Accumulating evidence indicates an activated immune system as a vulnerability factor for the development of schizophrenia (SCZ) and bipolar disorder (BD). In support we detected:

1. 1. Monocytosis and monocyte activation (e.g. a specific gene expression signature of inflammation related genes in a coherent pattern) in naturalistically treated SCZ and BD patients, and

2. 2. T cell activation in the same patients, be it that it were Treg cells that were more numerous in BD, while in SCZ Treg and Th17 cells numbers were raised.

We also tested 70–80 children at ages of 16 and 21 yrs, having1-2 parent(s) with BD. This offspring has a higher chance of developing a mood disorder and over 25% had developed a mood disorder at 21 yrs. Not only the offspring with a lifetime diagnosis of mood disorder had activated monocytes and more Treg cells (similar as BD patients), but also around 40–50% of euthymic offspring had this immune activation profile. Importantly children who were psychiatrically healthy at 16yrs, and had developed a mood disorder at 21 yrs of age, all had activated monocytes at 16yrs.

Our data show that both the monocyte and T cell arm of the immune system are activated in SCZ and BD, this activation preceding the onset of first episodes in individuals at risk. Our approach opens new avenues for early detection of psychiatric disease based on the immune state of individuals at risk, enabling possible selection of those individuals who might benefit from an immune modulation treatment to prevent disease.

Considering the evidence that pro-inflammatory cytokines play a causal role in depressive illness, the ability of antidepressants to induce anti-inflammatory effects is a subject of considerable interest. In an in vivo context we observe that antidepressants that enhance noradrenaline availability are the most effective anti-inflammatory agents; a fact consistent with the established anti-inflammatory actions of noradrenaline. Specifically, we have observed that noradrenaline reuptake inhibitors (NRIs) inhibit microglial activation and inhibit expression of pro-inflammatory cytokines (IL-1beta and TNF-alpha), iNOS, and inflammatory chemokines (IP-10 and RANTES) in rat brain following a systemic inflammatory challenge. These in vivo anti-inflammatory actions of NRIs are mimicked by in vitro exposure of primary glial cells to noradrenaline, but not by in vitro exposure of glial cells to the drugs themselves. These data suggest that NRIs promote an anti-inflammatory environment in rat brain in vivo by increasing noradrenaline availability at glial cells. We have also observed that even in the absence of any overt inflammation, chronic treatment with the NRI reboxetine promotes an anti-inflammatory phenotype in the CNS characterised by reduced expression of pro-inflammatory cytokine IFN-gamma, and increased expression of the anti-inflammatory cytokine IL-10. Current experiments are focused on the activation of the inflammatory response system in animal models of depression secondary to inflammation. The models are used subsequently to assess the anti-inflammatory effects of antidepressants in vivo.

Proinflammatory cytokines, such as IL-6, IL-1 and TNF-a appear to be elevated at least in the peripheral blood of depressed patients. Thus, the activity of the enzyme IDO, which is driven by pro-inflammatory cytokines and regulates the tryptophan/kynurenine metabolism may be enhanced in depressed patients through these cytokines. Although IL-6 does not directly act on IDO, its elevated levels in serum may contribute to IDO activation within the CNS by the stimulatory effect on PGE2, which acts as cofactor in the activation of IDO. This fits with a report on the correlation of increased in vitro IL-6 production with decreased tryptophan levels in depressed. Due to the increase of proinflammatory cytokines and PGE2 in some psychiatric patients, antiinflammatory treatment would be expected to show advantagous effects in schizophrenic and depressed patients. Cyclo-oxygenase-2 inhibitors have been evaluated in major depression. We were able to demonstrate a statistically significant therapeutic effect of the COX-2 inhibitor on depressive symptoms in a randomized double blind pilot add-on study using the selective COX-2 inhibitor celecoxib in MD. Another randomized double-blind study in fifty depressed patients suffering from MD also showed an statistically significant better outcome of the COX-2 inhibitor celecoxib plus fluoxetine compared to fluoxetine alone. Additionally, results of the clinical study of celecoxib add-on to sertraline and the effects of this anti-inflammatory therapy approach to inflammatory markers planned by the MOODINFLAME consortium will be presented as far as available. Further on, alternative therapeutic strategies based on immune-modulatory effects will be discussed.

Anxiety disorders are common, have an early onset, run a long course, cause substantial distress, impair overall function, reduce quality of life and impose a major economic burden, and therefore represent an important public health problem. Many patients do not present or are not recognized, the standard of care is often sub-optimal, and the effectiveness of interventions in real-world practice can be disappointing: there is considerable room for improvement in recognition, care and treatment.

