Structural brain changes in schizophrenia patients have been reported in many studies. It is still unclear how these changes relate to psychopathological symptom clusters. The aim of the present study was to investigate whether scores of the subscales from a five factorial model of the PANSS correlate with changes of brain morphology.

High-resolution magnetic resonance imaging scans from 54 patients with schizophrenia were analyzed with voxel based morphometry, a voxel-wise whole brain morphometric technique. We correlated grey matter density with the subscales of a five factor component analysis of the PANSS score. Additionally we performed a two group comparison with 101 healthy control subjects.

Significant negative correlations of the disorganization score with grey matter density were found for clusters of voxels in the right inferior frontal, right insular cortex, left temporal pole and left superior temporal gyrus, as well as cingulate cortex and cerebellum. No morphological correlate was found for the other four subscales. P atients showed significant less grey matter density than control subjects in the left and right insula lobe and superior temporal gyrus, left inferior frontal gyrus, right middle frontal gyrus and left anterior cingulate cortex.

The disorganisation syndrome in schizophrenia is linked to particular morphological grey matter reductions in key areas of the disorder. The data support the hypothesis that different symptom clusters in schizophrenia might have different neural substrates.

Dissociative disorders are heterogeneous group of mental disorders with dissociation as dominant symptoms. Dissociation is often defined as partial or total disconnection between memories of the past, awareness of identity and of immediate sensations, and control of bodily movements, often resulting from traumatic experiences, intolerable problems, or disturbed relationships. Etiopatogenezis of dissociative disorders have not exactly known yet. The process of dissociation is independently associated with several distressing conditions such as psychiatric diagnoses, somatization, current psychological distress, and past sexual and physical victimization. The disturbance may have a sudden or gradual onset and may be temporary or chronic in its course. Dissociation has a negative impact on treatment oucome. Additionaly, dissociative patients may have an insecure attachment pattern negatively affecting the therapeutic relationship. Conceptually, the course of treatment is to improve coping, maintain reality, and establish normal integrative functions. Goals:

1. 1. improve thought processes;

2. 2. maintain a sense of reality;

3. 3. improve coping skills;

4. 4. develop stress management abilities;

5. 5. increase identity integration.

The treatment is possible with psychotherapy or pharmacotherapy or both. We will introduce the CBT approach. Participants will learn:

• • pharmacological possibilities in the treatment of dissociative disorders;

• • CBT model of dissociative disorders;

• • motivational interviewing with dissociative patient;

• • how to develope therapeutic relationship with dissociative patient;

• • conceptualization of dissociative disorder with the patient;

• • Socratic questioning;

• • working with cognitive, emotional and behavioral avoidance;

• • exposure technique with dissociative problems;

• • problem solving.

Supported by the research project IGA NR 9323-3.

Epidemiological studies have reported that the increased risk of developing psychosis in cannabis users is dose related. In addition, experimental research has shown that the active constituent of cannabis responsible for its psychotogenic effect is Delta-9-Tetrahydrocannabinol (THC) (Murray et al, 2007). Recent evidence has suggested an increased in potency (% TCH) in the cannabis seized in the UK (Potter et al, 2007). We predicted that first episode psychosis patients are more likely to use higher potency cannabis and more frequently than controls.

We collected information concerning socio-demographic, clinical characteristics and cannabis use (age at first use, frequency, length of use, type of cannabis used) from a sample of 191 first-episode psychosis patients and 120 matched healthy volunteers. Cases were more likely to be regular users (p=0.05), to be current users (p=0.04) and to have smoked cannabis for longer (p=0.01). Among cannabis users, 86.8% of 1st Episode Psychosis Patients preferentially used Skunk/Sinsemilla compared to 27.7% of Controls. Only 13.2 % of 1st Episode psychosis Patients chose to use Resin/Hash compared to 76.3% of controls (OR*= 7.4 95% CI 3.4- 17.2, Adjusted for age, gender, ethnicity, level of Education and employment status).The concentration of TCH in these in South East London, ranges between 8.5 and 14 % (Potter et al, 2007). Controls (47%) were more likely to use Hash (Resin) whose average TCH concentration is 3.4% (Potter et al, 2007).

