Alexithymia represents a risk factor for psychiatric and psychosomatic disorders and is associated with a less favourable outcome in various treatments modalities. With prevalence rates up to 30% in subjects seeking psychiatric or psychotherapeutic treatment, there is an urgent need for a better understanding of the psychobiology of alexithymia. Previous studies have described an association between alexithymic traits of mothers and their offspring but did not investigate the fathers´ contribution. Therefore, psychological mechanisms like the mother-child bonding may exclusively account for the observed association. The aim of the present study was to extent this research strategy to fathers, too.

The familial transmission of alexithymia was assessed in 86 child-parents trios. Significant associations between the TAS-20 scores of the children and mothers and children and fathers were found. The results were adjusted for age, gender and education. Factor 1 (difficulties identifying feelings) showed the largest intrafamilial association.

The significant association of both fathers´ and mothers´ TAS-20 scores with the TAS-20 scores in the offspring strongly support a familial transmission of alexithymia. As both parents contributed to the TAS-20 score of their offspring, psychological and genetic factors may be responsible for the observed association. Thus, in addition to psychological research of affect development and differentiation the search for genetic mechanism for alexithymia should be started.

No studies exist dealing with alexithymia and cellular phone (=CP) use. We hypothesised that there is an association between alexithymia and 1.not owing a CP and 2. with sparse use of CP.

The material consisted of 696 primary health care patients in Finland. Data was gathered with a questionnaire. Alexithymia was measured with the Toronto Alexithymia Scale-20. In addition to owing and using of CP several other factors were measured. The sociodemographic background factors consisted of gender, age, marital status, working status, living situation, and interpersonal relationships. The health status was measured with two subjective assessments (self perceived general health and functional ability) and with three standardized scales (the Depression Scale, Mood Disorder Questionnaire, and 22 questions from the core psychosis section of the Composite International Diagnostic Interview). In addition the childhood emotional, sexual and physical abuse was measured with the Traumatic and Distress Scale.

Only 9 % of the participants did not own a CP. Among them the means of TAS total score and TAS-factor3 (externally oriented thinking) were significantly higher than among other participants. Among those who used CP at least daily the means of all alexithymia measures: TAS total score, and the three factors (difficulty in identifying feelings, difficulty in describing feelings, externally-oriented thinking) were significantly lower than among other participants. In case of TAS total score and difficulty in describing feelings these associations still remained after controlling for all the above mentioned other factors. These findings fit well with the alexithymia construct.

Prion diseases, or Transmissible Spongiform Encephalopathies (TSEs), are a group of fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrPC) into a self-feplicating and proteinase K (PK)-resistant conformer, scrapie PrP (PrPSc). Aggregates of PrPSc around neurons lead to neuropathologyical change including neuronal loss, astrogliosis, spongiform degeneration and deposition of amyloid plaques. Currently no effective treatment for prion disease exists. The development of novel therapeutic strategies against prion diseases has become a priority. Several reports have demonstrated that passive and active immune-based therapy can significantly prolong the incubation period of prionoses in vivo, and also some anti-PrP monoclonal can prevent PrP peptide toxicity in vitro. In this study, we have first time identified and purified anti-PrP antibodies from human intravenous immunoglobulin (IVIG) by using PrP peptide affinity chromatography column. The ratio of anti-PrP antibody and IVIG is about 1:1200. In vitro study indicates these anti-PrP antibodies strongly block PrP A117V peptide fibril formation and disrupt formation of fibrillar structures. Furthermore, these antibodies almost completely prevented neurotoxicity of PrP A117V peptide in cultured rat cerebellar granule neuron cultures (CGN). In contrast, immunoglobulins depleted of anti-PrP antibodies had little effect on PrP fibril formation or protection of neuronal cells. Our study suggests that human anti-PrP antibodies may interfere with the pathogenesis of prion disease and these purified antibodies may be a potential therapeutic agent to prevent or slow prion disease progression.

