The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

Genetic risk and outcome of psychoses (GROUP) is a 6 year longitudinal cohort study that focus on gene–environment vulnerability and resilience in patients with psychotic disorders, their unaffected family members and non-related controls. Its main aim is to elucidate etiological and pathogenetic factors that influence the onset and course of psychotic disorders. In this substudy, we will examine medication use over time, its relation with (the change in) metabolic syndrome status and effects on the brain.

A consortium of four university psychiatric centers and their affiliated mental health care institutions, conducted the GROUP study. At baseline, 1120 patients, 1057 siblings, 919 parents and 590 healthy controls were included. After inclusion, participants, except parents, were evaluated again after three and six years of follow-up. Extensive assessment of genetic factors, environmental factors, medication use, metabolic parameters and outcome were performed. Moreover, brain imaging was performed in a subset of participants, using a 1.5 Tesla MRI scanner.

At baseline 65% of patients used atypical antipsychotics, 16% used conventional antipsychotics and 19% used clozapine. Siblings and controls used no antipsychotics. Forty-three percent of patients, 21.3% of siblings and 9.1% of controls used antidepressants; 43.9% of patients, 2.1% of siblings and none of the controls used a mood stabilizer. We are currently analyzing the medication data over time in relation to (change in) metabolic syndrome status and the effects on the brain.

GROUP is a longitudinal cohort study in patients with psychotic disorders, their healthy siblings and controls without psychosis. This naturalistic substudy examines medication use, its association with (change of) metabolic status and effects on the brain in subjects with (high risk of) psychosis.

The authors have not supplied their declaration of competing interest.

Long-term functional outcome of dose-reduction/discontinuation strategies in first-episode psychosis (FEP) has not been studied before. The present study compared 7-year outcome of an early antipsychotic dose-reduction/discontinuation (DR) strategy with maintenance treatment (MT). Primary outcome was (symptomatic and functional) recovery; relapse rates, functional and symptomatic remission were secondary outcomes.

FEP patients (n = 128) symptomatically remitted for 6 m during their first treatment year who completed an 18 months trial comparing MT and DR were followed-up at 7 years. Symptomatic remission criteria were adopted from Andreasen et al., functional remission criteria were based on a functioning scale. Recovery was defined as meeting both criteria sets. MT or DR strategy, and baseline parameters were entered in a logistic regression analysis with symptom and functional remission and recovery at 7-years follow-up as dependent variables.

One hundred and three patients consented to participate. DR-patients showed twice the recovery-rate of MT-patients (40% against 18%), odds ratio 3.5 (P = .014). Symptomatic remission-rates were equal (69% and 67%). Better DR recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR. Predictors of recovery were DR, baseline living together and less severe negative symptoms. During the last 2 years of follow-up the mean daily dose in haloperidol equivalents was 2.20 mg in DR vs. 3.60 mg in MT (P = .031).

Relapse rates were initially higher in DR but leveled at 3 years; 61.5% relapsed in DR and 68.6% in MT in 7 years.

DR of antipsychotics during early stages of remitted FEP significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment. Though initially relapse rates in GD were higher, these equalled those in MT from 3 years to the end of the study. While the necessity of immediate antipsychotic treatment in FEP and positive symptoms relapse is robustly demonstrated in a great number of studies, this study suggests that we are faced with a dilemma concerning the drawbacks of long-term maintenance antipsychotic treatment on functional capacity. Though antipsychotic discontinuation appears only feasible without relapse in a substantial minority of patients, guided dose-reduction as far as positive symptoms remain subsided and allow it, appears a feasible strategy in view of functional recovery, doing justice to both sides of the dilemma.

The authors have not supplied their declaration of competing interest.

ADHD is defined in DSM-5 by developmentally inappropriate and impairing levels of inattentive and hyperactive-impulsive symptoms. However, emotional dysregulation is considered to be an associated feature of the disorder that supports the diagnosis of ADHD. The common co-occurrence of emotional liability (EL) in ADHD raises the question of whether EL should be viewed as a component of ADHD or reflecting a comorbid condition.

To address the question of whether EL should be viewed as a third dimension of ADHD.

We investigated the association of EL with ADHD and impairment scores, in a sample of adults with ADHD that had been carefully selected for absence of comorbid conditions that could give rise to EL using both rating scale and experience sampling methods to measure emotional instability. We reviewed the effects of stimulants and atomoxetine on EL and the covariation of EL with ADHD inattention and hyperactivity-impulsivity. We further considered the phenotypic and genetic association of EL with ADHD using population twin data.

From these studies, we found that EL is strongly associated with ADHD even in non-comorbid cases and gives rise to additional impairments after ADHD symptoms are controlled for in the analysis. Stimulants and atomoxetine both improve EL and these improvements are correlated with changes in ADHD symptoms, indicating a shared treatment response. Genetic model fitting suggests a common pathway model, consistent with a single genetic liability for inattention, hyperactivity-impulsivity and EL.

