the onset of schizophrenia.

Evaluation of GPs diagnostic knowledge and treatment practice in detection and treatment of early schizophrenia: a French postal survey in Brittany.

AIMS: Evaluating French general practitioners (GPs) diagnostic knowledge and practice in the detection and treatment of early schizophrenia as well as needs and preferences with specialist services. METHODS: A postal survey comprising 27 questions was conducted among 2,039 GPs from three counties of Western France. Composite scores were calculated to determine a level of diagnostic knowledge. RESULTS: A total of 515 GPs (25.3%) responded to the survey. The mean score to determine a level of knowledge on the most important aspects in detecting early stages of schizophrenia was 5.3 ± 2.50 [median = 6 (range 0-10)]. The mean score to determine the overall knowledge of schizophrenia was 8.1 ± 2.98 [median = 8 (range 1-16)]. The majority of surveyed GPs (76.1%) would treat early schizophrenia pharmacologically. A majority of GPs (53.9%) advise an insufficient duration of anti-psychotic treatment for first episode psychosis. The vast majority (90.8%) were in favour of a specialized outpatient service. CONCLUSIONS: French GPs tend to have a deficit in diagnostic knowledge and practice in detection and treatment of early schizophrenia. It seems important to provide GPs with continuing medical education (CME) on detection and management of early schizophrenia and to set up relevant specialized outpatient services.

[Towards early diagnosis of schizophrenia]. / Vers un diagnostic précoce de la schizophrénie.

Schizophrenia is a serious, chronic illness which, when treated early, can result in a better prognosis. The putting in place of treatment is often delayed because it is difficult to identify early schizophrenic disorders. At this stage of the illness, the doctor participates as much as the family and the patients themselves in the delay of the diagnosis. In order to encourage early diagnosis of people with schizophrenia, Brest regional university hospital has created a specialised consultation.