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Functional recovery is a treatment goal that goes beyond symptomatic remission and encompasses multiple aspects of schizophrenia patients’ lives, including quality of life, physical, and mental functioning. There is evidence that long-acting injectable (LAI) treatments promote adherence and reduce rehospitalisation and functional decline, which could facilitate patients’ ability to reach functional recovery. Despite this, LAIs are underused in the first-episode (FEP) and early-phase (EP) patient population, due to physician hesitancy and concerns around stigma. A Delphi panel was held to gain expert consensus on an approach to the domains and assessment of functional recovery elements in FEP and EP schizophrenia patients.A literature review and input from a steering committee of 5 experts in psychiatry informed statements development for a three-round modified Delphi process. Round one was conducted via one-to-one video conference interviews, and the successive rounds were conducted via electronic surveys, which enabled international collaboration. Statements on the different domains and assessment for functional recovery were presented to 17 psychiatrists, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK), experienced in the treatment of schizophrenia with LAIs. Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists look at their previous responses in the context of the overall group.A consensus was reached (defined a priori as ≥80% agreement) on all 27 statements covering the dimensions, assessment, and level of achieved functional recovery for FEP and EP patients. The following domains are important to consider when assessing functional recovery: depression, aggressive behaviour, social interaction, family functioning, education/employment, sexual functioning, and leisure activities. Additionally, panellists reached consensus that dimensions should be minimally impairing, if present (excluding sexual functioning) and asked about at every encounter with the patient (excluding sexual functioning and leisure activities). In summary, this Delphi panel yielded agreement that functional recovery is multidimensional and should be assessed regularly as part of usual care on an individual patient level in FEP and EP schizophrenia patients.FundingLundbeck Otsuka Alliance

Schizophrenia is among the top ten causes of years lost due to disability. Goals of treatment are evolving beyond remission of psychotic symptoms to include physical and mental functioning, quality of life, and long-term functional recovery. Evidence has shown long-acting injectables (LAIs) are beneficial for schizophrenia patients by increasing treatment adherence and decreasing relapse and rehospitalisation. This potentially reduces disease progression and facilitates functional recovery. However, LAIs are underused and often seen as a last resort for first-episode (FEP) and early-phase (EP) patients, due to physicians’ lack of familiarity and stigma.A three-round modified Delphi panel was held to gain expert consensus on an approach to functional recovery in FEP and EP patients with LAIs. A literature review and input from a steering committee of 5 experts in psychiatry informed the development of statements. Round one was carried out via one-to-one video conference interviews, and the subsequent rounds were conducted via electronic surveys, which enabled international collaboration. Delphi panellists were 17 psychiatrists with schizophrenia treatment experience, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK). Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendencies (mode, mean) and variability (interquartile range) of aggregated responses from the previous round were reported to panelists to understand their response in relation to the group.There was consensus (defined a priori as ≥80% agreement) on the 8 statements relating to long-term treatment goals and LAI links to functional recovery. LAI treatment in FEP and EP patients increases adherence and reduces treatment burden and functional decline compared to the same and other oral medication. Additionally, there was consensus that LAIs lead to better treatment outcome and functional recovery. Other important factors to achieving functional recovery include patient attitude towards treatment and psychoeducation. Furthermore, consensus was reached that functional recovery and quality of life are linked. In summary, this Delphi panel yielded agreement that functional recovery is a reachable goal for FEP and EP patients and can be enhanced using LAIs.FundingLundbeck Otsuka Alliance

BackgroundThe Leuven Affect and Pleasure Scale (LAPS) was developed as an outcome measure in major depressive disorder (MDD) tha treflects patient treatment expectations. The present report investigates whether the LAPS negative affect, the LAPS positive affect, and the LAPS hedonic tone have added value on top of the Hamilton Depression Rating Scale (HAMD) in explaining generic as well as patient-centered outcomes.MethodsA total of 109 outpatients with Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for MDD were assessed over 8 weeks of antidepressant treatment. At baseline and after 2, 4, and 8 weeks, the LAPS, HAMD, Snaith–Hamilton Pleasure Scale (SHAPS), Positive and Negative Affect Scale (PANAS), and Sheehan Disability Scale were administered. The Clinical Global Impression of Improvement (CGI-I) and the Patient Global Impression of Improvement (PGI-I) were also administered at endpoint.ResultsChanges in LAPS negative affect, LAPS positive affect, and LAPS hedonic tone explain 14% of the additional variance in CGI-I, 21% in PGI-I, 37% in cognitive functioning, 32% in overall functioning, 31% in “my life is meaningful,” and 45% in “I feel happy.” Compared to standard scales (PANAS and SHAPS), the LAPS negative affect, LAPS positive affect, and LAPS hedonic tone differentiate better between different levels of CGI-I or PGI-I.ConclusionsThe LAPS has added value (on top of the HAMD) in explaining changes in both generic outcomes (CGI-I/PGI-I) and patient-centered dimensions. The LAPS negative and positive affects and the LAPS hedonic tone differentiate CGI-I and PGI-I scores better than corresponding scales supposed to cover the same domains.

