The cycle of violence theory proposed in the early sixties suggested that children growing up exposed to violence would themselves become violent.

Testing this theory incidence studies found elevated levels of child abuse in offender populations compared to the general public, whereas prospective studies found significant associations between child abuse and subsequent adult criminality. However, prospective studies also showed that a large proportion of children exposed to violence did not grow up to become violent or criminal, which in turn lead to the assumption that the cycle of violence theory was to be rejected.

Recent studies have found indications of more specific relationships between early traumata and subsequent adult criminality. For example elevated levels of both risky sexual behavior as well as adult sexual victimization experiences have been found in persons having suffered childhood sexual abuse (CSA). These findings have raised the question if a specific association exists between the experience of CSA and subsequent adult sex offending.

Many investigations have shown a strong relationship between childhood sex abuse (CSA) and severe negative health and social outcomes among female and male victims of childhood sex abuse. The risk for unintended pregnancies, risky sexual behavior in general, and HIV-risk behavior is considerably elevated, leading to the contraction of sexually transmitted diseases. Furthermore, CSA victims are likely to be assaulted again as adults and a minority of CSA victims can become a perpetrator themselves. With respect to mental health outcomes, a higher prevalence of alcoholism, drug abuse, addiction, and pathologic gambling is found in CSA survivors. Additionally, CSA survivors are more vulnerable to anorexia nervosa, affective disorders, post-traumatic stress disorder (PTSD), or suffer personality disorders, especially borderline personality disorder (BPD). Furthermore, childhood sex abuse victims are more vulnerable to suicidal behaviour, showing frequent suicidal ideation and suicide attempts.

Every person has the right to not become a victim of violent or sex offenses.

There is neither absolute certainty, nor “the solution” when dealing with violent and sex offenders. A society has many options for lowering the risks and for protecting its citizens. The focus on aspects of prevention in handling offenders plays a central role. Unfortunately, many countries show sizable deficits in areas of prevention:

• • No effective, social lobby for subjects on victim protection.

• • Political discussions are often characterized by ideologies and follow stereotypical rightist-leftist-schemata.

• • For legal- dogmatic reasons, the principle of prevention is treated subordinate to that of guilt.

• • This is where the Zurich Victim Protection Charter comes into play.

The charter was formulated in Zurich in 2008 and has recently been posted on the internet with the aim of collecting enough signatures to give it political weight.

The initiators are convinced that subjects on victim protection can gain (social) political majorities and that the focus on prevention during criminal proceedings and correctional practices must receive the same status as the guilt principle. This is the central demand of the Zurich Victim Protection Charter, the contents and goals of which will be presented.

Depressive disorders constitute a major health problem worldwide. From feelings of grief of daily human life to psychotic melancholic states, many different forms of depression are recognized. This fact also raises problems of classification in depressive disorders.

This presentation aims to review issues of “threshold level”, “comorbidity”, “the importance of patients’ narrative”, and “identification of core symptoms” in depression.

It is widely accepted that a common core shared in depression is anhedonia; thus, vitality of the person is lost. Mortality and vitality are the two key phenomena to consider in understanding depression.

The reality of mortality has always been a task to overcome emotionally. Human sciences and belief systems have accumulated a huge amount of theory on this issue. But, it is a crucial inevitable challenge for every human being, and this confrontation may also lead to face some sort of depressive way of being. The degree of psychological awareness and of working through the reality of mortality may determine the odds and the forms of depressive state that a person may develop. The phenomenology of depressive disorders will also be discussed in the context of mortality vs. vitality using clinical vignettes from the authors’ clinical practice to broaden the scope of discussion.

Depression has became the main focus of psychiatry care and research, due to its epidemiologic and economic wheight in health. As a matter of fact depression is now the second condition after cardio-vascular diseases contributing to the costs in haelth in our modern societies attending to the Daly"s measures.

From an old ethiologic prespective psychiatry shift to a pragmatic way to solve the main therotical issues in care and research. By this, we have now standard clinical methods to diagnose and classify depression, easy to use by any clinician (Psychiatrists and GPs), but we don"t know the essencial psychologic and biologic mechanisms of this disease as well as how the supposed ethiologic factors interact with these mechanisms.

