Major Depressive Disorder (MDD) is a complex mental health condition characterized by a wide spectrum of symptoms. According to the Diagnostic Statistical Manual 5 (DSM-5) criteria, patients can present with up to 1,497 different symptom combinations, yet all receive the same MDD diagnosis. This diversity in symptom presentation poses a significant challenge to understanding the disorder in the wider population. Subtyping offers a way to unpick this phenotypic diversity and enable improved characterization of the disorder. According to reviews, MDD subtyping work to date has lacked consistency in results due to inadequate statistics, non-transparent reporting, or inappropriate sample choice. By addressing these limitations, the current study aims to extend past phenotypic subtyping studies in MDD.

(1) To investigate phenotypic subtypes at baseline in a sample of people with MDD;

(2) To determine if subtypes are consistent between baseline 6- and 12-month follow-ups; and

(3) To examine how participants move between subtypes over time.

This was a secondary analysis of a one-year longitudinal observational cohort study. We collected data from individuals with a history of recurrent MDD in the United Kingdom, the Netherlands and Spain (N=619). The presence or absence of symptoms was tracked at three-month intervals through the Inventory of Depressive Symptomatology: Self-Report (IDS-SR) assessment. We used latent class and three-step latent transition analysis to identify subtypes at baseline, determined their consistency at 6- and 12-month follow-ups, and examined participants’ transitions over time.

We identified a 4-class solution based on model fit and interpretability, including (Class 1) severe with appetite increase, (Class 2), severe with appetite decrease, (Class 3) moderate, and (Class 4) low severity. The classes mainly differed in terms of severity (the varying likelihood of symptom endorsement) and, for the two more severe classes, the type of neurovegetative symptoms reported (Figure 1). The four classes were stable over time (measurement invariant) and participants tended to remain in the same class over baseline and follow-up (Figure 2).

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We identified four stable subtypes of depression, with individuals most likely to remain in their same class over 1-year follow-up. This suggests a chronic nature of depression, with (for example) individuals in severe classes more likely to remain in the same class throughout follow-up. Despite the vast heterogeneous symptom combinations possible in MDD, our results emphasize differences across severity rather than symptom type. This raises questions about the meaningfulness of these subtypes beyond established measures of depression severity. Implications of these findings and recommendations for future research are made.

C. Oetzmann Grant / Research support from: C.O. is supported by the UK Medical Research Council (MR/N013700/1) and King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences., N. Cummins: None Declared, F. Lamers: None Declared, F. Matcham: None Declared, K. White: None Declared, J. Haro: None Declared, S. Siddi: None Declared, S. Vairavan Employee of: S.V is an employee of Janssen Research & Development, LLC and hold company stocks/stock options., B. Penninx : None Declared, V. Narayan: None Declared, M. Hotopf Grant / Research support from: M.H. is the principal investigator of the RADAR-CNS programme, a precompetitive public–private partnership funded by the Innovative Medicines Initiative and the European Federation of Pharmaceutical Industries and Associations. The programme received support from Janssen, Biogen, MSD, UCB and Lundbeck., E. Carr: None Declared

Research has shown that factors related with the migratory process (such as travelling alone, living away from family, and discrimination after arrival) considerably increase the risk of mental health problems in young migrants. Moreover, they are among the most vulnerable migration groups with a high risk of social exclusion.

To identify coping strategies and behavioural changes used to deal with perceived discrimination and its impact on the emotional well-being and mental health of newly arrived young migrants in Spain.

A subsample of 15 audio-recorded in-depth qualitative interviews were analysed from the national action-research Migrasalud project (II IN 190517 EN 162 FA 01). The interviews were transcribed, translated from Arabic to Spanish, and analysed through content analysis.

Most participants were males (93.3%; n=14), ranging from 18 to 20 years, and from Morocco (93.3%; n=14). All participants were from foster care placements in Barcelona and arrived to Spain as minors. Newly arrived young migrants reported that they perceived themselves as being healthy before the migratory process. Adverse experiences during the journey and discrimination after arrival impacted their well-being and mental health. Specifically, they reported perceived discrimination in their daily life due to culture, language, or origin. This negatively impacted their well-being and mental health, increasing their emotional distress response and ‘undervalued or inferior’ and ‘vulnerable’ feelings about themselves. Concerning coping with discrimination, they reported using internalised coping strategies such as ‘ignoring’ or ‘not responding’ for fear of having their legal documents revoked or not obtaining them. Their behavioural changes often occurred when they perceived unfair treatment or prejudice towards their migrant status or their socioeconomics, culture or religion. These changes were motivated by being more accepted by the local community by ‘westernisation or cultural assimilation’ and by ‘creating a good image’ of oneself and its culture.