Objectives:Poststroke depression (PSD) is a public health issue, affecting one-third of stroke survivors, and is associated with multiple negative consequences. Reviews tried to identify PSD risk factors with discrepant results, highlighting the lack of comparability of the analyzed studies. We carried out a meta-analysis in order to identify clinical risk factors that can predict PSD.Design:PubMed and Web of Science were searched for papers. Only papers with a strictly defined Diagnostic and Statistical Manual of Mental Disorders depression assessment, at least 2 weeks after stroke, were selected. Two authors independently evaluated potentially eligible studies that were identified by our search and independently extracted data using standardized spreadsheets. Analyses were performed using MetaWin®, the role of each variable being given as a risk ratio (RR).Results:Eighteen studies were included in the meta-analysis. Identified risk factors for PSD with RR significantly above 1 were previous history of depression (RR 2.19, confidence interval (CI) 1.52–3.15), disability (RR 2.00, CI 1.58–2.52), previous history of stroke (RR 1.68, CI 1.06–2.66), aphasia (RR 1.47, CI 1.13–1.91), and female gender (RR 1.35, CI 1.14–1.61). Fixed effects model leads to identification of two more risk factors: early depressive symptoms with an RR of 2.32 (CI 1.43–3.79) and tobacco consumption (RR 1.40, CI 1.09–1.81). Time bias was found for alcohol consumption. Sample size was significantly involved to explain the role of “alcohol consumption” and “cognitive impairment.”Conclusion:Five items were significantly predictive of PSD. It might be of clinical interest that depressive-related risk factors (such as past depressive episodes) were having the largest impact.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

Background:Applying the concept of burnout to medical students before residency is relatively recent. Its estimated prevalence varies significantly between studies. Our objective was to estimate the prevalence of burnout in medical students worldwide.Methods:We systematically searched Medline for English-language articles published between January 1, 2010 and December 31, 2017. We selected all the original studies about the prevalence of burnout in medical students before residency, using validated questionnaires for burnout. Statistical analyses were conducted using the OpenMetaAnalyst software.Results:Prevalence of current burnout was extracted from 24 studies encompassing 17,431 medical students. Among them, 8060 suffered from burnout and we estimated the prevalence to be 44.2% [33.4%–55.0%]. The information about the prevalence of each subset of burnout dimensions was given in nine studies including 7588 students. Current prevalence was estimated to be 40.8% for ‘emotional exhaustion’ [32.8%–48.9%], 35.1% [27.2%–43.0%] for ‘depersonalization’ and 27.4% [20.5%–34.3%] for ‘personal accomplishment’. There is no significant gender difference in burnout. The prevalence of burnout is slightly different across countries with a higher prevalence in Oceania and the Middle East than in other continents.Conclusions:The results of this meta-analysis suggest that one student out of two is suffering from burnout, even before residency. Again, our findings highlight the high level of distress in the medical population. These results should encourage the development of preventive strategies.

Background.Impaired decision-making is a potential neurocognitive phenotype of eating disorders. It is therefore important to disentangle the decision-making deficits associated with the eating disorder subtypes and determine whether this putative impairment is a state or trait marker of the disease or more related to starvation. We systematically reviewed the literature on decision-making in eating disorders and conducted a meta-analysis to explore its role in anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED).Method.A search of the Medline and EMBASE databases and article references was performed. A total of 23 studies (2044 participants) met the selection criteria. When the Iowa gambling task (IGT) was used in at least three of the studies, a meta-analysis was run.Results.IGT performance was significantly worse in patients with an eating disorder diagnosis (AN, BN or BED) compared with healthy controls, indicating that eating disorders have a negative effect on decision-making. Hedges’ g effect sizes were moderate to large (−0.72 in AN, −0.62 in BN, and −1.26 in BED). Recovered AN patients had IGT scores similar to those of healthy controls. Restrictive AN patients had significantly lower IGT net scores than purging AN patients, and both AN subtypes had worse performances than healthy controls. Age and body mass index did not explain results.Conclusions.Decision-making was significantly altered in patients with eating disorders. Poor decision-making was more pronounced during the acute phase than in the recovered state of AN. Nutritional status during the acute phase of the disease did not seem to influence decision-making skills.