With the evolving pharmacological era for the treatment of Alzheimer's disease (AD), there is a growing urgency to develop biochemical markers, as well as biomarkers based on imaging techniques to aid early accurate diagnosis, characterize patient populations and quantify the extent to which new drugs reach intended targets, alter proposed pathophysiological mechanisms and achieve clinical outcomes. Biomarkers support stratification of patient populations or quantification of drug benefit in primary prevention or disease-modification studies. Enrichment of trials with patients with similar prognosis according to a particular biomarker or combination of biomarkers could speed up proof-of-concept and dose-ranging studies. A wide range of imaging-based biomarkers are presently being studied for AD. These include an ever growing array of manual or fully automated MRI post-processing techniques of whole brain, grey or white matter, fiber tracts or specific brain regions, as well as metabolic, functional MRI and PET investigations. Multiple biochemical analytes in blood, urine or cerebrospinal fluid (CSF) have been proposed and studied, the most obvious of which are CSF β-amyloid related proteins, including abeta-antibodies and BACE 1, or tau proteins (total and phosphorylated tau), as they seem intimately involved in key mechanisms of AD. However, there are many different therapeutic approaches predicated on different pathophysiological hypotheses that might require different mechanistic markers. It is therefore likely that a multi-modal biomarker approach stratified for ease of use, sensitivity and specificity will be needed in AD. This paper will focus on advances in the development of an immunotherapy for AD. In summary, clinically useful biochemical and imaging derived markers are clearly required in AD to inform regulatory and therapeutic decision making regarding candidate drugs and their indications in order to help bring new medicines to the right patients faster than they are today. Clearly, for AD a good biomarker could significantly reduce drug development timelines and optimize resources, thereby facilitating the evaluation of multiple molecules and therapeutic approaches. Currently, biomarkers, as well as novel therapeutic strategies need to be simultaneously developed and synergistically implemented in clinical AD research.

Depressive disorders are highly prevalent, have a high incidence, and are associated with huge losses in quality of life in patients and their relatives, with increased mortality rates, with high levels of service use, and with huge economic costs. Prevention is an alternative to treatment that has not been studied elaborately until now. In this presentation, the current state-of-the-art on prevention of depression will be presented. Some recent methods will be shown to identify high risk groups that can be target populations for these interventions. These studies have made it clear that the majority of the first-ever incident cases of depression can be predicted with some simple risk-indicators. In the next part of the presentation, the research that has been conducted on the effects of preventive interventions will be summarized. In the past decade, several randomised studies have examined the effects of preventive interventions on the incidence of depressive disorders. These studies show that indicated prevention (with subjects who already have some symptoms but no DSM-disorder) can reduce the incidence of major depression with about 30%. Finally, an overview of interventions that are used as prevention in routine practice will be presented. Most of these interventions are based on cognitive-behavior therapy and are aimed at subjects who have some symptoms of depression but do not meet diagnostic criteria for a mood disorder. New developments in the prevention field and innovative interventions that are now being tested, will be presented.

The melancholic type is a phenomenological construct useful to recognize and assess persons vulnerable to develop major depression. Its main features are consciousness, orderliness, hyper-heteronomia and intolerance of ambiguity. These features, which mainly describe the social behaviour and the value system of these persons, were first described in qualitative studies mainly developed in Continental and Japanese psychopathology, and later established through quantitative research. The evolution of this construct nicely illustrates how qualitative and quantitative methods may be integrated in an epistemologically sound research agenda.

While there is growing evidence for the efficacy of programs aimed at preventing depression, extensive variability exists in related research designs and methodology. The present contribution focuses on conceptual, methodological and practical considerations relevant to prevention research and practice in depression. First, it will outline characteristics of particular types of prevention (universal, selected, and indicated prevention) along with their strengths and weaknesses. It will also address the problem of reliable case identification, the adequate assessment of key symptomatology and relevant risk, protective, and vulnerability factors, the significance of preceding comorbidity which may affect the course of depressive symptoms, and, finally, the necessity for instruments allowing the longitudinal examination of subjects over long time periods or over developmental transitions. Furthermore, it will discuss the use of different outcome criteria (e.g., case status, symptoms, risk factors) and related implications, as well as effects of base rates and length of follow-up intervals on the efficacy of interventions. Finally, it will address the evidence of targeted intervention components in relation to particular risk groups, and will point to adequate implementation and related adherence measures. Recommendations for future prevention research and clinical work will also be provided.