Taken together these findings suggest that EL can be viewed as a third dimension of ADHD. Patients presenting with chronic emotional instability should always be screened for ADHD.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Affective dysregulation is a core feature of bipolar disorder (BD) and a significant predictor of clinical and functional outcome. Affective dysregulation can arise from abnormalities in multiple processes. This study addresses the knowledge gap regarding the precise nature of the processes that may be dysregulated in BD and their relationship to the clinical expression of the disorder.

Patients with BD (n = 45) who were either in remission or in a depressive or manic state and healthy individuals (n = 101) were compared in terms of the intensity, duration and physiological response (measured using inter-beat intervals and skin conductance) to affective and neutral pictures during passive viewing and during experiential suppression.

Compared to healthy individuals, patients with BD evidenced increased affective reactivity to neutral pictures and reduced maintenance of subjective affective responses to all pictures. This pattern was present irrespective of clinical state but was more pronounced in symptomatic patients, regardless of polarity. Patients, regardless of symptomatic status, were comparable to healthy individuals in terms of physiological arousal and voluntary control of affective responses.

Our study demonstrates that increased affective reactivity to neutral stimuli and decreased maintenance of affective responses are key dimensions of affective dysregulation in BD.

The author has not supplied his declaration of competing interest.

To explore if emotional instability is a useful construct in adults with autism spectrum disorder (ASD) and intellectual disability (ID).

The current diagnostic criteria for ASD and ID will be outlined and related to any relevant literature on emotional instability in those with ASD or ID. Recent cross-sectional studies in a clinic and a prison of adults with ASD and/or ID using standardised screening and diagnostic tools will be described.

Current literature indicates there is little research on emotional instability in adults with ASD and ID. Studies across clinic and forensic settings indicate high levels of comorbidity such as attention-deficit hyperactive disorder (ADHD) and mood disorders in adults with ASD and ID.

At present emotional instability as a construct may not have validity for adults with ASD and ID but may do in the context of other comorbid conditions such as ADHD.

The author has not supplied his declaration of competing interest.

A meta-analysis was conducted to determine the effect sizes of placebo effect in 21 controlled studies on rTMS in the treatment of AVH in schizophrenia. MRI was also acquired in patients treated by rTMS to evaluate the scalp to cortex distances (SDCs) and the gray matter densities (GMDs) at the target of stimulation. Finally, we evaluated the efficacy of high (20 Hz) frequency stimulation in a controlled placebo study.

Weak or no placebo effect in the control groups led to reveal a superiority of active rTMS over sham rTMS in the treatment of AVH. Clinical efficacy of rTMS was also correlated with the SCD or the GMD at the region of the target stimulation. Finally, we also demonstrated that more responders were observed after 2 weeks in the active group treated by 20 Hz than in the placebo group.

We clearly demonstrated that several factors such as high frequency, the placebo effect, anatomical cortical variations can impact on the efficacy of rTMS. These results fundamentally inform the design and the method of further controlled studies, particularly with respect to studies of rTMS in the treatment of AVH.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

Depression and anxiety disorders are among the most common childhood psychiatric disorders. Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line treatment for both depression and anxiety in this age group. However, it has been reported that 30%–40% of all patients who receive a sufficient dose and duration of treatment fail to respond. Moreover, SSRI use is frequently associated with serious adverse events (SAE), including activation symptoms, manic switch and increased suicidal behavior. These are particularly relevant in pediatric populations because of concerns about the suicide threat of SSRIs, resulting in a black-box warning. Currently there is no way of knowing in advance who of the patients will respond. Identification of biomarkers that would be early predictors of response and of the occurrence of SAE could help to maximize the benefit–risk ratio for the use of SSRIs, and speed up the matching of treatment to patient. The main objective of this project is therefore to identify and validate biomarkers predicting response and SAE in depressed children and adolescents, thus improving treatment, enabling the development of novel diagnostic tests and suggest novel therapeutic targets for future related drug development.

As a preliminary pilot, we already obtained blood samples from 80 depressed and anxious children and adolescents over the last year before, during and after eight weeks of fluoxetine (FLU) therapy. Genetic and epigenetic samples were collected from all participants. The patients were treated with FLU 20–40 mg/day for 8 weeks. Clinical response was measured with several scales including the Children's Depression Rating Scale–Revised (CDRS-R), the Beck Depression Inventory (BDI) and the Screen for Child Anxiety Related Emotional Disorders (SCARED).

