Values Based practice is a new skills-based approach to balanced clinical decision making where complex and conflicting values are in play. In medicine, complex and conflicting values have traditionally been associated in particular with ethical issues of the kind raised by treatment. This paper will use a clinical case history to show that complex and conflicting values are no less important in diagnostic assessment than in treatment. Various interpretations of the importance of values in diagnosis in psychiatry will be outlined. In the final part of the presentation I will outline some of the practical applications of a values-based approach in supporting policy and service developments that are both evidence based and person centred.

The Self in Schizophrenia: Jaspers, Schneider and beyond.

The concept of self-disorders has always played a major role for the psychopathology of the psychoses. In his General Psychopathology, Jaspers distinguished what he called ego-consciousness from object-consciousness and characterized it by the sense of activity, unity, identity and ego-demarcation. On this basis, Kurt Schneider later coined the term “Ich-Störungen” (ego-disorders) for the schizophrenic experience of one's thoughts, actions, feelings or bodily sensations being influenced or manipulated by others. In contrast, in ICD 10 or DSM IV these symptoms are regarded as bizarre delusions, commonly referred to as delusions of control or of passivity.

In my paper, I will give a short historical introduction into the problem of self-disorders. Then I will analyse the possible connection of ego-disorders with more basic disorders of self-awareness. I will argue that full-blown delusional convictions of alien control are based on a disturbance of the intentionality of thinking, feeling and acting. This disturbance of intentionality, for its part, may be traced back to a lack of prereflective self-awareness which has been emphasized by more recent phenomenological approaches to schizophrenia.

The concept of self-disorders has always played a major role for the psychopathology of the psychoses. In his General Psychopathology, Jaspers distinguished what he called ego-consciousness from object-consciousness and characterized it by the sense of activity, unity, identity and ego-demarcation. On this basis, Kurt Schneider later coined the term “Ich-Störungen” (ego-disorders) for the schizophrenic experience of one's thoughts, actions, feelings or bodily sensations being influenced or manipulated by others. In contrast, in ICD 10 or DSM IV these symptoms are regarded as bizarre delusions, commonly referred to as delusions of control or of passivity.

In my paper, I will give a short historical introduction into the problem of self-disorders. Then I will analyse the possible connection of ego-disorders with more basic disorders of self-awareness. I will argue that full-blown delusional convictions of alien control are based on a disturbance of the intentionality of thinking, feeling and acting. This disturbance of intentionality, for its part, may be traced back to a lack of prereflective self-awareness which has been emphasized by more recent phenomenological approaches to schizophrenia.

Genome-wide association studies (GWAS) have been successful in identifying replicable susceptibility loci for schizophrenia. The most replicated GWAS association is at chromosome 6p (MHC). However, identifying the causal gene networks, the specific genes, and functional variants has proven difficult for schizophrenia, just like for most other complex disorders.

Since almost all GWAS associated SNPs are either intergenic or intragenic but uncorrelated with obvious candidate functional variation such as missense or nonsense SNPs, it is likely that gene regulation is involved in schizophrenia susceptibility. This suggests that an integrative systems biology approach, one that combines DNA sequence and structural information with functional data, will be useful to study the biological mechanisms underlying the GWAS statistical associations and to identify new disease genes. To this end, we are investigating the genetic etiology of SZ by generating transcriptional profiles under conditions designed to reveal biological mechanisms involved in conferring risk, for example, by using environmental perturbations of etiological and pharmacological relevance on simple cellular models. This strategy, by refocusing transcriptional activity towards targets of specific environmental perturbations, is also useful for testing specific hypotheses of schizophrenia pathophysiology independently of GWAS results. I will be presenting transcriptional profiles at baseline that show association with schizophrenia, and the results of applying a number of external stimuli.

