New title, or subtitle: „Current knowledge on the neurobiology of classical hallucinogens and their relevance for the treatment of mood and anxiety disorders‘

Hallucinogenic substances have been used for millenia. Still, the scientific investigation into the effects and mechanisms of classical hallucinogens in humans has only commenced with the discovery of LSD by Albert Hofmann in 1943. In the 1960’s, there were more than a thousand clinical studies that reported promising therapeutic effects of LSD and psilocybin in psychiatric patients. Only recently, however, the neuropharmacological and neurobiological underpinnings of hallucinogenic drugs have undergone systematic investigations. Despite having different chemical structures, classical hallucinogens produce striking similar subjective and behavioral effects in both animals and humans. Activation of the serotonin 2A (5-HT2A) receptor is a core feature in hallucinogenic pharmacology. Recent neuroimaging studies have begun to elucidate the brain mechanisms underlying hallucinogen-induced changes of thought, perception, and mood. Among the many networks involved in hallucinogen-related states of consciousness, the prefrontal cortex and the limbic regions appear to be especially relevant to the putative antidepressant effects of classical hallucinogens. Furthermore, hallucinogens may foster neuroplastic adaptations within cortico-subcortical brain networks. This appears to be a promising mechanism with regard to future clinical studies into the effects of classical hallucinogens in depression and anxiety.

Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition.

In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test.

The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy.

These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.

Alzheimer’s disease is now seen as a process that starts decades before cognitive impairment occurs and becomes severe enough to cause dementia.

It has been acknowledged, that biomarkers of this process (e.g.: CSF, structural MRI,FDG-PET (positron emission tomography), Amyloid-PET) increase diagnostic certainty and facilitate early diagnosis under the ultimate goal of early intervention.

This presentation will focus on PET-imaging of cerebral glucose metabolism by18-[F]-FDG-PET and cerebral beta-amyloid-deposition by the amyloid-binding PET Tracers (11-[C]-PiB, 18-[F]-Florbetapir, 18-[F]-Flutemetamol) and its value for the understanding, early detection and differential diagnosis of Alzheimer’sdisease.

It will highlight clinical situations in which these diagnostics are considered useful and potential caveats.

Finally it will provide a perspective how dementia diagnostics may evolve to in vivo assessment of pathology that predicts clinical phenotype and ideally therapeutic intervention.

Behavioural and psychological symptoms of dementia (BPSD) such as agitation, aggressive behaviour, repetitive vocalizations, apathy, etc. are a frequent challenge in the care for patients with dementia. BPSD are furthermore associated with individual suffering, reduced quality of life and caregiver burden. This talk will provide an update on current pharmacological and non-pharmacological treatment strategies for BPSD on the basis of the relevant guidelines and a review of the current literature. For pharmacological treatment, the focus has recently shifted from antipsychotics to antidepressants due to their more favourable risk/benefit profile. Treatment algorithms that include behavioural diagnostics and both pharmacological and non-pharmacological interventions will be presented as a tool to guide clinical practice.

Recent deliberations gave rise to the assumption that some forms of irritability, irritation, or cognate states might represent an independent mood disorder. Reports in responsiveness observed in some of these states to specific kinds of pharmacotherapy appear to additionally support this theory. Research into this field, however, is hampered by the fact that, to date, such conditions have eluded clear psychopathological definition. This situation might perhaps be ameliorated by closely reviewing the concepts of ‘dysphoria” – a term very irregularly utilized in designation of various outward manifestations of ill-humor.