Background:Older patients may be more vulnerable to the deleterious effect of depressive episodes on delayed narrative memory, a cognitive task which reflects hippocampal activity. We aimed to disentangle which factors could explain such increased vulnerability in the elderly, including the poorer response to treatment, a longer lifetime exposure to past depressive episodes, and lower baseline memory skills.Methods:From an initial sample of 8,229 depressed outpatients, we focused on the 2,424 treatment responders, and compared older (65 years old and over, N = 233) to younger (N = 2,191) ones. These patients were included through general practitioners’ assessment and tested for the Wechsler delayed paragraph recall index, a valid and sensitive test assessing verbal declarative memory (and a marker of the hippocampal function), at baseline and after six weeks of treatment.Results:As expected, older patients after response to antidepressants showed decreased narrative memory abilities compared to younger ones. As baseline memory performance and residual depressive symptoms were also found in excess in this sample, they could act as confounders. Indeed, after controlling for these two factors, the role of age in memory performance after treatment response was ruled out.Conclusions:The potential “toxicity” of a depressive episode to cognitive functions related to the hippocampus may not be more critical in older patients compared to younger ones. Limiting remaining depressive symptoms in older depressed patients might be a way to counteract the observed worsening of memory functions in depressed patients.

Symptomatic remission is often mentioned as one of the treatment goals for schizophrenia. However, the consistently with which this is documented in the schizophrenia literature since the introduction of the consensus criteria proposed by Andreasen and colleagues in 2005 has yet to be investigated. Similarly, additional treatment goals which are being discussed include improved functioning and quality of life, but whether these goals are being increasingly documented in the literature alongside symptomatic remission is as yet unknown. The objective of this article is therefore to review the use of the term ‘remission’ in the schizophrenia literature from Europe, USA and the rest of the world from 2002 to 2007, before and after the introduction of the Andreasen criteria. A second objective is to determine whether these manuscripts documenting symptomatic remission are also addressing other concepts such as functioning, quality of life and relationships. This literature review indicates that the use of the Andreasen criteria is indeed increasing, although there are manuscripts documenting alternative remission criteria or using the term remission without documentation of specific remission criteria. From 2004 to 2007 the number of manuscripts mentioning remission without documenting specific criteria has fallen by approximately 50%. Within these manuscripts there is increasing awareness of functioning and quality of life as outcome measures, in particular in manuscripts generated in Europe and the USA. This review highlights the growing importance of co-assessment of symptomatic remission and functional outcomes, and calls for further consideration of the most appropriate and consistent way to evaluate functioning of schizophrenia patients.

PurposeTo analyse factors associated with hospitalisation in patients with schizophrenia from four European countries, and to investigate whether national specificities might have an impact on the profile of inpatients.MethodA randomly selected sample of psychiatrists (N = 744), from Germany, Greece, Italy and Spain, collected data on the five last patients with schizophrenia they had seen in consultation (N = 3996).ResultsHigh positive symptoms, lack of insight, not living with the family, frequent past episodes, addiction to illegal drugs, global severity, uncooperativeness and smoking were significantly associated with hospitalisation, with OR between 4.1 and 1.26. Nevertheless, only high positive symptoms from the PANSS and lack of insight were systematically detected in the four countries. Among different results, the weight of “not living with the family” had national specificities, as Germany was the only country where this factor played no role (OR = 0.94).ConclusionAlthough some factors such as positive symptoms are associated with hospitalisation in a very homogenous way throughout different countries, discrepancies were detected between countries, for “living with the family”, “number of past acute relapses” and “uncooperativeness”. Linking these specificities to national healthcare systems might be useful to promote access to care for all patients.

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are the most common type of anxiety-mood comorbidity. Up to 80% of subjects with lifetime GAD also have a comorbid mood disorder during their lifetime. Many hypotheses have been raised to explain such high comorbidity. Pleiotropy, i.e. a single genetic mutation explains (apparently) different disorders, is one of them and is hereby reviewed. Importance and reliability of GAD and MDD comorbidity (1); Evidence in favour of co-aggregation of GAD and MDD within families (the risk of one disorder in a proband increasing the risk for the other in relatives) (2); substantial heredity for both disorders according to twin studies with evidence for genetic correlation of unity between the two disorders (3); existence of numerous mechanisms (4) potentially linking the two disorders to common vulnerability genes, are all in accordance with such a hypothesis. Some examples of potentially shared mechanisms (such as CRF dysregulation or abnormal transcription factors) and possible common vulnerability genes (for example, the serotonin transporter gene) are given to highlight the pleiotropy hypothesis.

A cross-sectional survey investigated the relationship between the number of previous depressive episodes and life events, testing the kindling hypothesis, in a sample of 13,377 treated patients with unipolar depression. A linear decline of average life events exposure is observed for more frequent past episodes, even when age, gender and severity are taken into account.