The pleasant effects of food and alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Dopamine release, on the other hand, was associated with attribution of incentive salience to reward-predicting stimuli. Once excessive alcohol consumption is established, GABAergic and glutamatergic neuroadaptation underlie tolerance development and withdrawal symptoms. Combined functional brain imaging studies and studies wit positron emission tomography suggest that in the brain reward system, neuroadaptation in dopaminergic and opioidergic neurotransmission seems to augment neuronal responses to well-established, alcohol-associated stimuli while interfering with the acquisition of new, reward-seeking behavior patterns. In imaging studies with positron emission tomography, the availability of central mu-opiate receptors was measured with the radioligand carbon 11-labeled carfentanil in the ventral striatum of alcoholics and controls matched for mu-opiate receptor genotype. An increased availability in the ventral striatum, the core area of the brain reward system, and in the medial prefrontal cortex was found in alcoholics correlated with the severity of alcohol craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). Dysfunction of dopaminergic and opioidergic neurotransmission may contribute to alterations in positive and negative affect. In detoxified alcoholics, a high brain activity elicited by affectively positive cues was associated with a reduced relapse risk and may thus provide a protective factor that could be influenced by psychotherapy or additive medication.

The presence of a Gene-Environment interaction means that when both factors are detected, the risk is increased compared to the sum (or the multiplication) of each of them.

A first way to use such interaction is to fix a known environmental factor (for example when all patients are being exposed to alcohol) and see how some genes may be involved on related- or endo-phenotypes.

The survival status of a male alcohol-dependent sample (n=126), recruited 9 years before, was for example analysed. We found that the C allele of the 5-HT1b gene, and tobacco dependence, were found in excess in the non-surviving patients, but that no endo-phenotypes are being directly involved.

With this same GxE approach, we also found that a haplotype of the DAT gene was involved in the risk of withdrawal seizures (Le Strat et al., in press) when all patients stopped, at least once in their lifetime, drinking alcohol.

A second strategy is to analyse some environmental factors potentially involved (such as early aggression) and compare these risk factors in patients with or without genetically related vulnerability (such as high initial tolerance to alcohol or familial history of dependence) to explain alcohol abuse or dependence. We will present a new study (S.A.G.E.) based on 3.000 young adults assessed for these factors.

Gene-Environment interactions approach could help to select more accurately specific candidate genes, identify more homogenous subgroups of patients, and ultimately, may lead to more focused, i.e. more efficient, prevention strategies.

Because cannabinoid (CB) and serotonin (5-HT) systems have been proposed to play an important role in drug craving, we investigated whether CB1 and 5-HT1A receptor ligands could affect voluntary alcohol intake in two mouse strains, C57BL/6J and DBA/2J, with marked differences in native alcohol preference. When offered progressively (3% to 10% ethanol) in drinking water, in a free-choice procedure, alcohol intake was markedly lower (~70%) in DBA/2J than in C57BL/6J mice. In DBA/2J mice, chronic treatment with the CB receptor agonist WIN 55,212-2 increased alcohol intake. This effect was prevented by both chronic CB1 receptor blockade by rimonabant or chronic 5-HT1A receptor stimulation by 8-OH-DPAT, which, on their own, did not affect alcohol intake. In C57BL/6J mice, WIN 55,212-2 had no effect but CB1 receptor blockade or 5-HT1A receptor stimulation significantly decreased alcohol intake. Parallel autoradiographic investigations showed that chronic treatment with WIN55,212-2 significantly decreased 5-HT1A-mediated [35S]GTP-γ-S binding in the hippocampus of both mouse strains. Conversely, chronic rimonabant increased this binding in C57BL/6J mice.

