The topic of this symposium is the evaluation of outcomes in individuals presenting with violent or sexual offending in a range of different settings. Violent offenders are of particular concern to psychiatrists who may face pressure from society to detain such individuals. At the same time evidence for the efficacy of any interventions to improve outcome and reduce re-offending remains limited. In recent years new initiatives (e.g. the programme for Dangerous and Severe Personality Disorders (DSPD) in the UK) have been developed to understand better what works for violent offenders, including those with personality disorders. Research in this area is complex not least as randomised controlled trials might not be seen as practical or ethical.

This symposium comprises speakers from three different countries, Sweden, Switzerland and UK. The Swedish contribution will present data from a naturalistic study comparing offenders with mental disorder and substance misuse who engage in community treatment following release to those who don’t. Researchers from Switzerland will introduce the “therapy evaluation project” of the Zurich Criminal Justice System and show data on recidivism (both convicted and non-convicted). Presenters from the UK are from one of the high secure DSPD sites and will present different methodologies, including single case studies, to evaluate the efficacy of this service and its different therapies. The implications of these findings for future research and service delivery will be discussed.

Suicidal behavior (SB) is a major burden in most nations world-wide and a major public health concern. The causes of SB are complex, in which both genetic set-up and exposure to overwhelming psychological stress (environmental factor) contribute to a person's final predisposition for SB. One candidate system reflecting this causal route to SB is the stress-modulating hypothalamic-pituitary-adrenal (HPA) axis, and dysregulation of HPA is considered to play a major role in depression and SB. The corticotrophin-releasing hormone and its main receptor (CRHR1) have key regulatory functions in the HPA axis, and we hypothesized that genetic variation in CRHR1 may be associated and linked with SB and related endophenotypes. We analyzed single nucleotide polymorphisms (SNPs) in an extended sample of family trios (n = 672) with suicide attempter offspring, by using family-based association tests. Results showed that the minor T-allele of exonic SNP rs12936511 was significantly transmitted to suicidal males with increased Beck Depression Inventory (BDI) scores (P = 0.0028). Analysis of haplotypes showed that risk alleles of three different SNPs segregated onto separate haplotypes, whereas a fourth ‘nonrisk’ haplotype (‘CGC’) was preferentially transmitted to suicidal males with lowered BDI scores (P = 0.0007). Conversely, the BDI scores of those who carried a homozygous combination of any of the three risk haplotypes were significantly increased (P = 0.000089). We concluded that depression intensity in male suicidal offspring was related to genetic variability in the 5’-end of CRHR1, while the characteristics of the suicide female attempters remained unknown.

Suicide is the leading cause of death in prisons. Number of studies has indicated disturbances in serotonin neurotransmission in persons displaying suicide behaviour and depression. We hypothesized that 5-HT2A -1438G/A polymorphism would modulate the influence of childhood trauma on suicide and depression among prisoners in a gene-environment-dependent manner.

Study participants were 427 male prisoners detained in jails of the District of Abruzzo-Molise in Italy. All were assessed through psychiatric interview, Hamilton Rating Scale for Depression (HRSD-21 items) and Childhood Trauma Questionnaire (CTQ). The component structure of the 21 HRSD items was determined using principal component analysis with varimax rotation and three components were extracted. We proposed a new gxe model with all components dichotomised at the median and used as dependent variables when creating logistic regression.

Significant interactions were found with the suicide/insomnia component only. The major findings were:

1. 1) emotional abuse during childhood interacts with 5-HT2A AA genotype to increase the risk for later-life suicide and insomnia,

2. 2) 5-HT2A AA genotype and childhood traumas (emotional abuse and physical neglect) independently of each other increased the risk for later-life suicide and insomnia,

3. 3) 5-HT2A AG and GG genotypes might be protective against suicide and insomnia, even when in interaction with childhood traumas.

Our results add evidence to the fact that suicide and insomnia are both complex traits shaped by interactions between genetic and environmental factors. These factors might interact dynamically throughout prenatal and postnatal periods, thus shaping the brain development and leaving long-term consequences on adult behaviour.

In the Netherlands, the Depression Initiative has been launched in 2006 as a nationwide attempt to implement the Multidisciplinary Guideline for Depression and to evaluate its cost effectiveness. An evaluation of the selected strategy to implement the guidelines, a Breakthrough Collaborative, was conducted as a quasi experimental trial. The intervention group consisted of around 530 patients coming from 10 multidisciplinary teams in primary care. The intervention teams received a set of implementation strategies, as part of the Breakthrough Method, developed by the Institute for Healthcare Improvement (www.ihi.org). The aim of the participants in this implementation project was to implement guideline recommendations directed at a reduction of unnecessary antidepressant treatment for patients with mild depression, better use of effective, but minimally invasive treatment options and improved antidepressant and psychotherapeutic treatment for patients with severe symptoms. Monitoring depression severeness was also one of the goals. This guideline derived, stepped care approach was compared to Care As Usual in the primary care setting, as provided in a different study group (NESDA). Outcomes were measured in terms of quality of care provided by the general practitioner (antidepressant prescription rates) and clinical outcomes (BDI, IDS-SR, WHODAS). A process evaluation and simple economic evaluation was part of the study design. In the presentation, preliminary results will be presented.

