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.

Current service configuration of distinct Child and Adolescent Mental Health (CAMHS) and Adult Mental Health Services (AMHS) is considered the weakest link where the care pathway should be most robust. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge for the EU.

The overall objective of the MILESTONE project is to improve transition from CAMHS to AMHS in diverse healthcare settings in Europe.

To improve the understanding of current transition-related service characteristics, and processes, outcomes and experiences of transition from CAMHS to AMHS using a bespoke suite of measures; to explore the ethical challenges of providing appropriate care to young people as they move to adulthood; to test a model of managed transition in a cluster randomized controlled trial (cRCT) for improving health, social outcomes and transition to adult roles; and to develop training modules for clinicians and policy guidelines.

Data will be collected via systematic literature reviews; bespoke surveys to CAMHS professionals, experts and other stakeholders; focus groups with service providers and users and members of youth and mental health advocacy groups; and a longitudinal cohort study with a nested cRCT in eight EU countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS service users, their parents/carers, and clinicians, with assessments at baseline, 9, 18 and 27 months.

First results are expected in 2016 with further major findings following in 2019.

The MILESTONE project will provide unprecedented information on the nature and magnitude of problems at the CAMHS-AMHS interface, and potential solutions to overcome these.

The authors have not supplied their declaration of competing interest.

Alcohol dependence has long been related to impaired processing and handling of negative emotions. This is the first study to compare emotion regulation (ER) at a behavioral and neural level in alcohol dependent patients (ADPs) and healthy controls (HCs). It also examines the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on ER abilities and related craving levels in ADPs.

Thirty-six ADPs and 32 HCs matched on age, sex, and education, were included in a within-subject fixed-order study with one functional magnetic resonance imaging (fMRI) session and one rTMS plus fMRI session, with high-frequency (10 Hz) rTMS over the right dorsolateral prefrontal cortex (dlPFC). An fMRI emotion regulation task (ERT) was administered during both sessions and craving was measured before and after each ERT.

ADPs were impaired in the regulation of negative emotion and showed a higher activation of ER related brain areas compared to HCs. Furthermore, active rTMS improved ER abilities in both ADPs and HCs, but was accompanied by a decrease in anterior cingulate and left dlPFC activity only in ADPs. In addition, the ERT-induced increase in craving levels in ADPs was trend-significantly reduced by active rTMS, with a large effect size.

ADPs are impaired in the regulation of negative emotion and show enhanced neural activity in the ER brain circuit. High-frequency rTMS improves ER in ADPs and HCs and normalizes neural activity and tends to reduce craving in ADPs. Future studies are needed to test the long-term effects of (multiple session) rTMS on ER, craving, and drinking.

The authors have not supplied their declaration of competing interest.

Preclinical and clinical data suggest modulating effects of the appetite regulating peptide ghrelin on food intake. Recent data suggest that in food intake the “endostatic” energy-homeostatic systems of the lateral hypothalamus (LH) and the motivational, mesolimbic reward system operate in dynamic interplay with each other. Ghrelin receptors have been detected in the ventral tegmentum of the midbrain (VTA), where they modulate the activity of dopaminergic neurons projecting to the NAc. Assuming that Ghrelin modulate mesolimbic reactivity, the question remains: is this only the case in response to food cues? Or is this the case in response to reward-associated cues in general (including those related to nicotine and alcohol)?

Study 1: a consecutive sample of 61 alcohol-dependent male inpatients was included. Blood was drawn at onset of withdrawal 12-24 hours after admission, and following 14 days of controlled abstinence in order to assess plasma concentrations of both active and total ghrelin. In parallel, we assessed alcohol craving applying the Obsessive Compulsive Drinking Scale (OCDS) as well as symptoms of depression (Beck Depression Inventory [BDI]) and anxiety (State Trait Anxiety Inventory [STAI]). The severity of alcohol dependence was assessed with the Alcohol Dependence Scale (ADS). Study 2: 54 non-treatment seeking smokers and 30 healthy controls with normal eating behavior, as measured by the Three Factor Eating Questionnaire (TFEQ) participated in this study. We measured plasma concentrations of both active and total ghrelin, using a blood sample taken two hours after a standardized meal during early nicotine abstinence in the smoking group. Additionally we quantified severity of addiction in the smoking group using the number of cigarettes smoked per day, cotinine plasma concentration and the Fagerström Test for Nicotine Dependence (FTND).

Study1: we found a significant positive correlation between the plasma concentration of active ghrelin and alcohol craving in both blood samples. Plasma concentrations of active ghrelin increased significantly during early abstinence. In a linear regression model, the plasma concentration of active ghrelin on day one, the scores of the ADS, and the BDI explained 36% of the variance in OCDS sum score (P < 0001). By day 14, these same factors accounted for 54% (P < 0.0001). We did not detect any association between the plasma concentration of total ghrelin and patients’ alcohol cravings. Study 2: plasma concentration of acetylated ghrelin but not total ghrelin was significantly higher in smokers than in non-smokers. Moreover, we found significant negative correlations between acetylated ghrelin and all measures of the severity of nicotine dependence.

