The author has not supplied his declaration of competing interest.

The CHANGE trial was an investigator-initiated, randomised, parallel-group, superiority, multi-centre trial with blinded outcome assessment. Patients diagnosed with schizophrenia spectrum disorders and increased waist circumference according (>88 cm for women, >102 cm for men), were recruited and centrally randomised 1:1:1 to 12-months of lifestyle coaching plus care coordination versus care coordination alone versus treatment as usual. The primary outcome was 10-year risk of cardiovascular disease assessed post-treatment and standardised to age 60, secondary outcomes included cardiorespiratory fitness and physical activity. Clinical.Trials.gov NCT01585493.

A total of 428 participants were randomly assigned to the CHANGE intervention (n = 138); care coordination (n = 142); or treatment as usual (n = 148). At 12 months, the mean 10 years risk of cardiovascular disease was 8.4% (SD 6.7) in the CHANGE group, 8.5% (SD 7.5) in the care coordination group and 8.0% (SD 6.5) in the treatment as usual group (P = 0.41). We found no intervention effects for any secondary or explorative outcomes, including weight, cardiorespiratory fitness, physical activity, diet or smoking.

The CHANGE trial did not support individual lifestyle coaching or care coordination as superior compared with treatment as usual in reducing the cardiovascular risk in patients with schizophrenia and increased waist circumference.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Tourette syndrome (TS) has long been thought to involve dopaminergic disturbances, given the effectiveness of antipsychotics in diminishing tics. Molecular-imaging studies have, by and large, confirmed that there are specific alterations in the dopaminergic system in TS. In parallel, multiple lines of evidence have implicated the motor cortico-basal ganglia-thalamo-cortical (CBGTC) loop in TS. Finally, several studies demonstrate that patients with TS exhibit exaggerated habit learning. This talk will present a computational theory of TS that ties together these multiple findings.

The computational theory builds on computational reinforcement-learning models, and more specifically on a recent model of the role of the direct and indirect basal-ganglia pathways in learning from positive and negative outcomes, respectively.

A model defined by a small set of equations that characterize the role of dopamine in modulating learning and excitability in the direct and indirect pathways explains, in an integrated way: (1) the role of dopamine in the development of tics; (2) the relation between dopaminergic disturbances, involvement of the motor CBGTC loop, and excessive habit learning in TS; (3) the mechanism of action of antipsychotics in TS; and (4) the psychological and neural mechanisms of action of habit-reversal training, the main behavioral therapy for TS.

A simple computational model, thoroughly grounded on computational theory and basic-science findings concerning dopamine and the basal ganglia, provides an integrated, rigorous mathematical explanation for a broad range of empirical findings in TS.

The author has not supplied his declaration of competing interest.

Hypersexual disorder (HD) defined as non-paraphilic sexual desire disorder with components of impulsivity, compulsivity and behavioral addiction, was proposed as a diagnosis in the DSM-5. Recent research shows some overlapping features between HD and substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. We have reported that HD was significantly associated to DST non-suppression and higher plasma DST-ACTH levels indicating HPA axis dysregulation in male patients with HD.

In this cohort, comprising 54 male patients diagnosed with HD and 33 healthy male volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality.

We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality in 87 male subjects, adjusting for depression, DST non-suppression status, CTQ total score, and plasma levels of TNF-alpha and IL-6.

Seventy-six individual CpG sites were tested, and four of these were nominally significant (P < 0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074–located 48 bp upstream of the TSS of the CRH gene–was significantly hypomethylated in hypersexual patients after corrections were made for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy male subjects. CRH is an important integrator of neuroendocrine stress responses in the brain, modulating behavior and the autonomic nervous system; our results show epigenetic changes in CRH gene related to hypersexual disorder in men.

The author has not supplied his/her declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Although controversial in many countries, in The Netherlands euthanasia or physician assisted death has increased in patients with early stages of dementia, psychiatric illness and in conditions described as ‘being tired of life’ in the oldest old. There is a strong debate about this practice in the community and among professionals often with exclamation marks ranging from medical murder to providing ultimate care.

To provide figures, describe current practice and debate in The Netherlands with regard to capacity evaluation in older psychiatric patients and end of life questions.

Review of literature, case reports and own experience in the past decade.

There are few studies on the important issue of capacity making in psychiatric patients. The research that was performed does not show that a high threshold of capacity is required for granting euthanasia. Research on physician-assisted death in early dementia is scarce. With regard to end of life questions the debate in The Netherlands is still ongoing.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

In some Swiss states, right-to-die associations are allowed to assist older people in nursing homes provided that certain requirements are fulfilled.