Patients with first episode psychosis have smoked higher potency cannabis, for longer and with greater frequency, than healthy controls.

It has long been known that cannabis can elicit an acute psychotic reaction. Recent work shows that, of the 60 cannabinoid molecules in the plant, delta-9-tetrahydrocannibinol is responsible for the central effects of cannabis. Here we aimed to investigate, in more detail, the psychological effects of synthetic intravenous THC in healthy subjects. Over 2 experimental sessions, participants (N=22) were administered 2.5mg IV THC or placebo under randomised, double-blind conditions. Psychological reactions were assessed using standard rating instruments and a battery of cognitive tests was completed.

Following THC, there was a significant increase in self-rated and observer-rated positive psychotic symptoms which were highly correlated (r=0.62, p=0.001).Phenomena centered on de-synchronisation of self-agency (ipseity disturbance) and hypersalience/paranoia. Participants also reported a significant increase in negative symptomatology under THC conditions, which was not explained by sedation. Finally, working memory/executive functioning was markedly and consistently impaired by THC.

Here we provide further evidence that THC can elicit an acute psychotic reaction in a proportion of healthy subjects. Acute THC-psychosis elicits positive, negative and cognitive symptoms. Compared with other drug models THC recreates symptomatology across 3 major dimensions of schizophrenic psychosis without sedation/clouding of consciousness. Here we also present preliminary evidence that the molecule cannabidiol (CBD) inhibits THC-elicited positive symptoms. Current work in our laboratory is exploring the underlying mechanisms.

It is well known that psychosis is one of the most severe consequences related to cannabis consumption. Despite the clear negative impacts that this kind of drug abuse might exert upon users, the rates of consumption in Spain are alarmingly high and becoming a serious concern for both politicians and clinicians. Within the Psychiatry Service of the University Hospital Vall d’Hebron, a study has been conducted in order to assess the level of adherence to treatment. The study focuses on the use of group therapy, as an method to reduce cannabis dependence/consumption. Data from this study is presented as are various factors related to an improvement in the adherence to treatment are described.

A clear structured approach to violence risk assessment that is both, evidence-based and gender specific- is high on the political and mental health agendas. The individual risk of perpetrators depends on several parameters that are incorporated into assessment instruments. Most data about risk factors included in risk assessment instruments were derived only on male offenders.

This study is part of Germany's biggest risk assessment study, -the Munich Prognosis project (MPP) - and focuses on factors included in risk assessment instruments associated with criminal and violent recidivism in a sample of male and female delinquents referred for forensic-psychiatric evaluation prior sentencing. The predictive validity of four instruments (HCR 20, ILRV, VRAG and PCL-R) for violent and general repeat offenses was analyzed.

When comparing the predictive validity of the four instruments for male offenders, the results were in favor of the PCL-R, i.e. PCL-R Factor 2 when focusing on violent recidivism.

For female offenders ROC analysis found superior results of the HCR 20-R items (AUC .793 p< .05), the ILRV D variables (AUC .814), p< .05) and the VRAG (AUC .864, p< .05) for violent recidivism. They were in favor of the PCL-R Factor 1 (AUC .666, p< .05) when focusing on general recidivism.

The importance of gender specific violence risk assessment will be discussed.

