An understanding of the epidemiology of alcohol and drug use in young women is important to appreciate the considerable morbidity and mortality associated with it and to understand the impact of such use on offspring. Although abstention rates are consistently higher among women than men in general substance misuse is increasing in young women. Differences in definitions, measurement techniques, availability, social acceptability and affordability partly explain the great variability in reported prevalence rates. Alcohol exposure among pregnant women varies from 0.2% to 14.8%. An Australian national survey revealed that nearly half of pregnant and or breast-feeding women up to 6 months postpartum were using alcohol. A Swedish study reported risky use of alcohol during the first 6 weeks of pregnancy, at 15%. Cannabis use among pregnant women varies from 1.8% to 15%. The reported prevalence of opiate use during pregnancy ranges from 1.65 to 8.5%. Cocaine use among pregnant women is reported to be between 0.3% and 9.5. Most pregnant women stop or reduce their substance use during pregnancy and this might be an opportune moment for detection and treatment. Substance use tends to increase sharply in the postpartum period with adverse consequences on mother and baby. Perinatal substance misuse interventions can reduce adverse neonatal outcomes. On the basis of relatively high rate of substance use disorders during pregnancy and postpartum period, effective screening and intervention strategies should be implemented.

Smoking, alcohol and illicit drug misuse during pregnancy lead to toxic harmful consequences for mother and especially for the fetus, neonate or child. In case of misuse of illicit substances pregnant women mostly suffer from polytoxicomania (3 substances and more) and the misuse of illicit substances is often accompanied by severe smoking and drinking of alcohol. Therefore it is often difficult to methodologically differentiate the single toxic effects. Basing on this knowledge in the presentation a view on the single toxic and /or chronic effects of addictive drugs will be given.

1. 1. To clarify single toxic effects of the addictive drugs diagnostic procedure about regulary and/ or ecstatical consume and the diagnose of abuse or dependence acc. to DSMIV or ICD 10 and the analysis of relapse behaviour for each substance should be done.

2. 2. The toxic effects of the different substances in pregnancy will be reported. Nearly al addictive substances (nicotine (+CO, +tar), alcohol, THC, psychostimulants, heroine) go into placenta and thereby have multiple toxic effects like f.e. decreased perfusion and infarct of the placenta leading f.e. to intrauterine retardation of growth, premature detaching of placenta, premature birth, to deformities, various later heavy postpartal effects (lung and breath diseases, sudden death, fetal alcohol syndrome, neurological dysdevelopment, cardial malformations, learning disturbances, ADHD etc). The toxic effects of the various substances will be differentiated so far it is possible.

3. 3. The different therapeutic approach of the various addictive drugs during pregnany (withdrawl treatment, opioid substitution) will be discussed.

Knowledge of the epidemiology of substance use and associated problems demonstrates that a sizeable minority of pregnant women are using substances, and following delivery the majority revert to higher levels of misuse which is to the detriment of themselves and their babies. There is a rapidly accumulating range of effective interventions for substance misuse. Pregnancy can be a turning point for the delivery of such treatments as women attend obstetric services. This is an opportune moment for detection and treatment, if generalists have the skills to manage less severe problems and referral to specialists is possible. It is important to be able to determine when a patient requires specialist referral for the health and safety of the patient, their baby and the family and for the integration of provision by professionals involved in their care. This symposium will outline the basis of expert assessment and judgement regarding appropriate psychological treatment interventions for this group of young women within the framework of comprehensive service models.

There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.

Investigation of molecular and cellular mechanisms of synaptic plasticity is the major focus of many neuroscientists. There are two major reasons for searching new genes and molecules contributing to central plasticity: first, it provides basic neural mechanism for learning and memory, a key function of the brain; second, it provides new targets for treating brain-related disease. Here, I propose that LTP in the anterior cingulate cortex (ACC) as a synaptic model for emotional fear and chronic pain in the brain. Integrative approaches including genetic, neurobiological and physiological methods are used to investigate the roles of cortical neurons and microglia in synaptic LTP, fear and chronic pain. We have identified several key calcium-stimulated signaling molecules including AC1, CaMKIV and FMRP for AMPA receptor mediated cingulate LTP, trace fear memory, and chronic pain. By contrast, microglia only contributes to changes in spinal dorsal horn, but not in the cortex. Our findings strongly suggest that ACC LTP may serve as a cellular model for studying central sensitization that related to fear and chronic pain, as well as pain-related cognitive emotional disorders.