There is a long lasting assumption in psychiatric genetics that common genetic variants with small effects are enhancing the risk to develop e.g. schizophrenia. Although debated for some time, the other side of the coin namely that rare genetic variations with large effects may account for a significant number of schizophrenia cases has been somehow neglected. However, rare variants with large effects on schizophrenia are known for a long time. One represents a private translocation in a Scottish family which disrupts DISC1. A more common deletion of chromosome 22q11 has also been repeatedly reported to substantially enhance the risk for developing schizophrenia. Structural chromosomal abnormalities are emerging as an important genomic cause of neuropsychiatric diseases, including mental retardation, autism and more recently schizophrenia. Did these new studies investigate only the tip of an ice berg? Are a substantial number of schizophrenia cases caused by rare copy number variations? It is also interesting that some of the genes may show association not only to schizophrenia but also to mental retardation and autism, an example is neurexin 1 or deletions at 1q21.1, 15q11.2 and 15q13.3. Are we going to define a number of new diseases at the interface between mental retardation.

A dysfunctional cerebral glutamate system is a major focus in neurobiological research in schizophrenia. Several glutamate modulating therapeutics are worldwide in phase I and II trials. Evidence for glutamate dysfunctions in psychiatric disorders are mainly provided by direct concentration measurements (MRS; magnetic resonance spectroscopy) functional brain imaging and neuroelectric studies informed by genetic variations of the glutamate system. The results of recent genome wide association studies together with the candidate gene approach identified genetic markers in schizophrenia and bipolar disorder targeting the glutamate system and other excitatory neurotransmitters. In addition, current brain imaging investigations and cerebral oscillation measures demonstrated that activation deficit patterns in major psychiatric diseases are in part determined by glutamate genetic variants or by the interaction of glutamate and other neurotransmitter variants. Recent advances in MRS allow the direct association of genetics and the absolute glutamate concentration in key regions of schizophrenic. This talk reflects the state-of-the-art in the human glutamate research presenting recently observed associations between glutamate genetics and 1) nosology, 2) clinical-behavioral measures and 3) brain imaging as important intermediate phenotypes.

Research into the genetic basis of psychiatric disorders has reached a turning point. Genome-wide association studies (GWAS), encompassing several thousand samples, have produced replicated evidence for some novel susceptibility genes; however, the genetic variants implicated so far account for only a fraction of disease liability, a phenomenon not limited to psychiatric phenotypes but characteristic of all complex genetic traits studied to date.

It appears that pure genomic approaches, such as GWAS alone, will not suffice to unravel the genetic basis of psychiatric phenotypes. Apart from sophisticated genomic, epigenomic, and neurobiological approaches, the comprehensive study of the phenotype will be a hallmark of 21st century psychiatric genetics. The analysis of cross-sectional, categorical disease phenotypes by traditional statistical tools alone will have to be replaced by novel approaches modeling the complexity of psychiatric phenotypes.

A framework is presented that encompasses strategies (1) to ascertain longitudinal phenotypes, (2) to systematically and prospectively assess environmental influences on phenotypic presentations, (3) to delineate phenotypes for pharmacogenetic studies, and (3) to define robust genotype-phenotype signatures or patterns using novel data-mining tools.

Each Year, in the 27 EU Member States, approximately 63,000 Europeans commit suicide; suicide rates are declining in most age groups; however, suicide mortality rates for youth have been increasing to its highest rate in both developed and developing countries. Research demonstrates that more than 90% of people who commit suicide have a diagnosable mental disorder, in most cases a depressive disorder. Depression is one of the most significant psychiatric disorders that influence both children and adolescents. Reports have illustrated that pre-school children have a prevalence rate at 0.3%; among school children, 2%; and ranging from 4–8% in adolescents. Depression affects both sexes; however, research demonstrates that it occurs twofold more frequent among females than males. Depression is suspected to be the cause of the majority of self-inflicted deaths, and has shown to be a major risk factor for suicide. The data presented here have been collected from the baseline evaluation of the Saving and Empowering Young Lives in Europe (SEYLE) study, comprising 12,395 adolescents from 11 countries. The presentation will specifically focus on the prevalence of suicidal behaviour among the recruited sample and on the correlation between suicidality and depression.