During the judicial process there are several decision points which require an assessment of recidivism risk: e.g. decisions regarding sentence severity or the form of detention (i.e. low or high security unit), level of treatment, or decisions regarding transfers to open correctional facilities or release. Psychiatric experts called on by the court are required to not only assess recidivism risk, but also state if risk may be lowered by forensic psychotherapy. In the case of treated sex and violent offenders treatment progress has to be evaluated by the therapist and by external experts, before an offender will be released from a correctional institution. When considering the variety of available risk assessment instruments the question arises, which instrument is most suited for decision making. For instance, the “value” of an instrument can be determined by its validity for a specific target population, and by its validity for a specific outcome: Is the instrument valid for a specific offender population or judicial or correctional setting? For what kind of outcome criterion has the instrument been developed and validated?

Risk assessment instruments have been the subject of validation studies which have primarily investigated the properties known from psychometrics (objectivity, reliability and validity). Validation of forensic risk assessment instruments is confronted with a whole row of methodical challenges, which differ considerably from the topics addressed in psychological test development. Risk assessments instruments state the probability of a particular offense to occur. To disregard the probabilistic nature of risk calculations leads to methodically faulty assumptions on the predictive validity of an instrument. Furthermore, test developers will use questionable statistical methods to assess the validity of the instruments such as ROC analyses. This analysis strategy is considered to be state of the art even though this method does not take into account the probabilistic nature of prognoses. Its results can thus be interpreted only to a limited degree. ROC analyses for example disregard certain aspects of an instrument’s calibration, which might lead in an instrument’s validation to high ROC values while demonstrating only low validity.

The granting of leave during terms of imprisonment plays an important part in the treatment of mentally ill offenders. According to German law, leave is to be granted in those cases where the abuse of this privilege or an attempt to flee can be negated. These regulations also, however, imply that the risk assessment of a patient's offence-related recidivism can not be the only criterion for the granting of leave.

So far, there have only been few studies about the prognostic risk assessment of the general abuse of leave. This is rather astonishing, as the granting of leave outside the institutional grounds, in particular, is a decision which often leaves those responsible fraught with anxiety. Furthermore, the abuse of a granted temporary release can lead to severe consequences on various levels.

As part of a study to be conducted in the German state of Rhineland-Palatinate, decisions about granting leave are to be analyzed and possible predictors of the abuse of leave are to be examined.

It is assumed that the abuse of leave is likely to be motivated by the conditions of particular situations and can primarily be explained by normal psychological factors.

However, it should be pointed out that, as the abuse of leave is such a rare occurrence, it poses a significant methodological problem. The criterion to be examined therefore needs to be exactly defined and particular attention must be paid to achieve an adequately high interreliability of the decision makers.

Auditory hallucinations are a common symptom of schizophrenia and florid psychotic conditions. As observed by Jaspers such psychopathological phenomena entail a rich and complex clinical manifestation that is irreducibly linked to an impression of reality grounded in perception. However, most contemporary research has interpreted the jaspersian description in a literal and rather concrete way, equating hallucinatory experiences to mere disordered perceptions. Besides being theoretically problematic, such reduction of hallucinations to “perceptions without an object” substantially neglects fundamental clinical features of the experiential structures implicated in psychotic states (e.g. flagrance, unescapability, feeling of passivity, self-reference, idiosincracy). In this perspective qualitative-phenomenological analysis maintains a crucial role in disclosing the structure of hallucinatory meaning-generation which is relevant for both clinical practice and research.

Within philosophy, hallucinations have served as a paradigmatic test-case for epistemology in general and for theories of perception in particular. The differentiation of hallucinations from “real-life-perception” poses some interesting problems. Here, I will focus on two opposing views: first the view of hallucination as a failure of a metacognitive ability, and second a phenomenologically based view of hallucinations as a disturbance of experiential world-directedness.

Our theoretical understanding of hallucinations however, should take the highly unsettling existential effects on the patients themselves into account as well. As one admits to have experienced a hallucination, this calls into question one's entire capability of perception in general. For how can one be sure not to be hallucinating again? The loss of a basic trust in one's own senses can be so stressful as to aggravate the existing symptoms. These existential effects show that perception cannot be taken as a singular faculty and strengthen the phenomenological approach to hallucinations.

