It is well known from twin, family and adoption studies that addictive behaviours are under a degree of genetic influence, which is reflected in moderate to high heritability coefficients for these phenotypes. In the last twenty years, considerable effort has been invested in attempting to determine the molecular genetic basis of this influence, with mixed success. While early candidate gene studies for the most part failed to identify genetic variants which were reliably associated with risk of substance use, more recent genomewide association methods have begun to yield promising findings and novel insights into the mechanisms of addictive behaviours.

The history of genetic studies of risk of substance use will be presented, including a brief overview of twin, family and adoption studies, and of candidate gene and linkage studies. More recent findings, in particular focusing on genomewide association studies, will be discussed in detail. Finally, emerging findings from gene x environment and intermediate phenotype studies will be highlighted. This presentation will provide a comprehensive overview of the current state of the field of addiction genetics, placed in the historical context of heritability, candidate gene and linkage studies.

While the study of the genetics of addictive behaviours remains in relative infancy, some compelling findings are beginning to emerge. Genetic variants which influence the metabolism of specific substances, such as alcohol and nicotine, appear to influence the intake of those substances. A number of genes which encode drug targets also appear to influence drug-taking behaviour, such as the alpha-5 nicotinic acetylcholine receptor subunit, which has been robustly shown to associate with heaviness of smoking. However, the proportion of phenotypic variance explained by these variants remains small. Potential reasons for this will be discussed.

Multiple neurochemical pathways have been identified to be involved in mediating craving and relapse to alcohol. Additionally, animal models greatly assist in investigating pharmacological interventions of relapse behaviour. Opioidergic and glutamatergic systems play a key role in alcoholism as demonstrated by clinically effective compounds. Moreover, many new targets have been identified and several new compounds are currently undergoing clinical testing. Given the heterogeneity in treatment response, genetic and protein markers as well as endophenotypes are currently characterised for individualised pharmacotherapy.

Biological markers are an important objective in psychiatric research. Molecular and functional neuroimaging techniques are promising tools to provide these biomarkers that may be used for early detection, indication of presence and severity of psychiatric disorders, prediction of treatment response and clinical prognosis. In this lecture, recent results from molecular imaging with positron emission tomography (PET) will be presented, including cerebral quantification of several major players in serotonergic neurotransmission, i.e. the serotonin transporter, the serotonin 1A, 2A, and 1B receptor subtypes, and the degrading enzyme MAOA. Differences between psychiatric disorders will be discussed. Furthermore, pharmacological effects on these targets and brain activation will be shown using PET and functional magnetic resonance imaging (fMRI).

Hyperalgesia frequently results from injuries or inflammation of peripheral tissues, including nervous tissue and paradoxically also from the treatment with μ-opioid receptor agonists. Compelling evidence indicates that signal amplification in central pain pathways plays an important role for the maintenance of hyperalgesia1. In superficial spinal dorsal horn synaptic transmission between nociceptive C-fibres and lamina I projection neurons can be potentiated for prolonged periods of time in an activity dependent manner. These forms of synaptic long-term potentiation (LTP) can be securely prevented when opioids are applied during afferent stimulation. The blockage of LTP induction by opioids is a likely mechanism or pre-emptive analgesia. Upon withdrawal from high doses of opioids, however, LTP may develop at C-fibre synapses. During the latter form of LTP induction presynaptic activity at C-fibres is depressed rather than enhanced. Despite these fundamental differences in the induction, activity dependent- and opioidergic LTP share signalling pathways. This includes the activation of NMDA receptors, the rise in postsynaptic Ca2+ concentration and the activation of protein kinase C. Induction of opioidergic LTP further requires postsynaptic G-protein coupling which is in contrast to the presynaptic inhibition by opioids. LTP induction is abolished by blocking the Ca2+ rise upon withdrawal from the opioids. It is likely that the potentiation in synaptic strength translates into enhanced pain behaviour1. Plasticity at the first synapse in pain pathways is a promising target for the prevention and treatment of hyperalgesia of various origins.

Recent nation-wide epidemiological data confirm the well-known clinical observation of a strong relationship between pain syndromes and disordered sleep.

In experimental settings of pain patients as well as healthy subjects, pain perception shows a strong circadian pattern exhibiting significant variation over the 24-hour sleep-wake period. Several lines of scientific evidence indicate that homoeostatic components of sleep may mask circadian pain perception, which results in a two-process model of pain regulation depending on the circadian sleep-wake status.