The causes remain largely unknown and this hinders accurate diagnosis, prediction of prognosis, and development of refined treatment approaches. There is much co-morbidity between the disorders and with conditions such as bipolar disorder, depressive illness and physical illness. Research findings in patient samples without co-morbidity may have limited applicability to wider practice, and there is a need to undertake research in fully representative groups. Little is known about determinants of non-response, or next steps in management after the failure of first-line interventions, and there is a clear need for research in the substantial proportion with ‘treatment-resistant’ conditions.

The unmet public health, clinical and research needs could therefore be addressed by developing an independent collaborative European Anxiety Disorders Research Network. This would facilitate harmonization of research and clinical databases and refinement of research methodologies. It should contribute to greater accuracy when predicting clinical outcome, and encourage the evaluation of innovative interventions, particularly in important groups such as in the early stages of illness, those with comorbid disorders, and those who have not responded to initial treatment approaches.

Anxiety disorders are chronic, disabling conditions with prevalence rates higher than the ones of schizophrenia or diabetes.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are standard treatments for anxiety disorders. The calcium-channel modulator pregabalin is a treatment option for generalized anxiety disorder. Tricyclic antidepressants (TCAs) are as effective as modern antidepressants, but less well tolerated. For short-term treatment and in treatment-resistant cases, benzodiazepines like alprazolam may be used when the patient does not have a history of dependency and tolerance. Combining drug treatment with cognitive behaviour therapy is the most successful treatment strategy in anxiety disorders. Strategies of treatment-resistant anxiety disorders and future anxiolytics will be presented in the symposium.

In many psychotherapeutic theories the aim of therapeutic interventions is a restructuring of cognitive appraisals of past and current situations. The question is whether such a ‘dry’ and formal cognitive approach does not unjustly leave out the body. Especially in anxiety disorders brain/bodily changes appear to play an important role in the etiopathogenesis.

There is now a great deal of experimental evidence that the brain does not only store mental representations, but that the brain/body is actively involved in mental operations. As an example of this I will discuss recent evidence indicating that early adverse life events not only lead to psychological (cognitive) disorders, but also leads to abnormal functioning of brain mechanisms and bodily functions.

These changes occur on different levels of organization. Children who have been neglected or abused have smaller brains and a reduced complexity of neuronal dendrites, and also exhibit dysfunctions in neurotransmitter systems and the immune system.

I will specifically discuss recent investigations conducted in our centre in which severely traumatized patients were studied using positron emission tomography, one of the neuroimaging techniques which yields information about brain functioning in vivo.

As a final point I will discuss genetic differences that may explain differences in sensitivity for stressful life events, which may lead to the deveopment of a spectrum of anxiety disorders.

Twin studies propose a strong genetic contribution to the pathogenesis of anxiety disorders with a heritability of about 50%. The dissection of the complex-genetic underpinnings of anxiety disorders requires a multi-level approach using molecular genetic, imaging genetic, (cognitive)-behavioral genetic and pharmacogenetic techniques linking basic and clinical research.

The present talk will first give an overview of results from linkage and association studies yielding support for several candidate genes contributing to the genetic risk for anxiety and panic disorder in particular such as the adenosine 2A receptor, the catechol-O-methyltransferase, the neuropeptide S receptor and the serotonin receptor 1A genes. Results from the first genome-wide association studies in the field of anxiety disorders will be discussed. Additionally, studies on gene-environment interactions between anxiety disorder risk variants and environmental factors will be presented. Imaging genetics approaches have yielded evidence for several risk genes to crucially impact activation in brain regions critical for emotional processing. Gene variation has furthermore been found to potentially confer an increased risk for panic disorder via elevated autonomic arousal and dysfunctional cognitions regarding bodily sensations. Finally, there is first evidence for genetic variants impacting treatment response to antidepressant pharmacotherapy in anxiety disorders.

Thus, converging lines of evidence will be presented for several candidate genes of anxiety to exert an increased disease risk potentially via a distorted cortico-limbic interaction during emotional processing, increased physiological arousal or dysfunctional cognition. Additionally, a possible impact of genetic variants on pharmacoresponse in anxiety disorders and its potential clinical implications will be discussed.

Revision 5 of the diagnostic and statistical manual for mental disorders (DSM-V) has stimulated a debate about the inclusion of a risk for psychosis syndrome in order to facilitate the prevention of psychosis.

The presentation critically outlines the course of this debate, focusing particularly on the question of how the inclusion of such a syndrome could be justified in DSM-V and ICD-11.