It has been proposed that depressive episodes could be “neurotoxic”, decreasing memory skills and/or regularly increasing neurocognitive retardation with the repetition of episodes. We describe two protocols which could reinforce the likelihood of this neurotoxic hypothesis, and a study showing that it is indeed possible to reduce the time before getting treatment response. On the first protocol a large sample of depressed outpatients was tested for narrative delayed memory (Weschleer paragraph), before and after antidepressant treatment (Gorwood et al., 2008). Delayed memory skills after treatment response was strongly correlated to the length and the number of past depressive episodes. The second protocol assessed neurocognitive retardation during a depressive episode and after clinical remission is obtained. Once again we observed that neurocognitive retardation (TMT-A and -B) in remitted patients was highly correlated to the number of past depressive episodes (Gorwood et al., 2014). We then tested if treatment resistance could be detected a bit earlier than the 4 to 6 weeks observation usually considered as required. Indeed, we found that a two weeks observation is enough to decide if we should continue or change the present treatment. We furthermore saw that assessing emotions rather than depressive symptoms might be even more predictive of the chances of treatment success. These studies reinforce the concept of neurotoxicity of depressive disorder, wich means that an important part of treatment resistence is acquired during the process of the disorder, and therefore stress the importance of treating early and completely each depressive episode, not only for an acute relief, but also to improve the long term prognosis of mood disorders.

Introduction Many patients with schizophrenia show major difficulties in performing basic social roles. Occupational and social functioning (and independent living) are considered domains of functioning. Improvement in functioning is recognized as an important aim in treatment guidelines and as an outcome by regulatory agencies. Objectives The Europe, Middle East and Africa (EMEA) functioning survey canvassed opinions of psychiatrists (and neurologists with psychiatric backgrounds in Germany) across the region. Aim To ascertain psychiatrists' perceptions of the clinical importance, assessment and management of functioning amongst their patients with schizophrenia. Methods The survey comprised 17 questions and was conducted from March-April 2011, in 39 EMEA countries. Respondents' demographics and their opinions regarding personal and social functioning in patients with schizophrenia were collected. Results Results were obtained from 3610 clinicians. Psychiatrists reported that they perceived more than two in three of their patients show impaired/very poor levels of functioning. 91% believed that personal and social functioning was an important treatment goal for patients with schizophrenia and 90% believed it was an important goal for patients' families. The majority of psychiatrists assess the personal and social functioning of their patient at each visit but 81% determine the level of functioning through clinical interview. To manage personal and social functioning in their patients, 26% of psychiatrists prefer pharmacological interventions while 47% prefer psychosocial interventions. Conclusion Although psychiatrists recognize that functioning is impaired/very poor in patients with schizophrenia, there is still a need to address it as a main treatment goal for patients with schizophrenia.

Introduction Partial/non-adherence to medication is common amongst patients with schizophrenia. Nurses play an important role in assessing and managing mental health problems and are often involved in helping patients manage and adhere to their medication. As such, the perception of nurses regarding the burden and potential causes of non-adherence is vital in addressing the adherence problem. Objectives The ADHES nurses survey collected opinions of nurses across the EMEA (Europe, Middle East and Africa) region. Aim To ascertain nurses' perceptions of assessment, potential causes and management of partial/non-adherence to medication in patients with schizophrenia. Methods The survey was conducted from January-March 2010 in 29 countries across EMEA, comprising 14 questions addressing the issue of partial/non-adherence and the use of long-acting injectable (LAI) antipsychotic medication in patients with schizophrenia. Results Results were obtained from 4120 respondents. Nurses estimated high levels of partial/non-adherence (mean 54%) amongst patients with schizophrenia and 85% believed improving medication adherence would have a huge/sizable impact on patient outcomes. 93% believed that continuous medication with an LAI would have long-term benefits for patients with schizophrenia, and that many patients (mean 40%) would prefer LAI medication. Conclusion Nurses recognize the issue of partial/non-adherence to medication in patients with schizophrenia. Most nurses believe patients are well informed about LAI antipsychotics, however, approximately a third of nurses believe patients to be poorly informed. There is a need to address the problem of partial/non-adherence in clinical practice with a multidisciplinary approach to avoid suboptimal treatment outcomes in patients with schizophrenia.

Aims: The short (S) allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR) contributes to the risk of alcohol dependence and co-occurring clinical features. We studied the putative link between this allele and relapse. Methods: 48 alcohol-dependent male patients were recruited and genotyped for the 5-HTTLPR. Relapse to alcohol drinking was monitored during 3 months after standardized withdrawal. Results: The S allele was significantly associated with relapse ( p = 0.008) while no other factor that was measured played a significant role. Conclusions: The S allele of the 5-HTTLPR polymorphism may influence the risk of relapse in abstinent alcohol-dependent patients, possibly through intermediate phenotypes.