Findings establish that the cumulative experience of post-migration stressors (such as discrimination) negatively impacts their mental health and well-being in the long term. This suggests the need for specific policies and services to address this population’s effects of post-migration risk factors. Further research is needed to explore the causes and effects of perceived discrimination on mental health more closely and to develop more targeted and effective interventions.

None Declared

Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation.

Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months.

10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation.

Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.

To assess whether there is a change in the prevalence of depression and suicidal ideation after the strict lockdown measures due to the first wave of the COVID-19 pandemic in Spain, and to assess which are the factors associated with the incidence of a depressive episode or suicidal ideation during the lockdown.

Data from a longitudinal adult population-based cohort from Madrid and Barcelona were analysed (n = 1103). Face-to-face home-based (pre-pandemic) and telephone interviews were performed. Depression and suicidal ideation were assessed through an adaptation of the Composite International Diagnostic Interview (CIDI 3.0). Population prevalence estimates and multivariable logistic regressions were computed.

Prevalence rates of depression changed significantly from before to after the COVID-19 outbreak (from 3.06% to 12.00%; p = 0.01) and per sex and age groups. Individuals reporting COVID-19 concerns (odds ratio [OR] = 3.11; 95% confidence interval [CI] = 1.45–6.69) and those feeling loneliness (OR = 1.99; 95% CI = 1.52–2.61) during the lockdown were at increased risk of developing depression during the confinement. Resilience showed a protective effect against the risk of depression (OR = 0.57; 95% CI = 0.39–0.83), while individuals perceiving social support during the confinement were at lower risk of developing suicidal thoughts (OR = 0.21; 95% CI = 0.09–0.46). Greater disability during the lockdown was also associated with the risk of suicidal ideation (OR = 2.77; 95% CI = 1.53–5.03).

Continuous reinforcement of mental health preventive and intervening measures is of global importance, particularly among vulnerable groups who are experiencing the most distress. Future research should strive to evaluate the long-term effects of the COVID-19 crisis on mental health.

Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity.

Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions.

Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms.

Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.

Bipolar disorder (BD) is a psychiatric disorder characterized by alternating episodes of high mood and low mood similar to depression. To differentiate BD patients from unipolar (UN) depressed patients remains a challenge and the clinical scales available failed to distinguish these 2 populations. ALCEDIAG developed EDIT-B, the first blood test able to make a differential diagnosis of BD. Based on RNA editing modifications measurement and AI, the test requires a simple blood draw and equipment available in most central laboratories. A first study on 160 UN and 95 BD patients allowed a differential diagnosis with an AUC of 0.935 and high specificity (Sp=84.6%) and sensitivity (Se=90.9%). A multicentric clinical study has been set up to validate these performances.

The objective of this project is to run a multicentric clinical study in Europe and assess the performances of the test.

The EDIT-B project, led by Alcediag, is supported by EIT-Health grant (European institute of Innovation and Technology) and gathers 4 clinical centers in 3 countries (France, Spain, Danemark), a CRO for the clinical study management (Aixial), a CRO for the development of a diagnostic kit (Veracyte), a diagnostic lab for molecular biology analyses (Synlab), and a regulatory company (PLG).

At the end of the study, the EDIT-B performance will be confirmed and the test will be CE-marked.

This test will address the needs of millions of patients suffering from misdiagnosis and therefore allow them to receive the correct treatment.

JDA, NS and DW are employees of Alcediag.

Longitudinal data on the mental health impact of the coronavirus disease 2019 (Covid-19) pandemic in healthcare workers is limited. We estimated prevalence, incidence and persistence of probable mental disorders in a cohort of Spanish healthcare workers (Covid-19 waves 1 and 2) -and identified associated risk factors.

8996 healthcare workers evaluated on 5 May–7 September 2020 (baseline) were invited to a second web-based survey (October–December 2020). Major depressive disorder (PHQ-8 ≥ 10), generalised anxiety disorder (GAD-7 ≥ 10), panic attacks, post-traumatic stress disorder (PCL-5 ≥ 7), and alcohol use disorder (CAGE-AID ≥ 2) were assessed. Distal (pre-pandemic) and proximal (pandemic) risk factors were included. We estimated the incidence of probable mental disorders (among those without disorders at baseline) and persistence (among those with disorders at baseline). Logistic regression of individual-level [odds ratios (OR)] and population-level (population attributable risk proportions) associations were estimated, adjusting by all distal risk factors, health care centre and time of baseline interview.

