Negative symptoms encompass a broad constellation of psycho-behavioral phenomena, including affective flattening, poverty of speech, alogia, avolition, social withdrawal, apathy and anhedonia. These phenomena obviously exert a substantial impact on personal autonomy, quality of life and broad functional outcomes, ultimately being an important challenge for clinical decision-making and therapeutic support. In recent years, the attention to negative symptoms in schizophrenia has revamped, boosting the development of new rating tools as well as a broader conceptualization of derivative constructs (e.g. apathy, amotivation, anhedonia). However, despite its behavioral expressivity, the in-depth phenotypic characterization of negative symptoms remains partly unaddressed. Similarly, their clinical intertwining with other non-productive clinical features (e.g. anomalous subjective experiences, cognitive-perceptual basic symptoms and schizotypal features) is generally overlooked. Therefore, the current presentation specifically offers a stratified overview of the phenomenology of negative symptoms filtered through lens of clinical psychopathology.

Early persistent negative symptoms (ePNS) refer to the presence of potentially idiopathic or primary negative symptoms and have been observed following a first episode of psychosis (FEP). There is evidence for cortical changes associated with ePNS and given that a FEP often occurs during a period of ongoing brain development and maturation, neuroanatomical changes may have a specific age related component. The current study examined cortical thickness (CT), hippocampal/amygdala volume and shape as a function of clinical trajectories and age using longitudinal structural imaging in FEP. T1-MRI scans were acquired for early (n = 21), secondary (n = 30), non-(n = 44) PNS patients with a FEP, and controls (n = 44). Cortical thickness and amygdalar–hippocampal volumes and surface area (SA) metrics were extracted from three time points over a two-year period. Linear mixed models were applied to test for a main effect of group, and age group interactions. Relative to the other groups, ePNS patients showed cortical thinning over time in temporal regions and a thickening with age primarily in prefrontal areas. They also exhibited reduced left amygdalar and right hippocampal volumes. Morphometry revealed decreased surface area in ePNS compared to other groups in left central amygdala. The current study demonstrates that FEP patients with ePNS show significantly different CT trajectories with age. Increased CT may be indicative of disruptions in cortical maturation processes within higher-order brain regions. Amygdalar-hippocampal changes with age are also linked to ePNS with converging results from volumetric and morphometric analyses. Taken together, these results could represent dynamic endophenotypes setting these ePNS patients apart from their non-symptomatic peers.

Despite the high burden of bipolar disorder and the noticeable progress in its treatment, the disorder still goes frequently misdiagnosed, unrecognized, or not optimally treated. To date, no medication has been specifically developed on the basis of a precise understanding of the pathophysiology of the disorder, or based on the unique characteristics of several subtypes of bipolar disorder or on the medication mechanism of action. Lithium remains on of the gold standard treatments for bipolar disorder. Its mood-stabilizing properties are thought to occur via specific cellular signaling pathways, such as inhibition of glycogen synthase kinase 3, which is considered to regulate cellular apoptosis. Divalproex, carbamazepine and several atypical antipsychotics are also approved for bipolar disease Evidence also suggests that antipsychotics show the ability to treat and prevent mania and/or depression but are often burdened by side effects such as sedation, hortostatic hypotension and weight gain. Hence, while it is clear that there still are several unmet needs especially for what pertains tolerability, efficacy for specific subtypes, and predictability. Novel and more effective treatments are needed and researchers are currently engaging in targeted drug development for bipolar illness, aimed at improving pharmacological strategies with marked and sustained effects. A variety of newer medications are being tested. Some of these drugs target pathways that are similar to those targeted by lithium, while others focus on newer targets, such as opiate receptor and N-methyl-D-aspartate (NMDA) receptors. Newer and older treatment strategies for bipolar disorder will be presented and critically reviewed.

Antipsychotics are widely used for the short and long-term treatment of bipolar disorder. Depot and long-acting injectable formulations (LAIs) can be particularly useful for certain subgroups of patients. This lecture will discuss the available data from randomized controlled trials of LAIs in bipolar disorder. A recently published meta-analysis and individual studies assessing depot medications, as well as modern LAIs such as risperidone, paliperidone and aripiprazole, will be reviewed, looking carefully into the prevention of either pole of illness and tolerability. Potential indications and patient profile, based on data and clinical experience, will be discussed.

Cognitive dysfunction, including memory and concentration difficulty, is an emerging treatment target in bipolar disorder. However, a key challenge in the management of these cognitive deficits is the lack of treatments with robust effects on cognition. Further, it is unclear how cognitive dysfunction should be assessed and addressed in the clinical treatment of the disorder. This talk will review the evidence for cognitive impairment in bipolar disorder, including its severity, persistence and impact on patients’ functional recovery. It will then discuss when and how to assess cognition and present some new feasible screening tools for cognitive dysfunction. Finally, it will highlight some novel candidate cognition treatments.