Suicide is an important public health issue, and there are substantial indications showing that suicidal behavior coincides with many underlying social, psychological and psychiatric conditions in addition to other risk behaviors. Risk behaviors and suicidality are significant predictors of subsequent mental health problems, thus, there is a paramount need to promote the adoption of healthy and positive lifestyles, especially during the early years of life. In order to achieve these tasks, the Saving and Empowering Young Lives in Europe (SEYLE) project has been developed to prevent risk behaviors, mental ill-health and suicidal behaviors by examining specific mental health promoting and suicide preventing intervention strategies. The main objectives of the project are to lead adolescents to better mental health through decreased risk-taking and suicidal behaviours, to evaluate outcomes of different preventive programmes and to recommend effective culturally-adjusted models for promoting adolescent mental health in different European countries.

Although it has been reported that suicide-preventive interventions can be effective in decreasing suicidal behavior, well-documented and randomized studies are lacking. The effects of such interventions in terms of combating unhealthy lifestyles in young people, which often characterize suicidal individuals, have never been reported. We know that unhealthy and risk-taking behaviors are detrimental to individuals’ current and future health. Preliminary data analyses illustrate that risk behaviors among European adolescents are much higher than originally expected, and the prevalence of high-risk cases displaying signs of mental illness is also higher than estimated.

About 30 to 45% of adequately treated major depressive disorder (MDD) episodes in a psychiatric setting fail to achieve an adequate response, e.g. demonstrate an ‘insufficient response’ for which the European Medicines Agency (EMA) recently granted indication. For this group of patients and also for the ones considered as ‘treatment resistant depression’, ‘treatment refractory’, and ‘chronic resistant depression’ patients, the question emerges if switching strategies from one mechanism to another is the way to go. Although there is a plethora of hints in textbooks that switching the mechanism of action should be obtained when a patient does not respond to one medication, the results of controlled studies and the European Study Group of Resistant Depression (GSRD) challenge this notion. Switching is associated with withdrawal symptoms in most cases and the antidepressant response needs to be built up again in another 3 to 4 weeks time frame. Another set of newly obtained evidence indicate that augmentation with an atypical antipsychotic, like quetiapine XR results in a quick and sustained response and remission rate. Antidepressant combination, lithium or T3 augmentation would be other options, although not thoroughly studied for augmentation therapy. It seems that switching the mechanism of action of antidepressant therapy should only be obtained as a first step when intolerably side effects are evident, but for efficacy it should be considered at a later step after antidepressant combination and augmentation strategies have been administered. There are as yet no biomarkers available to guide the strategy which medication to choose.

Drug assumption is related to several specific time disorders. Beyond classic temporal disorientation the Author describes qualitative modification in lived-time perceptions. Hashish, hallucinogenics, heroin and ecstasy are examined separately in their different effects on time experience. Some typical experiences of addicted patients, like craving, withdrawal, flash and tolerance, are reviewed in a temporal perspective. From a phenomenological and psychopathological point of view, the alteration of time experience is important in order to understand clinical conditions and therapeutical development in drug addiction.

At our university hospital we are also responsible for the patient-centred care (for the city of Zuerich). About 20% of our patients are migrants. These patients need a treatment that is in accordance with their complex biographies and social circumstances.

We established a specialized procedure for trans-cultural psychiatry and psychotherapy. So we work closely with an ethnologist and translaters on our acute ward.

In the hospital setting it is especially important to avoid allocating certain mental symptoms to particular cultures or placing an overdue emphasis on the ‘culture’ of the patient in question.

In the talk I will describe our setting and give an example of a therapy.

Migrants have a substantial risk to experience traumatic events and refugees are definitely a high risk group. Consequently, there is evidence that migrants more likely develop Posttraumatic Stress Disorder (PTSD). On one hand it is to consider that there is no culture specific symptomatology of PTSD, on the other hand certain regional trauma-related syndromes are described, namely Latah, Susto, eg, known as culture-bound syndromes. Various studies have evaluated the elevated prevalence rates of PTSD in migrant settings worldwide. It is evident that origin, cultural context and ethnical background are of significant relevance and worth to be considered in research and clinical practice. The aim of this contribution is to emphasis the ethnical background in the discussion of trauma and PTSD.

