In early stage psychosis research the identification of neurobiological correlates of vulnerability to schizophrenia is an important hurdle. Structural and functional imaging techniques have shown the potential to clarify the correlates of an increased vulnerability to psychosis and to address the changes underlying transition from a prodromal state to a first episode of disease. sMRI studies found decreased prefrontal, cingulate, insular and cerebellar gray matter volume in high risk subjects with transition(HR-T) as compared to high-risk subjects without transition (HR-NT). Meta-analysis revealed relatively larger whole brain volumes in HR-T compared to HR-NT subjects Compared to HR-NT, HR-T subjects showed in functional imaging studies reduced brain activation in prefrontal cortex, reduced neuronal density, increased membrane turnover in frontal and cingulate cortex. Structural and neurochemical abnormalities in prefrontal, anterior cingulate, medial temporal and cerebellar cortex might be predictive for development of psychosis within high risk subjects.

The disturbances of explicit memory functions in schizophrenia are widely recognized. More precisely the mechanisms related to the episodic memory subsystem seem to play a significant role in the pathophysiology of the disease. Errors during the encoding phase could be responsible for this dysfunction even if retrieval per se is not totally spared. The main process in encoding episodic memory is contextual binding as evidenced by numerous neuropsychological studies. Since the hippocampal formation is considered to be the central element for contextual binding the neural support of this last mechanism is most likely rooted in the hippocampus. This assumption is confirmed by numerous neuroanatomical, neurodevelopmental, biochemical and genetic studies reporting a significant disorganization of the neural network and its scaffolding structure at the level of the hippocampus. More precisely a synaptic disorganization within the CA3 and CA1 regions (pyramidal cells and neurons) could explain for which reason episodic memory processes are impaired in schizophrenia. Associative binding occurred at the CA3 the level of the hippocampus. This corresponds to the crucial role of this region for acquiring representations of stimulus conjunction. In particular the spatial characteristics of a stimulus are probably bound thanks to the activity of the CA3 area. We hypothesize that separated CA3 representations are not correctly formed in schizophrenia. Consequently the flow which comes to the cortex into the entorhinal pathway and then to the dentate gyrus and CA3 does not result in a pattern of separated representations. Evidences supporting this hypothesis will be presented.

Psychiatry deals with morbid psychological experience. This suggests that centralto psychiatry's concern is the mind as opposed to the body. Yet, it isoften the afflicted body rather than the mind that the patient presents to theclinician. In addiction, psychiatry classification has an underlyinghierarchical bias for organic (somatic) disorders. Furthermore, many disorderssuch as generalised anxiety disorder and mood disorders have bodilymanisfestations that are taken for granted in the consultation process ortranslated and relabelled as pointing towards psychological/emotional distress.This suggests that Cartesian mind-body dualism continues to significantlyinfluence psychiatric concepts, classification and practice. In thispresentation, the role of the body as model, metaphor, symbol, object andexperiencing subject will be analysed with illustrative examples from clinicalpractice and literature. I will rely on Kafka's Letter toFather, Elfriede Jelinek's Piano Teacher,and Minkowsky's Lived Time.

The psy fields are predicated on the cartesian notion of a mind-body dualism.Suffering is understood to stem either from problems of mind or from problems ofphysiology. A related dualism is that of the “biological” and thatof “cultural”. Recent commentators have worked at great length tocollapse this dualism in day to day work with patients. At the same time, itclearly forms a fundamental part of medical epistemology. From a transculturalperspective, it is increasingly clear that there exists the possibility forconsiderable difference in the four “Es”: Experience, expression,explanation and expectations related to suffering. This variation is in largepart related to the epistemic structure underlying any given culture, and, takenas such, can present a considerable challenge to consultation-liason psychiatry.A patient may experience suffering that is expressed in the form of strangesensations in a specific parts of the body. This is then explained as aconsequence of a certain process that is culturally syntonic, and then expects acertain course of suffering as well as treatment. Given that we tend to take ourepistemic perspectives for granted as representative of the “world as itis”. The C-L psychiatrist who does not take these variations intoconsideration could all to easily arrive at a misdiagnosis and as sucherroeneous treatment.