Psychopharmacologic treatments opened some doors to this mechanisms, but the knowledge is still unsatisfactory in order to differenciate the several types of depression and to drive specific treatments to patients.

In this presentation included in the Symposium BACK TO THE BASICS: CHALLENGES IN CLASSIFICATION OF DEPRESSION it will be revised the actual knowledge concerning ethiology and phisiopathology of depression.

The etiology of bipolar disorder is thought to involve multiple genes and environmental factors. Recently the immune system has been implicated in the pathogenesis. Various abnormalities indicate the presence of an activated inflammatory response system. In this presentation evidence will be presented on:

1. 1. A higher susceptibility for autoimmune diseases (thyroiditis, gastritis, type 1 diabetes), not only in patients but also in first degree relatives independent from mood disturbances.

2. 2. An inflammatory gene-expression signature comprising of 19 pro-inflammatory genes in monocytes, the monocyte (and its descendent cells) being important in the activation of the inflammatory response. The inflammatory gene-expression profile was also found in the monocytes of bipolar offspring, especially in those developing a mood disorder (prognostic value of the test?).

3. 3. Common environmental factors (infection, stress and dietary components?) as the factors causing the inflammatory monocyte gene-expression signature (evidenced in a twin study).

4. 4. A general T cell activation not only linked to the trait of the disorder, but also to the state of the disorder (i.e. with mania) and in part due to genetic factors (evidenced in a twin study). Also T cell activation is not linked to monocyte activation.

5. 5. A poor T regulator activation which is genetically determined and correlates with the presence of above-described autoimmune diseases.

It was reported that cytokines such as IFN-γ reduce the synthesis of 5-HT by stimulating the activity of indoleamine 2,3 dioxygenase (IDO) enzyme which degrades tryptophan to kynurenine. Kynurenine is further metabolized to kynurenic acid (KYNA), 3-hydroxykynurenine (3OHK) and quinolinic acid (QA) by kynurenine aminotransferase (KAT), kynurenine 3-monooxygenase (KMO) and kynureninase. Both KMO and kynureninase are also shown to be activated by IFNγ. The 3OHK is neurotoxic apoptotic while QA is the excitotoxic N-methyl-D-aspartate (NMDA) receptor agonist. Conversely KYNA is an antagonist of all three ionotropic excitatory amino acid receptors and considered neuroprotective. In the brain, tryptophan catabolism occurs in the astrocytes and. The astrocytes are shown to produce mainly KYNA whereas microglia and macrophages produced mainly 3OHK and QA. The astrocytes have been demonstrated to metabolise the QA produced by the neighbouring microglia.

Tryptophan breakdown has been found to be increased but KYNA, the neuroprotective metabolite is decreased in both blood and cerebrospinal fluid of the patients with major depression compared to healthy controls. Moreover, the ratio between KYNA and 3OHK showed significant correlation with response to treatment. These findings lead to the hypothesis an imbalance neuroprotection-neurodegener-ation in terms of kynurenine metabolites and their immunological and biochemical interactions in the brain might further induce the apoptosis of the neuroprotective astrocytes and the vulnerability to stress is thereby enhanced.

COX-2 inhibition seems to balance the type-1/type-2 immune response, possibly via inhibition of prostaglandin E2. COX-2 inhibition reduces proinflammatory cytokines. COX-2 inhibition has an impact to the glutamatergic neurotransmission and influences the tryptophan/kynurenine metabolism: all three components seem to be involved in the pathophysiology of psychiatric disorders, particularly in schizophrenia and major depression.

Due to the increase of proinflammatory cytokines and PGE2 in depressed patients, antiinflammatory treatment would be expected to show antidepressant effects. An antidepressant effect of rofecoxib was found in patients with osteoarthritis. An own randomized double blind pilot add-on study using the selective COX-2 inhibitor celecoxib in MD showed a significant therapeutic effect of the COX-2 inhibitor on depressive symptoms. Although those preliminary data have to be interpreted cautiously, those results are encouraging for further studies dealing with the inflammatory hypothesis of depression.