Since pain may worsen sleep, sleep deprivation increases pain, and quality of sleep not only affects nocturnal pain but influences pain during daytime hours, models of interactive pathomechanisms of pain and sleep are widely accepted.

Clinical consequences include various treatment methods that consider both, pain and sleep. E.g., intake of pain medication should follow circadian aspects which assure sufficient pain reduction at early morning hours; ideal pain medication at night should have hypnotic properties, including the promotion of deep sleep; pain medication during daytime hours should activate patients to support good sleep during the following night. Psychotherapy needs to support both, the management of pain and of sleep.

Patients presenting with bodily symptoms and complaints that are not sufficiently explained by organic pathology or well known pathophysiological mechanisms present a major challenge to any health delivery system. From a perspective of psychiatric classification these medically unexplained somatic symptoms may be diagnosed as primary psychiatric disorders such as depressive and anxiety disorders on the one hand, as somatoform disorders on the other. Among medical specialties a separate diagnostic approach is taken to conceptualize functional somatic syndromes. Unfortunately, both diagnostic systems do not conform to each other very well.

The concept of somatoform disorders as outlined in DSM-III to DSM-IV-TR and in ICD-10 refers to a group of heterogeneous disorders with prominent somatic symptoms or special body-focussed anxieties, or convictions of illness. These disorders seem to indicate medical conditions that cannot, however, fully be explained either in terms of medical diagnostics or of other primary psychiatric disorders. There is one major conceptual assumption that postulates a decisive impact of psychosocial stress on the origin, onset and/or course of these somatic symptoms and complaints. And there is one major path of diagnostic steps to be taken, i.e. just to count the number of medically unexplained somatic symptoms, to determine their reference to any main organ system, to prove that they are not self-induced, to put special stress on prevailing pain symptoms and to separately assess dominant health anxieties or illness convictions.

Since introduction of the diagnostic concept of somatoform disorders there have been arising many critical issues regarding the soundness of this diagnostic category. These issues, among other things, refer to a problematic mind-body dichotomy overemphasizing psychosocial and psychological factors and neglecting major neurobiological processes, to the impracticable criterion of “medically unexplained”, to the demand of conceptual clarity and coherence of this diagnostic category, to the rather trivial diagnostic procedure of just counting the number of medically unexplained somatic symptoms whereas not assessing typical dimensions of illness behaviour in a corresponding way, to the major overlap between subgroups of somatoform disorders on the one hand and factitious disorders, anxiety disorders and depressive disorders on the other, to a principal focus on the epidemiologically rare condition of somatisation disorder as core disorder thereby undervaluing much more prevalent subthreshold conditions, to the difficult communication of the whole diagnostic group to medical colleagues dealing with the same problems by using a different conceptual approach, however.

These critical issues surrounding the concept of somatoform disorder will be reflected in respect of some major revisions projected in future diagnostic classification systems of DSM-V and ICD-11.

In most of the somatic disciplines of medicine there is no doubt about the importance of diagnosis for patient care, research, teaching and regulatory affairs. In psychiatry however, the status of diagnosis has been antiguous for long times. In this paper the reasons for this difference will be discussed in the light of the historical development of diagnosis and classification in the beginnings of modern psychiatry. Especially during the period of antipsychiatric reasoning it was even regarded as harmful and dangerous for patients for be diagnosed in a scientific terminology. As a consequence the research in the field of mental disorder was hindered and blurred, and in addition also the scientific basis of our discipline was questioned. The American Psychiatric Association published in 1952 the „Diagnostic and Statistical Manual of Mental Disorders” (DSM-I), which was the first official manual of mental disorders to contain a glossary of descriptions of the diagnostic categories. A major breakthrough was the publication of DSM-III in 1980, which was not only characterized by explicit criteria for inclusion and exclusion, but also by strictly defined algorithms and by systematic field trials during the development of the manual. The DSM-approach to diagnosis in psychiatry became of major importance for research and practice in our field. Later, ICD-9 was transformed into ICD-10 by WHO with a certain tendency to adopt the basic principles of the DSM-system. Contemporary psychiatry is completely ruled by these two schemes of operationalized diagnosis. Advantages and disadvantages of this approach to classification for patient care, research and administration as well as possible alternatives and future directions will be analyzed. Special attention is given to the question, whether psychopathology and phenomenology are still relevant as methodological elements in psychiatry, even in an era of major progress of neurobiology in the sense of natural sciences.