Most participants in the debate have initially opposed the inclusion of a risk for a psychosis syndrome. They justified this dismissive attitude with scientific, clinical and ethical arguments. The predictive power of eligible criteria for first psychotic episodes appeared to be too low. Their use as diagnostic criteria would involve the danger of hastily treating many falsely diagnosed individuals at risk for psychosis with antipsychotics and unjustifiably putting them at risk for side effects. In general, diagnoses should be based on grounds of manifest illnesses and not include at risk states for later diseases.

Meanwhile, the understanding, that the risk of disease symptoms already has a pathological significance and therefore requires treatment has by now begun to be accepted. This applies both to the risk symptoms in the early initial prodrome, as well as to the high risk symptoms in the late initial prodrome. It would therefore be reasonable to use these two sets of criteria for the definitional operationalisation of the new diagnostic category in the classification systems. This would allow the continuation of preventive efforts but also the development of evidence-based treatment within standard care.

Early intervention strategies have been developed over the past 20 years for psychotic disorders and recent studies have proven their efficacy. However, most of the attention has been drawn to schizophrenia, and affective psychoses have been neglected. In the recent past, new research has identified a similar need for earlier intervention in bipolar disorders, and prodrome to bipolar disorder has emerged as a key domain to investigate. Despite the complexity of this issue due to the lack of a clear consensus regarding definitions of the various stages of the disorder, some progress has been made in this domain.

Two recent retrospective studies have identified a prodromal phase to first episode mania lasting between 6 and 18 months, and have identified a range of symptoms that occur during this period. It is however likely that on the basis of symptomatic profile, identification of at risk patients would be difficult, considering their low specificity. Two complementary directions have been recently proposed in order to refine such an approach. The first strategy, based on at-risk profiles inspired by the Ultra High Risk concept developed for psychosis, has yielded some promising results on a small sample of patients. The second is based on the combination of identified risk symptoms with both risk factors and markers of vulnerability into a First Episode Mania Prodrome Inventory which is currently under validation.

The word empowerment has been used to describe the efforts to give disadvantaged groups in the population a better chance to state their opinion and influence decisions affecting the population as a whole as well as themselves. In psychiatry the word is used both when talking about the process of raising self-confidence of an individual and in speaking about the need to increase the role of people with a mental illness and of their families in the shaping of the services which are to serve them.

In these and other instances it would be possible to expect two positive outcomes if empowerment were to happen: firstly, disadvantaged individuals (including people with mental illness) who were empowered would feel better and be more likely to participate in the work of the group that has helped them to gain or regain self-confidence; and secondly, if given a chance people who were empowered would help to shape services that are to help them in harmony with their needs and the environment in which they are to work. The presentation will exemplify some of these points by a description of the experience gained in programmes that fought stigma and consequent discrimination.

People with mental health problems and their families have not been involved as equal partners in decision-making processes on mental health services, and they continue to be at risk of social exclusion and discrimination in all facets of life. In a mental health context, empowerment refers to the level of choice, influence and control that users of mental health services can exercise over events in their lives, and the key to empowerment is the removal of formal or informal barriers and the transformation of power relations between individuals, communities, services and governments. Despite all achievements that have been made over the past decade, there is still a strong need for empowerment of people with mental health problems and their families. The World Health Organization Regional Office for Europe and the European Commission started a three years lasting "Partnership Project on Empowerment in Mental Health" in 2008 which aims to support Member States in the European Region in creating societies in which people with mental health problems are enabled to develop and express their full potential as equal citizens. The WHO Statement on Empowerment in Mental Health has been published, about 100 examples of empowerment practice across Europe have been collected, and indicators for empowerment applicable at national level have been identified. The project outcomes and possibilities for their implementation at country level will be presented.

The active involvement of users of services and their families and friends into mental health care and research is essential for the success of mental health services and initiatives worldwide. Also, co-operations between mental health professionals, users and carers are needed to solve methodological problems of evaluative research and generate new models of needs-orientated interventions. However, accepting each other in a working partnership for a multiperspective evidence base is still a challenge for professionals as well as for users and relatives and friends. Changes in structures as well as in forms of communication are warranted.

In Trialogue-groups users, carers and mental health workers meet regularly in an open discussion forum, that is located on ‘neutral terrain’ - outside any therapeutic, familial or institutional context - with the aim of communicating about and discussing the experiences and consequences of mental health problems and ways to deal with them. This setting offers new possibilities for gaining knowledge and insight and developing new forms of communication. It also functions as a basis and starting point for trialogic activities on different levels - e.g. serving on quality control boards - and different topics - e.g. anti-stigma projects. In German speaking countries well over hundred Trialogue groups are regularly attended by altogether ∼ five thousand people. Trialogues are inexpensive and a great number of people seem to benefit from participation. Current ideas for the scientific evaluation of Trialogues regarding process as well as possible outcomes pose conceptual and methodological challenges.