An accumulating body of evidence shows that the retrieval process of long-term memory is not static and requires de novo protein synthesis. Thus long-term memories are dynamic and particularly become fragile during its retrieval. Importantly, memory retrieval is regarded as a step necessary for incorporating new information into preexisting memories. We have examined whether protein degradation is involved in the memory reorganization or not. In this presentation I will present the evidence that synaptic proteins are degraded by polyubiquitination and proteasome pathway in the hippocampus after the retrieval of contextual fear conditioning. In addition, we found that the infusion of a proteasome inhibitor into the hippocampus prevented the memory impairment induced by anisomycin, a protein synthesis inhibitor. This indicates that ubiquitin/proteasome-dependent protein degradation is involved in destabilization processes accompanying the memory retrieval. It also supports our hypothesis that preexisting memory is disrupted by synaptic protein degradation before updated memory is strengthened by protein synthesis. Our data also showed that synaptic protein degradation plays a critical role in fear memory extinction, a simple form of memory reorganization. Taken together, synaptic protein degradation is critically involved in the reorganization of the preexisting memories.

Elucidating the neural and genetic factors underlying psychiatric illness is hampered by current methods of clinical diagnosis. The identification and investigation of clinical endophenotypes may be one solution, but represents a considerable challenge in human subjects. Here I show that mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus (DG). The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. Transcriptome analysis of the hippocampus of these mutants revealed that the expression levels of more than 2000 genes were changed. Whereas BrdU incorporated cells in the mutant mouse DG was increased by more than 50 percent, the number of mature neuronsw as dramatically decreased. Morphological and physiological features of the DG neurons in the mutants were strikingly similar to those of immature DG neurons in normal rodents. Statistical clustering of human post-mortem brains using 10 genes derived from the mutant mice were used to classify individuals into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly half of the differentially-expressed probes in the schizophrenia-enriched cluster encoded genes that are involved in neurogenesis or in neuronal migration/maturation, including calbindin, a marker for mature DG neurons. Based on these results, we propose that an “immature DG” in adulthood might serve as a promising candidate endophenotype of schizophrenia and other human psychiatric disorders.

Activity-dependent gene expression through activation of Ca2+-CREB signal transduction pathways has been thought to play a central role in fear memory formation. On the other hand, retrieval of fear memory triggers two time-dependent phases of reactivated memory; reconsolidation and extinction. To understand the mechanisms for determining the fate of the reactivated fear memory, we investigated roles of CREB in reconsolidation and extinction of contextual fear memory and then analyzed the brain-regions regulating reconsolidation and extinction by identifying regions where CREB-mediated gene expression is activated and then examining the role of protein synthesis in those regions on reconsolidation and extinction. We first showed that activation of CREB-mediated transcription is required for reconsolidation and long-term extinction of contextual fear memory. Using immunocytochemical analyses, we demonstrated that CREB is activated in the hippocampus/amygdala and amygdala/medial prefrontal cortex (mPFC) in the reconsolidation and extinction phases, respectively. Similar results were observed by analyzing the expression of a CREB-dependent gene, Arc. We finally showed that reconsolidation and long-term extinction of the contextual fear memory depended on new gene expression in the hippocampus/amygdala and amygdala/mPFC, respectively. Thus reactivated contextual fear memory is reconsolidated or extinguished through distinct CREB-mediated gene expression regulation in the hippocampus, amygdala and mPFC.

Many risk factors for alcohol dependence have been pointed out on the basis of large cohort analyses, including antisocial personality disorder, familial history of substance abuse and initial effect of the first consumption of alcohol, these factors having large overlaps. In addition, a low level of response to first alcohol drink has been reported to increase the risk of future alcohol-dependence. This response to first dinks is a genetically influenced characteristic, but the genes involved remain unknown.

The Susceptibility Addiction Gene Environment (SAGE) cohort was designed to assess addictions and psychiatric disorders in a cohort of young adults. All 3.895 college students of the French region “Champagne Ardennes” were eligible. Of them, 3.056 (1.834 males and 1.224 females; mean age 20.42 years, s.d 1.4) were enrolled on their campus during a single day and completed an intake assessment. The final sample was based on 2.730 subjects (70.08%) who fulfilled the inclusion criteria, namely having ever drink at least once in their lifetime. The level of response to alcohol during early consumption was assessed, as well as the DSM criteria for alcohol dependence at the time of interview. DNA was also collected.