Classification is an important tool for scientific progress. It makes groups of individuals that share clinical symptomatology comparable and facilitates clinical communication. It should enable monitoring of treatment en guidance outcome through routine outcome measurement. But over the past decades classification systems have become increasingly popular with health and governmental authorities and insurance companies. The classification systems have acquired a fourth label that of a passport that gives access tot services. This should be a matter of concern for professionals and scientists in the field as it biases the primary scientific purpose of the exercise. ICD 10 and DSM IV and unfortunately also DSM V in progress have special sections for disorders occurring mostly in children and adolescents. This is an unfortunate categorization as most of the conditions met in childhood are in fact developmental disorders that persist well into adulthood. In this presentation the necessity for multilayer (genetic – brain – neuropsychology – behavioural signs and environment) will be presented and a stron plea made for disclosing child and adolescent conditions from their separate categories towards more developmentally geared dimensional perspectives.

Personality disorders are regarded as being among the more important categories within the DSM-IV diagnostic nomenclature, because they have the unique distinction of being placed on a separate diagnostic axis. However, empirical data have pointed out a number of disadvantages and concerns with the categorical system: excessive co-occurrence, inadequate coverage, heterogeneity within diagnoses, arbitrary and unstable diagnostic boundaries and inadequate scientific basis.

Alternative dimensional approaches have been considered. There is a surprising consistency over the number and descriptions of the main factors or dimensions both in normal population and among psychiatric patients, at least the following four: an externalizing factor aggression (antagonism), an internalizing anxious-emotional unstable second factor, an inhibited and constraint third factor and fourth factor of compulsivity and perfectionism. Beside this, severity of functional deficits, a number of trait domains and disturbances of self and identity are considered to be included as additional descriptors of personality pathology. It is proposed that only 5 or 6 of the current categories with highest clinical validity will be kept in the system. The aim is to maximize clinical utility, but the current suggestions seem to be too complex for the average clinician to follow.

If one of the major current challenges in the classification and diagnosis of mental disorders is the issue of multi-morbidities, a further one is the subtreshold states. These challenges could be partially considered as the by-products of the prevailing current categorical approaches in our classification systems.

The categorical approach needs and is based on vertical and horizontal boundaries to differentiate different states of human behavior. While, at a horizontal level the boundaries between mental disorders are elicited by strict diagnostic criteria, the issue of drawing a threshold at a vertical level requests some dimensional approaches. These thresholds in the description of many mental disorders in our current categorical approaches are defined by a combination of some dimensions; i.e., the duration of the symptoms, the severity of the symptoms, and the effects of the symptoms on social functioning and abilities.

Another problem in defining the thresholds for mental disorders is the consequence of the cross-sectional approach. Since, the clinical pattern of many mental disorders change in time, the cross-sectional approach does not reply to the requirements of a historical perspective from which the variation of a mental disorder over and under a given cut-off line in due course could be understood. It is a widely shared opinion that the necessity of defining thresholds for mental disorders is not only taking the clinical, scientific and research motives into consideration, but also the forensic and administrative grounds.

This presentation will mainly discuss the phenomenon of threshold and subtreshold states in the context of psychopathology, clinical practice and classification systems.

Interpersonal therapy of depression was created and established in American psychiatry in the 80ties. At that time european and especially german psychiatry was still dominated by the concept of endogenous depression, which suggested a somehow biologically determined aetiology which was not very likely to be influenced by psychotherapeutic access.

However, the empiric approach to evaluate therapy regardless of aetiology, which is very typical for IPT, produced strong evidence for the effectiveness of IPT in unipolar depression and many other psychiatric disorders.

On this basis, a diversity of biological studies became possible which aimed to the elucidation of neurobiological mechanisms of psychotherapy.

The first data indicate that biological state markers change when the patient responds, regardless if he received Psycho- or pharmacotherapy. However, no empirical findings suggested, how IPT might be linked to neurobiological phenomena.

We followed the suggestion by E. Kandel, that the phosphorylation of cAMP-responsive-binding-protein (pCREB) could be a crucial factor in the process of psychic improvement. Therefore we studied pCREB in human T-lymphocytes under different treatment conditions in unipolar depression. The results will be presented.