In conclusion, both studies supports the general idea that ghrelin's central effects go beyond the endostatic regulation of energy homeostasis, also involving pathways underlying reward expectation and craving. Physiologic factors modulating the reactivity of mesolimbic pathways represent an important research topic for developing pharmacologic treatments for disorders characterized by altered reward-related behaviors, such as substance use disorders and behavioral addictions.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Heritable factors account for approximately 50–60% of the risk for alcohol dependence. However, which genes confer this risk remains to elucidate. Moreover, genetic association studies are hampered by non-replication. Several strategies can be applied to approach this issue. One option is the application of intermediate phenotypes. Neurobiological measures that are closely related to the addiction phenotype may be more directly related to genetic variation. Intermediate phenotypes related to dopamine function seem particularly suitable, given the strong dopamine hypothesis in addiction. Another strategy is to include environmental factors, such as childhood adverse experience, in genetic association studies. We tested the effect of COMT Val158Met and DRD2 Taq1A genotypes, as modulators of brain dopamine function in the context of self-reported environmental factors, like childhood adverse experience.

Alcohol-dependent patients (n = 110) and healthy controls (n = 99) were genotyped for the COMT Val158Met and DRD2 Taq1A genotypes. Childhood adversity was measured using self-report questionnaires. Dopamine sensitivity was assessed using an apomorphine challenge with cognitive performance and plasma growth hormone levels as main outcome measures.

COMT genotype modulated the effect of apomorphine on cognitive performance, but was not directly associated with alcohol dependence. Yet, the interaction between childhood adversity and COMT genotype did predict alcohol dependence. DRD2 genotype modulated the effect of apomorphine on plasma growth hormone levels and was also not directly associated with alcohol dependence. Yet, the interaction between parental rule setting and DRD2 genotype did predict alcohol use in a separate population-based sample of adolescents.

This study provides evidence for a role of COMT and DRD2 genotypes in alcohol dependence using both the GxE and intermediate phenotype approach. This confirms that both an intermediate phenotype approach and GxE interaction analyses can be useful tools in understanding mechanisms mediating addiction vulnerability. The clinical relevance of dopamine genes and intermediate phenotypes for staging and profiling of alcohol use disorders remains to be investigated.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Consultation-liaison psychiatry (CLP) deals with clinical, research and training activities at the interface between psychiatry and the rest of medicine. The main clinical competencies of CLP include medical-psychiatric comorbidity (co-existing psychiatric and non-psychiatric disorders affecting reciprocally); medically unexplained physical symptoms, “somatization” and functional disorders; and liaison activities, addressed to medical workers and teams.

To describe and discuss typical clinical scenarios that CL psychiatrists have to work in, and suggest effective, evidence-based solutions.

Long-standing everyday clinical experience of the authors combined to evidence derived from international literature consented to create a list of the most common and complex problems or difficulties typical of the CLP clinical context, and related possible solutions.

Most common/complex problems include the following: stigma and prejudice (of patients, relatives, colleagues, and own); excessive technicality of language; short/unpredictable duration of hospital stay of patients, and more in general pressure in clinical practice due to shortness of time and resources; tendency of colleagues from other disciplines to disregard setting features related to time and space (inadequate rooms, e.g. too busy or noisy); limited time for face-to-face discussion of cases or problems; conflicts with patients/relatives/colleagues, and fear of reciprocal manipulation.

Moving on the interface between psychiatry and the somatic disciplines, CL specialists need to develop special skills, not only those strictly technical, but also those “soft skills” including relational abilities and flexibility. Understanding the systemic aspects of referrals in the relationship between physician, staff and patients is usually essential in the process of consultation.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

Multimorbidity and polipharmacotherapy are crucial features influencing the psychiatrist's prescription in the consultation-liaison psychiatry (CLP) setting.

to provide an example of computer-assisted decision-making in psychotropic prescriptions and to provide hints for developing pharmacological treatment strategies in the CLP setting.

Case report. A clinical vignette is presented, followed by a review of available online computer-assisted prescription software.

A woman in her seventies was repeatedly referred for psychiatric consultation. Eleven different medications were administered daily, because of multimorbidity. A diagnosis of distymia was established, with comorbid mixed pain (partly fulfilling the criteria of somatic symptom disorder) and substance use disorder (opioids). After the first assessment, six follow-up visits were needed during hospitalization. Mirtazapine and benzodiazepines were introduced. Beside the pharmacological intervention, conflict mediation was performed in the relationship with the patient, her relatives, the ward personnel and the GP, to develop a long-term rehabilitation project. Pros and cons of online computer-assisted prescription software were discussed together with the ward personnel, as well.

Computer-assisted decision-making in psychotropic prescription is becoming more common and feasible. The use of available software may contribute to safety, effectiveness and cost-effectiveness of clinical decision-making. Risks are also possible: depending for example from regional differences in prescription indications, different guidelines, pharmacogenomics, frequency with which databases are updated, sponsorships, possible conflicts of interest, and real clinical significance of highlighted interactions – all issues the clinician willing to benefit from this modern tools should pay attention to.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

In most European countries postgraduate training for specialization in psychiatry and psychotherapy is acquired over the course of 4–6-year programs. In the European Union, qualification in one country is recognized within other countries of the Union.

To analyze the present situation of psychopharmacology-pharmacopsychiatry postgraduate teaching in Europe and to present the needs and preliminary instruments for improving the situation by harmonization of the programs.

Analysis of the data available from national psychiatric societies and from the literature; development of a consensus among experts in this field.

Despite efforts to standardize post-graduate training, the curricula in different European countries vary greatly. This variability limits comparability between countries and international exchange while carrying consequences in the breadth and quality of education that trainees receive. Literature and curricula mainly published in USA as well as a recently published curriculum and learning catalogue in Germany [1] offer useful tools for the development of a curriculum at a European level.

There is clearly a need for standardization of psychopharmacology-pharmacopsychiatry teaching at the European level. This can be achieved by the introduction of a curriculum and learning catalogue developed by European experts and based on tools already available.

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.