To investigate how health and social care providers and their institutions reacted to and dealt with requests of assisted suicide.

An exploratory qualitative study was carried out in the States of Fribourg and Vaud among 40 professionals working in nursing homes, home care services or social welfare agencies.

The requests of assisted suicide questioned the professional mission, the quality of accompaniment provided to the older people and both professional and personal values. Health and social care providers were required to ponder over ethical dilemmas or decisions. Several challenges were reported, such as: taking into account and articulating personal freedom or needs with collective functioning or organizational constraints before, during and after the assisted suicide; reconciliating self-determination with protection towards vulnerable people (beneficere, non maleficere).

Assisted suicide challenges and changes professional end-of-life practices. Education and support should be provided to health and social care providers faced with it.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

In European countries, the quality of mental healthcare services is often limited due to scarce and inequitable distributed resources, and inefficient use of existing resources. Against this background, the EPA Guidance provides recommendations on how to optimize quality of mental healthcare for all European countries.

Provision of guidance recommendations in order to support optimization and harmonization of mental healthcare services in European countries.

By means of evidence and consensus-based methods EPA guidance papers are developed by experts in psychiatry and related fields [1].

As of 2012, five EPA guidance series have been developed and published [2]. They focus on various aspects of mental healthcare and clinical situations that have not been covered by medical guidelines yet but are considered important to deliver high quality mental healthcare. Papers deal amongst others with topics relating to quality assurance of mental health services, as quality of mental health service structures and processes, and building trust in mental health services.

EPA guidance recommendations can improve mental healthcare provision and thereby contribute to better mental health of persons receiving mental healthcare. For this purpose, recommendations need to be widely disseminated and implemented in European countries.

Unterstützung bei Symposien/Symposia Support

− Janssen-Cilag GmbH, Neuss

− Aristo Pharma GmbH, Berlin

− Lilly Deutschland GmbH, Bad Homburg

− Servier Deutschland GmbH, München− Fakultätsmitglied/Faculty Member

− Lundbeck International Neuroscience Foundation (LINF), Dänemark

The author has not supplied his declaration of competing interest.

To evaluate the length of the interval between the onset and the initial management of bipolar disorder (BD).

We conducted a meta-analysis using the preferred reporting items for systematic reviews and meta-analyses guidelines. Systematic searches located studies reporting estimates of the age of onset (AOO) and indicators of the age at initial management of BD. We calculated a pooled estimate of the interval between AOO and age at management. Factors influencing between-study heterogeneity were investigated using sensitivity analyses, meta-regression, and multiple meta–regression.

Twenty-seven studies, reporting 51 samples and a total of 9415 patients, met the inclusion criteria. The pooled estimate for the interval between the onset of BD and its management was 5–8 years (standardized difference, .53; 95% confidence interval, .45 to .62). There was very high between-sample heterogeneity (I2 ¼ 92.6; Q ¼ 672). A longer interval was found in studies that defined the onset according to the first episode (compared to onset of symptoms or illness) and defined management as age at diagnosis (rather than first treatment or first hospitalization). A longer interval was reported among more recently published studies, among studies that used a systematic method to establish the chronology of illness, among studies with a smaller proportion of bipolar I patients, and among studies with an earlier mean AOO.

There is currently little consistency in the way researchers report the AOO and initial management of BD. However, the large interval between onset and management of BD presents an opportunity for earlier intervention.

The authors have not supplied their declaration of competing interest.

Bipolar Disorders (BD) are common and complex diseases. Recent findings have provided evidence that impairments in cognition are evident in the various sub-groups of Bipolar Disorder and persist after resolution of acute episodes.

An opinion paper based on a narrative review of the field.

Quantifiable cognitive deficits are clearly found in Bipolar 1 and Bipolar 2 Disorders. These persist after recovery from acute episodes. The aetiopathogenesis of these phenomena is likely to be multifactorial. It seems clear that these cognitive impairments are not in general neurodevelopmental and for most are related to repeated episodes of illness [1]. However, the issues of subgroups with differential profiles of impairment and the trajectory of cognitive change remain to be fully established. The effects of putative treatments (e.g., pharmacological, neurostimulation, cognitive remediation) are at an early stage of evaluation.

Future efforts should focus on further integrating the current and emerging research findings into a coherent model, which generates testable hypotheses and allows treatment effects to be tested.

