Metabolic syndrome, obesity, diabetes and other cardiovascular risk factors are highly prevalent in people with SMI. Patients are at risk for premature mortality and the mortality gap with the general population has increased over recent decades. In part these cardio-metabolic risk factors are attributable to unhealthy lifestyle, including poor diet, high rates of smoking, alcohol/substance use/abuse and sedentary behaviour. But over recent years it has become apparent that antipsychotic agents and other psychotropic agents can have a negative impact on some of the modifiable risk factors. Also other somatic co-morbid disorders are also linked to antipsychotic treatment such as the consequences of hyperprolactinaemia, QTc-prolongation and constipation. Other somatic disorders such as poor dental care, HIV and other infectious diseases and some forms of cancer are also more prevalent in patients with schizophrenia. People with SMI also have limited access to effective screening and somatic care. The psychiatrist needs to be aware of the potential somatic side-effects of antipsychotic medication and to include them in the risk/benefit assessment when choosing a specific antipsychotic. He should also be responsible for the implementation of the necessary screening assessments and referral for treatment of any physical illness. Multidisciplinary assessment of psychiatric and medical conditions is needed. The somatic treatments offered to people with severe and enduring mental illness should be at par with general health care in the non-psychiatrically ill population.

IMPaCT is a five-year project funded by the Department of Health, UK. Running in the UK and now Sweden, the IMPACT Project aims to target the poor physical health and excessive substance use seen in people with SMI. There is evidence that behavioural interventions may be associated with an improvement in physical health and substance use in this population.

IMPaCT is a randomised controlled trial of a health promotion intervention which consists of a manualised modular approach to working with people with severe mental illness to empower them to improve their physical health and substance use habits. It consists of The Manual, The Reference Guide and The Better Health Handbook which make up a therapy package to support clients to become healthier.

The therapy is provided by care coordinators (mental health practitioners) over a 6–9 month period and combines Cognitive Behavioural Therapy (CBT) with Motivational Interviewing (MI) principles. The aim is to work with clients to help them identify their own problem health behaviours, e.g. smoking, diet, exercise, drug and alcohol use. Realistic goals are set and revised with the client, and individual and group sessions are used to develop personal motivation to change. Information, workbooks and diaries are provided to record progress and give helpful hints, while meaningful alternative activities are introduced to replace problem health behaviours.

Patients suffering from schizophrenia are usually treated with antipsychotic agents posing a threat both to their cognitive and physical skills. Anticholinergic and antihistaminic side effects are well known to have a negative impact on mental as well as physical health and pose a major hazard regarding progress in reintegration.

Strategies changing the fate of patients have moved away from just dampening dopaminergic noise in the limbic system. Nowadays, the new focus is on cognitive remediation. The centre of these efforts is to enhance strategic and executive skills and thereby alter patients' motivation to take their life into their own hands again.

The present report aims at presenting evidence from both physical treatment strategies with the power to enhance hippocampal circuit capacity as well as cognitive remediation tools with the the aim of augmenting executive skills by rewiring cognitive circuitry in the brain.

Preliminary results demonstrate not only improved processing of mental load found with fMRI measured circuitry connectivity, but they also point to the improvement of physical parameters taken in a continuous clinical context.

The reasons for these favourable findings are not straight forward and trivial, but they seem to be the result of complex interaction between various factors. The latter are to be pursued in a large cohort and presented at a later point in time.

Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. In particular, in a large study we showed that cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs in schizophrenia. This suggests, along with findings from other studies, that antipsychotic medication has a significant impact on brain morphology. In this presentation we will debate the effects of antipsychotic administration on the brain anatomy of patients suffering from schizophrenia as mainly detected by structural imaging studies; the perspectives in this field of research will also be drawn.