Secondly, we and other research-groups performed several studies of COX-2 inhibitors in schizophrenia. In a prospective, randomized, double-blind study with the COX-2 inhibitor celecoxib in acute exacerbation of schizophrenia, a therapeutic effect of celecoxib was observed. The finding of a clinical advantage of COX-2 inhibition could not be replicated in a second study. Further analysis of the data revealed that the efficacy of therapy with a COX-2 inhibitor seems most pronounced in the first years of the schizophrenic disease process.

It has to be considered, however, that therapy with COX-2 inhibitors is currently under discussion - as therapy with other non-steroidal antiphlogistics - due to cardiovascular side-effects.

High prevalence of self-destructive behaviours during adolescence - both as expression of early psychopathology and as “paraphysiological” developmental behaviors - challenges the implementation of health promotion strategies specifically addressed to an age bracket in which plasticity of psychical structure can favour an overall successful outcome.

SAYLE is a European research project with the aim of promoting healthy behaviours in adolescents, at a high school level of intervention. During the presentation targets and structure of the prevention program will be described. The projects has been designed in order to compare the efficacy of different prevention strategies for adolescents: a general health promotion program targeting students’ awareness on healthy/unhealthy behaviours and students" self-efficacy in diminishing unhealthy behaviours; a screening by professionals of at-risk students through a questionnaire (TeenScreen) - for adolescents identified as high risk (screen positives) the program includes referral to mental health treatment and ensuring compliance; a gatekeepers’ program, training all adult staff at schools (teachers, counselors, nurses etc.) and parents on how to recognize & refer a student with risk-taking behaviours or suffering from mental illness to mental-health help resources (QPR -Question, Persuade & Refer).

Adolescence is a critical period for suicidal risk. Suicide currently ranks as the second or third leading cause of mortality among adolescents in developped countries. It has been shown that a history of suicidal act, of depressive disorder and of a substance use disorder (SUD), alcohol and drugs, are the most prominent risk factors for suicidal behaviour among adolescents.

Data on alcohol and drug use disorders and suicide consisted primarily of reports on alcohol use disorders and, to a lesser extent, opioid use disorder. The magnitude of the association with other drugs is still unclear.

The relationships between substance use disorder and suicidal behaviour are multiple: In the long term, SUD may be associated with increases in stress and co-occuring psychopathology (poor self esteem, feeling of worthlessness, isolation).These elements may reach a level where a suicide attempt is viewed as a means to cope with perceived unsolvable difficulties. During life crises, SUD can also be responsible for inhibiting adaptative coping and desinhibiting suicidal behaviour. Finally, SUD and suicidal behaviour share common vulnerability factors: history of childhood abuse, genetically determined dimensions such as impulsivity or psychiatric disorders, particularly unipolar depressive and bipolar disorder.

Given the comorbidity between SUD and suicide, it is essential for treatment and prevention that all suicidal adolescents be screened for SUD and vice versa. Ideally, adolescents who receive diagnosis of SUD and co-occuring suicidality should follow an integrated treatment protocol that addresses both conditions.

Empathy has been a central focus of research and popular interest over the last decade. There has been several well acknowledged controversies in psychology, biology and ethology, over whether empathy is an emotional (sensing another"s feelings) versus cognitive (understanding another"s perspective) construct. In our studies we attempt to address this by combining lesion studies and psychiatry research to support the notion of two separate systems for empathy: an emotional system (involving the mirror neuron system) and a cognitive system (involving medial prefrontal cortices). We examined our model with several psychiatric populations such as schizophrenia, borderline personality disorder and psychopathy and show that the dissociation between cognitive and emotional empathy is implicated in these populations.