Employed by King's College London Honorary Consultant SLaM (NHS UK)

Paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders

No share holdings in pharmaceutical companies

Lead Investigator for Embolden Study (AZ), BCI Neuroplasticity study and Aripiprazole Mania Study

Investigator initiated studies from AZ, Eli Lilly, Lundbeck, Wyeth

Grant funding (past and present): NIMH (USA) CIHR (Canada) NARSAD (USA) Stanley Medical Research Institute (USA) MRC (UK) Wellcome Trust (UK) Royal College of Physicians (Edin) BMA (UK) UBC-VGH Foundation (Canada) WEDC (Canada) CCS Depression Research Fund (Canada) MSFHR (Canada) NIHR (UK).

Bipolar disorder (BD) typically starts in adolescence or young adulthood (early-onset; EO-BD), which may have different backgrounds and consequences than late-onset (LO) BD. There are controversies over pre-pubertal age of onset (AoO).

To give an overview of the various concepts of AoO in BD, the impact of AoO on subsequent illness course, and findings of the Stanley Foundation Bipolar Network (SFBN) with relationship to AoO.

literature review and additional analyses of SFBN database.

BD usually begins with a depressive episode. SFBN-data reveal that an earlier AoO is associated with a less favourable prospective illness course (more depression, mood instability and rapid cycling), longer delay to first treatment, past history of suicide attempts, being abused in childhood abuse, more psychiatric and medical comorbidities. Comparison of the US sample with the European sample of SFBN showed an earlier onset in US patients.

and early AoF of BD is associated with a poorer long-term outcome, despite adequate current treatment.

The author has not supplied his declaration of competing interest.

Studies conducted in child psychiatry suggest that patients with earlier onset of psychosis have poorer outcome. Similar findings have been published regarding onset of bipolar disorder. However, few studies have been conducted in youth mental health program where these patients may actually receive treatment. Identification of subgroups with distinct need and outcome among first episode mania patients would facilitate the development of specific treatment strategies better suited to the actual needs of patients.

Sixty-seven patients with a first episode of psychotic mania were followed up over 12 months after recovery from this initial episode. Syndromic and symptomatic outcome were determined with the brief psychiatric rating scale, functional outcome with the quality of life scale and premorbid adjustment scale sub items.

While 90% of patients achieved syndromic recovery (disappearance of manic syndrome) at 6 and 12 months, 40% had not recovered symptomatically, still presenting with depression and anxiety. Return to previous level of functioning was achieved only by 34% of patients at 6 months and 39% at 12 months. Age at the time of first manic episode with psychotic features was a significant predictor of recovery of functional level.

While manic symptoms reduce quickly in most patients after a first episode of psychotic mania, an important number of patients still display symptoms of depression and anxiety after 12 months and 2/3 do not reach functional recovery. Younger age at first episode predicts risk of poorer functional outcome.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

Negative symptoms represent a separate dimension of schizophrenia psychopathology, distinct from positive symptoms, disorganization and cognitive impairment. It is increasingly acknowledged that negative symptoms are associated with poor functional outcome and represent an unmet need in schizophrenia treatment. Improvement in definition of their phenomenology, assessment instruments and experimental models are needed in order to improve schizophrenia prognosis.

The presentation will review key aspects of the evolution of negative symptom constructs. In particular, findings concerning phenomenology, clinical assessment, association with functional outcome and brain imaging correlates will be presented.

We searched PubMed for English full-text publications with the keywords

Schizophrenia AND “negative symptoms”/“primary negative symptoms”/“deficit schizophrenia”/“persistent negative symptoms”/“affective flattening”/alogia/“expressive deficit”/apathy/asociality/“social withdrawal”/anhedonia/“anticipatory anhedonia”/avolition/neuroimaging.

The distinction between secondary negative symptoms (i.e., those due to identifiable factors, such as drug effects, psychotic symptoms or depression), and primary or persistent negative symptoms (i.e., those etiologically related to the core pathophysiology of schizophrenia) is grounded on solid research evidence and might have major implications for both treatment development and clinical care. The evidence that negative symptoms cluster in motivation- and expressive-related domains is founded on large consensus and empirical evidence and will foster pathophysiological modeling. The motivation-related domain is a stronger predictor of functional outcome than the expressive one.

An improved definition and assessment of negative symptoms needs to translate in large-scale studies to advance knowledge. In the short-term, the improved identification of treatable causes of secondary negative symptoms can translate into better care for people with schizophrenia.

AM received honoraria or advisory board/consulting fees from the following companies: Janssen Pharmaceuticals, Otsuka, Pfizer and Pierre Fabre.

SG received honoraria or advisory board/consulting fees from the following companies: Lundbeck, Janssen Pharmaceuticals, Hoffman-La Roche, Angelini-Acraf, Otsuka, Pierre Fabre and Gedeon-Richter.

The authors have not supplied their declaration of competing interest.