In the Netherlands, the Depression Initiative has been launched in 2006 as a nationwide attempt to implement the Multidisciplinary Guideline for Depression and to evaluate its cost effectiveness. Evaluation of a collaborative stepped care model in several health care settings is one of the objectives of the Depression Initiative. Currently a stepped collaborative care project is being evaluated in the primary care setting, evaluating stepped collaborative care for depressive disorder provided by the primary care practitioner, a nurse-care-manager, and a consultant psychiatrist, in a Randomised Controlled Trial. 150 Patients with depressive disorder are offered a treatment plan. They can choose from two options: Problem Solving Treatment with or without antidepressant treatment. The medication is prescribed by the PCP, PST and monitoring is provided by the care manager, and the psychiatrist can be consulted every 6 weeks in order to see if the intervention is sufficient to improve the symptoms of the patient. The PHQ is used for monitoring. A two step approach is aimed at; if the patient does not achieve remission after 18 weeks, the patient is referred to mental health care. This stepwise approach is supported by a training and supervision program and by a web-based tracking system in which the care-manager and the patient can monitor progress and consult the psychiatrist. This approach is compared with Care As Usual in the primary care setting. In the presentation, preliminary results will be presented.

A carefully planned comprehensive and integrated care model of in- and outpatient depression treatment is a promising way to achieve improvements in care. Within the framework of the Freiburg Model of integrated care for depressive disorders a network of psychiatrists and primary care physicians offers in collaboration with the Department of Psychiatry and Psychotherapy of the University of Freiburg a coordinated treatment for patients with depressive disorders. Complementary to an evidence-based outpatient treatment the department of Psychiatry and Psychotherapy offers a complex treatment where patients can use the different inpatient measures during their outpatient treatment. In addition patients with a chronic depression can make use of a specific treatment program.

In spite of the fact that suicidal behaviour is very complex, multicausal human behaviour, untreated current major Axis I affective disorder (bipolar and unipolar major depressive episode: 56-87%) is the most powerful predictor of suicide, particularly in the case of prior suicide attempt. Prospective and retrospective follow-up studies clearly support the eivedent clinical observation that if patients with unipolar or bipolar mood disorder committ or attempt suicide, they do it mostly during the major depressive episode (78-89%) and less frequently in dysphoric mania or mixed affective episode (11-20%) but very rearly during euphoric mania or euthymia, indicating that suicidal behaviour in mood disorder patients is a state-dependent phenomenon. Consequently, effective treatment of acute major mood episodes and successful long-term management is very important part of suicide prevention of patients with affective disorders. Indeed, it has been repeatedly demonstrated that long-term lithium treatment of bipolar disorder and unipolar depression reduces the risk of completed and attempted suicide markedly, even in this high-risk population. The marked anti-suicidal potential of lithium seems to be more than the simple reflexion of its phase-prophylactic effect, as it has been demonstrated that during the long-term prophylaxis of recurrent unipolar and bipolar affective disorder patients with at least one prior suicide attempt, a significant reduction in the number of suicide attempts was found not only in the excellent responders (93%), but also in moderate responders (83%) and in poor responders (49%).

Migration is perhaps best understood as a sociodemographic context that can increase vulnerability to both mental health problems and emotional crisis. Crisis can be understood as a specific moment of psychological upset that the individual experiences as beyond his or her capacity to cope with effectively. Migrants in crisis, from this perspective, are different from native born individuals on two major fronts. One has to do with the degree to which migration constitutes a stressor, and the other the degree to which culture and migration impact the stress process A contextual process model of acculturative stress will be presented as a means of making sense of migrants in crisis. Specifically, a crisis occurs with a sort of accumulation of stressors, that are appraised to constitute a grave danger to individual or collective well-being, and, in turn, the evaluation that the individual or collectivity does not have the necessary resources-psychological, social, and material—to mitigate the deleterious effects of the event or situation. Migrants may be more susceptible to crisis precisely because they have access to fewer social and material resources and because their psychological resources-particularly coping styles—may not be consistent with what is normative in the host culture. Effective response at both the clinical and institutional levels requires appreciation of the complexity of the issue without falling prey to cultural reductionism.

Migration-related factors could be additional risk factors for the development of depression and suicidal behaviour in migrant populations. In particular, the success or failure of migration will impact on migrants’ mental well-being. The premigration experiences, the act of migration itself, the motive for migration, postmigration experiences and the structural prerequisites in the host country play a central role. On the basis of the results of a population based study on the factors associated with mental distress in female Turkish migrants in two German cities (Berlin, Hamburg) the impact of migration-specific factors on the expression of mental distress will be discussed. Factors which will be examined among others are, reasons for migration, residence status, perceived ethnic discrimination and acculturation strategies, socio-economic status and traumatic experiences (pre- and post-migration).

A nationwide register study was carried out in Denmark comprising 50,877 persons aged 18-66, who were registered in 2003 in the Danish Psychiatric Register or the National Patient Register with a psychiatric ICD-10 diagnosis.