‘Dysphoria’ is often used as the most generic word for any kind of negative emotion. It can be better defined as an unmotivated and quasi-ineffable constellation of feelings that convey a nebula of vague sensations and impulses, an uncomfortable feeling characterized by being sorrowful and indignant. The intentional structure that characterizes much of human emotional experience is absent in dysphoria. Emotions are fluxes of intentionality that innervate the flesh and connect it to the world. Dysphoria is an emotional state saturated with a brimming constellation of feelings without any explicit object or target, a state of tension that may lead to spontaneously vigorous outbursts as well as to pale stagnation or emotional depletion. Dysphoria is empty intentionality devoid of the moderating power of language and representation which fragments the person’s representations of herself and of others and inducing painful experiences of incoherence and inner emptiness, threatening feeling of uncertainty and inauthenticity in interpersonal relationships, and excruciating sense of insignificance, futility and inanity of life. Dysphoric persons experience their own self as dim and fuzzy, and feel deprived of a defined identity and unable to be steadily involved in a given life project or social role. But it also entails a sense of vitality, although am aimless and explosive one – a desperate vitality. Dysphoria is felt as a disordered, overwhelming flux which is at the same time a disorganizing and compelling source of vitality. Dysphoria is felt as creative and destructive – a vigour that brings life as well as annihilation: a violent spasm that takes control of the body and a power that expresses vitality in touch with the source of all sensations.

Although often enlisted as just one of the possible mood symptoms of schizophrenia spectrum disorders, dysphoria-irritability can be particularly pervasive in patterning both the cross-sectional presentation and the longitudinal clinical trajectory. Dysphoric mood gives rise to divergent, parossistic and intense emotional states as well as to peculiar bodily feelings with a certain nuance of tension and reactivity. Most importantly, dysphoria transforms the significance of things in the world, infusing daily interpersonal experience with those preparatory features that could facilitate the nucleation of overt psychotic symptoms.

Differential phenomenology of dysphoria in affective, epileptic and borderline personality disorders

Dysphoria is a very vague and unspecific term in psychopathology. Neither in classical authors, such as Kraepelin or Wernicke, nor in modern handbooks or manuals, is it possible to find any precise definition of this symptom or state. In German texts sometimes appears as synonym of ‘”Verstimmung”, which simply means ‘alteration of the mood”. In Jaspers General Psychopathology the term is found in two occasions: one in relation to the fugue states of epilepsy and the other as mood-change appearing in form of attacks in ‘constitutional disorders”. ‘The change is a sudden fall into an abnormal state and as such is very often experienced subjectively with a great deal of anxiety”. A long experience in a general psychiatric hospital allows this author to suggest the use of this term for a specific form of mood disturbance, characterized by suddenly onset, irritability, dissatisfaction with oneself and a negative (depressive like) mood. This author has seen such mood changes in three different pathologies: affective disorders, epilepsy and borderline personality disorders. In this essay he tries to carry out a differential phenomenology of dysphoria, that is, to determine which the characteristics of this phenomenon in each one of the mentioned pathologies are.

Every individual is born into culture and has cultural values, norms and models integrated in their being. Cultural values affect cognitive schema and therefore our world view. Cultures determine deviance and abnormality and suggest which health care systems to be followed and what resources should be allocated to them. There is little doubt that, both in physical and mental illness, culture impacts upon presentation, development and perpetuation of symptoms. Cultural psychiatry has developed as a speciality in its own right during the last 75 years or so. Cultural competency is defined as an ability to understand and be aware of cultural factors in the therapeutic interaction between the therapist and the patient. These include awareness of social, cultural, religious factors, attitudes, behaviours, models and explanations. This should be applicable to all patients and all therapeutic interactions. Cultural competency training at its core is about good clinical practice and the clinicians. It is about an understanding of the concepts of culture and how cultures can influence human behaviour, interpretations of that behaviour and how that behaviour is evaluated. It is about the ability to understand one’s own prejudices, a willingness to identify and explore one’s own cultural base (values, beliefs and attitudes) and to identify useful and culturally appropriate strategies for working with people from diverse cultural backgrounds. The therapist must be aware of their own likes, dislikes, beliefs stereotypes, of their own identity; and must possess an ability to be neutral and open-minded, an ability to learn about other cultures and differences as well as the strengths and weaknesses of their own/other cultures.

Mental health systems in European countries are undergoing reform. In Central and Eastern European countries, this means a shift from institutionally centred care to community based mental health services. This requires changes to ways of working and competencies, both in hospital settings and in the community, stradling specialist mental health services and primary care.