4809 healthcare workers participated at four months follow-up (cooperation rate = 65.7%; mean = 120 days s.d. = 22 days from baseline assessment). Follow-up prevalence of any disorder was 41.5%, (v. 45.4% at baseline, p < 0.001); incidence, 19.7% (s.e. = 1.6) and persistence, 67.7% (s.e. = 2.3). Proximal factors showing significant bivariate-adjusted associations with incidence included: work-related factors [prioritising Covid-19 patients (OR = 1.62)], stress factors [personal health-related stress (OR = 1.61)], interpersonal stress (OR = 1.53) and financial factors [significant income loss (OR = 1.37)]. Risk factors associated with persistence were largely similar.

Our study indicates that the prevalence of probable mental disorders among Spanish healthcare workers during the second wave of the Covid-19 pandemic was similarly high to that after the first wave. This was in good part due to the persistence of mental disorders detected at the baseline, but with a relevant incidence of about 1 in 5 of HCWs without mental disorders during the first wave of the Covid-19 pandemic. Health-related factors, work-related factors and interpersonal stress are important risks of persistence of mental disorders and of incidence of mental disorders. Adequately addressing these factors might have prevented a considerable amount of mental health impact of the pandemic among this vulnerable population. Addressing health-related stress, work-related factors and interpersonal stress might reduce the prevalence of these disorders substantially. Study registration number: NCT04556565

The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.

Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.

3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.

ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

To assess whether there is a change in the prevalence of depression and suicidal ideation after the strict lockdown measures due to the first wave of the COVID-19 pandemic in Spain; and to assess which are the factors associated with the incidence of a depressive episode or suicidal ideation during the lockdown.

Data from a longitudinal adult population-based cohort from the provinces of Madrid and Barcelona were analysed (n = 1103). Structured face-to-face home-based interviews (pre-pandemic) and telephone interviews were performed. Both depression and suicidal ideation were assessed through an adaptation of the Composite International Diagnostic Interview (CIDI 3.0). A variety of validated instruments and sociodemographic variables including age, sex, educational level, occupational status, home quietness, screen time, resilience, loneliness, social support, physical activity, disability, economic situation and COVID-19-related information were also considered. Population prevalence estimates and multivariable logistic regressions were computed.

Overall, prevalence rates of depression and suicidal ideation did not change significantly from before to after the COVID-19 outbreak. However, the rates of depression among individuals aged 50+ years showed a significant decrease compared to before the pandemic (from 8.48 to 6.41%; p = 0.01). Younger individuals (odds ratio (OR) = 0.97 per year older; 95% confidence interval (CI) = 0.95–0.99) and those feeling loneliness (OR = 1.96; 95% CI = 1.42–2.70) during the lockdown were at an increased risk of developing depression during the confinement. Resilience showed a protective effect against the risk of depression (OR = 0.46; 95% CI = 0.32–0.66) and suicidal ideation (OR = 0.33; 95% CI = 0.16–0.68), whereas individuals perceiving social support were at a lower risk of developing suicidal thoughts (OR = 0.35; 95% CI = 0.18–0.69).

Continuous reinforcement of mental health preventive and intervening measures during and in the aftermath of the crisis is of global importance, particularly among vulnerable groups who are experiencing the most distress. Future research should strive to evaluate the long-term effects of the COVID-19 crisis on mental health.

To investigate the prevalence of suicidal thoughts and behaviours (STB; i.e. suicidal ideation, plans or attempts) in the Spanish adult general population during the first wave of the Spain coronavirus disease 2019 (COVID-19) pandemic (March−July, 2020), and to investigate the individual- and population-level impact of relevant distal and proximal STB risk factor domains.

Cross-sectional study design using data from the baseline assessment of an observational cohort study (MIND/COVID project). A nationally representative sample of 3500 non-institutionalised Spanish adults (51.5% female; mean age = 49.6 [s.d. = 17.0]) was taken using dual-frame random digit dialing, stratified for age, sex and geographical area. Professional interviewers carried out computer-assisted telephone interviews (1–30 June 2020). Thirty-day STB was assessed using modified items from the Columbia Suicide Severity Rating Scale. Distal (i.e. pre-pandemic) risk factors included sociodemographic variables, number of physical health conditions and pre-pandemic lifetime mental disorders; proximal (i.e. pandemic) risk factors included current mental disorders and a range of adverse events-experiences related to the pandemic. Logistic regression was used to investigate individual-level associations (odds ratios [OR]) and population-level associations (population attributable risk proportions [PARP]) between risk factors and 30-day STB. All data were weighted using post-stratification survey weights.

