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.

Although the onset of bipolar disorder (BD) is usually estimated in early adulthood (Burke et al., 1990; Kessler et al., 1997), it is still not clear which age-specific triggering factors may contribute to the underlying vulnerability.

The present meta-analysis attempts to clarify the number of untreated years of BD, from first symptoms appearance, to first actions carried out by health services (first diagnosis, treatment and hospitalization).

A literature search of three databases PubMed, Web of Science and Psychology and Behavioral Sciences Collection was performed, looking for peer-reviewed publications in English, French, German and Italian language that reported the AOO of BD; the search string adopted was “bipolar and onset”. Standardized mean differences were calculated between (i) mean AOO, operationally defined as onset of first symptoms/episodes, and (ii) mean AOO, operationally defined according to four criteria: first contact with services, date of the diagnosis, first pharmacological treatment, or first hospitalization.

The searches yielded 8710 articles; 2424 of these articles met the inclusion criteria. A final set of 19 studies presenting multiple definitions of AOO has been analyzed, revealing an overall effect size of 6.96 of untreated years (Cohen's d = 0.65)

To our knowledge, this is the first meta-analysis that addresses the definition and the modulation of the AOO in bipolar disorder. Identifying the time-frame of untreated illness is very important for the best planning of timely interventions.

The authors have not supplied their declaration of competing interest.

Age of onset of mental disorders: etiopathogenetic and treatment implications.

Age of onset (AOO) of anxiety disorders could serve as a vital statistic in the formulation of mental health policy. Previous reviews have reported on the AOO of anxiety disorders in the general population. However, these review studies did not systematically estimate the AOO of different anxiety disorder subtypes, and did not examine factors that might have influenced reported AOO.

The aims of the present study were (1) to estimate the AOO for all anxiety disorders and for specific subtypes, (2) to examine gender differences in AOO of anxiety disorders, and (3) to examine the influence of study characteristics on reported AOO.

Seven electronic databases were searched with keywords representing anxiety disorder subtypes, AOO and study design. The inclusion criteria were studies using a general population sample that provided data on AOO for all anxiety disorders, or specific anxiety disorders, according to DSM-III-R, DSM-IV or ICD-10 criteria. Meta-analysis was used to estimate AOO and gender differences, while meta-regression was used to examine the influence of study characteristics.

A total of 1028 titles were examined, which yielded 24 studies meeting the inclusion criteria. Meta-analysis found an average AOO of all anxiety disorders of 21.3 years (95% CI: 17.46 to 25.07). Separation anxiety disorder, specific phobia and social phobia had their mean onset before the age of 15 years, whereas AOO of agoraphobia, obsessive compulsive disorder, post-traumatic stress disorder, panic disorder and generalized anxiety disorder began on average between 21.1 and 34.9 years. Anxiety disorder is more common in women, but meta-analysis revealed no difference in AOO between genders. Prospective study design and higher developmental level of the study country were associated with earlier AOO.

Results from this meta-analysis indicate that anxiety disorder subtypes differ in mean AOO, with onsets ranging from early adolescence to young adulthood. These findings suggest that prevention strategies of anxiety disorders should be directed towards the factors associated with the development of subtypes of anxiety disorder in the age groups with the greatest vulnerability for developing those disorders.

The authors have not supplied their declaration of competing interest.

The sample is composed of 2200 AN subjects and 900 BN subjects without previous AN consecutively referred to our outpatient Unit in the period between 1985 and 2014. Time trends have been analysed according to the year of birth of subjects. All diagnoses were reviewed according to DSM-5 criteria.

Age of onset in AN showed a significant decrease according to year of birth. A regression model showed a significant independent effect of socio-economic status, age at menarche and number of siblings in predicting age of onset. A second analysis including a subsample representative of the general population confirmed the effect in AN. In BN, although the age of onset showed a decrease in new generations, the effect is not significant.

Age of onset of AN continues to decrease in younger generations. The implications of our findings in terms of long-term outcome remain to be understood. Biological and socio-cultural factors explaining this phenomenon need to be explored by future studies. It is important to acknowledge the clinical implications of this cohort effect.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

Transition to adulthood is the period of onset of most serious mental disorders. The current discontinuity of care between Child and Adolescent Mental Health (CAMHS) and Adult Mental Health (AMHS) Services is a major socioeconomic and societal challenge for the EU.

In the framework of the MILESTONE project this study aims to map current services and transitional policies across Europe, highlighting current gaps and the need for innovation in care provision.

An on-line mapping survey has been conducted across all 28 European countries through the administration of two ad-hoc instruments: the Standardized Assessment Tool for Mental Health Transition (SATMEHT) and the European CAMHS Mapping Questionnaire (ECM-Q). The survey systematically collected data about CAMHS organization and characteristics, with a specific focus on actual national transition policies and practice.

Response rate was 100%. Despite up to 49% of CAMHS service users need to continue with specialist AMHS care, written policies for managing the interface between these two services are available only in 4/28 countries and transition support services are reported as missing by half of the respondents. Lack of connection between CAMHS and AMHS is reported as the major (82%) difficulty experienced by young service users.

Preliminary results indicate a marked variability in characteristics of services and in data activity among the 28 European countries, with important missing information at national level about CAMHS and their functioning. All these conclusions warrant an improvement in data collection and service planning and delivery.

The authors have not supplied their declaration of competing interest.

Young people (YP) with attention deficit hyperactivity disorder (ADHD) are recognized to be a group who are particularly vulnerable to falling through the gap regarding transitioning from Child and Adolescent Mental health Services (CAMHS) to Adult Mental Health Services (AMHS). This presentation will combine a systematic review of the literature with some clinical examples of the pathway for a number of YP with ADHD who reach the transition boundary (TB).

(1) Databases (e.g., PubMed, PsycINFO, AMED, CINAHL, EMBASE, Web of Knowledge), and grey literature, were searched systematically with database-specific key words, variants and truncations, to cover six subject areas: ADHD; transition or transfer; age; experiences or views; service development; and policies or protocols. Hand searching of key journals, ancestry and forward searches of references, and expert consultation were conducted. Two reviewers critically evaluated studies using a validated appraisal tool for mixed methodologies and findings were synthesized. (2) Following ethical approval, CAMHS clinicians from 9 clinics in Republic of Ireland identified all cases where a YP with ADHD had reached the TB, and identified referral/service outcomes (n = 20).

The search yielded 27 studies, covering areas of service review and recommendations (7), guidelines (3), medication (5), case note audit (3), professional's views (5), pilot transition clinics (2). A further set of papers covered the perspective of the young person (4) and parent (2). Overall these highlighted the less than optimum experience by both clinicians and service users of the experience with suggestions for future developments. These findings were mirrored in the review of clinical notes and individual interviews of YP identified through their CAMHS. Of the 20 young people identified, only 1 was directly transferred to AMHS. Eight were retained in CAMHS, on average for over a year. A significant number (7) refused onward referral. A perception from CAMHS clinicians, that AMHS did not accept such cases or lacked relevant service/expertise, may have contributed to the low rate of referral.

Both the extant literature and the specific study presented highlight the lack of clear cut consensus about the appropriate management of young people with ADHD have who reach the transition boundary. Low rates of AMHS transfer may come from CAMHS clinicians’ perceptions of AMHS, and preferences of young people and families. Before assuming the very low rate of referral by CAMHS clinicians is poor practice, clinical outcomes need to be identified, young people's reasons for refusing transfer explored and service options identified.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.