The filmmaker’s trained intuition in ‘reading’ gesture on the one hand and the highly technical nature of the filmmaking process on the other allows for productive interdisciplinary science/art exchange in exploring neurological and psychopathological conditions. As an illustration, processes and observations of a cinema/neuroscience collaboration in the production of a short fiction film featuring a protagonist with visual agnosia will be presented. It will be suggested that challenges and conflicting approaches employed by the different disciplines in the interdisciplinary collaborative investigation are beneficial to both the neuroscience and the filmmaking process. Parallels will be drawn between the cinema/neuroscience collaboration on visual agnosia and the intentions of the current symposium’s interdisciplinary work. This will be discussed in relation to the depiction and interpretation of ‘the subjective’. A questioning of an individual’s subjective perception underpins both the experience of hallucinations and the neurological condition visual agnosia. The potential for clinical insights will be considered in the light of the particular nature of the medium of film and its preoccupation with the subjective experience in relation to aspects of psychosis.

The term auditory verbal hallucination (AVH) covers a diverse phenomenological experience. One model of AVHs proposes they result from self-monitoring deficits causing inner speech to be experienced as alien. The experimental evidence for such a model is briefly summarised. The fit of inner speech models with the phenomenology of AVHs is then critically examined. The form, function, and development of private and inner speech is discussed, and contrasted with the phenomenology of a range of AVHs. It is argued that only a subset of AVHs are phenomenologically consistent with inner speech models. Implications for the study of AVHs are discussed.

Interaction between neuroendocrine stress and metabolic signals has become increasingly linked to the pathogenesis of affective and cognitive disorders. Independent evidence shows that nuclear receptors represent an essential interface of communication between these signals and the central nervous system.

On the premise that lifelong brain functions are subject to programming by stressful and metabolic signals during early life, we induced voluntary hyperphagia in prepubertal male and female rats by providing them with a cafeteria-like choice between normal chow and foods with high motivational value (palatable, high fat/high energy). The cafeteria diet was withdrawn from one subset of animals during early adulthood (postnatal day, PND 80), and several endpoints of interest were monitored until PND 200. While both sexes displayed similar metabolic outcomes during exposure to the cafeteria diet, there were substantial sex differences in the metabolic, behavioral and endocrine consequences of withdrawal of palatable food. Consistently increased food consumption and body mass gain were recorded in males, whereas females that were pre-exposed to the cafeteria diet showed clear signs of adrenocortical hyperactivity. Thus, besides verification of sex-specific mal-programming of appetitive behavior and metabolic set-points by early life events, we also demonstrate evidence for differential translation of metabolic challenges during peripubertal development into aberrations suggestive of altered neuroendocrine responsiveness to stress.

Iodine is a trace element which is essential for the synthesis of thyroid hormones. If maternal iodine deficiency in pregnancy is severe, fetal brain damage will occur. This damage is irreversible after birth. Mild/moderate iodine deficiency during pregnancy and early postnatal life is associated with neuro/psycho-intellectual deficits in infants and children. The severity is not only related to the degree of iodine deficiency, but also to the developmental phase during which it is suffered, the most severe being the consequence of iodine deficiency during the first two trimesters of pregnancy. The close involvement between human brain development and thyroid hormones is widely accepted. The effects of T3 on the central nervous system are mediated by the regulation of the expression of genes that synthesize proteins implicated in cerebral neurogenesis, neuronal migration and differentiation, axonal outgrowth, dendritic ontogeny, and synaptogenesis. They are also necessary for cerebellar neurogenesis (predominantly during early postnatal life), gliogenesis (predominantly during late fetal life to 6 months postnatally), and myelogenesis (during the second trimester of gestation to 2 years of postnatal life). From clinical studies on the effect of iodine deficiency of both mother and fetus it becomes clear that T4 is required for brain development during gestation.