A concern expressed by policy makers annd managers is the absence of information about quality of care and cost and outcomes of interventions, both of old and new services. Management information systems are rudimentary, relying on basic process data related to reimbursements, and practice guidelines are often not availlable or monitored. This hinders changes of practice, since there are no indicators that show areas of poor care, or improvements in outcome or satisfaction following change. Incentives often are perverse, reinforcing the status quo in the absence of information that would encourage change.

The European Mental Health Action Plan is endorsed by all European Member States, and proposes actions to address these challenges. This requires a partnership between policy makers and professionals to agree practice guidelines and outcome indicators that are meaningful and feasible. EPA and WHO are considering steps to take this forward.

Serotonergic mechanisms can be investigated by experimental manipulations via drug challenges or by systematic variations of serotonergic genotypes. Both interventions should however converge on common mechanisms underlying human affective or cognitive processing or their deviation in depressive disorders. Alterations and variations of brain circuitry will be discussed as revealed by means of non-invasive fMRI studies in humans. Activations of brain regions and entire networks during explicit task paradigms will be compared to changes of brain network circuitry during resting state conditions.

This perspective shall shed light on the complex interaction of brain and environment during serontonergic modulation of social behavior.

Cortical 5HT2A receptors are largely expressed in layer 5 pyramidal neurons and appear to play a pivotal role in brain function in that they gate top-down descending inputs to local cortical microcircuits. There is evidence that they may play a role in depression in that the number of these receptors is increased in some people with depression and the augmenting action of atypical antipsychotics in depression is thought to be – at least in part – due to blockade of these receptors. We have explored this possibility by studying the effects of agonists at these receptors – the psychedelic druds psilocybin and LSD. We found they had profound effects to reduce brain activity particularly in regions that higly express the 5HT2A receptor such as the default mode network [DMN]. As this region is overactive in depression this may explain the improvements in mood that users of psychedelic often report. Based on these findings a study of psilocybin in resistant depression has been funded by the UK MRC and will start in early 2015.

Antidepressants represent the standard treatment for major depression. However, their efficacy is variable and incomplete. A growing number of studies suggest that the environment plays a major role in determining the efficacy of these drugs, specifically of selective serotonin reuptake inhibitors (SSRI). We recently hypothesized that the increase in serotonin levels induced by SSRI may not affect mood per se, but enhance neural plasticity and, consequently, renders the individual more susceptible to the environment. Thus, SSRI administration in a favorable environment would lead to a reduction of symptoms, while in a stressful environment might lead to a worse prognosis. To test this hypothesis, we treated C57BL/6 adult male mice with chronic fluoxetine while exposing them to either (i) an enriched environment, after exposure to a chronic stress period aimed at inducing a depression-like phenotype, or (ii) a stressful environment. A wide number of molecular, cellular and behavioral endpoints considered endophenotypes of depression were investigated. These include long-term potentiation, BDNF levels, hypothalamic-pituitary-axis activity, neurogenesis, anhedonia and optimistic attitude (cognitive bias). Mice treated with fluoxetine in an enriched condition improved their depression-like phenotype compared to controls, displaying an overall reduction of all endophenotypes of depression investigated. By contrast, when chronic fluoxetine administration occurred in a stressful condition, mice showed a more distinct worsening of the depression-like profile. Our findings suggest that the effect of SSRI on depression-like phenotypes in mice is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

Since 3 years matters of ethics are in an increasing way on the agenda of the European Psychiatric Association. Intensive discussions in the associations ethical committee have scrutinized the problems and elucidated the range of ethical dilemmas. A questionnaire sent by the Committee to European Psychiatric Associations has given a panorama of the ethical problems in European Psychiatry and shown their diversity and even communalities. This overview has been presented at different meetings of the EPA and has recently been reviewed, updated and additionally commented by all committed European national associations. Hereby, new problems in European psychiatry have emerged or became intensified, e.g. the demand on psychiatry’s involvement in end of life issues as well consequences of the limitation of resources, specificities of financing routines in times of resource limitations and ways of prioritizations within medical care and mental health support implied by an all more predominant market economical system.