These results show that CB neurotransmission can exert a permissive control on alcohol intake, possibly through CB1-5-HT1A interactions. However, the differences between C57BL/6J and DBA/2J mice indicate that such modulations of alcohol intake are under genetic control.

A synopsis of current treatment options shows only moderate effect sizes. They could be improved considerably if individual predictors were available.

Previous attempts to identify predictors for the treatment response in alcoholism have mainly concentrated on social and personality variables. Project MATCH was such an attempt which finally failed. The same holds true for similar attempts in pharmacotherapy. Therefore, we set out for a large oligocentre trial “Project PREDICT”. 432 patients are randomly assigned to treatment with acamprosate, naltrexone or placebo. At baseline patients are assessed with a battery of interviews, questionnaires and biological examinations (e.g. genetics). Specific emphasis is put on patients’ individual pathways into relapse. It is determined whether relapse drinking respresented a positive reinforcer (“reward craving”) or a negative reinforcer (“relief craving”). This is assessed with questionnaires, the startle reflex and fMRI. We hypothesize, that patients who are a priori identified as “positive reinforcers” better respond to naltrexone. Negative reinforcers should benefit most from acamprosate.

All patients have been included by now. Preliminary analyses suggest that it is possible to distinguish between the two craving types. The equivalent of positive reinforcement in the startle reflex correlates with fMRI responses to cues with a positive valence of about 0.7. These methods might offer a platform for a targeted pharmacotherapy in alcoholism.

Right from the very beginning as a medical discipline up to now in psychiatry the paradigms of a disease continuum and of a variety of different disease entities are opposed to each other. The analyses of the historical development of the currently used classification systems indicates that sticking to established terms and methodologies more and more develops to an obstacle in research and treatment. Modern brain research and genetic research require more homogenous clinical syndroms to examine them with scientifically based methodologies and technologies. One first step in this direction could be the widening of Kreapelin's dichotomy of endogenous psychoses with a third spectrum of diseases, the cycloid psychoses, placed between the (bipolar) affective and the schizophrenic spectrum. Cycloid psychoses have a low heritability and are mainly caused by neurodevelopmental disturbances. There are no prodromal negative symptoms before the onset of the disease. There is a liability of developing psychotic symptoms triggered by stress, life events and drugs. There is an acute onset within a few weeks, the course is mostly bipolar with depressive and manic features, remittend and there are no long lasting negative symptoms. Further studies are urgently required in order to confirm or refuse the validity of the concept of the spectrum of cycloid psychoses.

In contrast to the hypothesis of different nosological entities of so-called “endogenous” psychoses (e.g. schizophrenia, manic-depressive psychosis) the model of unitary psychosis has been discussed in controversial terms. The starting point of those discussions was the concept of a unitary nosological and pathogenic entity which may be traced back to Joseph Guislain and has inspired the work of Wilhelm Griesinger, who further elaborated the concept of Unitary Psychosis ("Einheitspsychose"). Griesinger, who was also influenced by Zeller's idea of the unified human soul or character (“Gemüt”), argued that madness was the consequence of a single disease of the brain. In comparison to that the Unitary Psychoses concept of Janzarik focuses not on the nosological position but on the pathogenetic mechanisms of endogenous psychoses (e.g. structural-dynamic coherence model). Recent co-morbidity studies as well as trans-nosographical analyses have called classical categorical diagnosing more and more in question. The development of dimensional diagnostics, as an alternative to categorical diagnostic systems led to a renaissance of the unitary psychosis ideas. Such dimensional diagnostics do not focus any longer on artificial disease constructs and their nosological position but on single psychopathological phenomena, on their plasticity during the pathological process, and their constellations of conditions. The main task of Dimensional Diagnostics, as introduced here in this paper, is not only the accurate description and explanation of psychopathological phenomena and processes but has to include also the understanding of the suffering person's deficiencies and resources.

As a result of the globalization process that is taking place all over the world during the last two or three decades, a strong pattern of migration is being observed in all regions of the world. This pattern usually is observed from emerging countries toward industrialized nations. Needless-to-say, this migration process is making a big impact in many nations of the European Union such as Spain, Germany, Sweden, and the United Kingdom.