Of the population 87.1% were ethnic Danes, 7.8% migrants, 4.0% descendants with one Danish born parent, 0.7% descendants with both parents born outside Denmark and 0.3% foreign adoptees. Males comprised 49%, women 51% of the population.

The 5 ethnic groups had significant differences in utilization of care, in diagnostic distribution and in the use of coercion.

Self-mutilating behaviour was seen more frequently among female descendants from non-Western countries than among migrant women from non -Western countries as well as among young adopted women. Similarly, we see that personality disorders were higher in adopted and descendant young women. In males, we found that substance abuse was higher among men in all ethnic groups, but lower among migrant groups compared to Danes.

The paper will discuss possible explanations to these findings in terms of e.g. cultural identity, acculturation and gender issues and relate findings to findings found in other European countries.

The process of migration can be a risk factor for suicidal behaviour. Factors such as circumstances of the migration and individual characteristics like age, education, and his offspring play an important role. The empiric evidence of today's suicide prevention therapy strategies - following a suicidal crisis or a suicide attempt - in order to prevent prospective crises are limited. There are not enough protective therapy recommendations. Psychotherapeutic interventions and antidepressants are not proven to be better than a standard treatment. An appropriate treatment of depression (antidepressant, psychotherapy, psychoeducation, self-help) seems to be preventive. In this contribution the current state of epidemiology, ethiopathogenesis, models of suicidal behaviour and suicide prevention will be discussed.

The classical mechanisms of action of antidepressants suggest that they act through inhibition of monoamine transporters. There is evidence that antipressants indirectly modulate GABA-A receptors through neurosteroids. We showed that antidepressants may also directly modulate the function of the serotonin type 3 (5-HT3) receptor in an allosteric fashion. This non-competitive inhibition of receptor function occurred with different classes of antidepressants including tricyclic antidepressants, SSRIs and NARIs. Moreover, these antidepressants were differentially accumulated in lipid rafts. Their concentartions in lipid rafts were related to their ability to allosterically modulate this ligand gated ion channel. However, lipid raft integrity was not a prerequisite for the allosteric modulation of this ion channel by antidepressants. Morover, differential results were observed with regard to NMDA and GABA-A receptors. Our data show that the allosteric modulation of ligand gated ion channels is an underestimated pharmacologcical principle which challenges the concept of target specificty of antidepressants for monoamine transporters.

Clinical studies have demonstrated an impairment of glucocorticoid receptor (GR)-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depression (GR resistance), and its resolution by antidepressant treatment. This GR impairment is driven by different pathophysiological mechanisms, including the effects of inflammatory mediators, changes in GR-associated proteins, reduction of intracellular access of glucocorticoid hormones, and GR gene variants. Our research has looked at the multitude of pathways affecting GR and MR function, using both clinical models and experimental systems, including most recently the use of prednisolone as a new neuroendocrine test, the in vitro evaluation of GR function in peripheral blood cells from depressed patients, the use of mice with knockout glucocorticoid transporter (p-glycoprotein) genes, and the examination of polymorphisms in inflammatory genes. This presentation will review our most important recent findings in this field, including:

1. 1) that GR in peripheral blood mononuclear cells is resistant to the modulating effects of antidepressants in the context of increased activation and production of interleukin (IL)-6;

2. 2) that p-glycoprotein knockout animals have normal entry of corticosterone into the brain but do not show the effects of antidepressants on the HPA axis;

3. 3) that polymorphisms in the IL-6, IL-10, phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2) genes regulate the interaction between stress, inflammatory challenges and the development of mood and somatic symptoms; and

4. 4) that, in contrast to the GR, the mineralocorticoid receptor (MR) function remains intact in depression, except in a subgroup of individuals who do not respond to treatment.

Growing evidence suggests that alterations in cytoskeletal microtubules dynamics may be involved in the effects of antidepressant drugs on brain structural neuronal plasticity phenomena such as remodelling of axons and dendrites. The speaker will review the most recent data in the field obtained in either naïve animals or in animal models of stress/depression. These results were gathered using a multidisciplinary approach, ranging from behavioural tests to neurochemistry and molecular analyses of specific markers of microtubule dynamics and synaptic remodelling. Several classes of antidepressant drugs have been shown to differentially modulate the expression of microtubular proteins and synaptic markers in specific rat brain regions depending from the dose and length of administration. Importantly, such antidepressant-induced effects on microtubular and synaptic proteins showed a very different pattern of changes in environmental (social isolation from weaning) or genetic (Flinders Sensitive Line) rat models of depression, which were not always accompanied by recover of the “depressive-like” behavioural phenotypes. Therefore, antidepressant drugs can modulate brain cytoskeletal and synaptic remodelling, but the pattern of these phenomena seems related to a complex gene-environment interaction. These data may be considered of translational human relevance when put in the context of partial- or non responders to antidepressant therapy. Finally, MAPREG developed new molecules specifically targeting neuronal microtubules and promoting structural neuronal plasticity, which may represent novel tools for the therapy of depressive disorders. Novel data on the antidepressant efficacy of one of these promising molecules in rat models of depression will be presented.