Our results confirm the strong association between low level of response to alcohol and the risk of dependence. Furthermore, the genotyping of several candidate genes allowed disentangling the potential intermediate factors between the first consumption and the development of later dependence. These findings emphasize the utility of the endophenotype approach in the genetic study of addictive disorders

Several randomised clinical trials (RCT) have demonstrated the efficacy of cognitive behavioral therapy in the treatment of Posttraumatic Stress Disorder (PTSD). However, the external validity of these studies is limited with regard to PTSD related to childhood sexual abuse which often results in severe and complex sympomatology accompanied by a variety of concurrent disorders or symptoms, for example self-mutilation, suicidal ideation, or severe dissociation. Nearly 30% of patients with PTSD have a co-occuring borderline personality disorder (BPD). The prevalence rates of PTSD in patients with BPD vary between 40% and 60%.

Several RCTs have shown the efficacy of Dialectical Behavioral Therapy (DBT) in the treatment of borderline patients, who exaggerate severe behavioural dyscontrol. However specific treatment for co-occuring PTSD has been lucking.

Clinical lore suggests that exposure to trauma-relevant memories can potentially aggravate dysfunctional behaviour in patients with BPD. Empirical research however reports discrepant results with two studies documenting deleterious effects of comorbid BPD on treatment outcome, whereas one study did not find an impact.

DBT-P was specifically tailored to treat patients with PTSD after sexual abuse during childhood. DBT-P includes training in emotion regulation and mindfulness, cognitive interventions and exposure elements, usually in combination with the use of skills. To evaluate the efficacy of DBT-P as compared to a wait list control group a RCT is currently carried out. Preliminary data, which will be presented, revealed large between effect sizes for the primary outcome measures (PDS, CAPS).

The basis for decision making in pharmacopsychiatry is not as trivial as one might think. There was a tradition to believe that we have more or less specific drugs with a more or less specific mode of pharmacological mode of action for special indications, such as schizophrenia depression etc. However, the situation is apparently much more complex and the clinical decision making is far from being that trivial. The current development of new psychopharmaca is heading for different directions: either broadening the indication for one compound, or looking for subtypes of a more general indication. Some of these main aspects shall be discussed in the presentation.

The decision making in pharmacopsychiatry is rather complex, involving nosological and syndromatological aspects. We have to understand that the pharmacological mechanism of a psychopharmacon is not directly associated with only one psychiatric disorder but often with several. This is already true for psychopharmaca, which have only one mechanism, such as SSRIs, but even more so for drugs like the modern antipsychotics, which have a wide spectrum of receptor interactions and can therefore be effective in quite a variety of psychiatric disorders. Apart from broadening the indication of a psychopharmacon, a development in the direction of exceeding specification and, amongst others, of involving new mechanisms of action can be observed.

The preparations of DSM V/ICD-11 are in progress. The frustrations and limitations engendered by the categorical model in psychiatry led to the suggestion of alternative dimensional models of classification, e.g. to the suggestions for a dimensional view of psychosis. However there are strong arguments for keeping the categorical classification maybe with inclusion of new criteria, such as neurocognitive impairment for schizophrenia and even there are suggestions for new categories such as nonaffective remitting acute psychosis.

Therapeutic indications of drugs are developed by the industry and are approved by regulatory agencies (FDA, EMEA). Indications are linked to diagnostic categories as defined by DSM-IV/ICD-11, e.g. one antipsychotic is indicated for the treatment of both schizophrenia and bipolar disorder, while another is only indicated for the treatment of schizophrenia. These indications are used by the insurance industry to manage financing of drug treatment.

Changes in the criteria of a diagnostic category will result in a revision of approval which may include the obligation for new studies. Generic companies are now an important part of the major pharmaceutical markets, however many of them do not have the capacity to launch clinical studies, which may lead to the withdrawal of marketing authorization of important drugs. Clinical studies seem to be unavoidable for licensing recently available drugs for the new diagnostic categories of DSM V/ICD 11. The introduction of diagnostic categories by a dimensional approach may lead to “double book keeping”: a dimensional diagnosis used for the medical practice and a categorical one for the insurance.