Estimated prevalence of 30-day STB was 4.5% (1.8% active suicidal ideation; n = 5 [0.1%] suicide attempts). STB was 9.7% among the 34.3% of respondents with pre-pandemic lifetime mental disorders, and 1.8% among the 65.7% without any pre-pandemic lifetime mental disorder. Factors significantly associated with STB were pre-pandemic lifetime mental disorders (total PARP = 49.1%) and current mental disorders (total PARP = 58.4%), i.e. major depressive disorder (OR = 6.0; PARP = 39.2%), generalised anxiety disorder (OR = 5.6; PARP = 36.3%), post-traumatic stress disorder (OR = 4.6; PARP = 26.6%), panic attacks (OR = 6.7; PARP = 36.6%) and alcohol/substance use disorder (OR = 3.3; PARP = 5.9%). Pandemic-related adverse events-experiences associated with STB were lack of social support, interpersonal stress, stress about personal health and about the health of loved ones (PARPs 32.7–42.6%%), and having loved ones infected with COVID-19 (OR = 1.7; PARP = 18.8%). Up to 74.1% of STB is potentially attributable to the joint effects of mental disorders and adverse events−experiences related to the pandemic.

STB at the end of the first wave of the Spain COVID-19 pandemic was high, and large proportions of STB are potentially attributable to mental disorders and adverse events−experiences related to the pandemic, including health-related stress, lack of social support and interpersonal stress. There is an urgent need to allocate resources to increase access to adequate mental healthcare, even in times of healthcare system overload.

NCT04556565

Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.

The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.

Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.

Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.

There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.

Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.

Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.

Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.

To compare CATIE, a randomized double blind study, and SOHO, a 3-year prospective non-randomized observational European study of outpatients with schizophrenia, on the Number Needed to Treat (NNT) for all-cause medication discontinuation. NNTs place data into a clinically meaningful context - the number of patients needed to be treated with one antipsychotic instead of another to prevent one negative outcome, defined here as one additional medication discontinuation for any cause.

Rate of medication discontinuation for any cause during the 18 months post initiation was calculated for patients newly initiated on olanzapine (N=4247), risperidone (N=1549), quetiapine (N=583), amisulpride (N=256), clozapine (N=274), oral typicals (N=471) or depot typicals (N=348). Cox models were employed to adjust for treatment group differences at baseline. NNTs with their 95% confidence intervals were calculated and compared with published NNTs for CATIE (Phase 1).

The NNTs for all-cause discontinuation of olanzapine vs. each studied atypical antipsychotic during the 18 month following medication initiation in SOHO were comparable to CATIE: 4.3(95% CI: 3.6–5.3) for olanzapine vs. quetiapine (5.5 in CATIE); 16.1(11.0–28.1) for olanzapine vs. risperidone (10.1 in CATIE); 6.9(5.2–10.1) for olanzapine vs. oral typicals (9.0 in CATIE for olanzapine vs. perphenazine).

The NNTs for all-cause medication discontinuation based on CATIE appeared comparable to NNTs based on SOHO. The NNTs for olanzapine therapy were consistently better when compared to each studied atypical antipsychotic (except clozapine) and when compared to typical antipsychotics. Results should be interpreted conservatively, due to the observational design of SOHO.

Antidepressants are recommended to be withdrawn during a manic episode. This analysis explored the characteristics of patients receiving antidepressants during an acute manic episode in the context of a large, observational study.

EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year prospective observational study of acute mania/mixed mania. Of 2416 patients, 345 (14%) were taking an antidepressant (AD) and 2071 (86%) were not (NAD) during acute mania. Demographic and clinical variables were collected at baseline and at outpatient visits up to 2 years. Illness severity was measured using Clinical Global Impressions–Bipolar Disorder (CGI-BP), 5-item Hamilton Depression Rating Scale (HAM-D-5), and Young Mania Rating Scale (YMRS). Logistic regression analysis was used to identify variables associated with AD use.