Evidence-based medicine is a method to establish best practice recommendations based on graded recommendations for diagnostic and therapeutic issues in health care. In mental healthcare, evidence-based medicine has shown that the therapeutic procedures are efficient and can help to not only ameliorate the symptoms of mental disorders, but also to improve the quality of life of those affected by mental disorders. Evidence-based medicine is not, however, cookbook medicine. While evidence is mostly generated in larger group trials and should be applicable to the majority of cases, aspects of the personal situation, social support systems and legal boundaries all affect mental healthcare and may modulate the interpretation of the findings of evidence-based medicine. A human-based psychiatry will therefore need to use the methods of evidence-based medicine as a basis for diagnostic and therapeutic recommendations, but will also need to extend into the acknowledgements of personal accounts, traditions and the cultural framework, in which mental healthcare is provided. This presentation will highlight some of the issues associated with the questions of the roles of evidence-based medicine in mental healthcare, and in a human-based approach towards mental healthcare.

Every medical intervention is embedded in the prevailing spirit of its particular time. The world of modern medicine that is still shaped by positivism is often revered as a world of rational calculation and reason, a world in which mathematical calculation and so-called objectivity are prized above all else. Indeed, today's modern medicine in general and its battlewagon evidence-based medicine is a world of sober number games, reduction and fragmentation, of demystification and de-subjectification. As important and indispensable the achievements of EbM are, it nevertheless needs to be expanded by a medicine, which focuses not just on illness and its treatment but which places the concrete individual with all his or her sufferings and potentials. Such a human-based medicine (HbM) is no longer indebted to modern positivism, but seeks its foundations in the maxims of post-modernism. Moving away from classical “indication-based medicine” toward a medicine based on human sufferings and potentials necessarily requires a fundamental change in diagnostics and treatment.

Human based medicine and human based psychiatry are contemporary approaches to the theory and practice of medicine and psychiatry. It is a post-modern way of re-thinking psychiatry enriched by humanities, especially philosophy. In questioning the current research and praxis of psychiatry, it shares the statement by Wittgenstein, “what a curious attitude scientists have″: ‘We still don’t know that; but it is knowable and it is only a matter of time before we get to know it as if that went without saying. So, here, our problematic is not only ‘what and how much we do‘ but also ‘how and why we do‘. The clinician‘s main challenge is harmonizing the current available ‘scientific universal knowledge‘ and the ‘uniqueness’ of that specific person in need of help. In achieving this task, the importance of the synthesis of the clinician's perspective and patient's perspective will be elaborated using depression as a case example. It will be stated that an empathetic understanding of depression, through a subjective, experiential and narrative-centered approach must become a primary concern by building a joint, ongoing, re-construction process of clinical assessment, formulation and treatment. There is no meta-theory explaining “the clinical truth”. From the perspective of a human based psychiatric practice, in fact, we do not need such a meta-theory, but instead, we need multi-level/multi-dimensional approaches, also taking the narrative into consideration. We suggest the clinicians to be modest, honest and respectful towards “the clinical truth”.

Graef-Calliess Iris (Germany).

Germany has always been an important host country for asylum seekers. Although recently an increasing number of investigations about mental health of specific migrant groups have been published in Germany, there is a paucity of research concerning mental health of traumatized asylum seekers. The aim of the presentation is to present study results which describe socio-demographics, types and frequency of traumatic experiences, psychiatric diagnoses, suicidality and time to access to mental health care in traumatized asylum seekers who applied to an outpatient department of a clinical center with high expertise in transcultural psychiatry and psychotherapy in Hannover, Germany. The study shows that most of the traumatized asylum seekers had experienced multiple pre-migratory traumatic events, had unfavorable post-migratory conditions, had PTSD and depressive disorders as diagnoses, and had high suicidality and late access to mental health care. This is indicative of the mental health situation of asylum seekers in Germany in general. Ways of dealing with this challenge for the mental health care system and options for clinical management will be presented.

Role of detention in the process of radicalization and opinions about detention regime and approach for the prevention of radicalization in jail.

Following the terrorist attacks in Paris and Brussels, more attention is being paid to the factors, which play a role in the radicalization process of some Western youth. It was found that a large number of radicalized youth have a history of detention and that often this period of detention played a key role in radicalization. As a psychiatrist working in a prison with a high security department where many suspects of terrorism are incarcerated stay, I was asked to advise on the detention regime and on the way of dealing with difficult inmates. In this presentation I would like to elaborate on the elements during detention which determine the process of radicalization of certain prisoners, based on the current knowledge about the radicalization process and on the knowledge about the background of radicalized individuals in combination with own observations and findings about the detention regime in prisons.