Empirical evidence for psychopharmacological treatment has grown over the past decade substantially. While it was quite difficult to perform metaanalyses 20 years before, we now have a large body of evidence available to perform metaanalytic studies, not only on data published in the literature, but also on individual databases called a pooled-analysis. The field moved from eminence-based psychiatry to evidence-based psychiatry. Since indications for psychotropic agents are with a few exceptions given for diseases and not syndromes, it is obvious that the available empirical database is diagnosis-driven. However, recent developments in psychopharmacology indicate that medications primarily used for one diagnosis can also be useful for other diagnoses as we learnt from the serotonin-reuptake-inhibitors (SSRIs), which were firstly used for depression and then for different forms of anxiety disorders. A recent example is quetiapine, for which the first indication was schizophrenia, then bipolar disorder and now depression and general anxiety disorders. Does this mean a denosologisation of psychopharmacology? Not really, however recent developments could be indicative that trials should be performed not only on a diagnostic but also on a syndromatology-level as has been shown for suicidality within schizophrenia, but for instance not in depression.

The issue of the differentiation between depression and “understandable” intense sadness (representing a “normal” response to an adverse life event) has significant clinical, scientific, political and ethical implications, which have become particularly visible in the past few decades, in parallel with the escalation of the prevalence rates of depression in the community, of the estimated social costs of depression, of the number of people on treatment for depression, and of the prescriptions of antidepressant medications. According to the DSM-IV, periods of sadness are inherent aspects of the human experience, which should not be diagnosed as a major depressive episode unless criteria are met for severity, duration and clinically significant distress or impairment. The implication of this statement is that “understandable” intense sadness following an adverse life event does qualify for the diagnosis of major depression if the severity, duration and impairment criteria are fulfilled. The proposal has been recently put forward to exclude loss-triggered uncomplicated intense sadness from the DSM-V diagnosis of major depression (i.e., to introduce a “contextual” criterion excluding intense sadness which appears “proportionate” to a loss). However, further research is needed to explore the applicability and reliability of this “contextual” criterion and its clinical utility for the prediction of treatment response and clinical outcome. The limited available research evidence suggests that “situational” major depression does not differ from “non-situational” major depression on many clinical and psychosocial variables, and that response to antidepressant medications is unrelated to whether or not major depression is preceded by a life event.

The DSM and ICD diagnostic systems have developed largely in response to clinical interests, though they are used for other purposes as well. Careful attention is also needed to consider the balance of ethical and commercial interests. Public health aims of representing the burden of disease and disorder help to mobilise resources globally, nationally and locally; and relevant diagnostics and assessments guide services and programmes for the mental health of patients and populations. Like other areas of public health, the scope of community mental health extends beyond the treatment orientation of clinical services and community psychiatry. Priorities also include reducing vulnerability to prevent mental health problems and enhancing resilience to promote mental health. As the next wave proceeds in revising our psychiatric systems of classification, advancing such an agenda will help ensure that efforts to achieve the mental health of populations are effective, as they become more responsive to current developments in public health-which have recently been characterised with reference to four revolutions.

The classification of mental disorders in the International Classification of Diseases (ICD) will be revised in the course of the next three years and its publication (as the 11th Revision of the ICD) will be published, after the approval of the World Health Assembly in 2014. In parallel, the American Psychiatric Association created a Task Force which has begun work on the proposals for the revision of its Diagnostic and Statistical Manual which is to be published as the DSM 5th Revision, in 2012. The World Health Organization has established a special advisory group that should assist it in developing proposals for the classification of mental disorders for the 11th Revision of the ICD and this group collaborates closely with the APA Task Force creating the DSM5 proposals.

Numerous ethical issues arise in this process and need to be discussed now so as to inform the process of agreeing on the proposals for the new classifications. They include the importance of an internationally accepted classification as a protection against abuses of psychiatric patients; the need to set the threshold for the diagnosis of a mental disorder at a level ensuring that people with such disorders receive help, the need to avoid imposition of diagnostic systems or categories without sufficient evidence and others. The presentation will briefly discuss the process of constructing the proposals for the new classifications and ways in which the groups established by the WHO and the APA handle these ethical questions.