In general, migrants go to industrialized nations with the hope of improving their socioeconomic conditions; however, they also bring with them language, religion, norms and heritage, that is their culture. Additionally, the migration process produces "acculturation stress", and this stress could lead to development of psychiatric conditions such as posttraumatic stress disorder, depression, substances use and abuse, alcoholism, suicide, etc. At times, however, migrants are capable to adjust well and, thus, to integrate with the host society.

It is, therefore, important for psychiatrists and other mental health professionals to understand the impact of migration vis-à-vis the development of "acculturative stress" as well as psychiatric disorders. This knowledge will permit psychiatrists and other mental health professional to more appropriately and effectively diagnose and treat psychiatric disorders in these migrant groups.

Structural brain imaging abnormalities in schizophrenia-resemble spectrum disorders in many respects. Similar to schizophrenia, cerebrospinal fluid (CSF) is increased and cortical volumes are decreased in schizotypal personality disorder (SPD). In this large sample study, MRI assessed white matter volumes and diffusion tensor anisotropy was assessed in the schizophrenia spectrum. The sample includes 230 schizophrenics (ages 13-78) and an approximately age matched group of 81 patients with schizotypal disorder and 230 normal volunteers. For the bipolar spectrum there were 44 patients with bipolar spectrum disorder. Results in a pilot subsample of patients revealed increases in white matter in the cingulate in SPD and Schizophrenia in comparison to the normal sample. However in prefrontal regions, a schizophrenia spectrum pattern was observed with greater white matter increases in patients with schizophrenia than patients with schizotypal disorder, and greater gray matter decreases in patients with schizophrenia than patients with schizotypal disorder. Anisotropy changes were widely observed across the prefrontal cortex and corpus callosum. Taken together these results suggest that prefrontal change appears associated with a continuous spectrum deficit while some changes in the cingulate and other brain regions may show protective or reactive change in schizotypal patients. Bipolar patients had significantly reduced volume of the white and the gray matter of the frontal cortex. Furthermore, compared with control subjects, BPS patients as a group showed alterations in anisotropy of the internal capsule adjacent to the striatum and thalamus and the frontal white matter.

There is strong qualitative and quantitative evidence of white matter abnormalities in schizophrenia and bipolar disorder from structural magnetic resonance imaging (MRI). There is also good evidence of altered connectivity in schizophrenia using diffusion tensor magnetic resonance imaging, but no study has yet addressed the diagnostic specificity of these findings or whether they are related to specific susceptibility genes.

Kraepelinian dichotomy between schizophrenia (SCZ) and bipolar disorder (BD) is based on the increased degree of overlap in the pathophysiology of the two disorders and white matter pathology has emerged as a possible marker for these illnesses. Indeed, genes regulating myelin and oligodendrocytes are downregulated in both SCZ and BD, suggesting oligodendrocyte dysfunction. Also, we and others have demonstrated using MRI intra- and inter-cortical white matter impaired connectivity in both disorders. These accumulating data suggests a possible common physiological pathway for SCZ and BD, involving white matter disconnection. White matter microstructure organization can now be explored by diffusion imaging. Recently, we have shown with diffusion MRI impairment of frontal and temporal white matter, corpus callosum, and thalamus in one of the largest population of patients with SCZ reported in the literature. Also, white matter microstructure alterations have also been found in BD, and our diffusion imaging data would confirm that in our population of BD patients. Therefore there is strong evidence suggesting that white matter pathology is present in both SCZ and BD, possibly representing a common intermediate endophenotype. This may potentially be sustained by dysfunctional olygodendrocytes, leading to white matter disruption and ultimately to cognitive disturbances. Impairments of executive functions are indeed reported in both SCZ and BPD and epidemiological studies have demonstrated family aggregation of both disorders. In conclusion, in this symposium we hope to inform on the current debate on the merits of the Kraepelinian dichotomy, characterizing the dimensional approach in the understanding of the functional psychoses.