Psychotherapy is regarded the first-line treatment of Borderline-Personality Disorder (BPD). This talk will summarize what is currently known from high-quality trials about the effects of different disorder-specific psychotherapies which have been developed to meet special needs of BPD patients. In total, 28 randomized-controlled studies covering 1804 study investigated both long-term treatments (≥ 6 months, up to 36 months) and short-term interventions (< 6 months). Among long-term treatments, the findings suggest benefits on core BPD pathology from dialectical behaviour therapy (DBT), mentalisation-based treatment (MBT), transference-focused therapy (TFP), schema-focused group therapy (SFT), and interpersonal psychotherapy adapted for BPD (IPT-BPD). Furthermore, results for BPD patients with comorbid conditions will be presented. Among short-term interventions, the findings suggest benefits for DBT-skills group training only, the Systems training for emotional predictability and problem solving for borderline personality disorder (STEPPS), an emotion-regulation group (ERG) based on acceptance and commitment therapy and DBT, manual-assisted cognitive therapy (MACT) as well as a psychoeducational workshop (PE). Although short-term interventions show encouraging results, it remains unclear whether treatment-naive people can profit or that a certain level of therapeutic experience is required, and whether the effects are stable over time. In total, there is evidence that disorder-specific psychotherapies are effective in treating BPD. However, one has to keep in mind that none of the treatments has a very robust evidence base, and that there are some concerns regarding the quality of evidence.

Dialectical Behavior Therapy (DBT) is now a well consolidated system of treatment for Borderline Personality Disorder (BPD) and for clinical conditions where emotional dysregulation plays an important role both in pathogenesis and in stability over time of dysfunctional phenomena. DBT treatment is made of different modes (individual psychotherapy, skills training, phone calls, team meeting) contributing in different ways to the outcome. What seems very important, in order to better understand the therapeutic process, is to clarify the role and effect of treatment components. Recent research is mainly focused on skills training and, in particular, on mindfulness. Research data show that Borderline subjects have strong difficulties in “being here and now in an accepting and non-judgmental stance”. This is significantly connected to their tendency to be emotionally and behaviorally dysregulated. Consequently, the possibility to modify the vicious circle connecting lack in mindfulness-emotional dysregulation-behavioral dysregulation appears a very powerful, and specific, component of DBT therapeutic method.

Transference-focused Psychotherapy (TFP) is an empirically validated treatment for borderline personality disorder (BPD). TFP is a modified psychoanalytic outpatient individual treatment with two sessions per week. TFP combines 1) a treatment frame with limit setting and containment of affects with 2) exploration of the intense affects that are in conflict within the individual. Similar to other specific treatments for BPD a treatment contract addresses potential threats to the patient’s and others’ lives and the continuation of the treatment. The TFP treatment manual provides a hierarchy of priorities to guide the therapist's interventions. TFP can be distinguished from other approaches by (1) its theoretical model of spilt-off mental states based on different internal images of self and other in the BPD patient, (2) the neutral position that guides the therapist to help the patient observe internal conflicts rather than to engage others in them, (3) the techniques of clarification, confrontation, and interpretation centered on the “here-and-now”, and (4) a focus on the transference relationship between patient and therapist as providing the data to understand the patient's internal relational world. The interpretation of relational aspects in the patient-therapist relationship is regarded as a core feature of TFP that paves the way for the integration of spilt-off internal concepts of the self and others and, thus, identity integration and integration more satisfying love, work, and leisure relations.

Our research has contributed to the understanding of the mechanism underlying HPA axis and inflammation hyperactivity iin depression. We have proposed an explanatory model centred around the glucocorticoid receptor (GR), that is, one of the most important receptors and transcription factors governing the stress response. Glucocorticoid hormones, like cortisol in humans and corticosterone in rodents, are the final output of the HPA axis, and the main hormones involved in the stress response. By binding to the GR (and to the mineralocorticoid receptor, MR), cortisol effects its cellular actions, including the negative feedback regulation of the HPA axis (by which stress-induced activation of the HPA axis is followed by a rapid return to normal functioning), and the restrain of the inflammatory response (which maintains a physiological control on excessive immune processes). In this talk I will review our clinical and cellular study implicating a reduced function of the GR (glucocorticoid resistance in key depression-related phenomena, such as the increased HPA axis and inflammation, the reduction in neurogenesis, and the therapeutic action of antidepressants.