The WPA has invited service users and family carers to join in its work as members of a taskforce, recognising their essential contribution to improving mental health in any country. WPA President Prof. Mario Maj established the project within the WPA Action Plan 2008 to 2011. The taskforce has prepared recommendations for the international mental health community on best practices in working with service users and carers. It has also worked with the WPA Standing Committee on Ethics to prepare a new paragraph for the WPA Declaration of Madrid. The WHO Department of Mental Health has offered its experience and advice.

Ten recommendations are ready for dissemination after extensive consultation. Each country will need specific guidelines to apply these recommendations. The recommendations begin by declaration that respecting human rights is the basis of successful partnerships for mental health. The second recommendation is that legislation, policy and clinical practice relevant to the lives and care of people with mental disorders need to be developed in collaboration with users and carers. The series continues with a recommendation that the best clinical care of any person in acute or rehabilitation situations is done in collaboration between the user, the carers and the clinicians. Education, research and quality improvement in mental health care also require this collaboration. The next step is developing a series of projects to apply these broad principles in each country and local communities. The WPA hopes to support partnership and participatory developments worldwide, and learn from these experiences.

Psychotherapists need to perform tasks such as being empathetic, performing an ongoing assessment of cases, self-disclosing, making explicit treatment contracts, validating patients’ experiences and promoting awareness of psychological experience, if they are to be effective in treating personality disorder (PD). Successful therapy also requires a systematic accurate PD model. We suggest here that it is still unclear how, when and according to what session markers therapists need to perform specific operations to maximize therapeutic gains. This article describes and operationalizes a step-by-step procedure for organizing and delivering the interventions necessary for effective outcomes, such as maintaining a good therapeutic relationship, increasing understanding of mental states, reducing symptoms and improving social adaptation. The procedure is illustrated by reference to the treatment of cases of emotionally overly-constricted PDs. We include a theoretical proposal to facilitate the development of measures for evaluating the efficacy of therapist actions.

According to recent literature, 50 to 90 percent of criminal offenders have personality disorders (PDs), with cluster B PDs being the most prevalent in forensic settings. The latter type of PD is associated with an increased risk of violence and recidivism. Among forensic patients with a cluster B diagnosis, psychopathic offenders are at particularly high risk for re-offending. Psychopaths are believed to be untreatable, but evidence for this view is weak.

The current study aims at determining the effectiveness of Schema Focused Therapy (SFT) versus ‘treatment as usual’ in male forensic patients (including psychopaths) with Antisocial, Borderline, Narcissistic, and Paranoid PDs, within a 3-year multi-center randomized clinical trial. SFT is an integrative form of psychotherapy combining cognitive, behavioral, psychodynamic object relations, and humanistic/existential approaches, and was developed as a treatment for PDs and other longstanding problems. SFT aims at changing early maladaptive schema modes, thereby producing changes on a structural, emotional level.

The goal of a second study that runs within the same project is to objectively determine the nature of the emotional deficiencies that are thought to be central to psychopathy. By administering forensic patients an extensive test battery that assesses various affective capacities (e.g., moral emotion, emotional expressive behavior, cognitive and emotional empathy), we aim at constructing an integrative picture of psychopaths’ emotional functioning. Within the SFT effectiveness study, patients are tested twice (with a one year interval), to see whether these affective capacities are subject to change in the context of therapy.

The European prevalence of dementias will increase of 40% during the next 40 years, with serious effects on families, communities and healthcare systems (1).

A correct diagnosis of dementia is the first step to plan treatment, care and support. There is no single test to identify the cause of dementia. The diagnostic process involves, medical history, mental status exam, physical exam, laboratory tests, psychiatric and (neuro)psychological tests and assessment of individual's functioning. An image of brain is suitable.

There is an idea that this diagnostic process can only be realized by highly specialized staff. WHO has recently published the mhGAP Intervention Guide for use in non-specialized health-care settings by health-care providers working at first- and second-level facilities. It includes guidance on evidence-based interventions to make the diagnosis and manage a number of priority conditions, including dementia (2).

The recent progress in pathological process understanding of Alzheimer's disease (AD), may help to the proposal of new research criteria that reconceptualise the diagnosis around both a specific pattern of cognitive changes and structural/biological evidence of Alzheimer's pathology (3).

These two recent developments are significant contributions to increase the accessibility to a proper diagnosis and care of dementia around the world.