Although schema or schema-focused therapy is now a well-established treatment for personality disorders such as borderline personality disorder, it was originally developed with long-lasting or chronic forms of depression in mind. In this presentation, I argue why schema therapy is a promising treatment for depression by giving an overview of currently available treatments; describing the theoretical framework of how schema therapy might apply to chronic depression; presenting empirical evidence on the early maladaptive schemas found in depressive patients receiving outpatient treatment; and by describing the design of an ongoing study in which the effectiveness and underlying mechanisms of change of schema therapy for chronic depression are examined.

Mindfulness-Based Cognitive Therapy (Segal, Williams, & Teasdale, 2002) is an eight-week treatment programme combining intensive training in mindfulness meditation and elements of cognitive therapy for depression that was specifically developed for the prevention of relapse in patients with recurrent course of the disorder. This talk will describe the rationale and format of the treatment programme and give an overview of recent findings regarding the effectiveness of the treatment and its mechanisms of action.

Chronic depression accounts for roughly a third of all mood disorders. It is a particularly disabling disorder, which is associated with greater comorbidity and suicidality, more significant impairments in functioning, and increased health care utilization than acute major depressive episodes. In the past, chronic depression was often considered as treatment-resistant since traditional pharmacological and psychological treatment approaches show at most modest success. In addition, relatively few psychotherapy studies have focused on chronic (mostly dysthymia) forms of depression. However, in chronic Major Depression a specific form of psychotherapy, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), proved to be equally effective than medication; the combination of CBASP and medication revealed significant superiority over both monotherapies.

CBASP-developed by James McCullough-is the only psychotherapeutic intervention specifically designed for chronic depression. The approach integrates behavioral, cognitive, psychodynamic, and interpersonal strategies. It focuses on problems resulting from an inhibition of maturation in early childhood often caused by early traumatization by using the therapeutic relationship in a disciplined personal way. In addition, other interpersonal strategies are applied to overcome preoperational thinking. By means of a specific behavioral technique, the Situation Analysis, patients learn to focus on the consequences of their behavior and to use efficient social problem-solving. The techniques of CBASP will be demonstrated.

Growing evidence suggest that disruption of cortical interneuron function is common to several psychiatric conditions, such as schizophrenia. Cortical interneurons play major roles in the function of the cerebral cortex. Through mostly inhibitory mechanisms, interneurons regulate the activity of pyramidal cells, prevent hyperexcitability, and synchronize the rhythmic output of cortical activity. In particular, the function of some classes of interneurons has been shown to be crucial for the generation and maintenance of gamma rhythms, a pattern of brain waves that is associated with perception and memory.

Work in my laboratory aims at elucidating the mechanisms controlling the development of cortical interneurons. We have recently found that several genes associated with schizophrenia, such as Nrg1 and ErbB4, control several aspects of the development of cortical interneurons. In this talk, I will summarize our current view on the biological mechanisms that may underlie the etiology of schizophrenia, linking susceptibility genes, cortical inhibitory function and brain development.

It has been traditionally accepted that antipsychotics have a 'delayed onset' of action with various authors claiming 2–3 weeks of delay. Data from the previous few years has contradicted this notion.

The talk will review this data, identify its theoretical implications and implications for practise. In an initial meta-analysis of over 8,000 patient data it was shown that antipsychotic action is not delayed at all but evident in teh first week, this change is not non-specific sedation but a specific anti-'psychotic' effect, and is seen with all evaluated antipsychotics. In more recent studies we have been able to show that this effect is even discernable in the first 24 hours, is related to dopmaine D2 occupancy achieved early on, and early non-response is a very strong predictor of subsequent non-response.

This early onset is not only an isolated improvement in psychosis-but, can also be seen on quality of life and social functionign indicators. These data raise interesting questions regarding the mechanism of improvement: they question the standard 'depolarisation block' hypothesis of antispychotic action-and suggest a simpler dopamine occupancy hypothesis instead; since change occurs early it is possible to map different trajectories and our most recent findigns show that drug-treated patients show a distinct trajectory from those observed in placebo-treated patients. Finally, these findings have implications for the design of clinical trials and clinical practise. In clinical trials it is possible to use early-response to devise adpative or enriched designs that are more clinically relevant - example of a recent such application will be discussed and at a clinical level it may be possible to reconsider the standard notion that an antipsychotic must be tried for 6 weeks before considering an alterative option.