Mental disorders carry heavy burden and come second only to cardiovascular disease. The disability adjusted life years, which is a measure for life years lost due to premature death, for mental disorders is about 15.4% compared to 18.6% for cardiovascular disease and 15% for all cancers put together. Fifteen to 25% of mental disorders become resistant or refractory to all conventional therapy including medications, behavioural therapy and ECT. Some of these patients might be helped by NMD. There are currently a number of surgical interventions that can be used to treat resistant and refractory OCD or MDD.

Ablative neurosurgery includes bilateral anterior cingulotomy, bilateral anterior capsulotomy and subarcuate tractotomy. Neurostimulation for mental disorders is also used includes VNS and DBS.

This symposium will cover the pros and cons of these interventions in detail including referral criteria, patient selection, referral pathways, outcome of these interventions, potential side effects and long term outcomes.

There will be time to ask questions and discuss all aspects of NMD.

Several recent meta-analysis agree that the effect size of antidepressant efficacy vs. placebo is around 0.32. This seems to be stable, irrespective of the data set used or the method of meta-analysis utilized. Some authors argue that this is because antidepressants have a preferential efficacy against the most severe cases of depression but their efficacy in the milder forms is negligible. This is rather an artifact, caused by the ‘mathematical coupling’ phenomenon which strongly binds baseline scores to change with a coefficient of 0.70 even when values are produced randomly. Even if one does not take into account the ‘mathematical coupling’, still the medication effect is superior to the response in the placebo group across all severity levels.

We argue that in our opinion the data suggest that placebo and drug effects are non-additive: antidepressants act independently of depression severity, while the placebo effect if present it is visible only in milder cases. While the response in the placebo group is due to unstable ‘noise’ and ‘artefacts’, the medication effect is reliable, valid and stable. The above should be viewed also under the light of recent meta-analysis suggesting the effect size of the difference between medication and psychotherapy is also around 0.32 and that the response in the psychotherapy arms also seems to be higher in more severe cases.

Considering the traditional experimental methodology of clinical psychopharmacology the best way to test efficacy of an antidepressant to placebo and at the same time taking into account the demand of EAM and FDA is the randomised controlled double-blind trial. Of course, such a trial has to be performed in the best methodological approach possible, avoiding all kinds of bias and confounders, avoiding especially statistical errors of different kinds etc.

The final result of a trial should never be seen as a final answer. The empirical methodology of clinical psychopharmacology demands confirmation by at least one other trial. Even then, the empirical process is not finished and e.g. the second trial might generate a negative result, thus conflicting with the two other positive results. This induces questions as to what might be the background for the inconsistent results and then possibly lead again to one or two other studies trying to support the former positive evidence. This is a way of empirical thinking in the sense of falsifications or confirmations. In the time of EBM, meta-analysis has become the preferred method to combine the outcomes of all informative, putatively conflicting studies on the question, whether a certain drug A is superior to a drug B or to placebo. However, it has to be understood that meta-analysis, depending on the applied methodology and depending on the inclusion or exclusion of certain studies can come to inconsistent results, although principally focussing on the same data base.

Bipolar II depression is characterized by the occurrence of depressive episodes in alternation with hypomanic, but not full blown manic episodes. Epidemiological studies show that it is situated on a continuum with bipolar I disorder on one side and unipolar major depressive disorder on the other side, with unclear boundaries. Various authors concluded that the treatment of bipolar II depression is unclear, poorly evidence based and thus controversial: should antidepressants be avoided as monotherapy and what is the place of lithium, anticonvulsants and atypical antipsychotics? A review of the literature shows that the risk of switch to mania/hypomania during acute treatment with antidepressants as monotherapy is smaller than in patients with bipolar I depression and that it concerns almost exclusively hypomanic switches. Therefore, there is no good evidence to avoid antidepressants as monotherapy. However, there is also no good evidence for their efficacy. Available data from a few randomized controlled trials with other drugs suggest also a place for anticonvulsants, especially lamotrigine, and for quetiapine. This is also reflected in some, but not all guidelines.