Ability for empathy and theory of mind are diminshed in patients with schizophrenia. These kinds of social cognition are, however, necessary to interact with other people and obtain a well-balanced psychosocial functioning level, i.e. to have friends, to go for work, to be in partnership and so on. Own studies revealed that disturbances in social cognition are accompanied by fMRI activation deficits in distinct regions of the underlying neuronanatomical loop in schizophrenia. The most significant difference compared to healthy controls was found in the region of the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC). We think that training of social cognition would improve both the neurobiological hypoactivation and the ability for empathy and theory of mind. As consequence, psychosocial functioning of the patients should be become better as measured e.g. by the personal and social performance scale (PSP). To emphazise the close relationship between social cognition, ist underlying neuobiology and psychosocial functioning is the main purpose of this lecture.

Previous studies in forensic patients with schizophrenia have shown that delinquent patients may outperform non-delinquent patients with regards to their ability to appreciate mental states. Findings were, however, confounded by a lack of control for neurocognitive functioning. We examined 33 forensic patients with schizophrenia regarding their mentalising abilities, intelligence, executive functioning and psychopathology. Results were compared with a non-forensic schizophrenia sample and a group of healthy controls. Both patient groups performed more poorly on most measures compared to controls. Forensic and non-forensic patients did not differ in task performance. In the forensic group mentalising correlated inversely with “excitement” and cognitive symptom scores of the PANSS. When “excitement” was co-varied out, forensic patients outperformed non-forensic patients with regards to their mentalising abilities. This study supports the hypothesis that schizophrenic patients with a criminal record are equally impaired in their ability to infer mental states compared to non-forensic patients, but for different reasons associated with a divergent psychopathological profile.

Acamprosate, naltrexone and disulfiram have been shown to reduce drinking and/or improve abstinence. We performed a randomized, multicenter study in two phases; first, 12-week continuous supervised medication, followed by targeted medication up to 52 weeks in addition to a 67-week follow up period. 243 voluntary treatment-seeking alcohol-dependent adult outpatients were randomized 1:1:1 to receive supervised naltrexone, acamprosate or disulfiram, 50 mg, 1998 mg or 200 mg respectively per day and brief manual-based cognitive behavioral intervention. The primary outcome measures were the time to first heavy drinking day (HDD) and time during the first 3 months to the first drinking day after medication started. All three study groups showed marked reduction in drinking from baseline to the end of the study. During the continuous medication phase, treatment with disulfiram was more effective in reducing HDDs and average weekly alcohol consumption, and increasing time to the first drink as well as the number of abstinent days. During the targeted medication period, there were no significant differences between the groups in time to first HDD and days to first drinking, but the abstinence days were significantly more frequent in the DIS group than ACA and NTX. However, naltrexone was better than acamprosate in reducing the severity of alcohol dependence indicator SADD scores. We conclude that acamprosate, naltrexone and disulfiram combined with brief manual-based cognitive behavioral intervention significantly reduce alcohol consumption and improve the quality of life. Supervised disulfiram was superior, especially during the continuous medication period, to naltrexone and acamprosate.

Alcohol intake is known to modulate plasma concentrations of neuroendocrine peptides. However, recent results suggest that the endocrine system may not only respond passively to alcohol intake, but that -vice versa- it also actively modulates alcohol intake behaviour. The most coherent body of data concerns the hypothalamo-pituitary-adrenocortical (HPA) axis, with low corticotropin releasing hormone (CRH) being associated with more intense craving and increased probability of relapse after acute detoxification. It is important to bear in mind that dysregulation of the HPA system, as observed in alcohol dependence, is also a feature of anxiety and depression, two conditions which are frequently linked with alcohol dependence and have been reported to be associated with a poor prognosis. In depression, increased secretion of CRH seems to be one crucial mechanism. It has been found as a marker of depressive symptoms, which normalises when depression is successfully treated. Hypersecretion of CRH is associated with a general hyperactivity of the HPA system, notably elevated plasma levels of ACTH and cortisol, a blunted cortisol stress response and a blunted dexamethasone suppression test. In any case, HPA dysregulation, alcohol dependence, and depression are closely interrelated. Exactly which component of this triad is the driving force behind the various neuroendocrine correlates of drinking behaviour is currently unclear, and will need to be elucidated by future research. This will allow for an enlightened choice of potentially therapeutic agents for the treatment of co-morbid anxiety, depression, and alcohol dependence, acting primarily on the HPA system.