Low T4 levels during neonatal life could be a negative factor contributing to the neurodevelopmental problems of very preterm infants. Indeed, retrospective studies have shown a relationship between hypothyroxinemia and developmental delay and an increased risk of disabling cerebral palsy.

Schizophrenia is a complex genetic disorder. The lack of concordance on disease manifestation in monozygotic twins provides clear evidence that environmental factors are key determinants in disease aetiology. In accordance, various environmental modulators such as hormones and vitamins may well contribute to the altered expression pattern of several genes identified in post-mortem brain tissue of patients. We constructed a microarray platform containing 1,808 human genes, where 142 belong to vitamin A, thyroid hormone and estrogens’ metabolic pathways, to specifically address whether these could contribute to a molecular signature of schizophrenia in peripheral lymphocytes. We found that the genes encoding for PLP1, UGT1A6, NTRK1, THRAP1, ESR2, TRIP13, MAPK8, TGFB2, IGFBP4 are differentially expressed in lymphocytes of patients under treatment with clozapine, risperdal or haloperidol. Some of these genes have been previously reported by others to be altered in brain regions of schizophrenic patients, and all are implicated in pathways suggested to be involved in the disease. These observations further support that:

1. 1. studies in peripheral blood lymphocytes may contribute to reveal candidate genes in schizophrenia;

2. 2. transcription modulation of several genes may occur through the mediation of vitamin and hormones, therefore linking genes and environment in schizophrenia.

In order to understand the involvement of these genes in schizophrenia, future studies should investigate whether some of the observed changes are replicated in animal models of the disease, and how antipsychotic treatment interferes with their expression.

There has been strong evidence in recent years that oxygen free radicals may play an important role in the pathophysiology of schizophrenia and bipolar disorder. More recent evidence of altered antioxidant defenses in major mental illnesses has been accumulating. Much of the focus on antioxidant defense mechanism has been on the key scavenging antioxidant enzymes: Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSH-Px). Of these, SOD activity has been the most frequently examined.

The imbalance between antioxidant and oxidant mechanisms increases what is called oxidative stress, when the oxygen free species react and could damage lipids, proteins, carbohydrates and DNA. Lipids are the main compound of cellular membrane and the oxygen free radicals reaction to them is called lipid peroxidation. Several plasma lipid peroxides, like MDA, are measured by Thiobarbituric acid reactive substances (TBARS). Increased levels of TBARS have been reported in the plasma of drug-free and medicated bipolar disorder and schizophrenic patients. It is hypothesized that psychotic symptoms seen in both disorders might be a consequence of peroxidative injury to membrane phospholipids. Moreover, neuronal functioning is affected by this injury either by changes in membrane fluidity or by alterations in membrane receptors, which can cause neurotransmitter uptake and release impairment and even cell death.

After eight years of tortured negotiations between government, professional psychiatrists and lay pressure groups, England and Wales will begin to use new Mental Health Legislation November 2008. This will not be a new Mental Health Act, but a substantial modification of the 1983 act. There are nine key changes:

1. 1. A single definition of mental disorder: ‘any disorder of mind or brain’.

2. 2. Criteria for compulsion: ‘appropriate medical treatment’ test.

3. 3. Age-appropriate services: special arrangements for under 18 years.

4. 4. Professional roles: approved clinicians and responsible clinicians (non-medical).

5. 5. Nearest relative: recognises Civil Partnerships, allows displacement.

6. 6. Supervised Community Treatment Orders.

7. 7. Mental health Review Tribunal: unified.

8. 8. Advocacy: Independent Mental Health Advocates.

9. 9. ECT: new safeguards.

The Code of Practice identifies five key principles:

1. 1. Purpose - to minimise adverse effects of Mental Disorder.

2. 2. Least Restriction.

3. 3. Respect - diverse needs, values and circumstances.

4. 4. Participation - involving patient in planning, developing and reviewing treatment and care.

5. 5. Effectiveness, efficiency and equity - optimal use of resources.