Other re-emerged problems are questions and problems in contact with private sectors of users organizations, care providers or pharmaceutical industries and the need and strategies for multisectorial involvement in psychiatric education and research support. Here, again a need of ethical guidelines in psychiatrists contact has become actualized, especially regarding the needs of young psychiatrists and is one of the focuses in this symposium.

In this contribution, these newly emerged ethical challenges will be elucidated, the positions of national psychiatric associations and their recently updated priorities regarding ethical challenges will be reviewed and the activities and structures of EPAs further activities on ethics will be presented for discussion.

Today‘s generation relies on the Internet as their main source of information and uses it for a variety of purposes, including professional networking and education.

With regard to the nature of a therapeutic relationship, it is necessary to establish certain professional boundaries between psychiatrists and their patients. These boundaries can be compromised by a patient‘s request to connect online via social networks. Moreover, disclosure of patient-identifiable information can undermine the assurance of doctor-patient confidentiality. Another potential drawback is the excessive and careless disclosure of private information by the psychiatrist.

The use of emails for psychiatric clinical work can cause concerns on different levels. Firstly, confidentiality of email conversations can not always be garanteed. Secondly, patients and families trying to directly reach clinicians by finding their emails on the internet can disrupt the usual course of care.

The use of smartphone apps and gathering of data through them also creates new ethical issues. The consequence of constantly monitoring citizens by state-sized private companies is a concern, like the use of private or medical data to promote products and influence behaviours, or to determine insurance policy rates.

Due to these ethical challenges, many psychiatrists simply ignore social media and new information technologies. However, they miss valuable opportunities to engage in public health and policy discussions, establish national and international professional networks, and facilitate patients’ access to information about health and services.

These questions and precautions should be inculcated as a part of the psychiatric training so that psychiatrists in the 21st century will be able to navigate themselves in the rapidly developing social media arena as cautious, yet active members.

Interactions between the pharmaceutical industry and physicians have recently received attention for their potential to create conflicts of interest in clinical practice, research and education. As a consequence, several medical and psychiatric associations including the EPA have published guidance papers to encourage best practice. In this context, the European Federation of Psychiatric Trainees (EFPT) performed a cross-sectional survey among European psychiatric trainees in order to ascertain the current level of interactions, as well as beliefs and attitudes towards interactions with the pharmaceutical industry. Responses from 1444 psychiatric trainees from 20 countries were obtained and reveal important differences in the level of interactions across Europe. Assigning a an educational role to the pharmaceutical industry and aid by senior psychiatrists in organizining industry-sponsored events were associated with a higher degree of interactions. Creating alternative, non-industry-sponsored educational opportunities and specific training dedicated to industry interactions may help to reduce the impact of the pharmaceutical industry on psychiatric training in the future.

The WHO World Suicide Report ‘Preventing suicide: a global imperative” is the first global report of its kind. The report provides a systematic, evidence-based approach to policy and programme development which can be adapted to suit existing health and social structures and, where countries have already commenced this process, provide guidance on strengthening their approaches. The report aims to increase the awareness of the public health significance of suicide and suicide attempts and to make suicide prevention a higher priority on the global public health and public policy agendas. It aims to encourage and support countries to develop or strengthen comprehensive suicide prevention strategies in a multisectoral public health approach.

The target audience includes Ministries of Health, policy makers, planners, advocates, nongovernmental organizations, academics, researchers, health workers, the media, and the general public. Governments in particular are in a unique position to develop and strengthen surveillance, to provide and disseminate data that are necessary to inform action, and to bring together a multitude of stakeholders who may not otherwise collaborate.

The presentation focuses on the global and regional epidemiology of suicide and suicide attempts, which is the first theme of the report; other themes include risk and protective factors, and related interventions; current situation and working towards a comprehensive national response for suicide prevention; and the way forward.