There are reports demonstrating anti-inflammatory action of antidepressants. Anti-inflammatory effect of both antidepressants and anti-inflammatory medication such as celecoxib or aspirin could be beneficial in treatment of depression since inflammatory changes are well documented to be involved in pathophysiology of depression. Moreover, inflammatory response system (IRS) activation could induce imbalances in kynurenine metabolites and could in turn induce neurotoxic changes. There is also report mentioning the action of antidepressants as rebalancing the kynurenines disturbance in in-vitro studies.

Therefore, series of experiments were performed to investigate how IRS activation could induce disturbances in kynurenines and how antidepressants and anti-inflammatory medications could work on immunologically challenged mouse astrocytes cultures. The Toll Like Receptor (TLR) 3 and 4 challenges using PolyI:C and LPS and Interferon (IFN)-γ were performed. The NFkb and IRF3 signallings and IL1β, interferon-β and tumour necrosis factor-α productions are analysed using commercial ELISA and tryptophan and kynurenines are measured using high performance liquid chromatography.

The results indicated that TLR4 activation could not directly affect on astrocytes whereas PolyI:C and IFN could induce significant disturbances in kynurenines. Regarding the effect of medication, imipramine showed the most significant reversal effect on immune challenges in mouse astrocytes.

Imipramine could be the treatment of choice for treatment resistant depression where there is IRS activation.

Social deprivation has been consistently found as a risk factor for the incidence of psychosis. This study aimed at investigating the effect of social deprivation on short-term outcome of patients with a recent onset of schizophrenia (< 2 years).

A social deprivation score was calculated taking into account a low/very low socio-economic status, unemployment, low school education, and living alone. Psychiatric symptoms were assessed by BPRS. Compulsory and voluntary hospitalizations, engagement with mental health services, and suicidal attempts were also considered as outcome measures.

The sample consists of 35 patients, who had a first episode of psychosis at 19.7 (±4.7) years. In the first two years of the illness, 28% of patients committed suicide attempts and 37% were hospitalized. Twenty-six per cent of the patients had high levels of social deprivation.

Patients with higher levels of social deprivation had a more acute clinical onset and a worse short-term outcome, characterized by more severe positive symptoms, an higher number of voluntary and compulsory hospitalizations, and a reduced engagement with outpatient mental health facilities. No significant differences were found as regards suicidal attempts.

These results highlight that social deprivation has a negative impact on short-term outcome of schizophrenia and on patients’ engagement with mental health services and on, and suggest the need of targeting interventions on the basis of patients’ clinical and social needs.

Host of studies have now examined QoL in patients with major depressive disorder and schizophrenia until recently few had specifically focused upon QoL in patients with bipolar disorder. The purpose of the present study was to find out the QoL data in patients suffering from bipolar disorder in clinical remission and examine the extent of the effects of the demographical and clinical data on QoL in these patients. The second aim was to compare the QoL data with the data of patients suffering from schizophrenia in clinical remission and with healthy controls.

Data were obtained by using the quality of life questionnaire (Quality of Life Enjoyment and Satisfaction - Q-LES-Q) for 41 bipolar patients in clinical remission. The data of these subjects were compared with the data of 40 schizophrenic patients in clinical remission and with 40 healthy controls.

There are statistically significant difference in comparison with schizophrenic patients, but not in comparison with healthy controls. There were higher mean scores in most Q-LES-Q summary scales in patients with bipolar disorder in comparison with schizophrenic patients and in some summary scales in comparison with healthy controls.