AD use varied across countries (p<0.05), more use with mixed episodes (p<0.001), rapid cyclers (p=0.02), more previous depressive episodes (p<0.001) and higher HAM-D-5 severity at baseline (p<0.001) but less use with higher education (p=0.029), YMRS (p=0.022), CGI-BP overall (p=0.006) severity and inpatients at baseline (p<0.001). There were no differences in alcohol abuse or suicide attempts. Depression recurrence rates were significantly higher with AD (p<0.001).

The EMBLEM study suggests that patients with mania receiving antidepressants are more likely to be outpatients with mixed mania or rapid cycling, and have a higher risk of depressive recurrence during follow-up. Clinicians seem to maintain antidepressants in manic patients to address depressive features during mania and prevent further depressive episodes.

EMBLEM was supported by Eli Lilly and Company.

To explore factors associated with work impairment at 2 years following an acute episode.

European Mania in Bipolar disorder Longitudinal Evaluation of Medication (EMBLEM) is a prospective, observational study on the outcomes of patients with a manic/mixed episode. Work impairment was measured using a Longitudinal Interval Follow-up Evaluation (slice of LIFE) item and patients were categorised with either low or high work impairment at each observation. Baseline factors associated with work impairment at 2 years were assessed using multivariate modelling.

At baseline (n = 2289), 69% of patients had high work impairment. At 2 years (n = 1393), high impairment reduced to 41%. Modelling identified rapid cycling as the strongest disease-related factor associated with high work impairment at 2 years, although high work impairment at baseline had the strongest association overall. Lower levels of education, recent admissions, CGI-BP overall severity in the 12 months prior to baseline and CGI-BP mania at baseline all predicted higher work impairment. Living together in a relationship and independent housing were both significantly associated with having low work impairment at 2 years.

Work impairment in bipolar disorder is maintained over long periods, and is strongly associated with relationship status, living conditions and various disease-related factors.

To contrast the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a RCT assessing the same treatments (Tohen et al., 2002).

EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2-year, prospective, observational study of health outcomes associated with treatment of mania. Severity of mania and depression was assessed at baseline and 6 weeks using the YMRS and 5-item version of the HAMD, respectively. The RCT was a 3-week, randomised, double-blind comparison of olanzapine (n=125) and divalproate-treated (n=123) patients hospitalised for acute manic or mixed episodes. The YMRS and HAMD were used to quantify manic and depressive symptoms, respectively.

621 EMBLEM patients were analysed (n=107 valproate, n=514 olanzapine). Both observed groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with significantly greater mean improvements in the olanzapine compared with the valproate group using linear regression to adjust for baseline differences. The RCT reported significantly greater mean YMRS improvement (but not HAMD) in the olanzapine-treated group. EMBLEM patients treated with olanzapine experienced significantly greater weight gain than patients treated with valproate, similar to RCT results. There was a significantly greater incidence of treatment-emergent gastrointestinal adverse events in EMBLEM patients treated with valproate.

The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy may be more effective than valproate monotherapy in the treatment of acute mania. Contrasting observational and RCT results present methodological challenges but can provide important complementary information.

Verbal working memory span is decreased in patients with schizophrenia, and this might contribute to impairment in higher cognitive functions as well as to the formation of certain clinical symptoms. Processing speed has been identified as a crucial factor in cognitive efficiency in this population. We tested the hypothesis that decreased processing speed underlies the verbal working memory deficit in patients and mediates the associations between working memory span and clinical symptoms.

Forty-nine schizophrenia inpatients recruited from units for chronic and acute patients, and forty-five healthy participants, were involved in the study. Verbal working memory span was assessed by means of the letter-number span. The Digit Copy test was used to assess motor speed, and the Digit Symbol Substitution Test to assess cognitive speed.

The working memory span was significantly impaired in patients (F(1,90) = 4.6, P < 0.05). However, the group difference was eliminated when either the motor or the cognitive speed measure was controlled (F(1,89) = 0.03, P = 0.86, and F(1,89) = 0.03, P = 0.88). In the patient group, working memory span was significantly correlated with negative symptoms (r = –0.52, P < 0.0001) and thought disorganisation (r = –0.34, P < 0.025) scores. Regression analyses showed that the association with negative symptoms was no longer significant when the motor speed measure was controlled (β = –0.12, P = 0.20), while the association with thought disorganisation was no longer significant when the cognitive speed measure was controlled (β = –0.10, P = 0.26).

Decrement in motor and cognitive speed plays a significant role in both the verbal working memory impairment observed in patients and the associations between verbal working memory impairment and clinical symptoms.