1/In juvenile patients, a cross-sectional ALE meta-analysis of both brain structure and function regional deviations in 270 articles allowed to cluster the diagnosed disorders into three sets with respectively marked affective, cognitive, and psychomotor phenomenology. The group with affective phenomenology was characterized by abnormalities of the frontal-limbic regions; the group with “cognition deficits” (incl. schizophrenia) mainly related to cortex abnormalities; and the psychomotor condition was associated with abnormalities in the basal ganglia. Therefore, early regional brain abnormalities might interact with the analysis of subsequent treatments effects in MR studies of brain structure and function of chronic mental disorders. 2/In chronic patients, brain imaging studies of antipsychotic drugs using dopamine receptor radioligands &PET scanner have consistently demonstrated the prevalence of their dose-dependent action in basal ganglia. This information has led to theoretical windows for optimal drug dosage. Recent measures of the dopamine transporter in chronic antipsychotic treatment, or in chronic use of drugs of addiction (e.g. tobacco, cannabis) suggest opposite changes of the adioligand uptake in both conditions. Therefore, control for the associated confounding addictions is required for in vivo analysis of antipsychotic action on the dopamine regulation in cortex and subcortical regions. 3/In treatment-resistant patients, MR & PET imaging studies have detected deviations of both brain structure and function, therefore suggesting biomarker of treatment response. 4/Conclusion: stage of illness, addictions, multimodal imaging, should be considered as covariates for brain imaging determinations of treatment effects in patients with chronic mental disorders.

Hypnosis may induce striking changes in consciousness and volition under the effect of particular suggestions. Popular theories often consider hypnosis as a state of consciousness where volition is abolished, while cognitive theories postulate that it involves inhibitory control processes mediated by frontal lobe areas. Moreover, since the time of Freud and Charcot, hypnotic effects have often been likened to the abnormal behaviour seen in some psychiatric disorders such as hysteria. However, the neural mechanisms of these different conditions and their putative relationships still remain unclear. By using functional neuroimaging methods in volunteers and patient, we can now identify specific changes in brain activity that underlie the behavioural and perceptual alterations observed during hypnosis and directly compare the latter with findings in hysteria conversion. Our recent results suggest both commonalities between these two conditions, as suggested by Freud and Charcot, but also clear differences that are consistent modern views on hysteria and brain functions. Moreover, hypnosis appears to reflect a state of heightened self-control and monitoring, in agreement with some cognitive theories. This research does not only provide novel insights on how the human mind can regulate itself, but also help better understand the neural underpinning of hysteria, a condition standing at the frontiers of psychiatry and neurology since more than a century.

Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.

Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.

It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.

These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.

Impairments in cognitive processes underlying social interaction (i.e. “social cognition”) have increasingly attracted interest in schizophrenia research during the last years. These impairments concern various components of social cognition, exist relatively independent from impairments in basic cognition and from clinical psychopathology, are already present at the onset of the disorder, and can even be detected in persons at high risk of developing schizophrenia. As social cognitive impairments are closely related to poor functional outcome, and because longitudinal studies have proven the stability of social cognitive impairments across the course of the disorder despite clinically efficacious traditional treatment, various specialized treatment and rehabilitation programs targeting social cognitive impairments have been developed during the last years. These programs differ significantly with regard to the conceptualization of the impairments and the required treatment strategies, i.e. whether the impairments are suggested to be represent cognitive “deficits” or cognitive “biases” requiring remediation vs. debiasing approaches. Moreover the programs differ with regard to the scope of cognitive subcomponents addressed, i.e. whether the program focuses on only one social cognitive subcomponent like affect recognition or whether several subcomponents are addressed in parallel. As the evaluation of such programs is still in an infant stage there is still debate about the most efficacious approach.

This presentation will give an overview on social cognitive impairments and on respective treatment strategies, before the subsequent presentations will exemplify three treatment programs, which may help schizophrenia patients to overcome their impairments in social cognition and social functioning.

Until recently, psychological therapy for schizophrenia was considered inefficient or even harmful by many clinicians. The reservation against psychotherapy is partly rooted in the assumption that delusions are not amenable to psychological understanding. However, meta-analyses suggest that cognitive intervention is effective in ameliorating schizophrenia symptoms. In addition, evidence has accumulated that cognitive biases, such as jumping to conclusions (JTC), are involved in the pathogenesis of schizophrenia positive symptoms, particularly delusions. A recently developed group program, called metacognitive training (MCT), is presented targeting cognitive biases. The MCT is a hybrid of psychoeducation, cognitive remediation and cognitive-behavioural therapy. Patients are taught strategies how to identify and defuse “cognitive traps”. The program can be downloaded at no cost at www.uke.de/mkt and is currently available in more than 20 languages. New evidence on the feasibility and efficacy of the MCT is presented. At the end, a novel individualized variant entitled MCT+ is demonstrated targeting individual delusional ideas. A random-controlled study asserts the efficacy of the MCT+ to reduce JTC as well as delusion severity and conviction.