The participant's age ranged from 6 to 18 (14.12 ± 2.30) years. The overall response rate was 56%. Ten percent responded with SAE. Regarding Pharmacogenetics, The 5-HTTLPR ss genotype was associated with a poorer clinical response with regard to depressive symptoms as well with fewer reports of agitation compared to the ll genotype. Regarding immune measures, we analyzed cytokine levels from 41 children. Plasma concentrations of TNF-α, IL-6 and IL-1β were measured by enzyme linked immunosorbent assays (ELISA) before and after FLU treatment. Antidepressant treatment significantly reduced TNF-α levels (P = 0.037), with no significant changes in the levels of IL-6 and IL-1β. All three pro-inflammatory cytokines were significantly (P < 0.05) higher in SSRI-refractory than SSRI-responsive patients, i.e.: higher levels of TNF-α, IL-6 and IL-1β might predict non-response to fluoxetine treatment in children.

Out of the study sample we selected 13 remitters and 13 non-responders and 10 children with SAE (activation symptoms, manic/hypomanic switch, increased suicidality), and analyzed expression profiles in peripheral blood at admission and after 8 weeks of treatment using illumine Truseq technique. Hopefully, we shall find significant differences in miRNA profiles between the different groups which may serve as biomarkers indicating AD treatment response and SAE. The differentially regulated miRNA's can be studied in depth in the future in animal models in order to support the hypothesis that they may be involved in the AD mechanism.

The authors have not supplied their declaration of competing interest.

In psychological autopsy studies, at least half of suicides have suffered from depressive or bipolar disorders at time of death. Improving access to care and provision of evidence-based pharmacotherapies can be important preventive measures.

To examine suicide risk and pharmacoepidemiology in mood disorders; evidence for efficacy of pharmacotherapies in mood disorders and in preventing suicidal behaviour in them, and limitations to effectiveness of treatment due to problems of adherence.

To evaluate potentials for suicide prevention in mood disorders by improved access to treatment, improved quality of treatment provision, improved adherence, or by specific pharmacotherapies.

Selective review of literature.

Risk of suicide death and attempts in mood disorders clusters into major depressive and mixed illness episodes, and time spent in them is a major determinant of risk, but direct evidence for preventive effects of effective pharmacotherapies remains limited. Observational and randomized studies indicate lithium treatment to reduce risk of suicide deaths and attempts. Ecological evidence from Europe shows increasing sales of antidepressants to consistently associate with declining regional suicide rates. Forensic chemical studies still find majority suicides negative for antidepressants. Poor adherence is a central problem in treatment provision.

Positive impact of increase in pharmacotherapy provision in the last few decades on suicide mortality remains uncertain. Lithium is the pharmacological agent with best evidence for preventive utility, but underused. Providing treatments for those at risk, improving quality and continuity of treatment, and integrating them with psychosocial approaches is likely to be beneficial for suicide prevention.

The author has not supplied his declaration of competing interest.

New knowledge has emerged about decision-making, mood regulation, social distortions and learning that is relevant for the diathesis for suicidal behavior. All four domains have identified underlying neural circuits and for decision-making and mood regulation also specific neurotransmitter systems.

We have conducted PET studies of the serotonergic system and CSF studies of the serotonin, norepinephrine and dopamine neurotransmitter systems in patients surviving suicide attempts to determine whether they have neurotransmitter abnormalities that resemble those found in the brain after suicide. We found alterations in the serotonin transporter and the 5-HT1A receptor that are similar to those seen in suicides and moreover the severity of the abnormality in 5-HT1A binding is correlated with the lethality of suicidal behavior. Other studies examining CSF levels of 5-HIAA are consistent with imaging data and extend the findings to the noradrenergic and dopaminergic systems. Finally, we will present data on use of these biomarkers to predict treatment outcome. Abnormal decision-making and mood regulation in suicidal patients is linked to abnormal brain biology and has direct implications for clinical practice in terms of selecting specific types of medication and how these may be best combined with psychotherapies.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

The goal of value-based healthcare is to improve the quality of care while also lowering healthcare costs. Values may also include societal or research benefits.

To outline the emergence and quality-related concepts of value-based healthcare.

To give a comprehensive overview and critical discussion of quality aspects of value-based mental healthcare including aspects of personal, societal and scientific values.

Review of quality aspects of value-based mental healthcare.

The quality aspect of value-based healthcare includes the implementation of patient-centered care and may include the assessment of societal values or values for research purposes. Current concepts focus on the reduction of disability-adjusted life years to measure the achievement of values, but may need to be broadened to include benefits to society as a whole or the progress of knowledge about mental disorders in research. Conceptually, addressing such broader value issues may lead to increased benefits and a better appraisal of the value of mental healthcare.

The trend towards value-based mental healthcare aims at creating an efficient care delivery model, that strongly focuses on achieving favorable patient outcomes and may in the future also include creating societal values. It includes the development and implementation of suitable mental health policies and comprehensive quality assessment, plus a broad conceptualization of the value-term and its assessment in value-based mental healthcare.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.