Somatization concept should be considered in biopsychosocial integrity. Thispresentation reviews the social aspects of somatization. The description ofsomatization evolved in time in order to include the social aspects. Thedifferences of somatization between societies, somatization concept in westernand Eastern medical thought, modernist theory on the evolution of somatization,research which confirm and which do not confirm the modernist theory werereviewed. The pos-modern approach which constitutes a new paradigm in culturalpsychiatry, prefers to study the mental disorders through the culture, insteadof comparing them cross-culturally. In this context, first the culture-boundsomatization diagnosis of non-Western cultures, then the fashionable diagnosisof Western culture in which the somatization is hiding were reviewed.

Diagnostic stability is the measure of the degree to which a diagnosis remains the same at subsequent assessments of the patient and constitutes a longitudinal validation of the original baseline diagnosis. Follow-up studies including evidence of diagnostic stability and diagnostic consistency over time have been proposed to test the validity of psychiatric diagnoses. Until this moment definitions for psychiatric diagnoses are based on expert opinion rather than on their biological basis, and the modest knowledge base regarding underlying etiologies has hindered the use of etiological factors in psychiatric classification systems. But it is assumed that the higher the diagnostic stability, the more likely is to reflect a consistent psychopathological or pathophysiological process. Being that the main clinical purpose of diagnosis, as a formulation, is to furnish the informational basis for planning and conducting clinical care, stability of a diagnosis gives a relevant base not only for prediction of the course and outcome of a disorder but also for effective planning and provision of treatment. The availability of longitudinal data, however, may cause significant fluctuations in diagnostic stability as changes in clinical presentation are seen. Thus, evolving longitudinal observations should lead to periodic updating of the comprehensive diagnostic formulation, and yet, despite the inherent problems derived from criteria based on cross-sectional observations, our diagnostic system relies on stable diagnoses. Accounting for the potentially harmful consequences of unsuitable treatment options or clinical interventions, the study of diagnostic stability remains an essential issue in psychiatry.

We know from neurological diseases that there is not only one way to hallucinate. This might also be the case in the psychiatric field. During a trial on refractory verbal hallucinations, we rediscovered a subgroup described under several names in France (Délire chronique d’évolution systématique 1882, Psychose Hallucinatoire Chronique 1911-1953), England (Late Paraphrenia, 1954) and Germany (Affective Paraphrenia - AP, 1968). Roughly, AP can be viewed as the core of paranoid schizophrenia.

We compared 10 AP patients with refractory hallucinations to 35 healthy controls with structural and functional MRI (fMRI). We looked for regions that presented with both grey matter deficit relative to controls and with hallucination-related activity. The lateral orbito-frontal cortex (LOF) was bilaterally involved both anatomically and functionally.

Using fMRI, we studied whole brain functional connectivity, both as a trait factor, i.e. hallucinators vs controls, and as a state factor, i.e. ON vs OFF hallucinations in the same patient. As a trait, functional connectivity was significantly increased between left and right LOF in patients relative to controls; however as a state, functional connectivity dropped to zero between left LOF, left and right superior temporal sulcus (STS) when ON relative to OFF hallucination.

In a larger group of AP patients without ongoing hallucinations, the LOF was still disconnected from the cingulate and temporal regions, in comparison not only to controls, but also relative to non AP type schizophrenias, most of whom also hallucinate during episodes.

We will discuss the “LOF-story hypothesis” for AP patients and their hallucinations.

Schziophrenia is widely considered the most “philosophical” of all mental disorders. One main reason is that many persons with schizophrenia undergo experiences akin to what some philosophers want to attain by the suspension of common-sense attitude and beliefs. This phenomenon is quintessential to the formation of schizophrenic delusions. The typical metaphysical tinge to the contents of schizophrenic delusions is supposed to be the final configuration that this condition eventually comes to take on.

Thus, the clinical characterisation of persons’ with schizophrenia - as it commonly argued by phenomenologically-oriented clinicians - may take profit from a philosophical understanding of the symptoms of this syndrome and from a rigorous and philosophically-informed definition of concepts like ‘consciousness’, ‘self’, ‘subjectivity’, ‘intersubjectivity’ and ‘identity’. A number of recent as well as classic papers and books contributed to establish a model of schizophrenic psychoses as disorders of pre-reflexive self-awareness and other-awareness. This model is now receiving increasing consensus from clinicians as well as from philosophers, and also empirical validation. This symposium will build on and extend these ideas.