Our results suggest the same or higher subjective quality of life in patients suffering with bipolar disorder in clinical remission in comparison with healthy controls and higher subjective quality of life in bipolar patients in clinical remission in comparison with schizophrenic patients in clinical remission.

Although medication is the most important part of treatment, psychotherapy can also play an important role in helping schizophrenics manage anxiety and deal with interpersonal relationships, and treatment for the disorder usually consists of a combination of medication, therapy, and various types of rehabilitation. Family therapy has worked well for many patients, educating both patients and their families about the nature of schizophrenia and helping them in their cooperative effort to cope with the disorder. Psychoeducational intervention, also at its first level (information group), has shown the capacity of increasing the adherence to pharmacological treatment. On the other hand, the second level (support group, psychoeducational family intervention) is able to reduce both the familial EE level and the rate of relapse in chronic schizophrenic patients. The stress-vulnerability model conceives of the symptoms of schizophrenia as resulting from the actions of environmental stresses on the vulnerable individual. Psychotherapies are ideally suited to address a number of stress and vulnerability factors. There now exists a body of literature, including a number of methodologically sound randomized controlled trials covering four types of psychotherapy of schizophrenia which can be implemented in the general clinical setting: family interventions; cognitive behavioural psychotherapy; social skills training; and psychoeducation. Data on effectiveness from these trials can be used to guide clinical practice.

It is well known that stress impacts on depression.The talk will discuss the mechanisms by which this impact occurs. We will consider the Hypothalamopituitary axis, as well as the role of serotonin, but, further than this, we will consider how stress ultimately affects the balance between trophic and atrophic factors within the cell and thence now stress may affect the balance between atrophy and neurogenesis. We will also discuss the possibility of a role for immunological factors.

The most prevalent mental disorders among suicide victims are depressive syndromes. Beside depression, research relates a wide range of psychosocial characteristics and stressors to suicide behaviour. Increasing amount of data about suicidal behaviour indicates that suicide is familial and that familial transmission of suicidal behaviour cannot be explained by the transmission of psychiatric disorder alone. Genetic and epigenetic effects are involved on suicidal behaviour beside environmental factors. Aberrant genes regulating serotoninergic, dopaminergic and noradrenergic systems could increase suicidal risk. Associations between catechol-O-methyltransferase (COMT) and tryptophan hydroxylase 2 (TPH2) polymorphisms, the rate-limiting enzyme for brain serotonin, and completed suicide were observed in suicide victims in populations with high suicide risk. On the other hand, it is also known that brain-derived neurotrophic factor (BDNF) influences a variety of neural processes during the development like neurogenesis, neuronal survival, and maturation of neural development pathways and it seems that BDNF plays a central role in neurobiology of suicidal behaviour and depression. The Met-carrying genotypes and Met allele seems to be connected with increased risk for suicide. The dynamic nature of the epigenetic mechanisms could be involved in the predominant episodic clinical picture of depression. The potential reversibility of epigenetic modifications could be important for management of patients with bipolar disorder offering the opportunity to influence aberrant gene expression by modifying environmental factors with the methods such as psychotherapy.

Since the nineties, the study of social cognition has benefited from advances in neuroimaging that allowed to cartography the “social brain”. The available literature reports results of PET or fMRI experiments that globally agree on the topography of the cortical regions involved in understanding/representing other's persons. Among these regions, medial prefrontal structures, the sensorimotor cortex, the temporoparietal cortex including the superior temporal sulcus have been implicated in different aspects of social cognition. Brain cartography was successful in separating networks that detect/process social cues from those that maintain shared representations (mirror system), or process inferences about others’ mental states (mentalization or theory of mind system). Although the neural bases of these systems are distinguished in many experiments, their mutual relations are yet hypothetical. Moreover, their main cognitive characteristics, such as their explicit/implicit or automatic/controlled nature, are mostly unknown. The use of cognitive electrophysiology (EEG and MEG) appears promising as a way to address these issues. Recent works based on these techniques demonstrate that theory of mind inferences are related with magnetic activation of the temporo-parietal junction as soon as 300 to 500 milliseconds post-stimuli when comic-strips with intentional characters are presented to subjects. Furthermore, these activations are modulated by top-down influences such as prior instructions urging the subjects to focus on the characters’ mental states.