According to a stress diathesis model, genes and environment, as well as possible interactions in-between (GxE), may result in vulnerability towards suicidal behaviors (SB), characterized by behavioral trigger endophenotypes such as increased depression-intensity and aggression/anger/impulsivity.

Excessive stress has the potential to induce unfavorable effects in a variety of higher brain-functions, incurred as side effects to maladaptive responses in the genetically controlled stress-responsive neurosystems eg. in the hypo- thalamic-pituitary-adrenal(HPA) axis. Childhood traumatic experiences are particularly relevant as stressful experiences are they frequently occur in the early childhood, when susceptibility to external stressors is higher. Childhood abuse has been found in several study as directly associated with suicidal behavior, independently from other psychological or psychopathological risk factors.

HPA-axis dysregulation is regarded as an endo- phenotype of depression-, anxiety- and alcohol abuse disorders, commonly found also in suicide behaviors. Various neurobiological alterations, suggesting abnormal HPA-axis activity and reactivity, have also been demonstrated to occur in suicidal behaviors including completed suicides.

The HPA axis is a major systemic stress-modulator being mainly controlled by the regulatory corticotropin releasing hormone receptor 1 (CRHR1) gene. An overview will be presented of the role of the HPA axis in suicidal behaviors with a focus on CRHR1 gene. and on interactions with childhood traumatic experiences.

There is robust evidence that stressful life events (SLE) are associated with an increase in risk of developing depression. However, humans display wide variation in response to adversity. Caspi et al (2003) reported that a functional length polymorphism (5-HTTLPR) in the promoter of the serotonin transporter gene moderated the influence of SLE on depressive symptoms, major depression, and suicidality, suggesting evidences of a gene-by-environment interaction.

Neuroimage data from healthy, non-depressed, s allele carriers of the 5-HTTLPR show an exaggerated amygdale response to threatening visual stimuli as well as reduced gray matter volume in limbic regions critical for processing of negative emotion compared with individuals with the LL genotype. These data suggest a potent modulatory effect of the 5-HTTLPR on amygdala reactivity to environmental threat.

In recent years, a growing number of molecular genetic studies have focused on the serotonin system, suggesting that this system may be involved in the pathogenesis of suicidal behaviour. Meta-analytic evidences support a link between the s allele of the 5-HTTLPR and the risk of suicidal behaviour. However, several case-control association studies show an association between the short allele and the violence, the number, and the medical lethality of the attempts.

On the other hand, recent data suggest that biological stress reactivity, mediated by the hypothalamic-pituitary-adrenocortical axis, might be a plausible mechanism underlying the association between the 5-HTTLPR genotype and exposure to life stress in predicting psychopathology.

In this presentation we discuss data regarding the complex relationship between the above mentioned systems, stress, and suicidal behaviour.

Early traumatic experiences have been consistently associated with a higher risk to develop psychopathological symptoms in adulthood. Resilience, a trait reflecting tolerance of negative affect, positive acceptance of change and an action-oriented approach to problem solving, has been hypothesized to be a protective factor against stressors. Genetic aspects have been also hypothesized influencing resilience to stress and risk to develop psychopathological symptoms in response to both early and recent adverse events. In particular, a common polymorphism within the gene coding for serotonin transporter (5-HTTLPR s/l) has been consistently associated to the risk to develop depressive-anxious symptoms in response to stressful life events. In the present study we aimed to investigate the role of childhood traumas and 5-HTTLPR on measures of resilience and depression in a sample of individuals at a high risk for psychological distress.A large sample of male prisoners was investigated (n = 1516). 5-HTTLPR genotype was available for 762 individuals. Overall, childhood traumas were significantly correlated to poor resilience and more severe depressive symptoms. 5-HTTLPR genotype did not influence resilience and depressive severity. However, a significant interaction was observed between 5-HTTLPR and childhood traumas on both resilience and depressive severity. Contrary to expectations, s/s individuals exposed to a high number of early traumas had a current higher resilience and less depressive symptoms than l-allele carriers. Present data did not confirm the 5-HTTLPR s-allele as the genetic risk variant for psychopathology in individuals exposed to stressors.