Many psychiatric disorders have been associated with increased risk of mortality and various aging-related somatic diseases. In addition to unhealthy lifestyles, also various stress-related physiological processes likely play a role in explaining these detrimental health consequences of psychiatric disorders. The impact could be visible at the cellular level, with psychiatric patients presenting more signals of physiological aging for instance as determined by measuring telomere length. In this talk we will first highlight the current state-of-the art evidence that various psychiatric conditions, including e.g. depression, anxiety and PTSD, are associated with shorter telomere length. Second, we will provide results from the Netherlands Study of depression and anxiety (n = 2981) that tested longitudinal associations using 6 year data on psychiatric status and telomere length. These results indicate that the association between depressive and anxiety disorders with telomere length is stable over time, and doesn’t show many dynamic associations. Finally, in the same study we have also tested to what extent lifestyle and dysregulations of physiological stress systems such as the immune, HPA-axis and autonomic nervous systems are partly responsible for the observed shorter telomere length in depressed or anxious patients. Results indicate that especially smoking behavior and systemic inflammation partly contribute to the shorter telomere length, but can’t completely explain found associations.

In sum, this talk will highlight the current state-of-evidence for an association between various psychiatric conditions with shorter telomere length, and will provide insights into its dynamics and its contributing mechanisms.

Originally studied in relation to aging and cancer research, telomeres and telomerase are now also investigated in relation to psychiatric disorders and treatments. Based on findings emerging from clinical and preclinical data, we hypothesize that the telomere–telomerase system represents a novel element mediating the mechanism of action of certain psychopharmacological interventions.

In this symposium I’ll present the preliminary evidence on the complex translational relationships between specific psychiatric medications (i.e. antidepressants, lithium and antipsychotics), the telomere–telomerase system and clinical outcomes. The modulation of intracellular Wnt/b-catenin or PI3 K/Akt signaling pathways, the interaction with BDNF and 5-HT, and the antioxidant properties could represent possible mechanisms by which the different types of psychiatric medications could modulate telomere length and telomerase activity. The potential of the telomere–telomerase system in promoting cellular survival and/or function in the brain and in the periphery could, in turn, represent a neurobiological substrate through which these molecules can mediate the therapeutic effect of such interventions.

Further, in the present symposium I’ll show data from our research team on telomere length and telomerase activity in leukocytes predicting clinical response to serotonin–specific reuptake inhibitors (SSRIs) in subjects with major depressive disorder.

Specific types of cognitions and mental processes may lead to greater stress arousal and may subsequently impact cell longevity. The study of telomeres and telomere-related molecular systems may provide a pathway for exploring the link between psychological domains and cell physiology. Based on findings emerging from clinical and preclinical data, we hypothesize that the telomere-telomerase system contributes to explain certain biological underpinnings of psychological interventions.

In this symposium we’ll present the preliminary evidence on the complex translational relationships between specific psychological domains (i.e. childhood adversities, stressful life events, mindfulness-based interventions and perceived distress), the telomere-telomerase system and clinical outcomes. Further, we’ll discuss preliminary data on the effect of mindfulness- and meditation-based interventions on cellular ageing and disease-associated molecular phenotypes.

Post-traumatic stress disorder (PTSD) is a common and debilitating condition, affecting between 10–20% of soldiers returning from combat zones, and with even higher prevalence rates in Veterans Affairs healthcare settings. PTSD is associated with an increased risk for various medical illnesses, many of which are commonly seen with older age. This raises the possibility that PTSD is associated with accelerated biological aging at the cellular level. Accelerated biological aging occurs when biological age outpaces chronological age, and this process is driven by a number of biological mechanisms including immune activation, oxidative stress, and mitochondrial dysfunction.

In this workshop I will present data from our research group and others pertaining to the biological mechanisms underlying accelerated cellular aging in PTSD. Most, but not all, studies have found that PTSD is associated with shorter mean leukocyte telomere length, an indicator of accelerated cellular aging. Mitochondrial dysfunction has been implicated in PTSD and our research group found evidence of a “u-shaped” relationship between PTSD symptom severity and mitochondrial DNA copy number. For what concerns immunity, we have recently found that PTSD subjects have increased blood levels of pro-inflammatory markers, a more senescent and dysfunctional profile of NK cells and impaired synthesis of nitric oxide. Finally, I will discuss the possibility of accelerated epigenetic aging in combat-exposed individuals with and without PTSD, using DNA methylation data.