These results will be discussed with respect to their impact on schizophrenia research.

The ability to read faces is a basic component of social cognition, and has gained considerable interest over the past decades in schizophrenia research. It has been shown to be closely related to psychosocial functioning and quality of life in schizophrenia. Use of event-related potential (ERP) paradigms to measure neural activity during emotion processing has become a major approach in affective neuroscience, since this method captures the exact time course of the emotional information-processing cascade from early to later processing stages with a millisecond-resolution. Emotional stimuli have been shown to elicit an increased processing of perceptual information, and increased attentional allocation. ERP studies of emotion recognition paradigms with schizophrenia patients have rapidly accumulated in the past years. However, results are still divergent and often controversial as to where and when abnormal activation patterns occur in the course of emotion processing as compared to healthy controls. The variability of findings has given room for interpreting results as supporting both a bottom-up, initial sensory-encoding-deficit-view, and also a later, top-down contextual-attentional-deficit view. This presentation will give an overview on findings of emotion recognition deficits as measured by the ERP technique in schizophrenia patients. Finally, we present our own results of fearful face processing and relate electrophysiological results to the clinical symptomatology of fear in schizophrenia. Thus, we attempt to broaden the context of interpreting electrophysiological abnormalities seen in face processing in schizophrenia via linking electrophysiological and clinical findings.

There is a large variation between and within European countries in the number of psychiatric emergencies and involuntary admissions, although there is discussion about the reliability of these figures. The number of involuntary admissions is rising in some countries, including Belgium and the Netherlands. Reasons for an increase in involuntary admissions are unknown. Factors found to be associated with an increase in involuntary admissions include change in mental health laws. When the numbers of involuntary admissions continue to increase, more hospital beds are needed.

Preventive interventions such as assertive outreach, compliance therapy, and crisis plans are needed to stop the increase in psychiatric emergencies and involuntary admissions. Assertive outreach in Europe failed to show reductions in involuntary admissions. There has been less research on the effects of compliance therapy or crisis plans. One study on the effects of compliance therapy showed a trend in the reduction of involuntary admissions. One other study on the effects of crisis plans showed a beneficial effect on the number of involuntary admissions, but two other studies failed to show an effect. Moreover, the use of crisis plans seems to be very limited in clinical practice. More effective interventions to reduce the number of psychiatric emergencies and involuntary admissions are urgently needed. We will discuss the ingredients of such an intervention based on results of earlier studies.

There is growing evidence of abnormalities of high-frequency oscillations in the gamma range of the electroencephalography in schizophrenia. The generation of neural activity in the gammaband was shown to be critically related to a glutamatergic and GABAergic microcircuit which is also known to be involved in the pathophysiology of schizophrenia. One example of such gamma oscillations is the early auditory evoked gamma band response (aeGBR). We aimed to investigate whether there are altered aeGBR and activity of its sources in the anterior cingulate cortex and/or the auditory cortex (identified as sources of the GBR previously) in schizophrenic patients and in first-degree relatives of schizophrenia patients.

We investigated the early aeGBR and its sources (LORETA source localisation) in 90 medicated patients with schizophrenia and in 17 unaffected first-degree relatives of patients with schizophrenia using an auditory reaction task (comparison with age-, gender- and educational-level-matched control groups).

Evoked power and phase locking of the aeGBR was reduced in schizophrenia patients and healthy first-degree relatives of patients with schizophrenia. This effect was due to a reduced activity in the auditory cortex and the anterior cingulate cortex. The findings are in line with the hypothesis of a disturbed GABAergic interneural modulation of pyramidal cells in schizophrenia and findings of different schizophrenia risk genes associated with transmission at glutamatergic and GABAergic synapses. The results regarding the first-degree relatives of patients with schizophrenia point to the applicability of this marker as a heritable intermediate phenotype for schizophrenia.