Cognitive impairment (CI) is present in the majority of subjects with schizophrenia, is not an epiphenomenon of symptoms, is a risk factor for psychotic disorders and contributes to poor functional outcome. Most probably, in the near future clinicians will be faced with the need of assessing CI in order to complete the diagnostic work-up and to choose among treatment options aimed to target cognitive deficits.

In spite of the progress made by research in this field, relationships between cognitive impairment and other dimensions of schizophrenia remain controversial. On the one hand, empirical data show that CI is independent from psychopathological dimensions, on the other hand, significant associations between CI and negative symptoms have been frequently reported, and associations with positive symptoms or disorganization were also found, although less consistently. Reasons for discrepancies include differences between study samples, cognitive test batteries, medication status, variability of dimensions severity, but also the lack of adequate modelling of the investigated associations. In the presentation, the role of CI in cognitive accounts of psychopathological dimensions will be discussed, limitations of current research on the topic will be highlighted and directions for future research will be outlined.

For the individual a psychotic episode involves the profound experience of distress and identity confusion. The process of recovery includes redefining the self, understanding what has happened and finding new meaning and purpose in order to establish a personally satisfying, hopeful and contributing life.

Hope may be defined as a primarily future-orientated expectation of attaining personally valued goals that will give or restore meaning to one's own experiences. As such it may be seen as a pre-requisite for recovery but also as an important outcome of the recovery process.

This presentation will explore the connection between hope and the attribution of meaning in the process of overcoming demoralisation, resolving psychological defense and integrating the experience of severe mental illness from a psychological, philosophical, and therapeutic viewpoint. Empirical data on hope and its relation to personal explanations following a psychotic episode will be presented.

Schizophrenia is characterised by profound distortions of the tacit world-embeddedness, which can be articulated both in flamboyant, characteristic symptoms - such as positive, negative and disorganised ones - or more subtle, quasi-ineffable changes in the structure of subjective experience. Such dislocation from the tacit milieu of common sense, rests in-between the jaspersian articulations of understanding and explanation, and remains problematically unsaturated even in the comprehensive post-jaspersian frames offered by existential, narrative-hermeneutic, psychodynamic, constructivist and cognitive-behavioural modes of understanding.In this context, a phenomenologically-informed approach can illuminate - in the very hic et nunc of the clinical-therapeutic encounter - those structural changes in the field of awareness which constitute the antepredicative, pre-psychological matrix of schizotropic vulnerability.

Immune system dusfunction is a consistent finding in mood disorder research. One of the relevant metabolic pathways in this regard is the kynurenine pathway which forms a bridge between immune activation, serotonergic deficiency and disturbed NMDA-R function. Given the potential importance of the kynurenine pathway in the pathogenesis of MDD, a SNP based gene association analysis was undertaken, focusing on three major players in this pathway: the genes coding for Trytophan Hydroxylase 2 (neuronal THP, TPH2), Kynurenine-3-MonoOxygenase (K3MO), and Kynurenine AminoTransferase III (KATIII). In order to assess the potential role of these three genes, SNP maps covering the gene were constructed, and single SNP and haplotype association analyses were performed in a sample of 338 German patients with mood disorders and 310 control individuals matched for age, ethnicity and gender.

At the single SNP level, SNP rs1053230 in the K3MO gene shows borderline significant evidence for association. Looking at the haplotype analysis (using the Plink program), the KATIII gene showed significantly different overall haplotype distributions (OMNIBUS) between patients and control individuals for all windows (p-values between 1.75 × 10−5 and 0.006). These findings were mainly due to an overrepreseantation of the CGCTCT risk haplotype, with a frequency of 7,1% in bipolar patients, 5,3% in MDD patients and 1,9% in healthy control individuals.

The identification of a KATIII risk haplotype for mood disorders should be considered preliminary. A next step would be to completely sequence the KATIII promoter, exons and intron-exon-boundaries in patients carrying the risk haplotype.

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 IDO activity 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. Further therapeutic strategies based on immune-modulatory effects will be discussed, too.