Suicide is a major public health concern, especially for older adults, who have higher rates of completed suicide than any other age group in most countries of the world. However, understanding suicidal behaviour remains a challenging task particularly among the elders who have been poorly studied. Decision making has been recently found to be altered in suicide attempters under 65.To test wether decision making would be a neuropsychological trait of vulnerability to suicidal behaviours, the authors used the Iowa Gambling Task to investigate normothymic non demented elders with a history of suicidal behaviour (N = 35) and compared it to decision making in non suicide attempters with a past history of depression (N = 52) and comparison subjects (N = 43). The data also were compared to those of similar groups of younger normothymic subjects. Moreover, the old suicidal patients were assessed according to the age at the onset of suicidal behaviour (before or after 60).Old suicide attempters did not significantly differ from the other aged groups and according to the age of first suicidal behaviour. Old suicide attempters presented better performances than that of younger suicidal patients.Vulnerability to suicidal behaviour in older people may proceed from cognitive processes which are different from the ones involved in suicidal vulnerability of younger subjects. These results are preliminary and further studies are needed to explore vulnerability cognitive patterns to suicide among elders.

To test the validity of two different social cognitive mechanisms as mediators of CBASP-treatment effects, we conducted fMRI-studies in

i) healthy and

ii) healthy compared to chronically depressed subjects.

The first fMRI experiment included in these studies explored the neural representations and behavioral correlates of causal contingencies between action and response in social interaction and the regulatory effect of successful/erroneous affective response prediction on the limbic system. In the second experiment we examined the ability to infer on the affective states of another person and the correlated activation of the neural “Theory of Mind” (ToM)-Network comprising superior temporal and dorsomedial prefrontal cortices.

In the first experiment we demonstrated for the first time, that the probability of an interaction partner's contingent response to an action is inversely correlated with the activation of a network of medial, ventrolateral prefrontal and inferior-parietal cortices in healthy controls. The congruence of predicted and actual responses modulated activations of amygdala (aversive responses) and ventral striatum (positive responses). The Second experiment actually replicated previous observations, that mentalizing of affective states predominantly activates anterior parts of the ToM-network.

Preliminary results of the comparison between healthy and chronically depressed individuals indicate dysfunctional differentiation of social partners’ predictability in chronic depression as well as altered neural representations of contingencies. For the second experiment we found altered activation within the Theory of Mind network in the patient group.

Finally we will demonstrate pre-post measurements of neural and behavioral changes in both systems of social cognition after 12 CBASP sessions.

Depression and other co-morbidities, such as alcoholism, frequently co-occur and make effective treatment more complex and challenging. There is a growing interest in the co-occurrence of substance use disorders and mood and anxiety disorders, but knowledge about effective behavioral treatment options is far from complete. Research supports the hypothesis that an integrated therapy such as CBASP, which possesses components of motivational, cognitive, behavioral therapy, as well as management of interpersonal reinforcements, to target co-occurring depression and alcoholism may be most effective for chronic depression and co-occurring disorders. CBASP has been shown to be effective in treating chronically depressed individuals and is a promising behavioral approach for use with chronically depressed patients who may report treatment resistance, traumatic developmental histories, manifest impoverished interpersonal relations, interactions, and coping skills, and demonstrate additional chronic under-functioning similar to alcohol dependent individuals with chronic depression. We review the application and research findings regarding the use of CBASP in chronically depressed individuals with co-occurring alcoholism. In addition, we explore the relationship between acquisition learning of the two primary skills in CBASP and treatment outcome. Learning acquisition is assessed in order to capture increases in felt emotional safety with the therapist, as well as perceived functionality on the part of the patient. We hypothesize that patients receiving CBASP will demonstrate an improvement in both symptoms of depression and their co-morbid disorders and that the amount of learning will be proportionally related to improvement in symptoms. We also explore patient characteristics that predict outcome.